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GFR decline and subsequent risk of established kidney outcomes: a meta-analysis of 37 randomized controlled trials.
Am J Kidney Dis. 2014 Dec; 64(6):860-6.AJ

Abstract

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<15mL/min/1.73m(2), 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.

LIMITATIONS

Observational study subject to residual confounding.

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.

Authors+Show Affiliations

Department of Clinical Pharmacy & Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.Division of Nephrology, Tufts Medical Center, Boston, MA.Department of Epidemiology, Johns Hopkins, Baltimore, MD.Department of Epidemiology, Johns Hopkins, Baltimore, MD.Division of Nephrology, Tufts Medical Center, Boston, MA.Department of Epidemiology, Johns Hopkins, Baltimore, MD.Department of Epidemiology, Johns Hopkins, Baltimore, MD.Division of Nephrology, Tufts Medical Center, Boston, MA.Division of Nephrology, Tufts Medical Center, Boston, MA. Electronic address: linker@tuftsmedicalcenter.org.

Pub Type(s)

Journal Article
Meta-Analysis
Observational Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25441439

Citation

Lambers Heerspink, Hiddo J., et al. "GFR Decline and Subsequent Risk of Established Kidney Outcomes: a Meta-analysis of 37 Randomized Controlled Trials." American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, vol. 64, no. 6, 2014, pp. 860-6.
Lambers Heerspink HJ, Tighiouart H, Sang Y, et al. GFR decline and subsequent risk of established kidney outcomes: a meta-analysis of 37 randomized controlled trials. Am J Kidney Dis. 2014;64(6):860-6.
Lambers Heerspink, H. J., Tighiouart, H., Sang, Y., Ballew, S., Mondal, H., Matsushita, K., Coresh, J., Levey, A. S., & Inker, L. A. (2014). GFR decline and subsequent risk of established kidney outcomes: a meta-analysis of 37 randomized controlled trials. American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, 64(6), 860-6. https://doi.org/10.1053/j.ajkd.2014.08.018
Lambers Heerspink HJ, et al. GFR Decline and Subsequent Risk of Established Kidney Outcomes: a Meta-analysis of 37 Randomized Controlled Trials. Am J Kidney Dis. 2014;64(6):860-6. PubMed PMID: 25441439.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - GFR decline and subsequent risk of established kidney outcomes: 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, Y1 - 2014/10/16/ PY - 2014/04/02/received PY - 2014/08/22/accepted PY - 2014/12/3/entrez PY - 2014/12/3/pubmed PY - 2015/2/7/medline 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 SP - 860 EP - 6 JF - American journal of kidney diseases : the official journal of the National Kidney Foundation JO - Am J Kidney Dis VL - 64 IS - 6 N2 - 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<15mL/min/1.73m(2), 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. LIMITATIONS: Observational study subject to residual confounding. 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. SN - 1523-6838 UR - https://www.unboundmedicine.com/medline/citation/25441439/GFR_decline_and_subsequent_risk_of_established_kidney_outcomes:_a_meta_analysis_of_37_randomized_controlled_trials_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0272-6386(14)01185-8 DB - PRIME DP - Unbound Medicine ER -