The bad habit of ACEI!!!!

Coming to the transplant clinic from 2 years of CKD clinic, prescribing ACEI/ARBs was a habit, a good one I guess. Does this hold truth in the transplant world, well... I am not sure anymore after I read this meta analysis in Transplantation last year. The reason simply is that kidney recipients are biologically different from CKD patients. Most of our kidney transplant patients are on calcineurin inhibitors (CNI) which induce afferent arteriolar vasoconstriction. Thus, the advantage of calcium channel blockers (CCB) over ACEI in this population is that it may promote vasodilation of afferent arterioles which may counteract CNI’s effect.

In this meta analysis of 60 trials, enrolling 3802 recipients:

· 29 trials (2262 patients) compared calcium channel blockers (CCB) with placebo or no treatment

· 10 trials (445 patients) compared angiotensin-converting enzyme inhibitors (ACEi) with placebo or no treatment

· 7 studies (405 patients) compared CCB with ACEi

CCB compared with placebo or no treatment (plus additional agents in either arm as required) reduced graft loss (risk ratio [RR] 0.75, 95% confidence intervals [CI] 0.57–0.99) and improved glomerular filtration rate (GFR; mean difference [MD] 4.5 mL/min, 95% CI 2.2–6.7).

Data on ACEi versus placebo or no treatment were inconclusive for GFR (MD -8.1 mL/min, 95% CI -18.6–2.4) and inconsistent for graft loss, precluding meta-analysis.

In direct comparison with CCB, ACEi decreased GFR (MD 11.5 mL/min, 95% CI 7.2–15.8), proteinuria (MD 0.28 g/day, 95% CI 0.10–0.47), hemoglobin (MD 11.5 g/L, 95% CI 7.2–15.8), and increased hyperkalemia (RR 3.7, 95% CI 1.9–7.7). Graft loss data were inconclusive (RR 7.4, 95% CI 0.4–140).

So according to this study there is no advantage of ACEI/ARBs over CCB, with more side effects from angiotensin inhibitors. Obviously, a good randomized trial is needed to resolve this issue.

These data suggest that CCB may be preferred as first-line agents for hypertensive kidney transplant recipients and the KDIGO guidelines consider ACEI/ARB as first line therapy for HTN in renal transplant patients only if their proteinuria is > 1gm/day. A good practice would be to hold them in acute illness as those patients are very sensitive to dehydration due to afferent arterioles vasoconstriction by CNI.