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 P.
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
N1 - Publisher Copyright:
© 2019 by the American Society of Nephrology.
PY - 2019/9
Y1 - 2019/9
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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U2 - 10.1681/ASN.2019010008
DO - 10.1681/ASN.2019010008
M3 - Article
C2 - 31292199
AN - SCOPUS:85071786534
SN - 1046-6673
VL - 30
SP - 1746
EP - 1755
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 9
ER -