Effectiveness of Renin-Angiotensin-Aldosterone System Blockade on Residual Kidney Function and Peritoneal Membrane Function in Peritoneal Dialysis Patients: A Network Meta-Analysis

Abstract

We performed a network meta-analysis of randomised controlled trials (RCTs) and non-randomised studies in adult peritoneal dialysis patients to evaluate the effects of specific renin-angiotensin aldosterone systems (RAAS) blockade classes on residual kidney function and peritoneal membrane function. Key outcome parameters included the following: residual glomerular filtration rate (rGFR), urine volume, anuria, dialysate-to-plasma creatinine ratio (D/P Cr), and acceptability of treatment. Indirect treatment effects were compared using random-effects model. Pooled standardised mean differences (SMDs) and odd ratios (ORs) were estimated with 95% confidence intervals (CIs). We identified 10 RCTs (n = 484) and 10 non-randomised studies (n = 3,305). Regarding changes in rGFR, RAAS blockade with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) were more efficacious than active control (SMD 0.55 [0.06-1.04] and 0.62 [0.19-1.04], respectively) with the protective effect on rGFR observed only after usage ≥12 months, and no differences among ACEIs and ARBs. Compared with active control, only ACEIs showed a significantly decreased risk of anuria (OR 0.62 [0.41-0.95]). No difference among treatments for urine volume and acceptability of treatment were observed, whereas evidence for D/P Cr is inconclusive. The small number of randomised studies and differences in outcome definitions used may limit the quality of the evidence.

Figure 1

Selection of studies. Abbreviations: RCTs, randomised-controlled trials.

Figure 2

Network plot of eligible comparisons for primary outcomes. Notes: The circles (nodes) represent the available treatments and the lines (edges) represent the available comparisons. Size nodes and width of edges indicate weighting according to the numbers of studies involved for each treatment and comparison, respectively. Abbreviations: ACEIs, angiotensin-converting enzyme inhibitors; ARBs, angiotensin II receptor blockers; D/P Cr, dialysate-to-plasma creatinine; MRAs, mineralocorticoid receptor antagonists; rGFR, residual glomerular filtration rate.

Figure 3

Network meta-analysis of RAAS blockade compared with active control for primary outcomes. Abbreviations: ACEIs, angiotensin-converting enzyme inhibitors; ARBs, angiotensin II receptor blockers; CI, confidence interval; D/P Cr, dialysate-to-plasma creatinine; MRAs, mineralocorticoid receptor antagonists; NA, not applicable; OR, odd ratio; RAAS, renin-angiotensin-aldosterone system blockade; RCTs, randomised-controlled trials; rGFR, residual glomerular filtration rate; SMD, standardised mean difference.

Figure 4

Mean change in rGFR by duration of treatment: evidence from NMA (RCTs and non-randomised studies). Note: Bold values indicate statistical significance. For study duration <6 or <12 months, SMDs >0 indicate that the treatment specified in the row is more efficacious than that in the column. For study duration ≥6 to <12 or ≥12 months, SMDs >0 indicate that the treatment specified in the column is more efficacious than that in the row column. To obtain SMDs for comparisons in the opposite direction, positive values should be converted into negative values, and vice versa. Abbreviations: ACEIs, angiotensin-converting enzyme inhibitors; ARBs, angiotensin II receptor blockers; CIs, confidence intervals; NMA, network meta-analysis; RCTs, randomised-controlled trials; rGFR, residual glomerular filtration rate; SMDs, standardised mean differences.

Figure 5

Two-dimension rank plot of effect estimates according to efficacy on preservation of rGFR and incidence of anuria. Abbreviations: ACEIs, angiotensin-converting enzyme inhibitors; ARBs, angiotensin II receptor blockers; rGFR, residual glomerular filtration rate; SUCRA, surface under the cumulative ranking curve.