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DRUG INFORMATION ROUNDS

Use of Renin-Angiotensin-Aldosterone System Inhibitors Within the First Eight to Twelve Weeks After Renal Transplantation

Cardiovascular Research Fellow, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI

David J Taber, PharmD

Clinical Specialist-Solid Organ Transplantation, Department of Pharmacy Services, Medical University of South Carolina, Charleston, SC

Reprints: Dr. Jennings, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Ave., Detroit, MI 48201, fax 313/916-1302, ag4098{at}wayne.edu

OBJECTIVE: To evaluate the safety and efficacy of early initiation of inhibitors of the renin-angiotensin-aldosterone system (RAAS) in renal transplant patients.

DATA SOURCES: A literature search was conducted using MEDLINE (1950-September 2007), PubMed (1966-September 2007), and International Pharmaceutical Abstracts (1970-September 2007) with combinations of the following terms: angiotensin-converting enzyme (ACE) inhibitors, angiotensin II type 1 receptor blockers (ARBs), and kidney transplant. Articles obtained from this search were cross-referenced and bibliographies were checked for all relevant information.

STUDY SELECTION AND DATA EXTRACTION: All articles that examined the early (within 12 wk) initiation of either an ACE inhibitor or an ARB in renal transplant patients were included.

DATA SYNTHESIS: A search of the literature revealed 7 studies that had examined the safety or efficacy of early use of ACE inhibitors and ARBs in posttransplant patients. One study examined only plasma levels of a common marker for tissue fibrosis and one included only patients who had early graft dysfunction. Of the other 5 studies, 3 primarily reported safety endpoints and 2 reported clinical efficacy endpoints. Safety data in patients with functioning grafts (serum creatinine ranged from <2.5 to 3.0 mg/dL) show that early therapy with inhibitors of the RAAS did not result in appreciable increases in serum creatinine or potassium levels after up to 9 months of therapy. Results from the efficacy trials indicate that early initiation of an ACE inhibitor may be more effective than a β-blocker in reducing left ventricular hypertrophy and proteinuria after 24 months of treatment.

CONCLUSIONS: It appears that the early initiation of RAAS inhibitors is safe in posttransplant patients with functioning grafts. It is reasonable to consider these agents as first-line pharmacotherapy in patients with hypertension and compelling indications (ie, diabetes or heart failure) in the first 12 weeks following transplant. Data are insufficient to recommend these drugs in patients with early graft dysfunction.

Key Words: angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, kidney transplant

Published Online, December 19, 2007. www.theannals.com, DOI 10.1345/aph.1K471