Plum J, Bünten B, Németh R, Grabensee B
Department of Nephrology and Rheumatology, Medizinische Einrichtungen der Heinrich Heine Universität, Düsseldorf, Germany.
J Am Soc Nephrol. 1998 Dec;9(12):2223-34. doi: 10.1681/ASN.V9122223.
Angiotensin II receptor antagonists have become clinically available for the treatment of arterial hypertension. Presently, there is little information about their effects on BP, proteinuria, and renal function in patients with moderate or advanced renal failure. This study examines the effects of the angiotensin II antagonist Valsartan (80 mg/d) on proteinuria and glomerular permselectivity in patients with chronic renal failure during a 6-mo treatment, using a double-blind, randomized, placebo-controlled study (treatment group [V-group]: n = 5, age 57 +/- 7 yr, serum creatinine 365 +/- 122 micromol/L; placebo group [P-group]: n = 4, age 62 +/- 11 yr, serum creatinine 346 +/- 61 micromol/L). Study parameters included BP, 24-h proteinuria, GFR, and effective renal plasma flow (ERPF) as determined by inulin and para-aminohippurate clearance. Changes in glomerular permselectivity were assessed by measuring the fractional clearances of neutral dextrans by HPLC gel-permeation chromatography. Valsartan lowered the mean arterial pressure on average by 13 +/- 7 mmHg during the 6-mo treatment (P < 0.05). GFR and ERPF remained almost unchanged. However, after 6 mo of Valsartan treatment, proteinuria was reduced by 396 +/- 323 mg/24 h (26 +/- 18%) and albuminuria by 531 +/- 499 mg/24 h (41 +/- 21%) with regard to baseline values (P < 0.05). In the P-group, both proteinuria and albuminuria increased slightly with time (by 30 +/- 43% and 30 +/- 54%, respectively, NS). The fractional clearances of high molecular weight dextrans >66 A were significantly reduced after 6 mo of Valsartan treatment (P < 0.05), indicating a reduction of the glomerular shunt volume by 54 +/- 20% (P < 0.05) according to the model of Deen et al. (Am J Physiol 249: 347-389, 1985). The mean pore size radius of the glomerular membrane remained unchanged. This effect was independent of glomerular hemodynamic changes. Valsartan persistently lowered proteinuria in patients with chronic renal failure. Although GFR and ERPF remained nearly stable, this effect could be attributed to an improvement in glomerular permselectivity.
血管紧张素II受体拮抗剂已在临床上用于治疗动脉高血压。目前，关于它们对中度或重度肾衰竭患者血压、蛋白尿和肾功能影响的信息很少。本研究采用双盲、随机、安慰剂对照研究（治疗组[V组]：n = 5，年龄57±7岁，血清肌酐365±122μmol/L；安慰剂组[P组]：n = 4，年龄62±11岁，血清肌酐346±61μmol/L），考察血管紧张素II拮抗剂缬沙坦（80mg/d）在6个月治疗期间对慢性肾衰竭患者蛋白尿和肾小球滤过选择性的影响。研究参数包括血压、24小时蛋白尿、肾小球滤过率（GFR）以及通过菊粉和对氨基马尿酸清除率测定的有效肾血浆流量（ERPF）。通过高效液相色谱凝胶渗透色谱法测量中性葡聚糖的分数清除率，评估肾小球滤过选择性的变化。在6个月治疗期间，缬沙坦使平均动脉压平均降低了13±7mmHg（P<0.05）。GFR和ERPF几乎保持不变。然而，缬沙坦治疗6个月后，相对于基线值，蛋白尿减少了396±323mg/24小时（26±18%），白蛋白尿减少了531±499mg/24小时（41±21%）（P<0.05）。在P组，蛋白尿和白蛋白尿均随时间略有增加（分别增加30±43%和30±54%，无统计学意义）。缬沙坦治疗6个月后，分子量>66A的高分子量葡聚糖的分数清除率显著降低（P<0.05），根据Deen等人的模型（《美国生理学杂志》249:347 - 389，1985），表明肾小球分流体积减少了54±20%（P<0.05）。肾小球膜的平均孔径半径保持不变。这种作用独立于肾小球血流动力学变化。缬沙坦持续降低慢性肾衰竭患者的蛋白尿。尽管GFR和ERPF几乎保持稳定，但这种作用可归因于肾小球滤过选择性的改善。
