Néphropathie diabétique et traitement antihypertenseur : quelles sont les leçons des essais cliniques ?

A.-N. Lasaridis, P.-A. Sarafidis
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Abstract

Diabetic nephropathy is the most serious problem among current issues in nephrology, as 40 % of the cases of end-stage renal disease are due to this entity. The close relationship between type 2 diabetes and hypertension makes the problem even more severe. The knowledge of the intrarenal effects of angiotensin II and the greater effect of angiotensin converting enzyme inhibitors (ACEI) on reducing albuminuria suggested in the past a trend toward preferable use of these drugs in diabetic nephropathy. The first relevant clinical trials yielded rather poor conclusions because of lack of blind randomization and short duration. Subsequent double-blind studies with adequate numbers of patients and sufficient duration underlined the importance of blood pressure (BP) control as well as the rather poor response of diabetic nephropathy to any treatment. In most of these studies, the changes in albuminuria or microalbuminuria were a substitute end point for the renal function. Three clinical trials using angiotensin II receptor blockers (ARB), planned specifically to monitor the progression of renal damage, have been recently published. They showed better renal protection by ARB, as compared with placebo or calcium channel blockers (CCB), beyond or independently of the BP reduction. Nevertheless, these recent trials, like the previous ones with similar results, invariably demonstrate slightly better control of BP in the groups of the active drug. Another issue is that the vast majority of the patients need so many nonstudy drugs to keep their pressure under control, that the isolation of advantageous effects of certain drugs seems unrealistic.

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糖尿病肾病和抗高血压治疗:临床试验的教训是什么?
糖尿病肾病是目前肾病学中最严重的问题,因为40%的终末期肾病病例都是由这种疾病引起的。2型糖尿病和高血压之间的密切关系使这个问题更加严重。血管紧张素II的肾内作用以及血管紧张素转换酶抑制剂(ACEI)在减少蛋白尿方面的更大作用的知识表明,过去在糖尿病肾病中优选使用这些药物的趋势。由于缺乏盲随机化和持续时间短,第一次相关临床试验得出的结论相当差。随后的双盲研究有足够的患者数量和足够的持续时间,强调了控制血压(BP)的重要性,以及糖尿病肾病对任何治疗的不良反应。在大多数研究中,蛋白尿或微量蛋白尿的变化是肾功能的替代终点。最近发表了三项使用血管紧张素II受体阻滞剂(ARB)的临床试验,这些试验专门用于监测肾损伤的进展。与安慰剂或钙通道阻滞剂(CCB)相比,ARB对肾脏的保护作用更好,超过或独立于血压降低。然而,这些最近的试验,就像之前的试验一样,结果相似,总是证明活性药物组对BP的控制略好。另一个问题是,绝大多数患者需要如此多的非研究药物来控制压力,因此隔离某些药物的有利作用似乎是不现实的。
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