New J P, Marshall S M, Bilous R W
Department of Medicine, University of Newcastle upon Tyne, UK.
Diabetologia. 1998 Feb;41(2):206-11. doi: 10.1007/s001250050891.
Abnormalities of renal autoregulation with glomerular hyperfiltration and raised intraglomerular pressure have been suggested as important factors in the initiation and development of diabetic nephropathy. Angiotensin converting enzyme (ACE) inhibition appears to have a specific reno-protective role in diabetic nephropathy, possibly by reducing intraglomerular pressure. The acute effects of ACE inhibition on renal haemodynamics in normotensive, non-insulin-dependent diabetes mellitus (NIDDM) have not been previously reported. We measured simultaneous glomerular filtration rate (GFR) and renal plasma flow (RPF) in 29 (4 female) subjects, mean age 52 years (range 27-70), using 51Cr EDTA and 125I Hippuran. Clearances were corrected to 1.73 m(-2). All patients were normotensive (blood pressure < 75th centile for age and sex), newly diagnosed (< 30 days), taking no antihypertensive or hypoglycaemic medication. Subjects were randomly allocated (double blind) to receive the ACE inhibitor trandolapril 4mg day(-1) (H) (hypotensive dose), trandolapril 0.5 mg day(-1)(L) (non-hypotensive dose) or placebo (P) for 10 days after which renal haemodynamics were remeasured. For all subjects baseline GFR, RPF and filtration fraction (FF) were 97+/-21 ml min(-1) mean+/-SD, 439+/-120 ml min(-1) and 22.3+/-2.9 % respectively. Glomerular hyperfiltration (GFR> 120 ml min[-1]) was only demonstrated in 3 subjects (10.3 %). In group H mean arterial pressure (103+/-8 vs 93+/-9 mmHg, p < 0.001) and FF (23.8+/-2.3 vs 20.0+/-4.0%, p = 0.03) fell while RPF increased (376+/-111 vs 426+/-60 ml min(-1), p = 0.02), there was no significant change in GFR. No significant change in mean arterial pressure, GFR, RPF or FF occurred in groups P and L. These studies suggest that in newly diagnosed normotensive NIDDM subjects normal renal autoregulation occurs and glomerular hyperfiltration is uncommon.
肾小球高滤过和肾小球内压升高所导致的肾自身调节异常被认为是糖尿病肾病发生和发展的重要因素。血管紧张素转换酶(ACE)抑制似乎在糖尿病肾病中具有特定的肾脏保护作用,可能是通过降低肾小球内压来实现的。此前尚未有关于ACE抑制对血压正常的非胰岛素依赖型糖尿病(NIDDM)患者肾脏血流动力学急性影响的报道。我们使用51Cr乙二胺四乙酸和125I马尿酸对29名(4名女性)平均年龄52岁(范围27 - 70岁)的受试者同时测量了肾小球滤过率(GFR)和肾血浆流量(RPF)。清除率校正至1.73 m(-2)。所有患者血压正常(血压低于年龄和性别的第75百分位数),新诊断(<30天),未服用抗高血压或降糖药物。受试者被随机分配(双盲)接受ACE抑制剂群多普利4mg/天(H组)(降压剂量)、群多普利0.5mg/天(L组)(非降压剂量)或安慰剂(P组),持续10天,之后重新测量肾脏血流动力学。所有受试者的基线GFR、RPF和滤过分数(FF)分别为97±21 ml/min(均值±标准差)、439±120 ml/min和22.3±2.9%。仅3名受试者(10.3%)出现肾小球高滤过(GFR>120 ml/min[-1])。H组平均动脉压(103±8 vs 93±9 mmHg,p<0.001)和FF(23.8±2.3 vs 20.0±4.0%,p = 0.03)下降,而RPF升高(376±111 vs 426±60 ml/min,p = 0.02),GFR无显著变化。P组和L组的平均动脉压、GFR、RPF或FF均无显著变化。这些研究表明,在新诊断的血压正常的NIDDM受试者中,存在正常的肾自身调节,肾小球高滤过并不常见。