GFR at initiation of dialysis and mortality in CKD: a meta-analysis

Abstract

Background: The proportion of patients with advanced chronic kidney disease (CKD) initiating dialysis therapy at a higher glomerular filtration rate (GFR) has increased during the past decade. Recent data suggest that higher GFR may be associated with increased mortality.

Study design: A meta-analysis of cohort studies and trials.

Setting & population: Patients with advanced CKD.

Selection criteria for studies: We performed a systematic literature search in MEDLINE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, American Society of Nephrology abstracts, and bibliographies of retrieved articles to identify studies reporting on GFR at dialysis therapy initiation and mortality.

Predictor: Estimated or calculated GFR at dialysis therapy initiation.

Outcome: Pooled adjusted hazard ratio (HR) of continuous GFR for all-cause mortality.

Results: 16 cohort studies and 1 randomized controlled trial were identified (n = 1,081,116). By meta-analysis restricted to 15 cohorts (n = 1,079,917), higher GFR at dialysis therapy initiation was associated with a higher pooled adjusted HR for all-cause mortality (1.04; 95% CI, 1.03-1.05; P < 0.001). However, there was significant heterogeneity (I(2) = 97%; P < 0.001). The association persisted among the 9 cohorts that adjusted analytically for nutritional covariates (HR, 1.03; 95% CI, 1.02-1.04; P < 0.001; residual I(2) = 97%). The highest mortality risk was observed in hemodialysis cohorts (HR, 1.05; 95% CI, 1.02-1.08; P < 0.001), whereas there was no association between GFR and mortality in peritoneal dialysis cohorts (HR, 1.04; 95% CI, 0.99-1.08, P = 0.1; residual I(2) = 98%). Finally, higher GFR was associated with a lower mortality risk in cohorts that calculated GFR (HR, 0.80; 95% CI, 0.71-0.91; P = 0.003), contrasting with a higher mortality risk in cohorts that estimated GFR (HR, 1.04; 95% CI, 1.03-1.05; P < 0.001; residual I(2) = 97%).

Limitations: Paucity of randomized controlled trials, different methods for determining GFR, and substantial heterogeneity.

Conclusions: Higher estimated rather than calculated GFR at dialysis therapy initiation is associated with a higher mortality risk in patients with advanced CKD, independent of nutritional status. Although there was substantial heterogeneity of effect size estimates across studies, this observation requires further study.

Figure 1

Study selection flow diagram.

Figure 2

Forest plot of the glomerular filtration rate (GFR) (per 1 mL/min/1.73 m² increment) adjusted hazard ratio (with 95% confidence interval) for all-cause mortality. * The GFR is reported in mL/min and is not normalized to body surface area. The study by Stel et al included 2 cohorts with 2 accrual periods († cohort initiating dialysis in 1999; ‡ cohort initiating dialysis in 2003). The test for heterogeneity is significant (I²=97% and P<0.001 by Q test).

Figure 3

Subgroup analyses displaying the glomerular filtration rate (GFR) (per 1 mL/min/1.73 m² increment) adjusted hazard ratio (with 95% confidence interval) for all-cause mortality stratified by (3A) use of nutritional covariates in the multivariable models; (3B) initial dialysis modality; and (3C) GFR assessment method. * P=0.008 vs. cohorts that excluded nutritional covariates; † P<0.001 vs. cohorts that calculated GFR. The test for heterogeneity is significant (residual I²=97%, 98% and 97%, respectively).