Ruilope Luis M, Segura Julian
Hypertension Unit, Hospital 12 de Octubre, Madrid, Spain.
Clin Ther. 2003 Dec;25(12):3044-64. doi: 10.1016/s0149-2918(03)90091-9.
End-stage renal disease (ESRD) in patients with type 2 diabetes mellitus (DM) is associated with a bleak prognosis. The life span of patients with DM who have undergone renal transplantation or who are undergoing dialysis is up to 30% shorter than that of individuals in the general population. Preventing or delaying the progression of renal disease from microalbuminuria to nephropathy, and ultimately, to ESRD is thus a crucial goal of DM management.
This article reviews the growing worldwide problem of type 2 DM and ESRD, the renoprotective benefits of angiotensin II (AII) antagonists (AIIAs) such as losartan in patients with or without type 1 or 2 DM, potential mechanisms of renoprotection of AIIAs beyond blood pressure (BP) control, and the clinical-practice implications of available megatrials.
Articles included in this review were identified using a MEDLINE search for English-language studies published between 1990 and 2003 and included the search terms diabetic nephropathy, type 2 diabetes mellitus, microalbuminuria, proteinuria, angiotensin II antagonists, angiotensin-converting enzyme inhibitors, and cardiovascular disease. Articles describing major clinical trials, new data, or new mechanisms pertinent to the management of type 2 DM were selected for review.
Currently, AIIAs such as losartan represent the only evidence-based treatment strategy for patients with type 2 DM and proteinuria. The Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria (IRMA-2) study, the Reduction of End Points in Non-Insulin Dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan (RENAAL) study, and the Irbesartan Type 2 Diabetic Nephropathy Trial (IDNT) indicate that AIIAs postpone the progression of type 2 diabetic renal disease at all stages, ranging from microproteinuria to overt nephropathy and ESRD, RENAAL showed that losartan improves renal outcomes in patients with type 2 DM and nephropathy over and above that attributable to BP control alone. The renoprotective effect of losartan corresponded to an average delay of 2 years in the need for dialysis or kidney transplantation.
AIIAs such as losartan should perhaps be considered mandatory therapy in patients with diabetic nephropathy and should complement existing management strategies, such as reduced dietary protein intake, strict blood glucose control, and standard antihypertensive therapy. Collectively, these measures should improve survival and quality of life and reduce the health care burden of managing patients with diabetic nephropathy.
2型糖尿病（DM）患者的终末期肾病（ESRD）预后不佳。接受肾移植或正在接受透析的糖尿病患者的寿命比普通人群短30%。因此，预防或延缓肾病从微量白蛋白尿发展为肾病，最终发展为ESRD是糖尿病管理的关键目标。
本文综述了全球范围内日益严重的2型糖尿病和ESRD问题、血管紧张素II（AII）拮抗剂（AIIAs）如氯沙坦对1型或2型糖尿病患者和非糖尿病患者的肾脏保护作用、AIIAs在血压（BP）控制之外的肾脏保护潜在机制以及现有大型试验对临床实践的影响。
本综述纳入的文章通过检索MEDLINE数据库，查找1990年至2003年间发表的英文研究，检索词包括糖尿病肾病、2型糖尿病、微量白蛋白尿、蛋白尿、血管紧张素II拮抗剂、血管紧张素转换酶抑制剂和心血管疾病。选择描述与2型糖尿病管理相关的主要临床试验、新数据或新机制的文章进行综述。
目前，氯沙坦等AIIAs是2型糖尿病和蛋白尿患者唯一基于证据的治疗策略。厄贝沙坦治疗2型糖尿病合并微量白蛋白尿（IRMA - 2）研究、氯沙坦降低非胰岛素依赖型糖尿病终点事件（RENAAL）研究以及厄贝沙坦2型糖尿病肾病试验（IDNT）表明，AIIAs可延缓2型糖尿病肾病从微量蛋白尿到显性肾病和ESRD各个阶段的进展。RENAAL研究表明，氯沙坦在2型糖尿病和肾病患者中改善肾脏结局的作用超过单纯血压控制的效果。氯沙坦的肾脏保护作用相当于平均推迟2年进行透析或肾移植。
氯沙坦等AIIAs或许应被视为糖尿病肾病患者的强制性治疗药物，并应补充现有的管理策略，如减少饮食蛋白质摄入、严格控制血糖和标准抗高血压治疗。总体而言，这些措施应能提高生存率和生活质量，并减轻糖尿病肾病患者的医疗负担。
