Loriga Giacomina, Vidili Gianpaolo, Ruggenenti Piero, Faedda Rossana, Sanna Marcella, Satta Andrea E
Internal Medicine Department, University of Sassari, Sassari, Italy.
Nephron Clin Pract. 2008;110(4):c213-9. doi: 10.1159/000167868. Epub 2008 Oct 31.
Angiotensin II (AII) is the well-known determinant of kidney damage increasing intraglomerular pressure, matrix expansion and fibroblast proliferation. Renin-angiotensin system (RAS) inhibition, limiting the hemodynamic effects of AII, reduces proteinuria and is renoprotective in the long term.
We studied 15 chronic proteinuric patients by Doppler ultrasonography to clarify the intrarenal hemodynamic changes during RAS blockade by Benazepril (10-20 mg/day) alone and combined with Valsartan (80-160 mg/day). We also investigated the correlation between hemodynamic indices, RAS components and antiproteinuric effect.
After 1 month of Benazepril proteinuria, resistive index (RI) and pulsatility index (PI) significantly decreased and proteinuria reduction was directly correlated to decrease in RI (r = 0.55, p = 0.03). Contrarily, after 1 month of combined therapy, RI and PI restored to baseline and progressively increased in the following 3 months, while proteinuria decreased. Increase in RI was directly correlated to concomitant increase in plasma renin activity (r = 0.65, p = 0.01) suggesting a direct role of renin in restoring intrarenal resistances.
The hemodynamic changes caused by RAS inhibitors partially contribute to the antiproteinuric effect. Other RAS components, such as renin, may contribute to renal vasoconstriction and could be a further determinant of kidney damage besides a promising target for renoprotection.
血管紧张素II（AII）是导致肾损伤的一个众所周知的决定因素，它会增加肾小球内压力、基质扩张和成纤维细胞增殖。肾素-血管紧张素系统（RAS）抑制可限制AII的血流动力学效应，减少蛋白尿，且从长期来看具有肾脏保护作用。
我们通过多普勒超声对15例慢性蛋白尿患者进行研究，以阐明单独使用贝那普利（10 - 20毫克/天）以及联合缬沙坦（80 - 160毫克/天）进行RAS阻断期间的肾内血流动力学变化。我们还研究了血流动力学指标、RAS成分与抗蛋白尿作用之间的相关性。
使用贝那普利1个月后，蛋白尿患者的阻力指数（RI）和搏动指数（PI）显著降低，蛋白尿减少与RI降低直接相关（r = 0.55，p = 0.03）。相反，联合治疗1个月后，RI和PI恢复到基线水平，并在随后3个月逐渐升高，而蛋白尿减少。RI升高与血浆肾素活性的同时升高直接相关（r = 0.65，p = 0.01），提示肾素在恢复肾内阻力方面起直接作用。
RAS抑制剂引起的血流动力学变化部分促成了抗蛋白尿作用。其他RAS成分，如肾素，可能导致肾血管收缩，并且除了作为肾脏保护的一个有前景的靶点外，可能是肾脏损伤的另一个决定因素。
