Jennings Douglas L, Taber David J
Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA.
Ann Pharmacother. 2008 Jan;42(1):116-20. doi: 10.1345/aph.1K471. Epub 2007 Dec 19.
To evaluate the safety and efficacy of early initiation of inhibitors of the renin-angiotensin-aldosterone system (RAAS) in renal transplant patients.
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.
All articles that examined the early (within 12 wk) initiation of either an ACE inhibitor or an ARB in renal transplant patients were included.
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 beta-blocker in reducing left ventricular hypertrophy and proteinuria after 24 months of treatment.
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.
评估肾移植患者早期启用肾素 - 血管紧张素 - 醛固酮系统(RAAS)抑制剂的安全性和有效性。
使用MEDLINE(1950年 - 2007年9月)、PubMed(1966年 - 2007年9月)和国际药学文摘(1970年 - 2007年9月)进行文献检索,检索词组合如下:血管紧张素转换酶(ACE)抑制剂、血管紧张素II 1型受体阻滞剂(ARB)和肾移植。对检索获得的文章进行交叉引用,并检查参考文献以获取所有相关信息。
纳入所有研究肾移植患者早期(12周内)启用ACE抑制剂或ARB的文章。
文献检索发现7项研究探讨了移植后患者早期使用ACE抑制剂和ARB的安全性或有效性。1项研究仅检测了组织纤维化常见标志物的血浆水平,1项研究仅纳入了早期移植肾功能障碍的患者。在其他5项研究中,3项主要报告安全性终点,2项报告临床疗效终点。移植肾功能正常(血清肌酐范围为<2.5至3.0mg/dL)患者的安全性数据表明,RAAS抑制剂早期治疗长达9个月后,血清肌酐或钾水平没有明显升高。疗效试验结果表明,治疗24个月后,早期启用ACE抑制剂在减轻左心室肥厚和蛋白尿方面可能比β受体阻滞剂更有效。
对于移植肾功能正常的肾移植患者,早期启用RAAS抑制剂似乎是安全的。对于移植后前12周内有高血压且有明确适应证(即糖尿病或心力衰竭)的患者,将这些药物作为一线药物治疗是合理的。现有数据不足以推荐在早期移植肾功能障碍患者中使用这些药物。