TY - JOUR
T1 - GFR decline and subsequent risk of established kidney outcomes
T2 - A meta-analysis of 37 randomized controlled trials
AU - Lambers Heerspink, Hiddo J.
AU - Tighiouart, Hocine
AU - Sang, Yingying
AU - Ballew, Shoshana
AU - Mondal, Hasi
AU - Matsushita, Kunihiro
AU - Coresh, Josef
AU - Levey, Andrew S.
AU - Inker, Lesley A.
N1 - Publisher Copyright:
© 2014 National Kidney Foundation, Inc.
PY - 2014/12/1
Y1 - 2014/12/1
N2 - Limitations Observational study subject to residual confounding.Background The currently established end points for clinical trials of progression of chronic kidney disease (CKD) are end-stage renal disease and doubling of serum creatinine level, which approximates a 57% decline in estimated glomerular filtration rate (eGFR). There is increased interest in using alternative end points in clinical trials to shorten trial duration and reduce sample size. As part of an evaluation of using lesser declines in GFR as alternative end points, we examined the associations of various levels of eGFR decline with the subsequent development of established end points and assess the consistency of alternate levels of eGFR decline across varying clinical manifestations of kidney disease and interventions.Study Design Observational analysis of randomized controlled trials.Setting & Participants 9,488 participants in 37 randomized controlled trials in CKD. Predictor Alternative end points, defined as 30% and 40% declines in eGFR from baseline to month 12. Effect modification by baseline eGFR, proteinuria, cause of disease, and interventions. Outcomes Established end point, defined as end-stage renal disease, eGFR < 15 mL/min/1.73 m2, or doubling of serum creatinine level.Results From baseline to 12 months, 16.1% and 7.8% of participants had eGFR declines of ≥30% or ≥40%, respectively. Over a median follow-up of 2.0 (IQR, 1.2-3.1) years after the 12-month baseline period, 2,661 established end points were observed. A strong linear association was observed between eGFR decline and subsequent established end points. HRs for the established end point for 30% and 40% decreases in eGFR compared to a 0% decline were 9.6 (95% CI, 7.3-12.6) and 20.3 (95% CI, 14.1-29.3), respectively. The associations were consistent regardless of baseline eGFR, proteinuria, causes of disease, and interventions.Conclusions The strong associations between lesser declines in eGFR and the subsequent development of established end points were consistent across different clinical characteristics of kidney disease and interventions and support implementation of alternative end points in clinical trials of CKD progression.
AB - Limitations Observational study subject to residual confounding.Background The currently established end points for clinical trials of progression of chronic kidney disease (CKD) are end-stage renal disease and doubling of serum creatinine level, which approximates a 57% decline in estimated glomerular filtration rate (eGFR). There is increased interest in using alternative end points in clinical trials to shorten trial duration and reduce sample size. As part of an evaluation of using lesser declines in GFR as alternative end points, we examined the associations of various levels of eGFR decline with the subsequent development of established end points and assess the consistency of alternate levels of eGFR decline across varying clinical manifestations of kidney disease and interventions.Study Design Observational analysis of randomized controlled trials.Setting & Participants 9,488 participants in 37 randomized controlled trials in CKD. Predictor Alternative end points, defined as 30% and 40% declines in eGFR from baseline to month 12. Effect modification by baseline eGFR, proteinuria, cause of disease, and interventions. Outcomes Established end point, defined as end-stage renal disease, eGFR < 15 mL/min/1.73 m2, or doubling of serum creatinine level.Results From baseline to 12 months, 16.1% and 7.8% of participants had eGFR declines of ≥30% or ≥40%, respectively. Over a median follow-up of 2.0 (IQR, 1.2-3.1) years after the 12-month baseline period, 2,661 established end points were observed. A strong linear association was observed between eGFR decline and subsequent established end points. HRs for the established end point for 30% and 40% decreases in eGFR compared to a 0% decline were 9.6 (95% CI, 7.3-12.6) and 20.3 (95% CI, 14.1-29.3), respectively. The associations were consistent regardless of baseline eGFR, proteinuria, causes of disease, and interventions.Conclusions The strong associations between lesser declines in eGFR and the subsequent development of established end points were consistent across different clinical characteristics of kidney disease and interventions and support implementation of alternative end points in clinical trials of CKD progression.
KW - Randomized controlled trial
KW - chronic kidney disease (CKD)
KW - end-stage renal disease (ESRD)
KW - estimated glomerular filtration rate (eGFR) decline
KW - kidney disease outcome
KW - kidney disease progression
KW - kidney end point
KW - meta-analysis
KW - nephropathy
KW - renal end point
KW - renal function
KW - surrogate end point
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U2 - 10.1053/j.ajkd.2014.08.018
DO - 10.1053/j.ajkd.2014.08.018
M3 - Article
C2 - 25441439
AN - SCOPUS:84911421938
SN - 0272-6386
VL - 64
SP - 860
EP - 866
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 6
ER -