Erly use of renin-angiotensin-aldosterone system inhibitors after renal transplantation

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Abstract

BACKGROUND

Angiotensin-converting-enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) can lead to increases in serum creatinine and potassium levels, which could be misconstrued as acute rejection in renal transplant recipients.

OBJECTIVE

To review the use of ACEIs or ARBs soon after renal transplantation.

DESING AND INTERVENTION

The authors conducted a systematic review of studies that evaluated the safety and/or effi-cacy of using ACEIs or ARBs within 12 weeks of renal transplantation. Relevant studies were identified through searches of MEDLINE (from 1950), PubMed (from 1966) and International Pharmaceutical Abstracts (from 1970) in September 2007, with the terms 'angiotensin-converting enzyme inhibitors', 'angiotensin II type 1 receptor blockers' and 'kidney transplant'.

OUTCOME MEASUJRE

Safety outcome measures included serum creatinine level, serum potassium level, creatinine clearance and glomerular filtration rate (GFR). Efficacy outcome measures included blood pressure, left ventricular hypertrophy and albuminuria.

RESULT

Of the seven studies identified, one only examined the effect of an ARB on markers of fibrosis, and one only included patients with delayed graft function. The remaining studies comprised three safety and two efficacy studies. In the first safety study-a retrospective case-control study of patients with hypertension and stable graft function (n =36)-there was no significant difference in serum potassium level or creati-nine clearance at 3, 6 or 9 months between patients who began treatment with an ACEI or an ARB within 90 days of transplantation and those who received a calcium-channel blocker. Diagnoses of acute rejection were not adversely affected by use of ACEIs or ARBs. The second safety study, a retrospective chart review of adults who received deceased-donor transplants (n =289), reported that use of an ACEI or ARB from the first day after trans-plantation was associated with a significantly accelerated decrease in serum creatinine level during the 80 days following surgery (P <0.01). The third safety study (n =154) found that, after 2 weeks of treatment, patients with hyper-tension who were randomized to receive the ACEI lisinopril 1 -16 days after transplantation had similar GFRs to those randomized to receive the calcium-channel blocker nifedi-pine. At 1 year, however, GFR was significantly lower in ACEI-treated patients (P =0.0001). In the first efficacy study, patients with hypertension and stable renal function n =31) were randomized to receive the ACEI quinapril or the β-blocker atenolol. Only atenolol significantly reduced blood pressure at 2 years (P <0.05); however, only quinapril reduced left ventricular hypertrophy. The second efficacy study also evaluated these two agents in patients with hypertension and stable graft function (n =59); the two randomized groups showed no difference in blood pressure or serum creatinine level at 2 years, but only the quinapril group experienced a significant reduction in albuminuria (P <0.03 vs atenolol).

CONCLUSION

Early initiation of ACEIs and ARBs seems to be well tolerated in renal transplant recipients with stable graft function, but efficacy data are very limited.

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