Evaluating glomerular filtration rate slope as a surrogate end point for ESKD in clinical trials

An individual participant meta-analysis of observational data

Morgan E. Grams, Yingying Sang, Shoshana H. Ballew, Kunihiro Matsushita, Brad C. Astor, Juan Jesus Carrero, Alex R. Chang, Lesley A. Inker, Timothy Kenealy, Csaba Kovesdy, Brian J. Lee, Adeera Levin, David Naimark, Michelle J. Pena, Jesse D. Schold, Varda Shalev, Jack F.M. Wetzels, Mark Woodward, Ron T. Gansevoort, Andrew S. Levey & 1 others Josef Coresh

Research output: Contribution to journalArticle

Abstract

Background Decline in eGFR is a biologically plausible surrogate end point for the progression of CKD in clinical trials. However, it must first be tested to ensure strong associations with clinical outcomes in diverse populations, including patients with higher eGFR. Methods To investigate the association between 1-, 2-, and 3-year changes in eGFR (slope) with clinical outcomes over the long term, we conducted a random effects meta-analysis of 3,758,551 participants with baseline eGFR≥60 ml/min per 1.73 m2 and 122,664 participants with eGFR<60 ml/min per 1.73 m2 from 14 cohorts followed for an average of 4.2 years. Results Slower eGFR decline by 0.75 ml/min per 1.73 m2 per year over 2 years was associated with lower risk of ESKD in participants with baseline eGFR≥60 ml/min per 1.73 m2 (adjusted hazard ratio, 0.70; 95% CI, 0.68 to 0.72) and eGFR<60 ml/min per 1.73 m2 (0.71; 95% CI, 0.68 to 0.74). The relationship was stronger with 3-year slope. For a rapidly progressing population with predicted 5-year risk of ESKD of 8.3%, an intervention that reduced eGFR decline by 0.75 ml/min per 1.73 m2 per year over 2 years would reduce the ESKD risk by 1.6%. For a hypothetical low-risk population with a predicted 5-year ESKD risk of 0.58%, the same intervention would reduce the risk by only 0.13%. Conclusions Slower decline in eGFR was associated with lower risk of subsequent ESKD, even in participants with eGFR≥60 ml/min per 1.73 m2, but those with the highest risk would be expected to benefit the most.

Original languageEnglish (US)
Pages (from-to)1746-1755
Number of pages10
JournalJournal of the American Society of Nephrology
Volume30
Issue number9
DOIs
StatePublished - Sep 1 2019

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Glomerular Filtration Rate
Chronic Renal Insufficiency
Chronic Kidney Failure
Meta-Analysis
Biomarkers
Clinical Trials
Population

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Evaluating glomerular filtration rate slope as a surrogate end point for ESKD in clinical trials : An individual participant meta-analysis of observational data. / Grams, Morgan E.; Sang, Yingying; Ballew, Shoshana H.; Matsushita, Kunihiro; Astor, Brad C.; Carrero, Juan Jesus; Chang, Alex R.; Inker, Lesley A.; Kenealy, Timothy; Kovesdy, Csaba; Lee, Brian J.; Levin, Adeera; Naimark, David; Pena, Michelle J.; Schold, Jesse D.; Shalev, Varda; Wetzels, Jack F.M.; Woodward, Mark; Gansevoort, Ron T.; Levey, Andrew S.; Coresh, Josef.

In: Journal of the American Society of Nephrology, Vol. 30, No. 9, 01.09.2019, p. 1746-1755.

Research output: Contribution to journalArticle

Grams, ME, Sang, Y, Ballew, SH, Matsushita, K, Astor, BC, Carrero, JJ, Chang, AR, Inker, LA, Kenealy, T, Kovesdy, C, Lee, BJ, Levin, A, Naimark, D, Pena, MJ, Schold, JD, Shalev, V, Wetzels, JFM, Woodward, M, Gansevoort, RT, Levey, AS & Coresh, J 2019, 'Evaluating glomerular filtration rate slope as a surrogate end point for ESKD in clinical trials: An individual participant meta-analysis of observational data', Journal of the American Society of Nephrology, vol. 30, no. 9, pp. 1746-1755. https://doi.org/10.1681/ASN.2019010008
Grams, Morgan E. ; Sang, Yingying ; Ballew, Shoshana H. ; Matsushita, Kunihiro ; Astor, Brad C. ; Carrero, Juan Jesus ; Chang, Alex R. ; Inker, Lesley A. ; Kenealy, Timothy ; Kovesdy, Csaba ; Lee, Brian J. ; Levin, Adeera ; Naimark, David ; Pena, Michelle J. ; Schold, Jesse D. ; Shalev, Varda ; Wetzels, Jack F.M. ; Woodward, Mark ; Gansevoort, Ron T. ; Levey, Andrew S. ; Coresh, Josef. / Evaluating glomerular filtration rate slope as a surrogate end point for ESKD in clinical trials : An individual participant meta-analysis of observational data. In: Journal of the American Society of Nephrology. 2019 ; Vol. 30, No. 9. pp. 1746-1755.
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title = "Evaluating glomerular filtration rate slope as a surrogate end point for ESKD in clinical trials: An individual participant meta-analysis of observational data",
abstract = "Background Decline in eGFR is a biologically plausible surrogate end point for the progression of CKD in clinical trials. However, it must first be tested to ensure strong associations with clinical outcomes in diverse populations, including patients with higher eGFR. Methods To investigate the association between 1-, 2-, and 3-year changes in eGFR (slope) with clinical outcomes over the long term, we conducted a random effects meta-analysis of 3,758,551 participants with baseline eGFR≥60 ml/min per 1.73 m2 and 122,664 participants with eGFR<60 ml/min per 1.73 m2 from 14 cohorts followed for an average of 4.2 years. Results Slower eGFR decline by 0.75 ml/min per 1.73 m2 per year over 2 years was associated with lower risk of ESKD in participants with baseline eGFR≥60 ml/min per 1.73 m2 (adjusted hazard ratio, 0.70; 95{\%} CI, 0.68 to 0.72) and eGFR<60 ml/min per 1.73 m2 (0.71; 95{\%} CI, 0.68 to 0.74). The relationship was stronger with 3-year slope. For a rapidly progressing population with predicted 5-year risk of ESKD of 8.3{\%}, an intervention that reduced eGFR decline by 0.75 ml/min per 1.73 m2 per year over 2 years would reduce the ESKD risk by 1.6{\%}. For a hypothetical low-risk population with a predicted 5-year ESKD risk of 0.58{\%}, the same intervention would reduce the risk by only 0.13{\%}. Conclusions Slower decline in eGFR was associated with lower risk of subsequent ESKD, even in participants with eGFR≥60 ml/min per 1.73 m2, but those with the highest risk would be expected to benefit the most.",
author = "Grams, {Morgan E.} and Yingying Sang and Ballew, {Shoshana H.} and Kunihiro Matsushita and Astor, {Brad C.} and Carrero, {Juan Jesus} and Chang, {Alex R.} and Inker, {Lesley A.} and Timothy Kenealy and Csaba Kovesdy and Lee, {Brian J.} and Adeera Levin and David Naimark and Pena, {Michelle J.} and Schold, {Jesse D.} and Varda Shalev and Wetzels, {Jack F.M.} and Mark Woodward and Gansevoort, {Ron T.} and Levey, {Andrew S.} and Josef Coresh",
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TY - JOUR

T1 - Evaluating glomerular filtration rate slope as a surrogate end point for ESKD in clinical trials

T2 - An individual participant meta-analysis of observational data

AU - Grams, Morgan E.

AU - Sang, Yingying

AU - Ballew, Shoshana H.

AU - Matsushita, Kunihiro

AU - Astor, Brad C.

AU - Carrero, Juan Jesus

AU - Chang, Alex R.

AU - Inker, Lesley A.

AU - Kenealy, Timothy

AU - Kovesdy, Csaba

AU - Lee, Brian J.

AU - Levin, Adeera

AU - Naimark, David

AU - Pena, Michelle J.

AU - Schold, Jesse D.

AU - Shalev, Varda

AU - Wetzels, Jack F.M.

AU - Woodward, Mark

AU - Gansevoort, Ron T.

AU - Levey, Andrew S.

AU - Coresh, Josef

PY - 2019/9/1

Y1 - 2019/9/1

N2 - Background Decline in eGFR is a biologically plausible surrogate end point for the progression of CKD in clinical trials. However, it must first be tested to ensure strong associations with clinical outcomes in diverse populations, including patients with higher eGFR. Methods To investigate the association between 1-, 2-, and 3-year changes in eGFR (slope) with clinical outcomes over the long term, we conducted a random effects meta-analysis of 3,758,551 participants with baseline eGFR≥60 ml/min per 1.73 m2 and 122,664 participants with eGFR<60 ml/min per 1.73 m2 from 14 cohorts followed for an average of 4.2 years. Results Slower eGFR decline by 0.75 ml/min per 1.73 m2 per year over 2 years was associated with lower risk of ESKD in participants with baseline eGFR≥60 ml/min per 1.73 m2 (adjusted hazard ratio, 0.70; 95% CI, 0.68 to 0.72) and eGFR<60 ml/min per 1.73 m2 (0.71; 95% CI, 0.68 to 0.74). The relationship was stronger with 3-year slope. For a rapidly progressing population with predicted 5-year risk of ESKD of 8.3%, an intervention that reduced eGFR decline by 0.75 ml/min per 1.73 m2 per year over 2 years would reduce the ESKD risk by 1.6%. For a hypothetical low-risk population with a predicted 5-year ESKD risk of 0.58%, the same intervention would reduce the risk by only 0.13%. Conclusions Slower decline in eGFR was associated with lower risk of subsequent ESKD, even in participants with eGFR≥60 ml/min per 1.73 m2, but those with the highest risk would be expected to benefit the most.

AB - Background Decline in eGFR is a biologically plausible surrogate end point for the progression of CKD in clinical trials. However, it must first be tested to ensure strong associations with clinical outcomes in diverse populations, including patients with higher eGFR. Methods To investigate the association between 1-, 2-, and 3-year changes in eGFR (slope) with clinical outcomes over the long term, we conducted a random effects meta-analysis of 3,758,551 participants with baseline eGFR≥60 ml/min per 1.73 m2 and 122,664 participants with eGFR<60 ml/min per 1.73 m2 from 14 cohorts followed for an average of 4.2 years. Results Slower eGFR decline by 0.75 ml/min per 1.73 m2 per year over 2 years was associated with lower risk of ESKD in participants with baseline eGFR≥60 ml/min per 1.73 m2 (adjusted hazard ratio, 0.70; 95% CI, 0.68 to 0.72) and eGFR<60 ml/min per 1.73 m2 (0.71; 95% CI, 0.68 to 0.74). The relationship was stronger with 3-year slope. For a rapidly progressing population with predicted 5-year risk of ESKD of 8.3%, an intervention that reduced eGFR decline by 0.75 ml/min per 1.73 m2 per year over 2 years would reduce the ESKD risk by 1.6%. For a hypothetical low-risk population with a predicted 5-year ESKD risk of 0.58%, the same intervention would reduce the risk by only 0.13%. Conclusions Slower decline in eGFR was associated with lower risk of subsequent ESKD, even in participants with eGFR≥60 ml/min per 1.73 m2, but those with the highest risk would be expected to benefit the most.

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