Dialysis Initiation and All-Cause Mortality Among Incident Adult Patients With Advanced CKD: A Meta-analysis With Bias Analysis

Abstract

Rationale & objectives: Due to unmeasured confounding, observational studies have limitations when assessing whether dialysis initiation reduces mortality compared with conservative therapy among adults with advanced chronic kidney disease (CKD). We addressed this issue in this meta-analysis.

Study design: Meta-analysis with bias analysis for unmeasured confounding.

Setting & study population: Adults with stage 4 or 5 CKD who had initiated dialysis or conservative treatment.

Selection criteria for studies: Prospective or retrospective cohort studies comparing survival of dialysis versus conservatively managed patients were searched on MEDLINE and Embase from January 2009 to March 20, 2019.

Data extraction: HRs of all-cause mortality associated with dialysis initiation compared with conservative treatment.

Analytical approach: We pooled HRs using a random-effects model. We estimated the percentage of effect sizes more protective than HRs of 0.80 and severity of unmeasured confounding that could reduce this percentage to only 10%. Subgroup analysis was performed for studies with only older patients (aged ≥ 65 years).

Results: 12 studies were included that involved 16,609 dialysis patients and 3,691 conservatively managed patients. A random-effects model suggested that dialysis initiation was associated with a mean mortality HR of 0.47 (95% CI, 0.34-0.64), in which 92% (95% CI, 50%-100%) of the true effects were more protective than HRs of 0.80. To reduce the percentage of HRs < 0.80 to 10%, unmeasured confounder(s) would need to be associated with both dialysis initiation and mortality by relative risks of 4.05 (95% CI, 2.39-4.15), which is equivalent to shifting each study's estimated HR by 2.31-fold (95% CI, 1.51-2.36). Restricting studies to include only older patients did not modify the results.

Limitations: Limited number of studies and evidence on the absence of publication bias.

Conclusions: Our findings suggest that dialysis initiation considerably reduces mortality among adults with advanced CKD. Future bias-adjusted meta-analyses need to assess outcomes beyond mortality.

Keywords: Dialysis; conservative management; mortality; survival; treatment effects; unmeasured confounding.

Graphical abstract

Figure 1

Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) flow diagram. Literature search was performed on MEDLINE and Embase on March 30, 2019.

Figure 2

Forest plot shows results of standard random-effects meta-analysis.

Figure 3

Estimated proportion of true effects more protective than hazard ratio (HR) of 0.80 (upper) and harmful rather than protective effects (lower) as a function of hypothetical unmeasured confounding severity in each study. In each diagram, the lower and upper x-axes describe confounding severity, respectively, in terms of the bias factor in each study and the risk ratio by which hypothetical unmeasured confounder(s) would need to be associated with both dialysis initiation and mortality risk. Red horizontal line represents the threshold at which <10% of effects are more protective than HR of 0.80 (upper) or at least 50% of effects indicate harm, rather than benefits (lower); black vertical line is the estimated bias factor or, alternatively, confounding strength at which this occurs. The shaded bands represent 95% bootstrapped CIs.

Figure 4

Forest plot shows the results of standard random-effects meta-analysis for incident patients 65 years or older.

Figure 5

Estimated proportion of true effects more protective than hazard ratio (HR) of 0.80 (upper) and harmful rather than protective effects (lower) as a function of hypothetical unmeasured confounding severity in studies of adults 65 years and older. Abbreviation: RR, relative risk.