de Jong P E, Heeg J E, Apperloo A J, de Zeeuw D
Department of Medicine, State University Hospital, Groningen, The Netherlands.
J Cardiovasc Pharmacol. 1992;19 Suppl 6:S28-32. doi: 10.1097/00005344-199219006-00006.
The mechanism of the antiproteinuric effect of angiotensin-converting enzyme (ACE) inhibitors in diabetic and nondiabetic renal disease is as yet unknown. A meta-analysis of studies on the effects of ACE inhibitors and other antihypertensive drugs on proteinuria, blood pressure, and renal hemodynamics in nondiabetic renal disease revealed that ACE inhibitors lower proteinuria more than other antihypertensives. Moreover, a close correlation (p less than 0.01) between changes in urinary protein loss and in filtration fraction was found, whereas such a correlation could not be detected between changes in proteinuria and in blood pressure. This suggests that, at least in nondiabetic renal disease, the fall in proteinuria during ACE inhibition is the consequence of the intrarenal effect of the drug more than the systemic effect. Data on the mechanism of action of ACE inhibitors in diabetic microalbuminuria and in diabetic overt proteinuria are less consistent. A fall in proteinuria on antihypertensive drugs in these patients can be observed also without a significant fall in blood pressure, and without any change in filtration fraction. We therefore conclude that one should be cautious in extrapolating the data from studies in diabetic renal disease to patients with nondiabetic nephropathies. Moreover, we argue also that nonhemodynamic effects of ACE inhibitors also could be involved in the antiproteinuric effect of these drugs.
血管紧张素转换酶（ACE）抑制剂在糖尿病和非糖尿病肾病中发挥抗蛋白尿作用的机制尚不清楚。一项关于ACE抑制剂和其他降压药物对非糖尿病肾病患者蛋白尿、血压及肾血流动力学影响的研究的荟萃分析显示，ACE抑制剂降低蛋白尿的效果优于其他降压药。此外，研究发现尿蛋白丢失的变化与滤过分数的变化之间存在密切相关性（p<0.01），而蛋白尿变化与血压变化之间未检测到这种相关性。这表明，至少在非糖尿病肾病中，ACE抑制期间蛋白尿的下降是药物肾内作用的结果，而非全身作用。关于ACE抑制剂在糖尿病微量白蛋白尿和糖尿病显性蛋白尿中的作用机制的数据不太一致。在这些患者中，使用降压药物后蛋白尿下降，而血压无显著下降，滤过分数也无任何变化。因此，我们得出结论，将糖尿病肾病研究的数据外推至非糖尿病肾病患者时应谨慎。此外，我们还认为，ACE抑制剂的非血流动力学效应也可能参与了这些药物的抗蛋白尿作用。
