Pedersen E B, Madsen J K, Sørensen S S, Zachariae H
Research Laboratory of Nephrology and Hypertension, University Hospital, Aarhus, Denmark.
Kidney Int Suppl. 1996 Jun;55:S94-6.
The purpose was to study whether the calcium entry blocker, felodipine, could reduce the nephrotoxic and hypertensive effect of cyclosporine. The effect of felodipine on glomerular filtration rate (GFR), renal plasma flow (RPF), fractional excretion of sodium, lithium clearance and blood pressure was measured in three randomized, placebo-controlled studies of cyclosporine treated patients. In study one, 10 renal transplant recipients were examined within the first six months after transplantation in a cross-over design. Renal hemodynamics were determined after the acute ingestion of felodipine or placebo, with an interval of less than one week between the two examinations. In study two, 79 renal transplant recipients were randomized to a treatment with felodipine or placebo just before transplantation, and renal hemodynamics were determined after twelve weeks. In study three, 18 patients, who were treated with cyclosporine due to dermatological diseases, were examined in a cross-over design to determine their renal hemodynamics after four weeks of treatment with felodipine or placebo. Felodipine increased renal hemodynamics in study one (GFR 16%, RPF 33%, P < 0.01 for both), in study two (GFR 23%, RPF 28%, P < 0.05 for both), and in study three (GFR 13%, RPF 26%, P < 0.01 for both). FE(Na) was significantly increased by felodipine in studies one and three, but not in study two. Lithium clearance was significantly increased and blood pressure significantly reduced by felodipine in all three studies. It can be concluded that felodipine counteracts both the cyclosporine induced impairment in renal hemodynamics and the increase in blood pressure in acute and short-term studies.
目的是研究钙通道阻滞剂非洛地平是否能降低环孢素的肾毒性和高血压作用。在三项针对环孢素治疗患者的随机、安慰剂对照研究中,测量了非洛地平对肾小球滤过率(GFR)、肾血浆流量(RPF)、钠分数排泄、锂清除率和血压的影响。在研究一中,10名肾移植受者在移植后的前六个月内采用交叉设计进行检查。在急性摄入非洛地平或安慰剂后测定肾血流动力学,两次检查之间的间隔少于一周。在研究二中,79名肾移植受者在移植前随机接受非洛地平或安慰剂治疗,并在12周后测定肾血流动力学。在研究三中,18名因皮肤病接受环孢素治疗的患者采用交叉设计进行检查,以确定在接受非洛地平或安慰剂治疗四周后的肾血流动力学。在研究一中,非洛地平增加了肾血流动力学(GFR增加16%,RPF增加33%,两者P<0.01);在研究二中(GFR增加23%,RPF增加28%,两者P<0.05);在研究三中(GFR增加13%,RPF增加26%,两者P<0.01)。在研究一和三中,非洛地平使FE(Na)显著增加,但在研究二中没有。在所有三项研究中,非洛地平使锂清除率显著增加,血压显著降低。可以得出结论,在急性和短期研究中,非洛地平可抵消环孢素引起的肾血流动力学损害和血压升高。