title: Assessing the Validity of Surrogate Outcomes for ESRD: A Meta-Analysis.
abstract: Validation of current and promising surrogate outcomes for ESRD in randomized controlled trials (RCTs) has been limited. We conducted a systematic review and meta-analysis of RCTs to further inform the ability of surrogate outcomes for ESRD to predict the efficacy of various interventions on ESRD. MEDLINE, EMBASE, and CENTRAL (from inception through September 2013) were searched. All RCTs in adults with proteinuria, diabetes, or CKD stages 1-4 or renal transplant recipients reporting ≥10 ESRD events and a surrogate outcome (change in proteinuria or doubling of serum creatinine [DSCR]) for ESRD during a ≥1-year follow-up were included. Two reviewers abstracted trial characteristics and outcome data independently. To assess the correlation between the surrogate outcomes and ESRD, we determined the treatment effect ratio (TER), defined as the ratio of the treatment effects on ESRD and the effects on the change in surrogate outcomes. TERs close to 1 indicate greater agreement between ESRD and the surrogate, and these ratios were pooled across interventions. We identified 27 trials (97,458 participants; 4187 participants with ESRD). Seven trials reported the effects on change in proteinuria and showed consistent effects for proteinuria and ESRD (TER, 0.82; 95% confidence interval, 0.59 to 1.16), with minimal heterogeneity. Twenty trials reported on DSCR. Treatment effects on DSCR were consistent with the effects on ESRD (TER, 0.98; 95% confidence interval, 0.85 to 1.14), with moderate heterogeneity. In conclusion, DSCR is generally a good surrogate for ESRD, whereas data on proteinuria were limited. Further assessment of the surrogacy of proteinuria using prospective RCTs is warranted.
authors.affiliation: Department of Medicine, Division of Nephrology, The George Institute for Global Health, The University of Sydney, Sydney, Australia;
authors.forename: Min
authors.initials: M
authors.lastname: Jun
authors.affiliation: Department of Community Health Sciences, and Department of Family Medicine, University of Calgary, Calgary, Alberta, Canada;
authors.forename: Tanvir Chowdhury
authors.initials: TC
authors.lastname: Turin
authors.affiliation: Department of Community Health Sciences, and The George Institute for Global Health, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom; and.
authors.forename: Mark
authors.initials: M
authors.lastname: Woodward
authors.affiliation: The George Institute for Global Health, The University of Sydney, Sydney, Australia;
authors.forename: Vlado
authors.initials: V
authors.lastname: Perkovic
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Hiddo J
authors.initials: HJ
authors.lastname: Lambers Heerspink
authors.affiliation: Department of Medicine, Division of Nephrology, Department of Community Health Sciences, and.
authors.forename: Braden J
authors.initials: BJ
authors.lastname: Manns
authors.affiliation: Department of Community Health Sciences, and.
authors.forename: Marcello
authors.initials: M
authors.lastname: Tonelli
authors.affiliation: Department of Medicine, Division of Nephrology, Department of Community Health Sciences, and Brenda.Hemmelgarn@albertahealthservices.ca.
authors.forename: Brenda R
authors.initials: BR
authors.lastname: Hemmelgarn
mesh_terms: D015415:Biomarkers / Q000097:blood / Q000652:urine; D003404:Creatinine / Q000097:blood*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000628:therapy / Q000652:urine*; D011507:Proteinuria / Q000652:urine*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D003404:Creatinine
keywords: clinical epidemiology; end-stage renal disease; randomized controlled trials