Hilbrands L B, Hoitsma A J, van Hamersvelt H W, Wetzels J F, Huysmans F T, Koene R A
Department of Medicine, University Hospital Nijmegen, The Netherlands.
Am J Kidney Dis. 1994 Nov;24(5):838-45. doi: 10.1016/s0272-6386(12)80679-2.
Cyclosporine (CsA) impairs renal function, probably by preglomerular vasoconstriction. Vasodilating substances may therefore be of benefit to ameliorate CsA-induced renal dysfunction. We studied the acute effects on blood pressure and renal function of the dihydropyridine calcium antagonist nifedipine (10 mg orally) in 20 CsA-treated renal transplant patients. In addition, we compared the effects of nifedipine when given immediately before and 4 weeks after elective conversion from CsA to azathioprine. Compared with placebo (n = 14), administration of nifedipine led to a significant decrease in blood pressure and a strong natriuretic and diuretic response. Despite the reduction in blood pressure, glomerular filtration rate improved from 60 +/- 20 (mean +/- SD) to 69 +/- 24 mL/min/1.73 m2 (P < 0.001) and renal plasma flow (RPF) increased from 260 +/- 87 to 338 +/- 120 mL/min/1.73 m2 (P < 0.001). The combination of a decreased blood pressure with an increased RPF was reflected in a sharp decrease in renal vascular resistance (0.34 +/- 0.18 units v 0.23 +/- 0.10 units; P < 0.001). The conversion from CsA to azathioprine by itself led to significant increases in glomerular filtration rate (62 +/- 15 mL/min/1.73 m2 v 76 +/- 18 mL/min/1.73 m2; P < 0.05) and RPF (280 +/- 86 mL/min/1.73 m2 v 334 +/- 66 mL/min/1.73 m2; P < 0.05). During treatment with azathioprine an effect of nifedipine on glomerular filtration rate and RPF was no longer observed, although the natriuretic effect was similar on both occasions. The decrease in renal vascular resistance was larger during treatment with CsA than during treatment with azathioprine (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
环孢素(CsA)可能通过肾前血管收缩损害肾功能。因此,血管扩张物质可能有助于改善CsA诱导的肾功能障碍。我们研究了二氢吡啶类钙拮抗剂硝苯地平(口服10毫克)对20例接受CsA治疗的肾移植患者血压和肾功能的急性影响。此外,我们比较了在选择性从CsA转换为硫唑嘌呤之前和之后4周立即给予硝苯地平的效果。与安慰剂组(n = 14)相比,给予硝苯地平导致血压显著降低以及明显的利钠和利尿反应。尽管血压降低,但肾小球滤过率从60±20(平均值±标准差)提高到69±24毫升/分钟/1.73平方米(P < 0.001),肾血浆流量(RPF)从260±87增加到338±120毫升/分钟/1.73平方米(P < 0.001)。血压降低与RPF增加相结合反映在肾血管阻力急剧下降(0.34±0.18单位对0.23±0.10单位;P < 0.001)。从CsA转换为硫唑嘌呤本身导致肾小球滤过率(62±15毫升/分钟/1.73平方米对76±18毫升/分钟/1.73平方米;P < 0.05)和RPF(280±86毫升/分钟/1.73平方米对334±66毫升/分钟/1.73平方米;P < 0.05)显著增加。在硫唑嘌呤治疗期间,未再观察到硝苯地平对肾小球滤过率和RPF的影响,尽管两次的利钠效果相似。CsA治疗期间肾血管阻力的降低大于硫唑嘌呤治疗期间(P < 0.05)。(摘要截短于250字)