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CKD-EPI eGFR formula surpasses alternatives in young adults
PHILADELPHIA –
The two alternative formulas for calculating eGFR, the CKiD U25 (Chronic Kidney Disease in Children under 25) and the European Kidney Function Consortium equations, showed higher levels of bias that resulted in underestimates of kidney function, particularly in younger adults 18-25 years old and in those with higher eGFR values, Leslie A. Inker, MD, said at Kidney Week 2023, organized by the American Society of Nephrology.
However, for young adults with a history of childhood CKD and especially for those who continue under the care of pediatric clinicians even after they become young adults, use of the CKiD U25 equation, remains a reasonable option, said Dr. Inker, professor and director of the Kidney and Blood Pressure Center at Tufts Medical Center in Boston. The CKiD U25 equation is intended for people aged 1-25 years and came out in late 2020.
Pediatric nephrologists use the CKiD U25 but the results of the 2021 CKD-EPI race-free equation is what U.S. clinical labs routinely report for people aged 18 or older. “Our findings support the current practice of pediatric nephrologists” who may opt to use the CKiD U25 even when a patient turns 18 years or older, Dr. Inker said in an interview.
But the new results also support the current practice of U.S. labs, which is to focus on calculating eGFR in anyone at least 18 years old using the 2021 equation developed by the CKD-EPI, work led by Dr. Inker. The new findings confirm routine use of the 2021 CKD-EPI equation in adults as young as 18 years old, especially when they’re having their eGFR calculated for the first time, she said.
Discontinuity changing from CKiD U25 to CKD-EPI is ‘not huge’
“It’s important to understand that the 2021 CKD-EPI equation works in young adults,” noted Josef Coresh, MD, PhD, professor of clinical epidemiology at Johns Hopkins University, Baltimore, who collaborated on both the current study and on developing the 2021 CKD-EPI equation.
The new data show that the discontinuity in eGFR produced by switching from the CKiD U25 formula to the 2021 CKD-EPI formula “is not huge, maybe about 5 mL/min per 1.73 m2 higher. People should focus on the new baseline and subsequent trends, not the modest difference between equations,” Dr. Coresh advised in an interview.
The study run by Dr. Inker and her associates used 1,491 people aged 18-40 years and enrolled in a cohort created by the CKD-EPI. They compared measured GFR levels in each subject with the estimates generated by the 2021 race-free CKD-EPI equation, the CKiD U25 equation, and a third equation developed by the EKFC and introduced in 2021.
Less bias with the 2021 CKD-EPI equation
The researchers compared the three eGFR equations with their respective measured GFR values by two metrics: bias, defined as the median difference between measured and estimated GFR; and the percentage of eGFR values that fell within 30% of the corresponding measured GFR value.
The results showed that bias was lowest using the 2021 CKD-EPI equation, with an overall median difference of 0.5 mL/min per 1.73 m2. This compared with median differences of 7.2 with the CKiD U25 equation and 4.9 mL/min per 1.73 m2 with the EKFC equation. The disparity in bias was greatest among those with eGFR values in the range of 60-90 mL/min per 1.73 m2 and was also greatest for those 18-25 years old.
The CKD-EPI equation results also showed the greatest consistency of bias across the entire 18- to 40-year-old range. Between-group differences were small for the percentage of eGFR values that fell within 30% of measured GFR, with all three equations scoring in the range of 88%-90%.
The study received no commercial funding. Dr. Inker is a consultant to Diamtrix and her department receives research funding from Chinook, Omeros, Reata, and Tricida. Dr. Coresh is a consultant to Healthy.io and SomaLogic and he has an ownership interest in Healthy.io.
PHILADELPHIA –
The two alternative formulas for calculating eGFR, the CKiD U25 (Chronic Kidney Disease in Children under 25) and the European Kidney Function Consortium equations, showed higher levels of bias that resulted in underestimates of kidney function, particularly in younger adults 18-25 years old and in those with higher eGFR values, Leslie A. Inker, MD, said at Kidney Week 2023, organized by the American Society of Nephrology.
However, for young adults with a history of childhood CKD and especially for those who continue under the care of pediatric clinicians even after they become young adults, use of the CKiD U25 equation, remains a reasonable option, said Dr. Inker, professor and director of the Kidney and Blood Pressure Center at Tufts Medical Center in Boston. The CKiD U25 equation is intended for people aged 1-25 years and came out in late 2020.
Pediatric nephrologists use the CKiD U25 but the results of the 2021 CKD-EPI race-free equation is what U.S. clinical labs routinely report for people aged 18 or older. “Our findings support the current practice of pediatric nephrologists” who may opt to use the CKiD U25 even when a patient turns 18 years or older, Dr. Inker said in an interview.
But the new results also support the current practice of U.S. labs, which is to focus on calculating eGFR in anyone at least 18 years old using the 2021 equation developed by the CKD-EPI, work led by Dr. Inker. The new findings confirm routine use of the 2021 CKD-EPI equation in adults as young as 18 years old, especially when they’re having their eGFR calculated for the first time, she said.
Discontinuity changing from CKiD U25 to CKD-EPI is ‘not huge’
“It’s important to understand that the 2021 CKD-EPI equation works in young adults,” noted Josef Coresh, MD, PhD, professor of clinical epidemiology at Johns Hopkins University, Baltimore, who collaborated on both the current study and on developing the 2021 CKD-EPI equation.
The new data show that the discontinuity in eGFR produced by switching from the CKiD U25 formula to the 2021 CKD-EPI formula “is not huge, maybe about 5 mL/min per 1.73 m2 higher. People should focus on the new baseline and subsequent trends, not the modest difference between equations,” Dr. Coresh advised in an interview.
The study run by Dr. Inker and her associates used 1,491 people aged 18-40 years and enrolled in a cohort created by the CKD-EPI. They compared measured GFR levels in each subject with the estimates generated by the 2021 race-free CKD-EPI equation, the CKiD U25 equation, and a third equation developed by the EKFC and introduced in 2021.
Less bias with the 2021 CKD-EPI equation
The researchers compared the three eGFR equations with their respective measured GFR values by two metrics: bias, defined as the median difference between measured and estimated GFR; and the percentage of eGFR values that fell within 30% of the corresponding measured GFR value.
The results showed that bias was lowest using the 2021 CKD-EPI equation, with an overall median difference of 0.5 mL/min per 1.73 m2. This compared with median differences of 7.2 with the CKiD U25 equation and 4.9 mL/min per 1.73 m2 with the EKFC equation. The disparity in bias was greatest among those with eGFR values in the range of 60-90 mL/min per 1.73 m2 and was also greatest for those 18-25 years old.
The CKD-EPI equation results also showed the greatest consistency of bias across the entire 18- to 40-year-old range. Between-group differences were small for the percentage of eGFR values that fell within 30% of measured GFR, with all three equations scoring in the range of 88%-90%.
The study received no commercial funding. Dr. Inker is a consultant to Diamtrix and her department receives research funding from Chinook, Omeros, Reata, and Tricida. Dr. Coresh is a consultant to Healthy.io and SomaLogic and he has an ownership interest in Healthy.io.
PHILADELPHIA –
The two alternative formulas for calculating eGFR, the CKiD U25 (Chronic Kidney Disease in Children under 25) and the European Kidney Function Consortium equations, showed higher levels of bias that resulted in underestimates of kidney function, particularly in younger adults 18-25 years old and in those with higher eGFR values, Leslie A. Inker, MD, said at Kidney Week 2023, organized by the American Society of Nephrology.
However, for young adults with a history of childhood CKD and especially for those who continue under the care of pediatric clinicians even after they become young adults, use of the CKiD U25 equation, remains a reasonable option, said Dr. Inker, professor and director of the Kidney and Blood Pressure Center at Tufts Medical Center in Boston. The CKiD U25 equation is intended for people aged 1-25 years and came out in late 2020.
Pediatric nephrologists use the CKiD U25 but the results of the 2021 CKD-EPI race-free equation is what U.S. clinical labs routinely report for people aged 18 or older. “Our findings support the current practice of pediatric nephrologists” who may opt to use the CKiD U25 even when a patient turns 18 years or older, Dr. Inker said in an interview.
But the new results also support the current practice of U.S. labs, which is to focus on calculating eGFR in anyone at least 18 years old using the 2021 equation developed by the CKD-EPI, work led by Dr. Inker. The new findings confirm routine use of the 2021 CKD-EPI equation in adults as young as 18 years old, especially when they’re having their eGFR calculated for the first time, she said.
Discontinuity changing from CKiD U25 to CKD-EPI is ‘not huge’
“It’s important to understand that the 2021 CKD-EPI equation works in young adults,” noted Josef Coresh, MD, PhD, professor of clinical epidemiology at Johns Hopkins University, Baltimore, who collaborated on both the current study and on developing the 2021 CKD-EPI equation.
The new data show that the discontinuity in eGFR produced by switching from the CKiD U25 formula to the 2021 CKD-EPI formula “is not huge, maybe about 5 mL/min per 1.73 m2 higher. People should focus on the new baseline and subsequent trends, not the modest difference between equations,” Dr. Coresh advised in an interview.
The study run by Dr. Inker and her associates used 1,491 people aged 18-40 years and enrolled in a cohort created by the CKD-EPI. They compared measured GFR levels in each subject with the estimates generated by the 2021 race-free CKD-EPI equation, the CKiD U25 equation, and a third equation developed by the EKFC and introduced in 2021.
Less bias with the 2021 CKD-EPI equation
The researchers compared the three eGFR equations with their respective measured GFR values by two metrics: bias, defined as the median difference between measured and estimated GFR; and the percentage of eGFR values that fell within 30% of the corresponding measured GFR value.
The results showed that bias was lowest using the 2021 CKD-EPI equation, with an overall median difference of 0.5 mL/min per 1.73 m2. This compared with median differences of 7.2 with the CKiD U25 equation and 4.9 mL/min per 1.73 m2 with the EKFC equation. The disparity in bias was greatest among those with eGFR values in the range of 60-90 mL/min per 1.73 m2 and was also greatest for those 18-25 years old.
The CKD-EPI equation results also showed the greatest consistency of bias across the entire 18- to 40-year-old range. Between-group differences were small for the percentage of eGFR values that fell within 30% of measured GFR, with all three equations scoring in the range of 88%-90%.
The study received no commercial funding. Dr. Inker is a consultant to Diamtrix and her department receives research funding from Chinook, Omeros, Reata, and Tricida. Dr. Coresh is a consultant to Healthy.io and SomaLogic and he has an ownership interest in Healthy.io.
AT KIDNEY WEEK 2023
Blood pressure lowering reduces dementia risk
Results of a trial using an intensive, 4-year program aimed at blood pressure lowering showed that intervention reduced not only blood pressure, but also significantly reduced the risk of total dementia over that period.
and cognitive impairment no dementia (CIND), a secondary outcome, was also significantly reduced by 16%.
“Blood pressure reduction is effective in reducing the risk of dementia in patients with hypertension,” concluded Jiang He, MD, PhD, professor of epidemiology and medicine and director of Tulane University’s Translational Science Institute, New Orleans. “This proven, effective intervention should be widely scaled up to reduce the global burden of dementia.”
He presented these results from the China Rural Hypertension Control Project (CRHCP) at the annual scientific sessions of the American Heart Association.
Target organ damage
Keith Ferdinand, MD, also from Tulane University, commented on the findings during a press conference at the meeting, noting that the result “opens our opportunity to recognize that the target organ damage of hypertension also now includes dementia.”
The researchers were able to “rigorously lower blood pressure from 157 to 127.6 in the intervention, 155 to 147 in the controls – 22 mg Hg – and if you look at the P values for all the various outcomes, they were very robust,” Dr. Ferdinand said.
Another interesting feature about the strategy used in this trial is that “this was true team-based care,” he pointed out. The trained interventionists in the study, called village doctors, collaborated with primary care physicians and initiated medications. “They stayed on a simple treatment protocol, and they were able to assist patients to ensure they had free medications, health coaching for lifestyle, home blood pressure measurement, and ensuring adherence.”
So, Dr. Ferdinand added, “one of the questions is whether this is a model we can use in other places around the globe, in places with low resources, and in the United States in disadvantaged populations.”
Public health priority
It’s estimated that the global number of those living with dementia will increase from 57.4 million in 2019 to 152.8 million by 2050, Dr. He said. “In the absence of curative treatment, the primary prevention of dementia through risk factor reduction, such as blood pressure lowering, becomes a public health priority.”
Previous randomized trials have lacked sample size and duration but have reported a nonsignificant reduction in dementia associated with antihypertensive treatment in patients with hypertension or a history of stroke, Dr. He noted.
This new trial aimed to test the effectiveness of intensive BP intervention to reduce the risk of all-cause dementia and cognitive impairment over a 48-month intervention period versus usual care.
It was an open-label, blinded-endpoint, cluster-randomized trial, and included 33,995 individual patients from 325 villages in China, aged 40 years and older, with untreated hypertension. The villages were randomly assigned to an intervention group or usual care, stratified by province, county, and township.
Patients were eligible if they had mean untreated systolic BP greater than 140 mm Hg and/or diastolic BP greater than 90 mm Hg or mean treated systolic BP of greater than 130 and/or diastolic greater than 80 mm Hg. Patients with a history of cardiovascular disease, chronic kidney disease, or diabetes and a mean systolic BP greater than 130 mm Hg and/or diastolic BP greater than 80 mm Hg from six measures on two different days were also eligible.
All were enrolled in the China New Rural Cooperative Medical Scheme, which covers 99% of rural residents for health care services, Dr. He noted.
The intervention was a simple stepped-care protocol for hypertension treatment, aimed at achieving a target systolic BP of less than 130 mm Hg and diastolic of less than 80 mm Hg.
Village doctors started and titrated antihypertensive treatment based on a protocol and were able to deliver discounted and free medications to patients. They also did health coaching on lifestyle modification and adherence to medication, and instructed patients on home BP monitoring.
Patients were provided training, supervision, and consultation by primary care physicians and hypertension specialists.
At the month 48 follow-up visit, the participants were assessed by neurologists who were blinded to randomization assignments. Neurologists did a variety of tests and assessments including collecting data on the patient’s medical and psychiatric history and risk factors for dementia, as well as neurologic assessment using the Mini-Mental State Examination, the Functional Activities Questionnaire, and the Quick Dementia Rating System.
The primary outcome was all-cause dementia, defined according to recommendations from the National Institute on Aging–Alzheimer’s Association work groups on diagnostic guidelines for Alzheimer’s disease.
Secondary outcomes included CIND, a composite outcome of dementia or CIND, and a composite of dementia or deaths.
The final diagnosis of all-cause dementia or CIND was made by an expert adjudication panel blinded to the intervention assignment.
At 48 months, 91.3% of patients completed the follow-up for clinical outcomes. Participants were an average of 63 years of age, 61% were female, and 23% had less than a primary school education, Dr. He noted.
The net group differences in systolic and diastolic BP reduction were 22 and 9.3 mm Hg, respectively (P < .0001).
Significant differences were also seen between the groups in the primary outcome of all-cause dementia, as well as secondary outcomes of CIND, dementia or cognitive impairment, or dementia or deaths.
Serious adverse events were more common in the usual care group, and there was no difference between groups in the occurrence of falls or syncope.
The effect was consistent across subgroups, Dr. He said, including age, sex, education, cigarette smoking, body mass index, systolic BP, and fasting plasma glucose at baseline.
First definitive evidence
Invited discussant for the trial, Daniel W. Jones, MD, University of Mississippi Medical Center, Jackson, and past president of the AHA, pointed out that previous results from CRHCP on cardiovascular outcomes, reported earlier in 2023 in The Lancet, showed that, similar to results of the large SPRINT trial, lowering systolic BP to a goal of less than 130 mm Hg reduced a composite endpoint of MI, stroke, heart failure requiring hospitalization, and cardiovascular disease death over the 36-month follow-up.
The SPRINT findings also suggested a possible reduction in dementia, Dr. Jones said.
Now, in these new CRHCP results, “there was a clear benefit for intensive BP control in reducing risk for dementia and cognitive dysfunction,” he said. “This is, importantly, the first definitive evidence of dementia risk reduction demonstrated in a randomized controlled clinical trial. This outcome supports observational data that shows a strong relationship between BP and dementia.”
Since it is the first of its kind though, replication of the results will be important, he noted.
The study also showed that the intervention, using minimally trained village doctors, sustained BP control for 48 months. “This model could be used in any setting with modifications, including in the United States,” Dr. Jones said.
The study was supported by the Ministry of Science and Technology of China; U.S. investigators did not receive financial support from this study. The researchers and Dr. Jones disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Results of a trial using an intensive, 4-year program aimed at blood pressure lowering showed that intervention reduced not only blood pressure, but also significantly reduced the risk of total dementia over that period.
and cognitive impairment no dementia (CIND), a secondary outcome, was also significantly reduced by 16%.
“Blood pressure reduction is effective in reducing the risk of dementia in patients with hypertension,” concluded Jiang He, MD, PhD, professor of epidemiology and medicine and director of Tulane University’s Translational Science Institute, New Orleans. “This proven, effective intervention should be widely scaled up to reduce the global burden of dementia.”
He presented these results from the China Rural Hypertension Control Project (CRHCP) at the annual scientific sessions of the American Heart Association.
Target organ damage
Keith Ferdinand, MD, also from Tulane University, commented on the findings during a press conference at the meeting, noting that the result “opens our opportunity to recognize that the target organ damage of hypertension also now includes dementia.”
The researchers were able to “rigorously lower blood pressure from 157 to 127.6 in the intervention, 155 to 147 in the controls – 22 mg Hg – and if you look at the P values for all the various outcomes, they were very robust,” Dr. Ferdinand said.
Another interesting feature about the strategy used in this trial is that “this was true team-based care,” he pointed out. The trained interventionists in the study, called village doctors, collaborated with primary care physicians and initiated medications. “They stayed on a simple treatment protocol, and they were able to assist patients to ensure they had free medications, health coaching for lifestyle, home blood pressure measurement, and ensuring adherence.”
So, Dr. Ferdinand added, “one of the questions is whether this is a model we can use in other places around the globe, in places with low resources, and in the United States in disadvantaged populations.”
Public health priority
It’s estimated that the global number of those living with dementia will increase from 57.4 million in 2019 to 152.8 million by 2050, Dr. He said. “In the absence of curative treatment, the primary prevention of dementia through risk factor reduction, such as blood pressure lowering, becomes a public health priority.”
Previous randomized trials have lacked sample size and duration but have reported a nonsignificant reduction in dementia associated with antihypertensive treatment in patients with hypertension or a history of stroke, Dr. He noted.
This new trial aimed to test the effectiveness of intensive BP intervention to reduce the risk of all-cause dementia and cognitive impairment over a 48-month intervention period versus usual care.
It was an open-label, blinded-endpoint, cluster-randomized trial, and included 33,995 individual patients from 325 villages in China, aged 40 years and older, with untreated hypertension. The villages were randomly assigned to an intervention group or usual care, stratified by province, county, and township.
Patients were eligible if they had mean untreated systolic BP greater than 140 mm Hg and/or diastolic BP greater than 90 mm Hg or mean treated systolic BP of greater than 130 and/or diastolic greater than 80 mm Hg. Patients with a history of cardiovascular disease, chronic kidney disease, or diabetes and a mean systolic BP greater than 130 mm Hg and/or diastolic BP greater than 80 mm Hg from six measures on two different days were also eligible.
All were enrolled in the China New Rural Cooperative Medical Scheme, which covers 99% of rural residents for health care services, Dr. He noted.
The intervention was a simple stepped-care protocol for hypertension treatment, aimed at achieving a target systolic BP of less than 130 mm Hg and diastolic of less than 80 mm Hg.
Village doctors started and titrated antihypertensive treatment based on a protocol and were able to deliver discounted and free medications to patients. They also did health coaching on lifestyle modification and adherence to medication, and instructed patients on home BP monitoring.
Patients were provided training, supervision, and consultation by primary care physicians and hypertension specialists.
At the month 48 follow-up visit, the participants were assessed by neurologists who were blinded to randomization assignments. Neurologists did a variety of tests and assessments including collecting data on the patient’s medical and psychiatric history and risk factors for dementia, as well as neurologic assessment using the Mini-Mental State Examination, the Functional Activities Questionnaire, and the Quick Dementia Rating System.
The primary outcome was all-cause dementia, defined according to recommendations from the National Institute on Aging–Alzheimer’s Association work groups on diagnostic guidelines for Alzheimer’s disease.
Secondary outcomes included CIND, a composite outcome of dementia or CIND, and a composite of dementia or deaths.
The final diagnosis of all-cause dementia or CIND was made by an expert adjudication panel blinded to the intervention assignment.
At 48 months, 91.3% of patients completed the follow-up for clinical outcomes. Participants were an average of 63 years of age, 61% were female, and 23% had less than a primary school education, Dr. He noted.
The net group differences in systolic and diastolic BP reduction were 22 and 9.3 mm Hg, respectively (P < .0001).
Significant differences were also seen between the groups in the primary outcome of all-cause dementia, as well as secondary outcomes of CIND, dementia or cognitive impairment, or dementia or deaths.
Serious adverse events were more common in the usual care group, and there was no difference between groups in the occurrence of falls or syncope.
The effect was consistent across subgroups, Dr. He said, including age, sex, education, cigarette smoking, body mass index, systolic BP, and fasting plasma glucose at baseline.
First definitive evidence
Invited discussant for the trial, Daniel W. Jones, MD, University of Mississippi Medical Center, Jackson, and past president of the AHA, pointed out that previous results from CRHCP on cardiovascular outcomes, reported earlier in 2023 in The Lancet, showed that, similar to results of the large SPRINT trial, lowering systolic BP to a goal of less than 130 mm Hg reduced a composite endpoint of MI, stroke, heart failure requiring hospitalization, and cardiovascular disease death over the 36-month follow-up.
The SPRINT findings also suggested a possible reduction in dementia, Dr. Jones said.
Now, in these new CRHCP results, “there was a clear benefit for intensive BP control in reducing risk for dementia and cognitive dysfunction,” he said. “This is, importantly, the first definitive evidence of dementia risk reduction demonstrated in a randomized controlled clinical trial. This outcome supports observational data that shows a strong relationship between BP and dementia.”
Since it is the first of its kind though, replication of the results will be important, he noted.
The study also showed that the intervention, using minimally trained village doctors, sustained BP control for 48 months. “This model could be used in any setting with modifications, including in the United States,” Dr. Jones said.
The study was supported by the Ministry of Science and Technology of China; U.S. investigators did not receive financial support from this study. The researchers and Dr. Jones disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Results of a trial using an intensive, 4-year program aimed at blood pressure lowering showed that intervention reduced not only blood pressure, but also significantly reduced the risk of total dementia over that period.
and cognitive impairment no dementia (CIND), a secondary outcome, was also significantly reduced by 16%.
“Blood pressure reduction is effective in reducing the risk of dementia in patients with hypertension,” concluded Jiang He, MD, PhD, professor of epidemiology and medicine and director of Tulane University’s Translational Science Institute, New Orleans. “This proven, effective intervention should be widely scaled up to reduce the global burden of dementia.”
He presented these results from the China Rural Hypertension Control Project (CRHCP) at the annual scientific sessions of the American Heart Association.
Target organ damage
Keith Ferdinand, MD, also from Tulane University, commented on the findings during a press conference at the meeting, noting that the result “opens our opportunity to recognize that the target organ damage of hypertension also now includes dementia.”
The researchers were able to “rigorously lower blood pressure from 157 to 127.6 in the intervention, 155 to 147 in the controls – 22 mg Hg – and if you look at the P values for all the various outcomes, they were very robust,” Dr. Ferdinand said.
Another interesting feature about the strategy used in this trial is that “this was true team-based care,” he pointed out. The trained interventionists in the study, called village doctors, collaborated with primary care physicians and initiated medications. “They stayed on a simple treatment protocol, and they were able to assist patients to ensure they had free medications, health coaching for lifestyle, home blood pressure measurement, and ensuring adherence.”
So, Dr. Ferdinand added, “one of the questions is whether this is a model we can use in other places around the globe, in places with low resources, and in the United States in disadvantaged populations.”
Public health priority
It’s estimated that the global number of those living with dementia will increase from 57.4 million in 2019 to 152.8 million by 2050, Dr. He said. “In the absence of curative treatment, the primary prevention of dementia through risk factor reduction, such as blood pressure lowering, becomes a public health priority.”
Previous randomized trials have lacked sample size and duration but have reported a nonsignificant reduction in dementia associated with antihypertensive treatment in patients with hypertension or a history of stroke, Dr. He noted.
This new trial aimed to test the effectiveness of intensive BP intervention to reduce the risk of all-cause dementia and cognitive impairment over a 48-month intervention period versus usual care.
It was an open-label, blinded-endpoint, cluster-randomized trial, and included 33,995 individual patients from 325 villages in China, aged 40 years and older, with untreated hypertension. The villages were randomly assigned to an intervention group or usual care, stratified by province, county, and township.
Patients were eligible if they had mean untreated systolic BP greater than 140 mm Hg and/or diastolic BP greater than 90 mm Hg or mean treated systolic BP of greater than 130 and/or diastolic greater than 80 mm Hg. Patients with a history of cardiovascular disease, chronic kidney disease, or diabetes and a mean systolic BP greater than 130 mm Hg and/or diastolic BP greater than 80 mm Hg from six measures on two different days were also eligible.
All were enrolled in the China New Rural Cooperative Medical Scheme, which covers 99% of rural residents for health care services, Dr. He noted.
The intervention was a simple stepped-care protocol for hypertension treatment, aimed at achieving a target systolic BP of less than 130 mm Hg and diastolic of less than 80 mm Hg.
Village doctors started and titrated antihypertensive treatment based on a protocol and were able to deliver discounted and free medications to patients. They also did health coaching on lifestyle modification and adherence to medication, and instructed patients on home BP monitoring.
Patients were provided training, supervision, and consultation by primary care physicians and hypertension specialists.
At the month 48 follow-up visit, the participants were assessed by neurologists who were blinded to randomization assignments. Neurologists did a variety of tests and assessments including collecting data on the patient’s medical and psychiatric history and risk factors for dementia, as well as neurologic assessment using the Mini-Mental State Examination, the Functional Activities Questionnaire, and the Quick Dementia Rating System.
The primary outcome was all-cause dementia, defined according to recommendations from the National Institute on Aging–Alzheimer’s Association work groups on diagnostic guidelines for Alzheimer’s disease.
Secondary outcomes included CIND, a composite outcome of dementia or CIND, and a composite of dementia or deaths.
The final diagnosis of all-cause dementia or CIND was made by an expert adjudication panel blinded to the intervention assignment.
At 48 months, 91.3% of patients completed the follow-up for clinical outcomes. Participants were an average of 63 years of age, 61% were female, and 23% had less than a primary school education, Dr. He noted.
The net group differences in systolic and diastolic BP reduction were 22 and 9.3 mm Hg, respectively (P < .0001).
Significant differences were also seen between the groups in the primary outcome of all-cause dementia, as well as secondary outcomes of CIND, dementia or cognitive impairment, or dementia or deaths.
Serious adverse events were more common in the usual care group, and there was no difference between groups in the occurrence of falls or syncope.
The effect was consistent across subgroups, Dr. He said, including age, sex, education, cigarette smoking, body mass index, systolic BP, and fasting plasma glucose at baseline.
First definitive evidence
Invited discussant for the trial, Daniel W. Jones, MD, University of Mississippi Medical Center, Jackson, and past president of the AHA, pointed out that previous results from CRHCP on cardiovascular outcomes, reported earlier in 2023 in The Lancet, showed that, similar to results of the large SPRINT trial, lowering systolic BP to a goal of less than 130 mm Hg reduced a composite endpoint of MI, stroke, heart failure requiring hospitalization, and cardiovascular disease death over the 36-month follow-up.
The SPRINT findings also suggested a possible reduction in dementia, Dr. Jones said.
Now, in these new CRHCP results, “there was a clear benefit for intensive BP control in reducing risk for dementia and cognitive dysfunction,” he said. “This is, importantly, the first definitive evidence of dementia risk reduction demonstrated in a randomized controlled clinical trial. This outcome supports observational data that shows a strong relationship between BP and dementia.”
Since it is the first of its kind though, replication of the results will be important, he noted.
The study also showed that the intervention, using minimally trained village doctors, sustained BP control for 48 months. “This model could be used in any setting with modifications, including in the United States,” Dr. Jones said.
The study was supported by the Ministry of Science and Technology of China; U.S. investigators did not receive financial support from this study. The researchers and Dr. Jones disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
FROM AHA 2023
Obinutuzumab promotes renal preservation in lupus nephritis
TOPLINE:
Adults with lupus nephritis (LN) who received obinutuzumab (Gazyva) plus standard of care therapy experienced significantly improved kidney function and fewer flares compared with those given a placebo plus standard of care.
METHODOLOGY:
- Researchers conducted a post hoc analysis of the phase 2 NOBILITY study, a randomized trial in which 63 adults received 1,000 mg of obinutuzumab or placebo by infusion on day 1 and at weeks 2, 24, and 26.
- Outcomes were time to an unfavorable kidney outcome, defined by the first of any of the following events: treatment failure, doubling of serum creatinine, or death; researchers also measured LN flare outcomes including the first 30% and 40% declines in estimated glomerular filtration rate (eGFR) from baseline, chronic eGFR slope, and how many patients achieved complete renal response (CRR) on no more than 7.5 mg of prednisone.
TAKEAWAY:
- Adding obinutuzumab to the treatment of patients with LN reduced the risk of the composite outcome by 60% and reduced the risk for LN flare by 57%.
- The risk of first eGFR 30% and 40% decline was reduced by 80% and 91%, respectively, with obinutuzumab, and patients who took obinutuzumab had a significantly slower eGFR decline than with placebo (annualized eGFR slope advantage, 4.1 mL/min/1.73 m2 /year).
- At 76 weeks (1.5 years), 38% of patients receiving obinutuzumab achieved CRR on 7.5 mg or less of daily prednisone, compared with 16% of placebo patients, but this difference was not statistically significant at 104 weeks (2 years).
- The total numbers of unfavorable kidney outcomes for obinutuzumab vs. placebo were 12 vs. 24 for treatment failure, 1 vs. 6 for creatinine doubling, and 1 vs. 4 for death, respectively.
IN PRACTICE:
“By reducing flare risk, obinutuzumab should decrease the accumulation of chronic parenchymal kidney damage,” the authors wrote.
SOURCE:
The study was presented at the American College of Rheumatology (ACR) 2023 annual meeting and was published online in Arthritis & Rheumatology. The lead author was Brad H. Rovin, MD, of The Ohio State University in Columbus.
LIMITATIONS:
The analyses were post hoc and not prespecified, and the number of events was small, which prevented statistical confirmation, but the analyses are being repeated in an ongoing phase 3 study.
DISCLOSURES:
The study was supported by F. Hoffman–La Roche. Dr. Rovin reported receiving personal fees from F. Hoffman–La Roche during the conduct of the original trial. Several coauthors are F. Hoffman–La Roche employees.
A version of this article first appeared on Medscape.com.
TOPLINE:
Adults with lupus nephritis (LN) who received obinutuzumab (Gazyva) plus standard of care therapy experienced significantly improved kidney function and fewer flares compared with those given a placebo plus standard of care.
METHODOLOGY:
- Researchers conducted a post hoc analysis of the phase 2 NOBILITY study, a randomized trial in which 63 adults received 1,000 mg of obinutuzumab or placebo by infusion on day 1 and at weeks 2, 24, and 26.
- Outcomes were time to an unfavorable kidney outcome, defined by the first of any of the following events: treatment failure, doubling of serum creatinine, or death; researchers also measured LN flare outcomes including the first 30% and 40% declines in estimated glomerular filtration rate (eGFR) from baseline, chronic eGFR slope, and how many patients achieved complete renal response (CRR) on no more than 7.5 mg of prednisone.
TAKEAWAY:
- Adding obinutuzumab to the treatment of patients with LN reduced the risk of the composite outcome by 60% and reduced the risk for LN flare by 57%.
- The risk of first eGFR 30% and 40% decline was reduced by 80% and 91%, respectively, with obinutuzumab, and patients who took obinutuzumab had a significantly slower eGFR decline than with placebo (annualized eGFR slope advantage, 4.1 mL/min/1.73 m2 /year).
- At 76 weeks (1.5 years), 38% of patients receiving obinutuzumab achieved CRR on 7.5 mg or less of daily prednisone, compared with 16% of placebo patients, but this difference was not statistically significant at 104 weeks (2 years).
- The total numbers of unfavorable kidney outcomes for obinutuzumab vs. placebo were 12 vs. 24 for treatment failure, 1 vs. 6 for creatinine doubling, and 1 vs. 4 for death, respectively.
IN PRACTICE:
“By reducing flare risk, obinutuzumab should decrease the accumulation of chronic parenchymal kidney damage,” the authors wrote.
SOURCE:
The study was presented at the American College of Rheumatology (ACR) 2023 annual meeting and was published online in Arthritis & Rheumatology. The lead author was Brad H. Rovin, MD, of The Ohio State University in Columbus.
LIMITATIONS:
The analyses were post hoc and not prespecified, and the number of events was small, which prevented statistical confirmation, but the analyses are being repeated in an ongoing phase 3 study.
DISCLOSURES:
The study was supported by F. Hoffman–La Roche. Dr. Rovin reported receiving personal fees from F. Hoffman–La Roche during the conduct of the original trial. Several coauthors are F. Hoffman–La Roche employees.
A version of this article first appeared on Medscape.com.
TOPLINE:
Adults with lupus nephritis (LN) who received obinutuzumab (Gazyva) plus standard of care therapy experienced significantly improved kidney function and fewer flares compared with those given a placebo plus standard of care.
METHODOLOGY:
- Researchers conducted a post hoc analysis of the phase 2 NOBILITY study, a randomized trial in which 63 adults received 1,000 mg of obinutuzumab or placebo by infusion on day 1 and at weeks 2, 24, and 26.
- Outcomes were time to an unfavorable kidney outcome, defined by the first of any of the following events: treatment failure, doubling of serum creatinine, or death; researchers also measured LN flare outcomes including the first 30% and 40% declines in estimated glomerular filtration rate (eGFR) from baseline, chronic eGFR slope, and how many patients achieved complete renal response (CRR) on no more than 7.5 mg of prednisone.
TAKEAWAY:
- Adding obinutuzumab to the treatment of patients with LN reduced the risk of the composite outcome by 60% and reduced the risk for LN flare by 57%.
- The risk of first eGFR 30% and 40% decline was reduced by 80% and 91%, respectively, with obinutuzumab, and patients who took obinutuzumab had a significantly slower eGFR decline than with placebo (annualized eGFR slope advantage, 4.1 mL/min/1.73 m2 /year).
- At 76 weeks (1.5 years), 38% of patients receiving obinutuzumab achieved CRR on 7.5 mg or less of daily prednisone, compared with 16% of placebo patients, but this difference was not statistically significant at 104 weeks (2 years).
- The total numbers of unfavorable kidney outcomes for obinutuzumab vs. placebo were 12 vs. 24 for treatment failure, 1 vs. 6 for creatinine doubling, and 1 vs. 4 for death, respectively.
IN PRACTICE:
“By reducing flare risk, obinutuzumab should decrease the accumulation of chronic parenchymal kidney damage,” the authors wrote.
SOURCE:
The study was presented at the American College of Rheumatology (ACR) 2023 annual meeting and was published online in Arthritis & Rheumatology. The lead author was Brad H. Rovin, MD, of The Ohio State University in Columbus.
LIMITATIONS:
The analyses were post hoc and not prespecified, and the number of events was small, which prevented statistical confirmation, but the analyses are being repeated in an ongoing phase 3 study.
DISCLOSURES:
The study was supported by F. Hoffman–La Roche. Dr. Rovin reported receiving personal fees from F. Hoffman–La Roche during the conduct of the original trial. Several coauthors are F. Hoffman–La Roche employees.
A version of this article first appeared on Medscape.com.
Risk calculator for early-stage CKD may soon enter U.S. market
PHILADELPHIA – The analyses offer the possibility of focusing intensified medical management of early-stage CKD on those patients who could potentially receive the most benefit.
The Klinrisk model predicts the risk of an adult with early-stage CKD developing either a 40% or greater drop in estimated glomerular filtration rate or kidney failure. It calculates risk based on 20 lab-measured variables that include serum creatinine, urine albumin-to-creatinine ratio, and other values taken from routinely ordered tests such as complete blood cell counts, chemistry panels, comprehensive metabolic panels, and urinalysis.
In the most recent and largest external validation study using data from 4.6 million American adults enrolled in commercial and Medicare insurance plans, the results showed Klinrisk correctly predicted CKD progression in 80%-83% of individuals over 2 years and in 78%-83% of individuals over 5 years, depending on the insurance provider, Navdeep Tangri, MD, PhD, reported at the annual meeting of the American Society of Nephrology. When urinalysis data were available, the model correctly predicted CKD progression in 81%-87% of individuals over 2 years and in 80%-87% of individuals over 5 years. These results follow prior reports of several other successful validations of Klinrisk.
‘Ready to implement’
“The Klinrisk model is ready to implement by any payer, health system, or clinic where the needed lab data are available,” said Dr. Tangri, a nephrologist and professor at the University of Manitoba, Winnipeg, and founder of Klinrisk Inc., the company developing and commercializing the Klinrisk assessment tool.
For the time being, Dr. Tangri sees Klinrisk as a population health device that can allow insurers and health systems to track management quality and quality improvement and to target patients who stand to benefit most from relatively expensive resources. This includes prescriptions for finerenone (Kerendia, Bayer) for people who also have type 2 diabetes, and agents from the class of sodium-glucose cotransporter 2 (SGLT2) inhibitors such as dapagliflozin (Farxiga, AstraZeneca) and empagliflozin (Jardiance, Boehringer Ingelheim and Lilly).
He has also begun discussions with the Food and Drug Administration about the data the agency will need to consider Klinrisk for potential approval as a new medical device, perhaps in 2025. That’s how he envisions getting a Klinrisk assessment into the hands of caregivers that they could use with individual patients to create an appropriate treatment plan.
Results from his new analysis showed that “all the kidney disease action is in the 10%-20% of people with the highest risk on Klinrisk, while not much happens in those in the bottom half,” Dr. Tangri said during his presentation.
“We’re trying to find the patients who get the largest [absolute] benefit from intensified treatment,” he added in an interview. “Klinrisk finds people with high-risk kidney disease early on, when kidney function is still normal or near normal. High-risk patients are often completely unrecognized. Risk-based management” that identifies the early-stage CKD patients who would benefit most from treatment with an SGLT2 inhibitor, finerenone, and other foundational treatments to slow CKD progression “is better than the free-for-all that occurs today.”
Simplified data collection
“Klinrisk is very effective,” but requires follow-up by clinicians and health systems to implement its findings, commented Josef Coresh, MD, a professor of clinical epidemiology at Johns Hopkins Bloomberg, Baltimore. Dr. Coresh compared it with a free equation that estimates a person’s risk for a 40% drop in kidney function over the next 3 years developed by Dr. Tangri, Dr. Coresh, and many collaborators led by Morgan C. Grams, MD, PhD, of New York University that they published in 2022, and posted on a website of the CKD Prognosis Consortium.
The CKD Prognosis Consortium formula “takes a different approach” from Klinrisk. The commercial formula “is simpler, only using lab measures, and avoids inputs taken from physical examination such as systolic blood pressure and body mass index and health history data such as smoking, noted Dr. Coresh. He also speculated that “a commercial formula that must be paid for may counterintuitively result in better follow-up for making management changes if it uses some of the resources for education and system changes.”
Using data from multiple sources, like the CKD Prognosis Consortium equation, can create implementation challenges, said Dr. Tangri. “Lab results don’t vary much,” which makes Klinrisk “quite an improvement for implementation. It’s easier to implement.”
Other findings from the newest validation study that Dr. Tangri presented were that the people studied with Klinrisk scores in the top 10% had, over the next 2 years of follow-up and compared with people in the bottom half for Klinrisk staging, a 3- to 5-fold higher rate of all-cause medical costs, a 13-30-fold increase in CKD-related costs, and a 5- to 10-fold increase in hospitalizations and ED visits.
Early identification of CKD and early initiation of intensified treatment for high-risk patients can reduce the rate of progression to dialysis, reduce hospitalizations for heart failure, and lower the cost of care, Dr. Tangri said.
The validation study in 4.6 million Americans was sponsored by Boehringer Ingelheim. Dr. Tangri founded and has an ownership interest in Klinrisk. He has also received honoraria from, has ownership interests in, and has been a consultant to multiple pharmaceutical companies. Dr. Coresh had no disclosures.
PHILADELPHIA – The analyses offer the possibility of focusing intensified medical management of early-stage CKD on those patients who could potentially receive the most benefit.
The Klinrisk model predicts the risk of an adult with early-stage CKD developing either a 40% or greater drop in estimated glomerular filtration rate or kidney failure. It calculates risk based on 20 lab-measured variables that include serum creatinine, urine albumin-to-creatinine ratio, and other values taken from routinely ordered tests such as complete blood cell counts, chemistry panels, comprehensive metabolic panels, and urinalysis.
In the most recent and largest external validation study using data from 4.6 million American adults enrolled in commercial and Medicare insurance plans, the results showed Klinrisk correctly predicted CKD progression in 80%-83% of individuals over 2 years and in 78%-83% of individuals over 5 years, depending on the insurance provider, Navdeep Tangri, MD, PhD, reported at the annual meeting of the American Society of Nephrology. When urinalysis data were available, the model correctly predicted CKD progression in 81%-87% of individuals over 2 years and in 80%-87% of individuals over 5 years. These results follow prior reports of several other successful validations of Klinrisk.
‘Ready to implement’
“The Klinrisk model is ready to implement by any payer, health system, or clinic where the needed lab data are available,” said Dr. Tangri, a nephrologist and professor at the University of Manitoba, Winnipeg, and founder of Klinrisk Inc., the company developing and commercializing the Klinrisk assessment tool.
For the time being, Dr. Tangri sees Klinrisk as a population health device that can allow insurers and health systems to track management quality and quality improvement and to target patients who stand to benefit most from relatively expensive resources. This includes prescriptions for finerenone (Kerendia, Bayer) for people who also have type 2 diabetes, and agents from the class of sodium-glucose cotransporter 2 (SGLT2) inhibitors such as dapagliflozin (Farxiga, AstraZeneca) and empagliflozin (Jardiance, Boehringer Ingelheim and Lilly).
He has also begun discussions with the Food and Drug Administration about the data the agency will need to consider Klinrisk for potential approval as a new medical device, perhaps in 2025. That’s how he envisions getting a Klinrisk assessment into the hands of caregivers that they could use with individual patients to create an appropriate treatment plan.
Results from his new analysis showed that “all the kidney disease action is in the 10%-20% of people with the highest risk on Klinrisk, while not much happens in those in the bottom half,” Dr. Tangri said during his presentation.
“We’re trying to find the patients who get the largest [absolute] benefit from intensified treatment,” he added in an interview. “Klinrisk finds people with high-risk kidney disease early on, when kidney function is still normal or near normal. High-risk patients are often completely unrecognized. Risk-based management” that identifies the early-stage CKD patients who would benefit most from treatment with an SGLT2 inhibitor, finerenone, and other foundational treatments to slow CKD progression “is better than the free-for-all that occurs today.”
Simplified data collection
“Klinrisk is very effective,” but requires follow-up by clinicians and health systems to implement its findings, commented Josef Coresh, MD, a professor of clinical epidemiology at Johns Hopkins Bloomberg, Baltimore. Dr. Coresh compared it with a free equation that estimates a person’s risk for a 40% drop in kidney function over the next 3 years developed by Dr. Tangri, Dr. Coresh, and many collaborators led by Morgan C. Grams, MD, PhD, of New York University that they published in 2022, and posted on a website of the CKD Prognosis Consortium.
The CKD Prognosis Consortium formula “takes a different approach” from Klinrisk. The commercial formula “is simpler, only using lab measures, and avoids inputs taken from physical examination such as systolic blood pressure and body mass index and health history data such as smoking, noted Dr. Coresh. He also speculated that “a commercial formula that must be paid for may counterintuitively result in better follow-up for making management changes if it uses some of the resources for education and system changes.”
Using data from multiple sources, like the CKD Prognosis Consortium equation, can create implementation challenges, said Dr. Tangri. “Lab results don’t vary much,” which makes Klinrisk “quite an improvement for implementation. It’s easier to implement.”
Other findings from the newest validation study that Dr. Tangri presented were that the people studied with Klinrisk scores in the top 10% had, over the next 2 years of follow-up and compared with people in the bottom half for Klinrisk staging, a 3- to 5-fold higher rate of all-cause medical costs, a 13-30-fold increase in CKD-related costs, and a 5- to 10-fold increase in hospitalizations and ED visits.
Early identification of CKD and early initiation of intensified treatment for high-risk patients can reduce the rate of progression to dialysis, reduce hospitalizations for heart failure, and lower the cost of care, Dr. Tangri said.
The validation study in 4.6 million Americans was sponsored by Boehringer Ingelheim. Dr. Tangri founded and has an ownership interest in Klinrisk. He has also received honoraria from, has ownership interests in, and has been a consultant to multiple pharmaceutical companies. Dr. Coresh had no disclosures.
PHILADELPHIA – The analyses offer the possibility of focusing intensified medical management of early-stage CKD on those patients who could potentially receive the most benefit.
The Klinrisk model predicts the risk of an adult with early-stage CKD developing either a 40% or greater drop in estimated glomerular filtration rate or kidney failure. It calculates risk based on 20 lab-measured variables that include serum creatinine, urine albumin-to-creatinine ratio, and other values taken from routinely ordered tests such as complete blood cell counts, chemistry panels, comprehensive metabolic panels, and urinalysis.
In the most recent and largest external validation study using data from 4.6 million American adults enrolled in commercial and Medicare insurance plans, the results showed Klinrisk correctly predicted CKD progression in 80%-83% of individuals over 2 years and in 78%-83% of individuals over 5 years, depending on the insurance provider, Navdeep Tangri, MD, PhD, reported at the annual meeting of the American Society of Nephrology. When urinalysis data were available, the model correctly predicted CKD progression in 81%-87% of individuals over 2 years and in 80%-87% of individuals over 5 years. These results follow prior reports of several other successful validations of Klinrisk.
‘Ready to implement’
“The Klinrisk model is ready to implement by any payer, health system, or clinic where the needed lab data are available,” said Dr. Tangri, a nephrologist and professor at the University of Manitoba, Winnipeg, and founder of Klinrisk Inc., the company developing and commercializing the Klinrisk assessment tool.
For the time being, Dr. Tangri sees Klinrisk as a population health device that can allow insurers and health systems to track management quality and quality improvement and to target patients who stand to benefit most from relatively expensive resources. This includes prescriptions for finerenone (Kerendia, Bayer) for people who also have type 2 diabetes, and agents from the class of sodium-glucose cotransporter 2 (SGLT2) inhibitors such as dapagliflozin (Farxiga, AstraZeneca) and empagliflozin (Jardiance, Boehringer Ingelheim and Lilly).
He has also begun discussions with the Food and Drug Administration about the data the agency will need to consider Klinrisk for potential approval as a new medical device, perhaps in 2025. That’s how he envisions getting a Klinrisk assessment into the hands of caregivers that they could use with individual patients to create an appropriate treatment plan.
Results from his new analysis showed that “all the kidney disease action is in the 10%-20% of people with the highest risk on Klinrisk, while not much happens in those in the bottom half,” Dr. Tangri said during his presentation.
“We’re trying to find the patients who get the largest [absolute] benefit from intensified treatment,” he added in an interview. “Klinrisk finds people with high-risk kidney disease early on, when kidney function is still normal or near normal. High-risk patients are often completely unrecognized. Risk-based management” that identifies the early-stage CKD patients who would benefit most from treatment with an SGLT2 inhibitor, finerenone, and other foundational treatments to slow CKD progression “is better than the free-for-all that occurs today.”
Simplified data collection
“Klinrisk is very effective,” but requires follow-up by clinicians and health systems to implement its findings, commented Josef Coresh, MD, a professor of clinical epidemiology at Johns Hopkins Bloomberg, Baltimore. Dr. Coresh compared it with a free equation that estimates a person’s risk for a 40% drop in kidney function over the next 3 years developed by Dr. Tangri, Dr. Coresh, and many collaborators led by Morgan C. Grams, MD, PhD, of New York University that they published in 2022, and posted on a website of the CKD Prognosis Consortium.
The CKD Prognosis Consortium formula “takes a different approach” from Klinrisk. The commercial formula “is simpler, only using lab measures, and avoids inputs taken from physical examination such as systolic blood pressure and body mass index and health history data such as smoking, noted Dr. Coresh. He also speculated that “a commercial formula that must be paid for may counterintuitively result in better follow-up for making management changes if it uses some of the resources for education and system changes.”
Using data from multiple sources, like the CKD Prognosis Consortium equation, can create implementation challenges, said Dr. Tangri. “Lab results don’t vary much,” which makes Klinrisk “quite an improvement for implementation. It’s easier to implement.”
Other findings from the newest validation study that Dr. Tangri presented were that the people studied with Klinrisk scores in the top 10% had, over the next 2 years of follow-up and compared with people in the bottom half for Klinrisk staging, a 3- to 5-fold higher rate of all-cause medical costs, a 13-30-fold increase in CKD-related costs, and a 5- to 10-fold increase in hospitalizations and ED visits.
Early identification of CKD and early initiation of intensified treatment for high-risk patients can reduce the rate of progression to dialysis, reduce hospitalizations for heart failure, and lower the cost of care, Dr. Tangri said.
The validation study in 4.6 million Americans was sponsored by Boehringer Ingelheim. Dr. Tangri founded and has an ownership interest in Klinrisk. He has also received honoraria from, has ownership interests in, and has been a consultant to multiple pharmaceutical companies. Dr. Coresh had no disclosures.
AT KIDNEY WEEK 2023
Aprocitentan reduces resistant hypertension in CKD
PHILADELPHIA – (CKD). The results come from a prespecified subgroup analysis of data collected in the drug’s pivotal trial, PRECISION.
The findings provide support for potentially using aprocitentan, if approved for U.S. marketing in 2024, in patients with blood pressure that remains elevated despite treatment with three established antihypertensive drug classes and with stage 3 CKD with an estimated glomerular filtration rate of 30-59 mL/min per 1.73 m2. This is a key group of patients because “chronic kidney disease is the most common comorbidity in patients with resistant hypertension,” said George Bakris, MD, who presented the subgroup analysis at Kidney Week 2023, organized by the American Society of Nephrology.
The CKD subgroup analysis showed “good evidence for safety and evidence in stage 3 CKD,” a subgroup of 141 patients among the total 730 enrolled in PRECISION, said Dr. Bakris. Professor and director of the Comprehensive Hypertension Center at the University of Chicago, he acknowledged that while the results also showed a signal for safety and efficacy in the 21 enrolled patients with stage 4 hypertension, 15-29 mL/min per 1.73m2, this number of stage 4 patients was too small to allow definitive conclusions.
Nephrologist Nishigandha Pradhan, MD, who cochaired the session with this report, agreed. “Resistant hypertension is a particularly intractable problem in patients with CKD, and the risk is greatest with stage 4 CKD. If studies could show that aprocitentan is safe in people with stage 4 CKD, that would be a big plus, but we need more data,” commented Dr. Pradhan in an interview.
Incremental blood pressure reductions
The parallel-group, phase 3 PRECISION trial investigated the safety and short-term antihypertensive effect of aprocitentan in patients with resistant hypertension. The study’s primary efficacy endpoint was blood pressure reduction from baseline in 730 randomized people with persistent systolic hypertension despite treatment with three established antihypertensive agents including a diuretic. The study ran during June 2018–April 2022 at 191 sites in 22 countries.
The primary outcome after 4 weeks on treatment was a least-square mean reduction in office-measured systolic blood pressure, compared with placebo, of 3.8 mm Hg with a 12.5-mg daily oral dose of aprocitentan and 3.7 mm Hg with a 25-mg daily oral dose. Both significant differences were first reported in 2022. Twenty-four–hour ambulatory systolic blood pressures after 4 weeks of treatment fell by an average of 4.2 mm Hg on the lower dose compared with placebo and by an average of 5.9 mm Hg on the higher daily dose, compared with placebo.
Consistent blood pressure reductions occurred in the CKD subgroups. Among people with stage 3 CKD, daytime ambulatory blood pressure at 4 weeks fell by about 10 mm Hg on both the 12.5-mg daily and 25-mg daily doses, compared with placebo.
Among the small number of people with stage 4 CKD, the incremental nighttime systolic blood pressure on aprocitentan, compared with placebo, was even greater, with about a 15–mm Hg incremental reduction on 12.5 mg daily and about a 17–mm Hg incremental reduction on the higher dose.
“This is the first evidence for a change in nocturnal blood pressure in people with stage 4 CKD [and treatment-resistant hypertension], but it was just 21 patients so not yet a big deal,” Dr. Bakris noted.
Increased rates of fluid retention
Although aprocitentan was generally well tolerated, the most common adverse effect was edema or fluid retention, mainly during the first 4 weeks of treatment. In the full PRECISION cohort, this adverse event occurred in 2.1% of people treated with placebo, 9.1% of those on the 12.5-mg daily dose, and in 18.4% of those on the higher dose during the initial 4-week phase of treatment.
Among all stage 3 and 4 CKD patients on aprocitentan, edema or fluid retention occurred in 21% during the first 4 weeks, and in 27% during an additional 32 weeks of treatment with 25 mg aprocitentan daily. A majority of these patients started a diuretic to address their excess fluid, with only two discontinuing aprocitentan treatment.
“Fluid retention is an issue with aprocitentan,” Dr. Bakris acknowledged. But he also highlighted than only 6 of the 162 patients with CKD required hospitalization for heart failure during the study, and one of these cases had placebo treatment. Among the five with acute heart failure while on aprocitentan, none had to stop their treatment, and two had a clear prior history of heart failure.
The companies developing aprocitentan, Janssen and Idorsia, used the PRECISION results as the centerpiece in filing for a new drug approval to the FDA, with a March 2024 goal for the FDA‘s decision. Dr. Bakris called the application “a solid case for approval.” But he added that approval will likely require that all treatment candidates first undergo testing of their heart function or fluid volume, such as a measure of their blood level of N-terminal pro-B-type natriuretic peptide, with treatment withheld when the level is too high.
The upside of aprocitentan compared with current drug options for treating resistant hypertension is that it has not appeared to cause any increase in blood potassium levels, which is an issue with the current top agent for resistant hypertension, spironolactone.
“The problem with spironolactone is the risk for hyperkalemia, which keeps us looking for something with lower risk,” commented Dr. Pradhan, a nephrologist with University Hospitals in Cleveland. Hyperkalemia is an even greater risk for people with CKD. Although the PRECISION trial identified the issue of fluid retention with aprocitentan, titrating an effective dose of a loop diuretic for treated patients may effectively blunt the edema risk, Dr. Pradhan said.
Endothelin has a potent vasoconstrictive effect and is “implicated in the pathogenesis of hypertension,” Dr. Bakris explained. Aprocitentan antagonizes both the endothelin A and B receptors. The subgroup analyses also showed that in people with CKD, treatment with aprocitentan led to roughly a halving of the baseline level of urine albumin-to-creatinine ratio, a small and stable decrease in estimated glomerular filtration rate, and a modest and stable increase in blood levels of N-terminal pro-B-type natriuretic hormone.
The PRECISION trial was sponsored by Janssen Pharmaceuticals and Idorsia Pharmaceuticals, the companies jointly developing aprocitentan. Dr. Bakris has been a consultant to Janssen, and also a consultant to or honoraria recipient of Alnylam, AstraZeneca, Bayer, Dia Medica Therapeutics, Ionis, inREGEN, KBP Biosciences, Merck, Novo Nordisk, and Quantum Genomics. Dr. Pradhan had no disclosures.
PHILADELPHIA – (CKD). The results come from a prespecified subgroup analysis of data collected in the drug’s pivotal trial, PRECISION.
The findings provide support for potentially using aprocitentan, if approved for U.S. marketing in 2024, in patients with blood pressure that remains elevated despite treatment with three established antihypertensive drug classes and with stage 3 CKD with an estimated glomerular filtration rate of 30-59 mL/min per 1.73 m2. This is a key group of patients because “chronic kidney disease is the most common comorbidity in patients with resistant hypertension,” said George Bakris, MD, who presented the subgroup analysis at Kidney Week 2023, organized by the American Society of Nephrology.
The CKD subgroup analysis showed “good evidence for safety and evidence in stage 3 CKD,” a subgroup of 141 patients among the total 730 enrolled in PRECISION, said Dr. Bakris. Professor and director of the Comprehensive Hypertension Center at the University of Chicago, he acknowledged that while the results also showed a signal for safety and efficacy in the 21 enrolled patients with stage 4 hypertension, 15-29 mL/min per 1.73m2, this number of stage 4 patients was too small to allow definitive conclusions.
Nephrologist Nishigandha Pradhan, MD, who cochaired the session with this report, agreed. “Resistant hypertension is a particularly intractable problem in patients with CKD, and the risk is greatest with stage 4 CKD. If studies could show that aprocitentan is safe in people with stage 4 CKD, that would be a big plus, but we need more data,” commented Dr. Pradhan in an interview.
Incremental blood pressure reductions
The parallel-group, phase 3 PRECISION trial investigated the safety and short-term antihypertensive effect of aprocitentan in patients with resistant hypertension. The study’s primary efficacy endpoint was blood pressure reduction from baseline in 730 randomized people with persistent systolic hypertension despite treatment with three established antihypertensive agents including a diuretic. The study ran during June 2018–April 2022 at 191 sites in 22 countries.
The primary outcome after 4 weeks on treatment was a least-square mean reduction in office-measured systolic blood pressure, compared with placebo, of 3.8 mm Hg with a 12.5-mg daily oral dose of aprocitentan and 3.7 mm Hg with a 25-mg daily oral dose. Both significant differences were first reported in 2022. Twenty-four–hour ambulatory systolic blood pressures after 4 weeks of treatment fell by an average of 4.2 mm Hg on the lower dose compared with placebo and by an average of 5.9 mm Hg on the higher daily dose, compared with placebo.
Consistent blood pressure reductions occurred in the CKD subgroups. Among people with stage 3 CKD, daytime ambulatory blood pressure at 4 weeks fell by about 10 mm Hg on both the 12.5-mg daily and 25-mg daily doses, compared with placebo.
Among the small number of people with stage 4 CKD, the incremental nighttime systolic blood pressure on aprocitentan, compared with placebo, was even greater, with about a 15–mm Hg incremental reduction on 12.5 mg daily and about a 17–mm Hg incremental reduction on the higher dose.
“This is the first evidence for a change in nocturnal blood pressure in people with stage 4 CKD [and treatment-resistant hypertension], but it was just 21 patients so not yet a big deal,” Dr. Bakris noted.
Increased rates of fluid retention
Although aprocitentan was generally well tolerated, the most common adverse effect was edema or fluid retention, mainly during the first 4 weeks of treatment. In the full PRECISION cohort, this adverse event occurred in 2.1% of people treated with placebo, 9.1% of those on the 12.5-mg daily dose, and in 18.4% of those on the higher dose during the initial 4-week phase of treatment.
Among all stage 3 and 4 CKD patients on aprocitentan, edema or fluid retention occurred in 21% during the first 4 weeks, and in 27% during an additional 32 weeks of treatment with 25 mg aprocitentan daily. A majority of these patients started a diuretic to address their excess fluid, with only two discontinuing aprocitentan treatment.
“Fluid retention is an issue with aprocitentan,” Dr. Bakris acknowledged. But he also highlighted than only 6 of the 162 patients with CKD required hospitalization for heart failure during the study, and one of these cases had placebo treatment. Among the five with acute heart failure while on aprocitentan, none had to stop their treatment, and two had a clear prior history of heart failure.
The companies developing aprocitentan, Janssen and Idorsia, used the PRECISION results as the centerpiece in filing for a new drug approval to the FDA, with a March 2024 goal for the FDA‘s decision. Dr. Bakris called the application “a solid case for approval.” But he added that approval will likely require that all treatment candidates first undergo testing of their heart function or fluid volume, such as a measure of their blood level of N-terminal pro-B-type natriuretic peptide, with treatment withheld when the level is too high.
The upside of aprocitentan compared with current drug options for treating resistant hypertension is that it has not appeared to cause any increase in blood potassium levels, which is an issue with the current top agent for resistant hypertension, spironolactone.
“The problem with spironolactone is the risk for hyperkalemia, which keeps us looking for something with lower risk,” commented Dr. Pradhan, a nephrologist with University Hospitals in Cleveland. Hyperkalemia is an even greater risk for people with CKD. Although the PRECISION trial identified the issue of fluid retention with aprocitentan, titrating an effective dose of a loop diuretic for treated patients may effectively blunt the edema risk, Dr. Pradhan said.
Endothelin has a potent vasoconstrictive effect and is “implicated in the pathogenesis of hypertension,” Dr. Bakris explained. Aprocitentan antagonizes both the endothelin A and B receptors. The subgroup analyses also showed that in people with CKD, treatment with aprocitentan led to roughly a halving of the baseline level of urine albumin-to-creatinine ratio, a small and stable decrease in estimated glomerular filtration rate, and a modest and stable increase in blood levels of N-terminal pro-B-type natriuretic hormone.
The PRECISION trial was sponsored by Janssen Pharmaceuticals and Idorsia Pharmaceuticals, the companies jointly developing aprocitentan. Dr. Bakris has been a consultant to Janssen, and also a consultant to or honoraria recipient of Alnylam, AstraZeneca, Bayer, Dia Medica Therapeutics, Ionis, inREGEN, KBP Biosciences, Merck, Novo Nordisk, and Quantum Genomics. Dr. Pradhan had no disclosures.
PHILADELPHIA – (CKD). The results come from a prespecified subgroup analysis of data collected in the drug’s pivotal trial, PRECISION.
The findings provide support for potentially using aprocitentan, if approved for U.S. marketing in 2024, in patients with blood pressure that remains elevated despite treatment with three established antihypertensive drug classes and with stage 3 CKD with an estimated glomerular filtration rate of 30-59 mL/min per 1.73 m2. This is a key group of patients because “chronic kidney disease is the most common comorbidity in patients with resistant hypertension,” said George Bakris, MD, who presented the subgroup analysis at Kidney Week 2023, organized by the American Society of Nephrology.
The CKD subgroup analysis showed “good evidence for safety and evidence in stage 3 CKD,” a subgroup of 141 patients among the total 730 enrolled in PRECISION, said Dr. Bakris. Professor and director of the Comprehensive Hypertension Center at the University of Chicago, he acknowledged that while the results also showed a signal for safety and efficacy in the 21 enrolled patients with stage 4 hypertension, 15-29 mL/min per 1.73m2, this number of stage 4 patients was too small to allow definitive conclusions.
Nephrologist Nishigandha Pradhan, MD, who cochaired the session with this report, agreed. “Resistant hypertension is a particularly intractable problem in patients with CKD, and the risk is greatest with stage 4 CKD. If studies could show that aprocitentan is safe in people with stage 4 CKD, that would be a big plus, but we need more data,” commented Dr. Pradhan in an interview.
Incremental blood pressure reductions
The parallel-group, phase 3 PRECISION trial investigated the safety and short-term antihypertensive effect of aprocitentan in patients with resistant hypertension. The study’s primary efficacy endpoint was blood pressure reduction from baseline in 730 randomized people with persistent systolic hypertension despite treatment with three established antihypertensive agents including a diuretic. The study ran during June 2018–April 2022 at 191 sites in 22 countries.
The primary outcome after 4 weeks on treatment was a least-square mean reduction in office-measured systolic blood pressure, compared with placebo, of 3.8 mm Hg with a 12.5-mg daily oral dose of aprocitentan and 3.7 mm Hg with a 25-mg daily oral dose. Both significant differences were first reported in 2022. Twenty-four–hour ambulatory systolic blood pressures after 4 weeks of treatment fell by an average of 4.2 mm Hg on the lower dose compared with placebo and by an average of 5.9 mm Hg on the higher daily dose, compared with placebo.
Consistent blood pressure reductions occurred in the CKD subgroups. Among people with stage 3 CKD, daytime ambulatory blood pressure at 4 weeks fell by about 10 mm Hg on both the 12.5-mg daily and 25-mg daily doses, compared with placebo.
Among the small number of people with stage 4 CKD, the incremental nighttime systolic blood pressure on aprocitentan, compared with placebo, was even greater, with about a 15–mm Hg incremental reduction on 12.5 mg daily and about a 17–mm Hg incremental reduction on the higher dose.
“This is the first evidence for a change in nocturnal blood pressure in people with stage 4 CKD [and treatment-resistant hypertension], but it was just 21 patients so not yet a big deal,” Dr. Bakris noted.
Increased rates of fluid retention
Although aprocitentan was generally well tolerated, the most common adverse effect was edema or fluid retention, mainly during the first 4 weeks of treatment. In the full PRECISION cohort, this adverse event occurred in 2.1% of people treated with placebo, 9.1% of those on the 12.5-mg daily dose, and in 18.4% of those on the higher dose during the initial 4-week phase of treatment.
Among all stage 3 and 4 CKD patients on aprocitentan, edema or fluid retention occurred in 21% during the first 4 weeks, and in 27% during an additional 32 weeks of treatment with 25 mg aprocitentan daily. A majority of these patients started a diuretic to address their excess fluid, with only two discontinuing aprocitentan treatment.
“Fluid retention is an issue with aprocitentan,” Dr. Bakris acknowledged. But he also highlighted than only 6 of the 162 patients with CKD required hospitalization for heart failure during the study, and one of these cases had placebo treatment. Among the five with acute heart failure while on aprocitentan, none had to stop their treatment, and two had a clear prior history of heart failure.
The companies developing aprocitentan, Janssen and Idorsia, used the PRECISION results as the centerpiece in filing for a new drug approval to the FDA, with a March 2024 goal for the FDA‘s decision. Dr. Bakris called the application “a solid case for approval.” But he added that approval will likely require that all treatment candidates first undergo testing of their heart function or fluid volume, such as a measure of their blood level of N-terminal pro-B-type natriuretic peptide, with treatment withheld when the level is too high.
The upside of aprocitentan compared with current drug options for treating resistant hypertension is that it has not appeared to cause any increase in blood potassium levels, which is an issue with the current top agent for resistant hypertension, spironolactone.
“The problem with spironolactone is the risk for hyperkalemia, which keeps us looking for something with lower risk,” commented Dr. Pradhan, a nephrologist with University Hospitals in Cleveland. Hyperkalemia is an even greater risk for people with CKD. Although the PRECISION trial identified the issue of fluid retention with aprocitentan, titrating an effective dose of a loop diuretic for treated patients may effectively blunt the edema risk, Dr. Pradhan said.
Endothelin has a potent vasoconstrictive effect and is “implicated in the pathogenesis of hypertension,” Dr. Bakris explained. Aprocitentan antagonizes both the endothelin A and B receptors. The subgroup analyses also showed that in people with CKD, treatment with aprocitentan led to roughly a halving of the baseline level of urine albumin-to-creatinine ratio, a small and stable decrease in estimated glomerular filtration rate, and a modest and stable increase in blood levels of N-terminal pro-B-type natriuretic hormone.
The PRECISION trial was sponsored by Janssen Pharmaceuticals and Idorsia Pharmaceuticals, the companies jointly developing aprocitentan. Dr. Bakris has been a consultant to Janssen, and also a consultant to or honoraria recipient of Alnylam, AstraZeneca, Bayer, Dia Medica Therapeutics, Ionis, inREGEN, KBP Biosciences, Merck, Novo Nordisk, and Quantum Genomics. Dr. Pradhan had no disclosures.
AT KIDNEY WEEK 2023
EMR prompt boosts albuminuria measurement in T2D
PHILADELPHIA – An electronic medical record alert to primary care physicians that their adult patients with type 2 diabetes were due for an albuminuria and renal-function check boosted screening for chronic kidney disease (CKD) by roughly half compared with the preintervention rate in a single U.S. academic health system.
“Screening rates for CKD more rapidly improved after implementation” of the EMR alert, said Maggy M. Spolnik, MD, at Kidney Week 2023, organized by the American Society of Nephrology.
“There was an immediate and ongoing effect over a year,” said Dr. Spolnik, a nephrologist at Indiana University in Indianapolis.
However, CKD screening rates in the primary care setting remain a challenge. In the study, the EMR alert produced a urine albumin-to-creatinine ratio (UACR) screening rate of about 26% of patient encounters, she reported. While this was significantly above the roughly 17% rate that had persisted for months before the intervention, it still fell short of the universal annual screening for adults with type 2 diabetes not previously diagnosed with CKD recommended by medical groups such as the American Diabetes Association and the Kidney Disease: Improving Global Outcomes organization. The U.S. Preventive Services Task Force’s assessment in 2012 concluded inadequate information existed at that time to make recommendations about CKD screening, but the group is now revisiting the issue.
‘Albuminuria is an earlier marker’ than eGFR
“Primary care physicians need to regularly monitor albuminuria in adults with type 2 diabetes,” commented Karen A. Griffin, MD, a nephrologist and professor at Loyola University in Maywood, Ill. “By the time you diagnose CKD based on reduced estimated glomerular filtration rate (eGFR), a patient has already lost more than half their renal function. Albuminuria is an earlier marker of a problem,” Dr. Griffin said in an interview.
Primary care physicians have been slow to adopt at least annual checks on both eGFR and the urinary albumin-to-creatinine ratio (UACR) in their adult patients with type 2 diabetes. Dr. Spolnik cited reasons such as the brief 15-minute consultation that primary care physicians have when seeing a patient, and an often confusing ordering menu that gives a UACR test various other names such as tests for microalbuminuria or macroalbuminuria.
To simplify ordering, the EMR prompt assessed in Dr. Spolnik’s study called the test “kidney screening” that automatically bundled an order for both eGFR calculation with UACR measurement. Another limitation is that UACR measurement requires a urine sample, which patients often find inconvenient to provide at the time of their examination.
The study run by Dr. Spolnik involved 10,744 adults with type 2 diabetes without an existing diagnosis of CKD seen in an outpatient, primary care visit to the UVA Health system centered in Charlottesville, Va. during April 2021–April 2022. A total of 23,419 encounters served as usual-care controls. The intervention period with active EMR alerts for kidney screening included 10,204 similar patients seen during April 2022–April 2023 in a total of 20,358 encounters. The patients averaged about 61-62 years old, and about 45% were men.
Bundling alerts into a single pop-up
The primary care clinicians who received the prompts were generally receptive to them, but they asked the researchers to bundle the UACR and eGFR measurement prompts along with any other alerts they received in the EMR into a single on-screen pop-up.
Dr. Spolnik acknowledged the need for further research and refinement to the prompt. For example, she wants to assess prompts for patients identified as having CKD that would promote best-practice management, including lifestyle and medical interventions. She also envisions expanding the prompts to also include other, related disorders such as hypertension.
But she and her colleagues were convinced enough by the results that they have not only continued the program at UVA Health but they also expanded it, starting in October 2023, to the academic primary care practice at Indiana University.
If the Indiana University trial confirms the efficacy seen in Virginia, the next step might be inclusion by Epic of the CKD screening alert as a routine option in the EMR software it distributes to its U.S. clients, Dr. Spolnik said in an interview.
Dr. Spolnik and Dr. Griffin had no disclosures.
PHILADELPHIA – An electronic medical record alert to primary care physicians that their adult patients with type 2 diabetes were due for an albuminuria and renal-function check boosted screening for chronic kidney disease (CKD) by roughly half compared with the preintervention rate in a single U.S. academic health system.
“Screening rates for CKD more rapidly improved after implementation” of the EMR alert, said Maggy M. Spolnik, MD, at Kidney Week 2023, organized by the American Society of Nephrology.
“There was an immediate and ongoing effect over a year,” said Dr. Spolnik, a nephrologist at Indiana University in Indianapolis.
However, CKD screening rates in the primary care setting remain a challenge. In the study, the EMR alert produced a urine albumin-to-creatinine ratio (UACR) screening rate of about 26% of patient encounters, she reported. While this was significantly above the roughly 17% rate that had persisted for months before the intervention, it still fell short of the universal annual screening for adults with type 2 diabetes not previously diagnosed with CKD recommended by medical groups such as the American Diabetes Association and the Kidney Disease: Improving Global Outcomes organization. The U.S. Preventive Services Task Force’s assessment in 2012 concluded inadequate information existed at that time to make recommendations about CKD screening, but the group is now revisiting the issue.
‘Albuminuria is an earlier marker’ than eGFR
“Primary care physicians need to regularly monitor albuminuria in adults with type 2 diabetes,” commented Karen A. Griffin, MD, a nephrologist and professor at Loyola University in Maywood, Ill. “By the time you diagnose CKD based on reduced estimated glomerular filtration rate (eGFR), a patient has already lost more than half their renal function. Albuminuria is an earlier marker of a problem,” Dr. Griffin said in an interview.
Primary care physicians have been slow to adopt at least annual checks on both eGFR and the urinary albumin-to-creatinine ratio (UACR) in their adult patients with type 2 diabetes. Dr. Spolnik cited reasons such as the brief 15-minute consultation that primary care physicians have when seeing a patient, and an often confusing ordering menu that gives a UACR test various other names such as tests for microalbuminuria or macroalbuminuria.
To simplify ordering, the EMR prompt assessed in Dr. Spolnik’s study called the test “kidney screening” that automatically bundled an order for both eGFR calculation with UACR measurement. Another limitation is that UACR measurement requires a urine sample, which patients often find inconvenient to provide at the time of their examination.
The study run by Dr. Spolnik involved 10,744 adults with type 2 diabetes without an existing diagnosis of CKD seen in an outpatient, primary care visit to the UVA Health system centered in Charlottesville, Va. during April 2021–April 2022. A total of 23,419 encounters served as usual-care controls. The intervention period with active EMR alerts for kidney screening included 10,204 similar patients seen during April 2022–April 2023 in a total of 20,358 encounters. The patients averaged about 61-62 years old, and about 45% were men.
Bundling alerts into a single pop-up
The primary care clinicians who received the prompts were generally receptive to them, but they asked the researchers to bundle the UACR and eGFR measurement prompts along with any other alerts they received in the EMR into a single on-screen pop-up.
Dr. Spolnik acknowledged the need for further research and refinement to the prompt. For example, she wants to assess prompts for patients identified as having CKD that would promote best-practice management, including lifestyle and medical interventions. She also envisions expanding the prompts to also include other, related disorders such as hypertension.
But she and her colleagues were convinced enough by the results that they have not only continued the program at UVA Health but they also expanded it, starting in October 2023, to the academic primary care practice at Indiana University.
If the Indiana University trial confirms the efficacy seen in Virginia, the next step might be inclusion by Epic of the CKD screening alert as a routine option in the EMR software it distributes to its U.S. clients, Dr. Spolnik said in an interview.
Dr. Spolnik and Dr. Griffin had no disclosures.
PHILADELPHIA – An electronic medical record alert to primary care physicians that their adult patients with type 2 diabetes were due for an albuminuria and renal-function check boosted screening for chronic kidney disease (CKD) by roughly half compared with the preintervention rate in a single U.S. academic health system.
“Screening rates for CKD more rapidly improved after implementation” of the EMR alert, said Maggy M. Spolnik, MD, at Kidney Week 2023, organized by the American Society of Nephrology.
“There was an immediate and ongoing effect over a year,” said Dr. Spolnik, a nephrologist at Indiana University in Indianapolis.
However, CKD screening rates in the primary care setting remain a challenge. In the study, the EMR alert produced a urine albumin-to-creatinine ratio (UACR) screening rate of about 26% of patient encounters, she reported. While this was significantly above the roughly 17% rate that had persisted for months before the intervention, it still fell short of the universal annual screening for adults with type 2 diabetes not previously diagnosed with CKD recommended by medical groups such as the American Diabetes Association and the Kidney Disease: Improving Global Outcomes organization. The U.S. Preventive Services Task Force’s assessment in 2012 concluded inadequate information existed at that time to make recommendations about CKD screening, but the group is now revisiting the issue.
‘Albuminuria is an earlier marker’ than eGFR
“Primary care physicians need to regularly monitor albuminuria in adults with type 2 diabetes,” commented Karen A. Griffin, MD, a nephrologist and professor at Loyola University in Maywood, Ill. “By the time you diagnose CKD based on reduced estimated glomerular filtration rate (eGFR), a patient has already lost more than half their renal function. Albuminuria is an earlier marker of a problem,” Dr. Griffin said in an interview.
Primary care physicians have been slow to adopt at least annual checks on both eGFR and the urinary albumin-to-creatinine ratio (UACR) in their adult patients with type 2 diabetes. Dr. Spolnik cited reasons such as the brief 15-minute consultation that primary care physicians have when seeing a patient, and an often confusing ordering menu that gives a UACR test various other names such as tests for microalbuminuria or macroalbuminuria.
To simplify ordering, the EMR prompt assessed in Dr. Spolnik’s study called the test “kidney screening” that automatically bundled an order for both eGFR calculation with UACR measurement. Another limitation is that UACR measurement requires a urine sample, which patients often find inconvenient to provide at the time of their examination.
The study run by Dr. Spolnik involved 10,744 adults with type 2 diabetes without an existing diagnosis of CKD seen in an outpatient, primary care visit to the UVA Health system centered in Charlottesville, Va. during April 2021–April 2022. A total of 23,419 encounters served as usual-care controls. The intervention period with active EMR alerts for kidney screening included 10,204 similar patients seen during April 2022–April 2023 in a total of 20,358 encounters. The patients averaged about 61-62 years old, and about 45% were men.
Bundling alerts into a single pop-up
The primary care clinicians who received the prompts were generally receptive to them, but they asked the researchers to bundle the UACR and eGFR measurement prompts along with any other alerts they received in the EMR into a single on-screen pop-up.
Dr. Spolnik acknowledged the need for further research and refinement to the prompt. For example, she wants to assess prompts for patients identified as having CKD that would promote best-practice management, including lifestyle and medical interventions. She also envisions expanding the prompts to also include other, related disorders such as hypertension.
But she and her colleagues were convinced enough by the results that they have not only continued the program at UVA Health but they also expanded it, starting in October 2023, to the academic primary care practice at Indiana University.
If the Indiana University trial confirms the efficacy seen in Virginia, the next step might be inclusion by Epic of the CKD screening alert as a routine option in the EMR software it distributes to its U.S. clients, Dr. Spolnik said in an interview.
Dr. Spolnik and Dr. Griffin had no disclosures.
REPORTING FROM KIDNEY WEEK 2023
Piperacillin-tazobactam poses no renal risk in adults with sepsis
TOPLINE:
METHODOLOGY:
The coadministration of piperacillin-tazobactam and vancomycin may raise the risk for AKI, according to a warning from the Food and Drug Administration.
The ACORN trial included 2,511 adults presenting to emergency department or intensive care unit with suspected infection.
Within 12 hours of presentation, these individuals were prescribed either cefepime (n = 1,214) or piperacillin-tazobactam (n = 1,297).
The primary outcome was the risk for the highest stage of AKI or death within 14 days of randomization.
TAKEAWAY:
The highest stage of AKI or death within 14 days did not differ significantly between the cefepime and piperacillin-tazobactam groups (odds ratio, 0.95; P = .56).
The incidence of major adverse kidney events by day 14 was not significantly different between the two groups (absolute risk difference, 1.4%; 95% confidence interval, −1.0% to 3.8%).
Patients in the cefepime versus piperacillin-tazobactam group had fewer days alive and free of delirium and coma within 14 days (OR, 0.79; 95% CI, 0.65-0.95).
IN PRACTICE:
In an accompanying editorial, Steven Y. C. Tong, department of infectious diseases, University of Melbourne, and colleagues wrote: “Because institutions must make decisions about which antibiotics to position on medical wards for rapid administration in patients meeting sepsis criteria, these data should offer solace that if the choice is made to use piperacillin-tazobactam, there is not an increased risk of AKI.”
SOURCE:
The study was led by Edward T. Qian, MD, of Vanderbilt University Medical Center, Nashville, Tenn. It was published online in JAMA with an accompanying editorial.
LIMITATIONS:
The study was conducted at a single academic center, which may limit the generalizability of findings.
Both patients and clinicians were not blinded to group assignment, which may have influenced clinical assessments like Richmond Agitation-Sedation Scale and CAM-ICU or the frequency of laboratory measurements like creatinine.
DISCLOSURES:
The project was supported by the Vanderbilt Institute for Clinical and Translational Research and several other sources, including grants from the National Center for Advancing Translational Sciences. Some authors declared receiving travel grant, personal fees, honoraria, and unrelated research support from various sources.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
The coadministration of piperacillin-tazobactam and vancomycin may raise the risk for AKI, according to a warning from the Food and Drug Administration.
The ACORN trial included 2,511 adults presenting to emergency department or intensive care unit with suspected infection.
Within 12 hours of presentation, these individuals were prescribed either cefepime (n = 1,214) or piperacillin-tazobactam (n = 1,297).
The primary outcome was the risk for the highest stage of AKI or death within 14 days of randomization.
TAKEAWAY:
The highest stage of AKI or death within 14 days did not differ significantly between the cefepime and piperacillin-tazobactam groups (odds ratio, 0.95; P = .56).
The incidence of major adverse kidney events by day 14 was not significantly different between the two groups (absolute risk difference, 1.4%; 95% confidence interval, −1.0% to 3.8%).
Patients in the cefepime versus piperacillin-tazobactam group had fewer days alive and free of delirium and coma within 14 days (OR, 0.79; 95% CI, 0.65-0.95).
IN PRACTICE:
In an accompanying editorial, Steven Y. C. Tong, department of infectious diseases, University of Melbourne, and colleagues wrote: “Because institutions must make decisions about which antibiotics to position on medical wards for rapid administration in patients meeting sepsis criteria, these data should offer solace that if the choice is made to use piperacillin-tazobactam, there is not an increased risk of AKI.”
SOURCE:
The study was led by Edward T. Qian, MD, of Vanderbilt University Medical Center, Nashville, Tenn. It was published online in JAMA with an accompanying editorial.
LIMITATIONS:
The study was conducted at a single academic center, which may limit the generalizability of findings.
Both patients and clinicians were not blinded to group assignment, which may have influenced clinical assessments like Richmond Agitation-Sedation Scale and CAM-ICU or the frequency of laboratory measurements like creatinine.
DISCLOSURES:
The project was supported by the Vanderbilt Institute for Clinical and Translational Research and several other sources, including grants from the National Center for Advancing Translational Sciences. Some authors declared receiving travel grant, personal fees, honoraria, and unrelated research support from various sources.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
The coadministration of piperacillin-tazobactam and vancomycin may raise the risk for AKI, according to a warning from the Food and Drug Administration.
The ACORN trial included 2,511 adults presenting to emergency department or intensive care unit with suspected infection.
Within 12 hours of presentation, these individuals were prescribed either cefepime (n = 1,214) or piperacillin-tazobactam (n = 1,297).
The primary outcome was the risk for the highest stage of AKI or death within 14 days of randomization.
TAKEAWAY:
The highest stage of AKI or death within 14 days did not differ significantly between the cefepime and piperacillin-tazobactam groups (odds ratio, 0.95; P = .56).
The incidence of major adverse kidney events by day 14 was not significantly different between the two groups (absolute risk difference, 1.4%; 95% confidence interval, −1.0% to 3.8%).
Patients in the cefepime versus piperacillin-tazobactam group had fewer days alive and free of delirium and coma within 14 days (OR, 0.79; 95% CI, 0.65-0.95).
IN PRACTICE:
In an accompanying editorial, Steven Y. C. Tong, department of infectious diseases, University of Melbourne, and colleagues wrote: “Because institutions must make decisions about which antibiotics to position on medical wards for rapid administration in patients meeting sepsis criteria, these data should offer solace that if the choice is made to use piperacillin-tazobactam, there is not an increased risk of AKI.”
SOURCE:
The study was led by Edward T. Qian, MD, of Vanderbilt University Medical Center, Nashville, Tenn. It was published online in JAMA with an accompanying editorial.
LIMITATIONS:
The study was conducted at a single academic center, which may limit the generalizability of findings.
Both patients and clinicians were not blinded to group assignment, which may have influenced clinical assessments like Richmond Agitation-Sedation Scale and CAM-ICU or the frequency of laboratory measurements like creatinine.
DISCLOSURES:
The project was supported by the Vanderbilt Institute for Clinical and Translational Research and several other sources, including grants from the National Center for Advancing Translational Sciences. Some authors declared receiving travel grant, personal fees, honoraria, and unrelated research support from various sources.
A version of this article appeared on Medscape.com.
New calculator tool estimates fracture risk on dialysis
VANCOUVER – A new calculator that predicts short-term fracture risk at both 1 year and 3 years in patients on dialysis performed well in a study presented at the annual meeting of the American Society for Bone and Mineral Research.
The tool will soon be available on QxMD Calculate, which provides free decision-support tools for physicians, said presenter Andrea Cowan, MD, an assistant professor of medicine at the University of Western Ontario, London.
Dialysis patients have an approximately fivefold increased risk for fracture, Dr. Cowan noted, compared with the general population. However, treatments to prevent fracture risk are relatively limited and can have significant side effects. Therefore, “you really want to make sure that the person you’re targeting for treatment is actually going to be at a reasonable risk of fracture,” she said.
The Fracture Risk Assessment Tool (FRAX) is useful, but it estimates 10-year fracture risk, which is too long of a time frame to be useful for dialysis patients who experience a 50% 5-year mortality, according to Dr. Cowan. It does not take kidney failure or severe hyperparathyroidism into account, and it also requires information like bone mineral density, which poses an additional burden for a dialysis patient already undergoing multiple tests.
The new calculator could also be useful for research because it doesn’t rely on clinical data that might not be generally available, such as parental fracture, smoking status, or body mass index. “There’s a move towards things like pragmatic trials, which use more routinely collected data, have broader inclusion criteria, and are often more cost efficient to run. This calculator should be relatively easy to implement in trials using routinely collected data to perhaps define a subgroup of patients who may be at high risk of fracture without having to apply really cumbersome tools,” Dr. Cowan said.
The researchers included 11,599 patients between ages 40 and 89 years who were treated at a single center in Ontario between 2010 and 2017. The mean age was 66.18 years, 38.6% were women, 64.1% had diabetes, 11.9% had liver disease, and median time on dialysis was 0.81 years. The patients’ median parathyroid hormone level was 30 pmol/L.
At 3 years, the cumulative incidence of any fracture was 7.36% (95% confidence interval, 6.89-7.85), including 2.62% for hip fracture (95% CI, 2.34-2.93), 1.36% for spine fracture (95% CI, 1.16-1.59), 1.93% for wrist or forearm (95% CI, 1.69-2.20), and 2.15% for the pelvis (95% CI, 1.89-2.43). The incidence for all fractures at 1 year was 2.93 (95% CI, 2.62-3.26).
Variables associated with fracture risk included female sex (hazard ratio, 1.46; 95% CI, 1.27-1.67), a previous fracture more than 1 year in the past (HR, 1.65; 95% CI, 1.37-2.00), a fracture in the past year (HR, 3.63; 95% CI, 2.86-4.60), and proton pump inhibitor use (HR, 1.23; 95% CI, 1.04-1.45). After inclusion of vitamin D use, steroid use, time on dialysis, calcium levels, phosphate levels, presence of diabetes, rheumatoid arthritis, and chronic liver disease, the full model had an area under the curve of 77.7 at 1 year (95% CI, 73.3-84.4) and 69.9 at 3 years (95% CI, 68.0-72.2). For hip fracture, the model had an AUC of 80.1 at 1 year (95% CI, 77.0-83.5) and 71.9 at 3 years (95% CI, 70.1-74.2).
During the Q&A session, Dr. Cowan was asked how the tool could be implemented clinically. She said that it could have value in discussing fracture prediction and prevention with patients, but it could also increase fracture risk awareness among nephrologists. “I need to convince a lot of my colleagues because they’re focused on other things, so having this [calculator] I think is both good from a patient as well as a practitioner perspective. And the treatments that we have in people with end-stage renal disease are limited, so you want to know that you’re really targeting the high-risk person before you potentially put them on denosumab and increase the risk of severe hypercalcemia and things like that,” Dr. Cowan said.
The study points out the challenges of predicting fracture risk for specific populations, according to session comoderator Evelyn Hsieh, MD. She noted that the study needs follow-up. “I don’t think they had gotten to a validation [in a separate cohort] yet,” said Dr. Hsieh, an associate professor of medicine (rheumatology) and epidemiology (chronic diseases) at Yale University, New Haven, Conn.
Dr. Cowan and Dr. Hsieh have no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
VANCOUVER – A new calculator that predicts short-term fracture risk at both 1 year and 3 years in patients on dialysis performed well in a study presented at the annual meeting of the American Society for Bone and Mineral Research.
The tool will soon be available on QxMD Calculate, which provides free decision-support tools for physicians, said presenter Andrea Cowan, MD, an assistant professor of medicine at the University of Western Ontario, London.
Dialysis patients have an approximately fivefold increased risk for fracture, Dr. Cowan noted, compared with the general population. However, treatments to prevent fracture risk are relatively limited and can have significant side effects. Therefore, “you really want to make sure that the person you’re targeting for treatment is actually going to be at a reasonable risk of fracture,” she said.
The Fracture Risk Assessment Tool (FRAX) is useful, but it estimates 10-year fracture risk, which is too long of a time frame to be useful for dialysis patients who experience a 50% 5-year mortality, according to Dr. Cowan. It does not take kidney failure or severe hyperparathyroidism into account, and it also requires information like bone mineral density, which poses an additional burden for a dialysis patient already undergoing multiple tests.
The new calculator could also be useful for research because it doesn’t rely on clinical data that might not be generally available, such as parental fracture, smoking status, or body mass index. “There’s a move towards things like pragmatic trials, which use more routinely collected data, have broader inclusion criteria, and are often more cost efficient to run. This calculator should be relatively easy to implement in trials using routinely collected data to perhaps define a subgroup of patients who may be at high risk of fracture without having to apply really cumbersome tools,” Dr. Cowan said.
The researchers included 11,599 patients between ages 40 and 89 years who were treated at a single center in Ontario between 2010 and 2017. The mean age was 66.18 years, 38.6% were women, 64.1% had diabetes, 11.9% had liver disease, and median time on dialysis was 0.81 years. The patients’ median parathyroid hormone level was 30 pmol/L.
At 3 years, the cumulative incidence of any fracture was 7.36% (95% confidence interval, 6.89-7.85), including 2.62% for hip fracture (95% CI, 2.34-2.93), 1.36% for spine fracture (95% CI, 1.16-1.59), 1.93% for wrist or forearm (95% CI, 1.69-2.20), and 2.15% for the pelvis (95% CI, 1.89-2.43). The incidence for all fractures at 1 year was 2.93 (95% CI, 2.62-3.26).
Variables associated with fracture risk included female sex (hazard ratio, 1.46; 95% CI, 1.27-1.67), a previous fracture more than 1 year in the past (HR, 1.65; 95% CI, 1.37-2.00), a fracture in the past year (HR, 3.63; 95% CI, 2.86-4.60), and proton pump inhibitor use (HR, 1.23; 95% CI, 1.04-1.45). After inclusion of vitamin D use, steroid use, time on dialysis, calcium levels, phosphate levels, presence of diabetes, rheumatoid arthritis, and chronic liver disease, the full model had an area under the curve of 77.7 at 1 year (95% CI, 73.3-84.4) and 69.9 at 3 years (95% CI, 68.0-72.2). For hip fracture, the model had an AUC of 80.1 at 1 year (95% CI, 77.0-83.5) and 71.9 at 3 years (95% CI, 70.1-74.2).
During the Q&A session, Dr. Cowan was asked how the tool could be implemented clinically. She said that it could have value in discussing fracture prediction and prevention with patients, but it could also increase fracture risk awareness among nephrologists. “I need to convince a lot of my colleagues because they’re focused on other things, so having this [calculator] I think is both good from a patient as well as a practitioner perspective. And the treatments that we have in people with end-stage renal disease are limited, so you want to know that you’re really targeting the high-risk person before you potentially put them on denosumab and increase the risk of severe hypercalcemia and things like that,” Dr. Cowan said.
The study points out the challenges of predicting fracture risk for specific populations, according to session comoderator Evelyn Hsieh, MD. She noted that the study needs follow-up. “I don’t think they had gotten to a validation [in a separate cohort] yet,” said Dr. Hsieh, an associate professor of medicine (rheumatology) and epidemiology (chronic diseases) at Yale University, New Haven, Conn.
Dr. Cowan and Dr. Hsieh have no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
VANCOUVER – A new calculator that predicts short-term fracture risk at both 1 year and 3 years in patients on dialysis performed well in a study presented at the annual meeting of the American Society for Bone and Mineral Research.
The tool will soon be available on QxMD Calculate, which provides free decision-support tools for physicians, said presenter Andrea Cowan, MD, an assistant professor of medicine at the University of Western Ontario, London.
Dialysis patients have an approximately fivefold increased risk for fracture, Dr. Cowan noted, compared with the general population. However, treatments to prevent fracture risk are relatively limited and can have significant side effects. Therefore, “you really want to make sure that the person you’re targeting for treatment is actually going to be at a reasonable risk of fracture,” she said.
The Fracture Risk Assessment Tool (FRAX) is useful, but it estimates 10-year fracture risk, which is too long of a time frame to be useful for dialysis patients who experience a 50% 5-year mortality, according to Dr. Cowan. It does not take kidney failure or severe hyperparathyroidism into account, and it also requires information like bone mineral density, which poses an additional burden for a dialysis patient already undergoing multiple tests.
The new calculator could also be useful for research because it doesn’t rely on clinical data that might not be generally available, such as parental fracture, smoking status, or body mass index. “There’s a move towards things like pragmatic trials, which use more routinely collected data, have broader inclusion criteria, and are often more cost efficient to run. This calculator should be relatively easy to implement in trials using routinely collected data to perhaps define a subgroup of patients who may be at high risk of fracture without having to apply really cumbersome tools,” Dr. Cowan said.
The researchers included 11,599 patients between ages 40 and 89 years who were treated at a single center in Ontario between 2010 and 2017. The mean age was 66.18 years, 38.6% were women, 64.1% had diabetes, 11.9% had liver disease, and median time on dialysis was 0.81 years. The patients’ median parathyroid hormone level was 30 pmol/L.
At 3 years, the cumulative incidence of any fracture was 7.36% (95% confidence interval, 6.89-7.85), including 2.62% for hip fracture (95% CI, 2.34-2.93), 1.36% for spine fracture (95% CI, 1.16-1.59), 1.93% for wrist or forearm (95% CI, 1.69-2.20), and 2.15% for the pelvis (95% CI, 1.89-2.43). The incidence for all fractures at 1 year was 2.93 (95% CI, 2.62-3.26).
Variables associated with fracture risk included female sex (hazard ratio, 1.46; 95% CI, 1.27-1.67), a previous fracture more than 1 year in the past (HR, 1.65; 95% CI, 1.37-2.00), a fracture in the past year (HR, 3.63; 95% CI, 2.86-4.60), and proton pump inhibitor use (HR, 1.23; 95% CI, 1.04-1.45). After inclusion of vitamin D use, steroid use, time on dialysis, calcium levels, phosphate levels, presence of diabetes, rheumatoid arthritis, and chronic liver disease, the full model had an area under the curve of 77.7 at 1 year (95% CI, 73.3-84.4) and 69.9 at 3 years (95% CI, 68.0-72.2). For hip fracture, the model had an AUC of 80.1 at 1 year (95% CI, 77.0-83.5) and 71.9 at 3 years (95% CI, 70.1-74.2).
During the Q&A session, Dr. Cowan was asked how the tool could be implemented clinically. She said that it could have value in discussing fracture prediction and prevention with patients, but it could also increase fracture risk awareness among nephrologists. “I need to convince a lot of my colleagues because they’re focused on other things, so having this [calculator] I think is both good from a patient as well as a practitioner perspective. And the treatments that we have in people with end-stage renal disease are limited, so you want to know that you’re really targeting the high-risk person before you potentially put them on denosumab and increase the risk of severe hypercalcemia and things like that,” Dr. Cowan said.
The study points out the challenges of predicting fracture risk for specific populations, according to session comoderator Evelyn Hsieh, MD. She noted that the study needs follow-up. “I don’t think they had gotten to a validation [in a separate cohort] yet,” said Dr. Hsieh, an associate professor of medicine (rheumatology) and epidemiology (chronic diseases) at Yale University, New Haven, Conn.
Dr. Cowan and Dr. Hsieh have no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
AT ASBMR 2023
CKD linked to cardiac arrest in Hispanic, Latinx patients
TOPLINE:
new data show, suggesting early identification of CKD may provide an opportunity to reduce the risk in these groups. Other predictors included heavy drinking, atrial fibrillation, coronary artery disease, heart failure and diabetes.
METHODOLOGY:
- The study included 295 Hispanic or Latinx patients with out-of-hospital SCA from the PRESTO study in Ventura County, California, and 590 frequency-matched controls from the San Diego site of the population-based HCHS/SOL (Hispanic Community Health Survey/Study of Latinos); in both cohorts, men made up 70% of participants, and the median age was about 63 years.
- Researchers collected data on demographics, medical history, and current health conditions. Of note, 51.2% of SCA cases and 8.8% of control participants had CKD, and 20.0% of cases and 0.7% of the control group were on dialysis.
- Pre-SCA echocardiograms were available for 48% of SCA cases and baseline echocardiograms for more than 99% of control participants.
TAKEAWAY:
- In analyses adjusted for age, sex, and clinical variables, predictors significantly associated with higher odds of SCA included: CKD (odds ratio, 7.3; 95% confidence interval, 3.8-14.3; P < .001), heavy drinking (OR, 4.5), stroke (OR, 3.1), atrial fibrillation (OR, 3.7), coronary artery disease (OR, 2.9), heart failure (OR, 2.5), and diabetes (OR, 1.5).
- Hypertension, hyperlipemia, body mass index, and current smoking status were not significantly associated with SCA.
- In adjusted analyses, heart rate (OR, 1.8 per one standard deviation [1-SD] increase), QTc interval (OR, 2.5 per 1-SD increase) and left ventricular ejection fraction (OR, 4.4 per 1-SD decrease) were significantly associated with SCA, suggesting echocardiogram evaluations could help identify Hispanic or Latinx individuals at increased risk for SCA, wrote the authors.
IN PRACTICE:
“Our study, the first to include feasible numbers of Hispanic or Latino individuals, highlights the importance of renal dysfunction as a risk factor for SCA in the community,” the authors wrote, adding that early identification and management of chronic kidney disease could reduce risk for SCA in this population.
SOURCE:
The study was conducted by Kyndaron Reinier, PhD, MPH, Cedars-Sinai Health System, Los Angeles, and colleagues. It was published online in the Journal of the American Heart Association.
LIMITATIONS:
Most participants from the HCHS/SOL study were born outside the United States, compared with about half the SCA cases, which could have influenced cardiovascular disease risk, although results did not change considerably when models were adjusted for place of birth. Study participants were predominantly of Mexican heritage, so results may not be generalizable to Hispanic or Latinx individuals from other regions. As medical history was assessed differently in the two studies, there could be some error in estimating the strength of associations. Results from echocardiographic data should be viewed as hypothesis generating because of the potential for residual bias.
DISCLOSURES:
The Ventura PRESTO study was funded, in part, by the National Institutes of Health, and National Heart, Lung, and Blood Institute. The HCHS/SOL was carried out as a collaborative study supported by contracts from the NHLBI.
A version of this article first appeared on Medscape.com.
TOPLINE:
new data show, suggesting early identification of CKD may provide an opportunity to reduce the risk in these groups. Other predictors included heavy drinking, atrial fibrillation, coronary artery disease, heart failure and diabetes.
METHODOLOGY:
- The study included 295 Hispanic or Latinx patients with out-of-hospital SCA from the PRESTO study in Ventura County, California, and 590 frequency-matched controls from the San Diego site of the population-based HCHS/SOL (Hispanic Community Health Survey/Study of Latinos); in both cohorts, men made up 70% of participants, and the median age was about 63 years.
- Researchers collected data on demographics, medical history, and current health conditions. Of note, 51.2% of SCA cases and 8.8% of control participants had CKD, and 20.0% of cases and 0.7% of the control group were on dialysis.
- Pre-SCA echocardiograms were available for 48% of SCA cases and baseline echocardiograms for more than 99% of control participants.
TAKEAWAY:
- In analyses adjusted for age, sex, and clinical variables, predictors significantly associated with higher odds of SCA included: CKD (odds ratio, 7.3; 95% confidence interval, 3.8-14.3; P < .001), heavy drinking (OR, 4.5), stroke (OR, 3.1), atrial fibrillation (OR, 3.7), coronary artery disease (OR, 2.9), heart failure (OR, 2.5), and diabetes (OR, 1.5).
- Hypertension, hyperlipemia, body mass index, and current smoking status were not significantly associated with SCA.
- In adjusted analyses, heart rate (OR, 1.8 per one standard deviation [1-SD] increase), QTc interval (OR, 2.5 per 1-SD increase) and left ventricular ejection fraction (OR, 4.4 per 1-SD decrease) were significantly associated with SCA, suggesting echocardiogram evaluations could help identify Hispanic or Latinx individuals at increased risk for SCA, wrote the authors.
IN PRACTICE:
“Our study, the first to include feasible numbers of Hispanic or Latino individuals, highlights the importance of renal dysfunction as a risk factor for SCA in the community,” the authors wrote, adding that early identification and management of chronic kidney disease could reduce risk for SCA in this population.
SOURCE:
The study was conducted by Kyndaron Reinier, PhD, MPH, Cedars-Sinai Health System, Los Angeles, and colleagues. It was published online in the Journal of the American Heart Association.
LIMITATIONS:
Most participants from the HCHS/SOL study were born outside the United States, compared with about half the SCA cases, which could have influenced cardiovascular disease risk, although results did not change considerably when models were adjusted for place of birth. Study participants were predominantly of Mexican heritage, so results may not be generalizable to Hispanic or Latinx individuals from other regions. As medical history was assessed differently in the two studies, there could be some error in estimating the strength of associations. Results from echocardiographic data should be viewed as hypothesis generating because of the potential for residual bias.
DISCLOSURES:
The Ventura PRESTO study was funded, in part, by the National Institutes of Health, and National Heart, Lung, and Blood Institute. The HCHS/SOL was carried out as a collaborative study supported by contracts from the NHLBI.
A version of this article first appeared on Medscape.com.
TOPLINE:
new data show, suggesting early identification of CKD may provide an opportunity to reduce the risk in these groups. Other predictors included heavy drinking, atrial fibrillation, coronary artery disease, heart failure and diabetes.
METHODOLOGY:
- The study included 295 Hispanic or Latinx patients with out-of-hospital SCA from the PRESTO study in Ventura County, California, and 590 frequency-matched controls from the San Diego site of the population-based HCHS/SOL (Hispanic Community Health Survey/Study of Latinos); in both cohorts, men made up 70% of participants, and the median age was about 63 years.
- Researchers collected data on demographics, medical history, and current health conditions. Of note, 51.2% of SCA cases and 8.8% of control participants had CKD, and 20.0% of cases and 0.7% of the control group were on dialysis.
- Pre-SCA echocardiograms were available for 48% of SCA cases and baseline echocardiograms for more than 99% of control participants.
TAKEAWAY:
- In analyses adjusted for age, sex, and clinical variables, predictors significantly associated with higher odds of SCA included: CKD (odds ratio, 7.3; 95% confidence interval, 3.8-14.3; P < .001), heavy drinking (OR, 4.5), stroke (OR, 3.1), atrial fibrillation (OR, 3.7), coronary artery disease (OR, 2.9), heart failure (OR, 2.5), and diabetes (OR, 1.5).
- Hypertension, hyperlipemia, body mass index, and current smoking status were not significantly associated with SCA.
- In adjusted analyses, heart rate (OR, 1.8 per one standard deviation [1-SD] increase), QTc interval (OR, 2.5 per 1-SD increase) and left ventricular ejection fraction (OR, 4.4 per 1-SD decrease) were significantly associated with SCA, suggesting echocardiogram evaluations could help identify Hispanic or Latinx individuals at increased risk for SCA, wrote the authors.
IN PRACTICE:
“Our study, the first to include feasible numbers of Hispanic or Latino individuals, highlights the importance of renal dysfunction as a risk factor for SCA in the community,” the authors wrote, adding that early identification and management of chronic kidney disease could reduce risk for SCA in this population.
SOURCE:
The study was conducted by Kyndaron Reinier, PhD, MPH, Cedars-Sinai Health System, Los Angeles, and colleagues. It was published online in the Journal of the American Heart Association.
LIMITATIONS:
Most participants from the HCHS/SOL study were born outside the United States, compared with about half the SCA cases, which could have influenced cardiovascular disease risk, although results did not change considerably when models were adjusted for place of birth. Study participants were predominantly of Mexican heritage, so results may not be generalizable to Hispanic or Latinx individuals from other regions. As medical history was assessed differently in the two studies, there could be some error in estimating the strength of associations. Results from echocardiographic data should be viewed as hypothesis generating because of the potential for residual bias.
DISCLOSURES:
The Ventura PRESTO study was funded, in part, by the National Institutes of Health, and National Heart, Lung, and Blood Institute. The HCHS/SOL was carried out as a collaborative study supported by contracts from the NHLBI.
A version of this article first appeared on Medscape.com.
Redefining CVD risk: Cardiovascular-kidney-metabolic (CKM) syndrome
“This work was prompted by the fact that CKM syndrome leads to premature morbidity and mortality, primarily because of a higher burden of CVD,” writing committee chair Chiadi Ndumele, MD, PhD, said in an interview.
“While CKM syndrome is a public health emergency, there is also great potential for improving CKM health in the population, with an increasing number of therapies that favorably impact metabolic risk factors, risk for adverse kidney events, or both, which also protect against CVD,” added Dr. Ndumele, director of obesity and cardiometabolic research in the division of cardiology at Johns Hopkins University, Baltimore.
The AHA presidential advisory and accompanying scientific statement, which provides a synopsis of evidence for the science and clinical management of CKM, were published online in the journal Circulation.
CKM syndrome staging
According to the AHA, one in three U.S. adults have three or more risk factors that contribute to CVD, metabolic disorders, and/or kidney disease.
In addition to defining CKM syndrome, the advisory provides a “staging construct, to be used in both adults and youth, that reflects the progressive pathophysiology and risk within CKM syndrome, with therapeutic guidance tied to CKM stages,” Dr. Ndumele told this news organization.
The AHA outlines four stages of CKM syndrome:
Stage 0: At this stage, no CKM risk factors are present, and the goal is to prevent CKM syndrome (particularly unhealthy weight gain) by achieving and maintaining ideal health based on the AHA’s Life’s Essential 8 recommendations. Adults in this stage should be screened every 3-5 years to assess lipids, blood pressure, and blood sugar.
Stage 1: At this stage, excess weight, abdominal obesity, or dysfunctional adipose tissue (clinically manifest as impaired glucose tolerance or prediabetes) is present without other metabolic risk factors or CVD. Management includes providing support for healthy lifestyle changes (healthy eating and regular physical activity), with a goal of at least 5% weight loss and addressing glucose intolerance if needed. Screening adults with stage 1 CKM every 2-3 years is advised to assess blood pressure, triglycerides, cholesterol, and blood sugar.
Stage 2: At this stage, metabolic risk factors (hypertriglyceridemia, hypertension, metabolic syndrome, diabetes) and kidney disease are present. The goal is to address risk factors to prevent progression to CVD and kidney failure. Screening for stage 2 CKM syndrome aligns with AHA/ACC guidelines, which include yearly assessment of blood pressure, triglycerides, cholesterol, blood sugar, and kidney function. More frequent kidney screening is recommended for individuals with increased risk of kidney failure based on kidney function assessments.
Stage 3: This stage describes individuals with subclinical CVD with metabolic risk factors or kidney disease or those at high predicted risk for CVD. The goal is to intensify efforts to prevent progression to symptomatic CVD and kidney failure. This may involve increasing or changing medications, and additional focus on lifestyle changes. Coronary artery calcium (CAC) measurement in some adults is recommended to assess narrowing of the arteries when treatment decisions are unclear.
Stage 4: Individuals with stage 4 CKM syndrome have symptomatic CVD, excess body fat, metabolic risk factors, or kidney disease. Stage 4 CKM syndrome is divided into two subcategories: (4a) no kidney failure and (4b) kidney failure. In this stage, patients may have already had a myocardial infarction (MI) or stroke or may already have heart failure. They also may have additional CV conditions such as peripheral artery disease or atrial fibrillation. The goal of care is individualized treatment for CVD with consideration for CKM syndrome conditions.
The advisory also describes CKM syndrome regression, “an important concept and public health message in which people making healthy lifestyle changes and achieving weight loss may regress to lower CKM syndrome stages and a better state of health,” the AHA says in a news release.
They note that a “critical” next step is to update the pooled cohort equation (PCE) risk prediction algorithm to include measures of kidney function, type 2 diabetes control, and social determinants of health for a more comprehensive risk estimate.
The advisory also recommends risk calculator updates be expanded to assess risk in people as young as age 30 and to calculate both 10- and 30-year CVD risk.
“Clearly defining the patient with CKM syndrome, and providing new approaches for CKM syndrome staging and risk prediction, will help health care professionals to identify these individuals earlier and to provide timely, holistic, and patient-centered care,” Dr. Ndumele said.
This presidential advisory was prepared by the volunteer writing group on behalf of the AHA . The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
“This work was prompted by the fact that CKM syndrome leads to premature morbidity and mortality, primarily because of a higher burden of CVD,” writing committee chair Chiadi Ndumele, MD, PhD, said in an interview.
“While CKM syndrome is a public health emergency, there is also great potential for improving CKM health in the population, with an increasing number of therapies that favorably impact metabolic risk factors, risk for adverse kidney events, or both, which also protect against CVD,” added Dr. Ndumele, director of obesity and cardiometabolic research in the division of cardiology at Johns Hopkins University, Baltimore.
The AHA presidential advisory and accompanying scientific statement, which provides a synopsis of evidence for the science and clinical management of CKM, were published online in the journal Circulation.
CKM syndrome staging
According to the AHA, one in three U.S. adults have three or more risk factors that contribute to CVD, metabolic disorders, and/or kidney disease.
In addition to defining CKM syndrome, the advisory provides a “staging construct, to be used in both adults and youth, that reflects the progressive pathophysiology and risk within CKM syndrome, with therapeutic guidance tied to CKM stages,” Dr. Ndumele told this news organization.
The AHA outlines four stages of CKM syndrome:
Stage 0: At this stage, no CKM risk factors are present, and the goal is to prevent CKM syndrome (particularly unhealthy weight gain) by achieving and maintaining ideal health based on the AHA’s Life’s Essential 8 recommendations. Adults in this stage should be screened every 3-5 years to assess lipids, blood pressure, and blood sugar.
Stage 1: At this stage, excess weight, abdominal obesity, or dysfunctional adipose tissue (clinically manifest as impaired glucose tolerance or prediabetes) is present without other metabolic risk factors or CVD. Management includes providing support for healthy lifestyle changes (healthy eating and regular physical activity), with a goal of at least 5% weight loss and addressing glucose intolerance if needed. Screening adults with stage 1 CKM every 2-3 years is advised to assess blood pressure, triglycerides, cholesterol, and blood sugar.
Stage 2: At this stage, metabolic risk factors (hypertriglyceridemia, hypertension, metabolic syndrome, diabetes) and kidney disease are present. The goal is to address risk factors to prevent progression to CVD and kidney failure. Screening for stage 2 CKM syndrome aligns with AHA/ACC guidelines, which include yearly assessment of blood pressure, triglycerides, cholesterol, blood sugar, and kidney function. More frequent kidney screening is recommended for individuals with increased risk of kidney failure based on kidney function assessments.
Stage 3: This stage describes individuals with subclinical CVD with metabolic risk factors or kidney disease or those at high predicted risk for CVD. The goal is to intensify efforts to prevent progression to symptomatic CVD and kidney failure. This may involve increasing or changing medications, and additional focus on lifestyle changes. Coronary artery calcium (CAC) measurement in some adults is recommended to assess narrowing of the arteries when treatment decisions are unclear.
Stage 4: Individuals with stage 4 CKM syndrome have symptomatic CVD, excess body fat, metabolic risk factors, or kidney disease. Stage 4 CKM syndrome is divided into two subcategories: (4a) no kidney failure and (4b) kidney failure. In this stage, patients may have already had a myocardial infarction (MI) or stroke or may already have heart failure. They also may have additional CV conditions such as peripheral artery disease or atrial fibrillation. The goal of care is individualized treatment for CVD with consideration for CKM syndrome conditions.
The advisory also describes CKM syndrome regression, “an important concept and public health message in which people making healthy lifestyle changes and achieving weight loss may regress to lower CKM syndrome stages and a better state of health,” the AHA says in a news release.
They note that a “critical” next step is to update the pooled cohort equation (PCE) risk prediction algorithm to include measures of kidney function, type 2 diabetes control, and social determinants of health for a more comprehensive risk estimate.
The advisory also recommends risk calculator updates be expanded to assess risk in people as young as age 30 and to calculate both 10- and 30-year CVD risk.
“Clearly defining the patient with CKM syndrome, and providing new approaches for CKM syndrome staging and risk prediction, will help health care professionals to identify these individuals earlier and to provide timely, holistic, and patient-centered care,” Dr. Ndumele said.
This presidential advisory was prepared by the volunteer writing group on behalf of the AHA . The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
“This work was prompted by the fact that CKM syndrome leads to premature morbidity and mortality, primarily because of a higher burden of CVD,” writing committee chair Chiadi Ndumele, MD, PhD, said in an interview.
“While CKM syndrome is a public health emergency, there is also great potential for improving CKM health in the population, with an increasing number of therapies that favorably impact metabolic risk factors, risk for adverse kidney events, or both, which also protect against CVD,” added Dr. Ndumele, director of obesity and cardiometabolic research in the division of cardiology at Johns Hopkins University, Baltimore.
The AHA presidential advisory and accompanying scientific statement, which provides a synopsis of evidence for the science and clinical management of CKM, were published online in the journal Circulation.
CKM syndrome staging
According to the AHA, one in three U.S. adults have three or more risk factors that contribute to CVD, metabolic disorders, and/or kidney disease.
In addition to defining CKM syndrome, the advisory provides a “staging construct, to be used in both adults and youth, that reflects the progressive pathophysiology and risk within CKM syndrome, with therapeutic guidance tied to CKM stages,” Dr. Ndumele told this news organization.
The AHA outlines four stages of CKM syndrome:
Stage 0: At this stage, no CKM risk factors are present, and the goal is to prevent CKM syndrome (particularly unhealthy weight gain) by achieving and maintaining ideal health based on the AHA’s Life’s Essential 8 recommendations. Adults in this stage should be screened every 3-5 years to assess lipids, blood pressure, and blood sugar.
Stage 1: At this stage, excess weight, abdominal obesity, or dysfunctional adipose tissue (clinically manifest as impaired glucose tolerance or prediabetes) is present without other metabolic risk factors or CVD. Management includes providing support for healthy lifestyle changes (healthy eating and regular physical activity), with a goal of at least 5% weight loss and addressing glucose intolerance if needed. Screening adults with stage 1 CKM every 2-3 years is advised to assess blood pressure, triglycerides, cholesterol, and blood sugar.
Stage 2: At this stage, metabolic risk factors (hypertriglyceridemia, hypertension, metabolic syndrome, diabetes) and kidney disease are present. The goal is to address risk factors to prevent progression to CVD and kidney failure. Screening for stage 2 CKM syndrome aligns with AHA/ACC guidelines, which include yearly assessment of blood pressure, triglycerides, cholesterol, blood sugar, and kidney function. More frequent kidney screening is recommended for individuals with increased risk of kidney failure based on kidney function assessments.
Stage 3: This stage describes individuals with subclinical CVD with metabolic risk factors or kidney disease or those at high predicted risk for CVD. The goal is to intensify efforts to prevent progression to symptomatic CVD and kidney failure. This may involve increasing or changing medications, and additional focus on lifestyle changes. Coronary artery calcium (CAC) measurement in some adults is recommended to assess narrowing of the arteries when treatment decisions are unclear.
Stage 4: Individuals with stage 4 CKM syndrome have symptomatic CVD, excess body fat, metabolic risk factors, or kidney disease. Stage 4 CKM syndrome is divided into two subcategories: (4a) no kidney failure and (4b) kidney failure. In this stage, patients may have already had a myocardial infarction (MI) or stroke or may already have heart failure. They also may have additional CV conditions such as peripheral artery disease or atrial fibrillation. The goal of care is individualized treatment for CVD with consideration for CKM syndrome conditions.
The advisory also describes CKM syndrome regression, “an important concept and public health message in which people making healthy lifestyle changes and achieving weight loss may regress to lower CKM syndrome stages and a better state of health,” the AHA says in a news release.
They note that a “critical” next step is to update the pooled cohort equation (PCE) risk prediction algorithm to include measures of kidney function, type 2 diabetes control, and social determinants of health for a more comprehensive risk estimate.
The advisory also recommends risk calculator updates be expanded to assess risk in people as young as age 30 and to calculate both 10- and 30-year CVD risk.
“Clearly defining the patient with CKM syndrome, and providing new approaches for CKM syndrome staging and risk prediction, will help health care professionals to identify these individuals earlier and to provide timely, holistic, and patient-centered care,” Dr. Ndumele said.
This presidential advisory was prepared by the volunteer writing group on behalf of the AHA . The authors have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM CIRCULATION