Remuzzi A, Perticucci E, Ruggenenti P, Mosconi L, Limonta M, Remuzzi G
Mario Negri Institute for Pharmacological Research, Ospedali Riuniti di Bergamo, Italy.
Kidney Int. 1991 Jun;39(6):1267-73. doi: 10.1038/ki.1991.160.
Clearances of uncharged dextrans of broad size distribution were used to evaluate the effects of a 30 day course of enalapril on glomerular barrier function in 10 patients with IgA nephropathy and proteinuria (from 1.4 to 5.6 g/day). Dextran clearance experiments were repeated three times: before enalapril therapy, after 30 days of enalapril and again 30 days after enalapril withdrawal. GFR, but not RPF, was significantly reduced by enalapril (basal 38.3 +/- 11.9, enalapril 30.2 +/- 12.6 ml/min/1.73 m2) and returned to basal values after enalapril withdrawal. Urinary protein excretion and fractional clearance of albumin were both significantly reduced by enalapril (basal 2.3 +/- 1.1 g/day and 102 +/- 90 x 10(-5), enalapril 1.2 +/- 0.6 g/day and 51 +/- 23 x 10(-5), respectively) and returned to basal values after enalapril withdrawal. Transglomerular passage of large dextrans (radii 54 to 62 A), but not of lower size (26 to 42 A) were significantly lowered by enalapril. When enalapril was withdrawn the dextran-sieving profile returned comparable to the baseline levels. A theoretical analysis of dextran-sieving profiles indicated that enalapril lowered the radius of largest membrane pores. This effect was independent from glomerular hemodynamic changes. We conclude that angiotensin converting enzyme inhibitors (CEI) in humans with IgA nephropathy reduces urinary protein excretion by a primary action on the intrinsic glomerular membrane properties enhancing barrier size-selective function. The hypofiltration associated with enalapril therapy in these patients, which was eliminated by its withdrawal, has to be taken into account as a possible undesired effect of CEI in long-term treatment.
使用具有广泛大小分布的不带电荷右旋糖酐清除率来评估依那普利30天疗程对10例IgA肾病伴蛋白尿（1.4至5.6克/天）患者肾小球屏障功能的影响。右旋糖酐清除率实验重复三次：依那普利治疗前、依那普利治疗30天后以及依那普利停药30天后。依那普利显著降低了肾小球滤过率（GFR），但未降低肾血浆流量（RPF）（基础值38.3±11.9，依那普利治疗后30.2±12.6毫升/分钟/1.73平方米），停药后恢复到基础值。依那普利显著降低了尿蛋白排泄和白蛋白分数清除率（基础值分别为2.3±1.1克/天和102±90×10⁻⁵，依那普利治疗后分别为1.2±0.6克/天和51±23×10⁻⁵），停药后恢复到基础值。依那普利显著降低了大尺寸右旋糖酐（半径54至62埃）的跨肾小球通过率，但未降低较小尺寸（26至42埃）的通过率。停药后，右旋糖酐筛分曲线恢复到与基线水平相当。对右旋糖酐筛分曲线的理论分析表明，依那普利降低了最大膜孔的半径。这种作用独立于肾小球血流动力学变化。我们得出结论，在IgA肾病患者中，血管紧张素转换酶抑制剂（CEI）通过对肾小球固有膜特性的主要作用增强屏障大小选择性功能，从而减少尿蛋白排泄。在这些患者中，依那普利治疗相关的滤过减少在停药后消除，在长期治疗中必须将其视为CEI可能的不良影响加以考虑。
