Remuzzi Giuseppe, Macia Manuel, Ruggenenti Piero
Unit of Nephrology, Azienda Ospedaliera Ospedali Riuniti di Bergamo, Bergamo, Italy.
J Am Soc Nephrol. 2006 Apr;17(4 Suppl 2):S90-7. doi: 10.1681/ASN.2005121324.
Diabetic nephropathy (DN) is the leading cause of end-stage renal failure in Western countries and carries an increased risk for cardiovascular mortality. Studies have identified a number of factors that play a part in the development of DN. Among them, hypertension and proteinuria are the most important. In the early stages of DN, when albumin is present in the urine in very low quantities (microalbuminuria) and an increase is seen in BP, there is no loss of filtrate and patients respond well to prophylactic measures. Microalbuminuria is considered an early marker of DN. Prevention of the onset of microalbuminuria, therefore, could be considered as the primary means of preventing DN. The Bergamo Nephrologic Diabetes Complication Trial (BENEDICT) was a prospective, randomized, double-blind, parallel-group study that was organized in two phases. Phase A included 1204 patients and was aimed at assessing the efficacy of the angiotensin-converting enzyme (ACE) inhibitor trandolapril, the non-dihydropyridine calcium channel blocker verapamil, and the trandolapril plus verapamil combination as compared with placebo in prevention of microalbuminuria in hypertensive patients with type 2 diabetes and normal urinary albumin excretion rate. Phase B was aimed at assessing the efficacy of the combination as compared with trandolapril alone in prevention of macroalbuminuria in patients with microalbuminuria. The BENEDICT Phase A study showed that DN can be prevented by ACE inhibitor therapy. The beneficial effect of ACE inhibition is not enhanced by combined non-dihydropyridine calcium channel blocker therapy. The apparent advantage of ACE inhibitors over other agents includes a protective effect on the kidney against the development of microalbuminuria, which is a major risk factor for cardiovascular events and death in this population.
糖尿病肾病（DN）是西方国家终末期肾衰竭的主要原因，且心血管死亡风险增加。研究已确定了一些在DN发生过程中起作用的因素。其中，高血压和蛋白尿最为重要。在DN的早期阶段，当尿液中白蛋白含量极低（微量白蛋白尿）且血压升高时，滤过液并无损失，患者对预防措施反应良好。微量白蛋白尿被认为是DN的早期标志物。因此，预防微量白蛋白尿的发生可被视为预防DN的主要手段。贝加莫肾脏糖尿病并发症试验（BENEDICT）是一项前瞻性、随机、双盲、平行组研究，分两个阶段进行。A阶段纳入了1204例患者，旨在评估血管紧张素转换酶（ACE）抑制剂群多普利、非二氢吡啶类钙通道阻滞剂维拉帕米以及群多普利加维拉帕米联合用药与安慰剂相比，在预防2型糖尿病高血压患者微量白蛋白尿且尿白蛋白排泄率正常方面的疗效。B阶段旨在评估联合用药与单独使用群多普利相比，在预防微量白蛋白尿患者大量白蛋白尿方面的疗效。BENEDICT A阶段研究表明，ACE抑制剂治疗可预防DN。联合非二氢吡啶类钙通道阻滞剂治疗并不能增强ACE抑制的有益效果。ACE抑制剂相对于其他药物的明显优势包括对肾脏有保护作用，可防止微量白蛋白尿的发生，而微量白蛋白尿是该人群心血管事件和死亡的主要危险因素。
