Keane William F, Lyle Paulette A
Clinical Development, Merck & Co, Inc., Whitehouse Station, NJ, USA.
Am J Kidney Dis. 2003 Mar;41(3 Suppl 1):S22-5. doi: 10.1053/ajkd.2003.50078.
Diabetic nephropathy has become the single most important cause of end-stage renal disease (ESRD) worldwide. Strategies to slow the rate of loss of renal function in these patients recently have been developed. The renin-angiotensin-aldosterone system has proven to be an important target for intervention.
The Reduction of Endpoints in NIDDM with the Angiotensin II Receptor Antagonist Losartan (RENAAL) study was a randomized, double-blind, multinational, clinical trial that studied 1,513 patients with type 2 diabetes and nephropathy for a mean of 3.4 years. Patients were administered either losartan or placebo, each in addition to conventional antihypertensive therapy, with dosage adjustments as necessary to achieve a target blood pressure of less than 140/less than 90 mm Hg.
The study showed a significant benefit of losartan, beyond the effects of lowering blood pressure, on the primary composite end point of doubling serum creatinine level, ESRD, or death (-16%; P = 0.02). Losartan reduced the incidence of serum creatinine level doubling (-25%; P = 0.006) and ESRD (-28%; P = 0.002), but had no effect on rate of death. The composite end point of cardiovascular morbidity and mortality was similar in the two groups. The rate of first hospitalization for heart failure was reduced in the losartan group (-32%; P = 0.005), as was proteinuria (-35%; P < 0.001). The RENAAL study also provided the opportunity to evaluate risk factors that predict ESRD in patients with type 2 diabetes in whom blood pressure was aggressively treated. In our multivariate model, four independent risk factors, proteinuria (most important), serum creatinine level, hypoalbuminemia, and anemia, were identified that predicted the development of ESRD.
Proteinuria is the single most powerful predictor of ESRD in patients with type 2 diabetes and nephropathy. Thus, it is imperative that it be assessed in all patients with type 2 diabetes to identify those at risk for progressive renal disease. The routine availability of the urinary albumin-creatinine ratio as a diagnostic test provides an important opportunity to further improve the prognosis of individuals with type 2 diabetes and nephropathy.
糖尿病肾病已成为全球终末期肾病（ESRD）的首要单一病因。最近已开发出减缓这些患者肾功能丧失速率的策略。肾素 - 血管紧张素 - 醛固酮系统已被证明是干预的重要靶点。
用血管紧张素II受体拮抗剂氯沙坦降低NIDDM终点事件（RENAAL）研究是一项随机、双盲、多国临床试验，研究了1513例2型糖尿病肾病患者，平均随访3.4年。患者除接受常规抗高血压治疗外，分别给予氯沙坦或安慰剂，并根据需要调整剂量以达到目标血压低于140/低于90 mmHg。
该研究表明，除了降低血压的作用外，氯沙坦对血清肌酐水平翻倍、ESRD或死亡的主要复合终点有显著益处（降低16%；P = 0.02）。氯沙坦降低了血清肌酐水平翻倍的发生率（降低25%；P = 0.006）和ESRD的发生率（降低28%；P = 0.002），但对死亡率无影响。两组心血管疾病发病率和死亡率的复合终点相似。氯沙坦组心力衰竭首次住院率降低（降低32%；P = 0.005），蛋白尿也降低（降低35%；P < 0.001）。RENAAL研究还提供了评估积极治疗血压的2型糖尿病患者中预测ESRD的危险因素的机会。在我们的多变量模型中，确定了四个独立的危险因素，即蛋白尿（最重要）、血清肌酐水平、低白蛋白血症和贫血，这些因素可预测ESRD的发生。
蛋白尿是2型糖尿病肾病患者ESRD的最有力单一预测指标。因此，对所有2型糖尿病患者进行评估以识别那些有进行性肾病风险的患者至关重要。尿白蛋白 - 肌酐比值作为一种诊断测试的常规可用性为进一步改善2型糖尿病肾病患者的预后提供了重要机会。
