A Cochrane review [Abstract] 1 included 60 studies with a total of 3 802 subjects; 29 studies (n=2262) compared calcium channel blockers (CCB) to placebo/no treatment; 10 studies (n=445) compared angiotensin converting enzyme inhibitors (ACEi) to placebo/no treatment, and 7 studies (n=405) compared CCB to ACEi. Other drug comparisons were in small numbers of participants and studies.
CCB compared to placebo/no treatment (plus additional agents in either arm as required) reduced graft loss (RR 0.75, 95% CI 0.57 to 0.99; 17 studies, n=1255) and improved glomerular filtration rate (GFR), (MD, 4.45 mL/min, 95% CI 2.22 to 6.68; 16 studies, n=1119). There was no effect of CCB on risk of death at 12 months (RR 0.82, 95% CI 0.37 to 1.82; 12 studies, n=792).
Data on ACEi versus placebo/no treatment were inconclusive for GFR (MD -8.07 mL/min, 95% CI -18.57 to 2.43), and variable for graft loss, precluding meta-analysis.
In direct comparison with CCB, ACEi decreased GFR (MD -11.48 mL/min, 95% CI -5.75 to -7.21; 6 studies, n=296), proteinuria (MD -0.28 g/24 h, 95% CI -0.47 to -0.10; 2 studies, n=147), haemoglobin (MD -12.96 g/L, 95% CI -5.72 to -10.21; 5 studies, n=332) and increased hyperkalaemia (RR 3.74, 95% CI 1.89 to 7.43; 3 studies, n=211). Graft loss data were inconclusive (RR 7.37, 95% CI 0.39 to 140.35; 1 study, n=152). Death was reported in two studies with no difference in risk (RR 4.03, 95% CI 0.45 to 35.82; 2 studies, n=221).
A meta-analysis 2 assessing renin-angiotensin system inhibitors on survival in kidney transplant recipients included 9 RCTs and 15 cohort studies with 54 096 patients. ACEI/ARB was associated with decreased risks of patient death (RR 0.64; 95% CI 0.49 to 0.84; 14 trials) and graft loss (RR 0.59; 95% CI 0.47 to 0.74; 16 trials) compared with controls. Subgroup analysis of the cohorts revealed significantly reduced patient death (RR 0.61; 95% CI 0.50 to 0.74, 6 trials) and graft loss (RR 0.58; 95% 0.46 to 0.73; 12 trials), but this was not seen in RCTs (patient survival RR 0.84, 95% CI 0.39 to 1.81, 8 RCTs; graft survival: RR 0.70, 95% CI 0.17 to 2.79; 4 RCTs). Significantly less graft loss was noted among patients with biopsy-proved chronic allograft nephropathy (RR 0.26, 95% CI 0.16 to 0.44). Furthermore, the benefit of ACEI/ARB on patient survival (RR 0.62; 95% CI 0.47 to 0.83) and graft survival (RR 0.58, 95% CI 0.47 to 0.71) was limited to those with minimum 3 years' follow-up. ACEI/ARB decreased proteinuria (P < 0.001) and lowered haemoglobin (P = 0.002), but the haemoglobin change required no additional treatment (from 119-131 g/L to 107-123 g/L).
Comment: The quality of evidence is downgraded by study quality (unclear allocation concealment and blinding) and by imprecise results (limited study size for each comparison).
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