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 - Funding Information:
Dr. Matsushita reports funding and personal fees from Kyowa Hakko Kirin and personal fees from Akebia outside of the submitted work. Dr. Inker reports grants from the National Institute for Health (NIH) and grants from the National Kidney Foundation (NKF) during the conduct of the study. In addition, Dr. Inker has a patent pending (“Precise estimation of GFR from multiple biomarkers” to Drs. Inker, Levey, and Coresh). Dr. Inker reports funding to Tufts Medical Center for research and contracts with the NIH, NKF, Retrophin, Omeros Corp., Reata Pharmaceuticals, and Dialysis Clinic, Inc. She has consulting agreements with Tricida Inc. and Omeros Corp. Dr. Kovesdy reports personal fees from Amgen, personal fees from Sanofi-Aventis, personal fees from Fresenius Medical Care, personal fees from Keryx, grants from Shire, personal fees from Bayer, personal fees from Abbott, personal fees from Abbvie, personal fees from Dr. Schar, and personal fees from Astra-Zeneca outside the submitted work. Dr. Wetzels reports grants from Sanofi, grants from Pfizer, grants from Amgen, grants from Achillion, other from Shire, and other from Vifor Fresenius outside the submitted work. Dr. Woodward reports personal fees from Amgen and personal fees from Kirin outside the submitted work. Dr. Levey reports grants from the NKF and grants from the NIH during the conduct of the study and other from Siemens outside the submitted work. In addition, Dr. Levey has a patent pending (“Precise estimation of GFR from multiple biomarkers” to Dr. Inker, Dr. Levey, and Dr. Coresh). Dr. Coresh reports grants from the NIH and grants from the NKF during the conduct of the study.
Funding Information:
The CKD Prognosis Consortium (CKD-PC) Data Coordinating Center is funded in part by a program grant from the US National Kidney Foundation (which in turn, receives support from industry) and National Institute of Diabetes and Digestive and Kidney Diseases grant R01DK100446-01. Avariety of sources have supported enrollment; data collection, including laboratory measurements; and follow-up in the collaborating cohorts of the CKD-PC. These funding sources include government agencies, such as national institutes of health and medical research councils as well as foundations and industry sponsors listed in Supplemental Appendix 3.
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
VL - 30
SP - 1746
EP - 1755
JO - Journal of the American Society of Nephrology : JASN
JF - Journal of the American Society of Nephrology : JASN
SN - 1046-6673
IS - 9
ER -