Madsen J K, Sørensen S S, Hansen H E, Pedersen E B
Department of Medicine and Nephrology C, Skejby Hospital, University Hospital in Aarhus, Denmark.
Nephrol Dial Transplant. 1998 Sep;13(9):2327-34. doi: 10.1093/ndt/13.9.2327.
Due to their vasodilatory effect, calcium antagonist may have a renoprotective against cyclosporin (CsA)-induced nephrotoxicity and rise in blood pressure (BP) seen in renal transplantation.
In order to evaluate the effect of the calcium antagonist felodipine on renal function and BP during cyclosporin treatment, 79 CsA-treated renal transplant recipients were investigated during the first 3 months after transplantation in a randomized, double-blind, placebo-controlled study with two parallel groups. Felodipine (ER tablets, 10 mg) or placebo was given prior to transplantation and each day during the study period. The patients were assessed twice, i.e. at 4-6 weeks and at 10-12 weeks after transplantation. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured by constant infusion technique. Tubular function was estimated from clearance of lithium.
At 6 weeks after transplantation, felodipine caused a significantly higher RPF [felodipine: 219 +/- 70 ml/min; placebo: 182+/-56 ml/min (mean+/-1 SD); P=0.03]. No differences were found in GFR, filtration fraction (FF), tubular sodium handling, or sodium excretion. Felodipine lowered BP significantly. At 12 weeks after transplantation, felodipine caused a significantly higher GFR (felodipine: 49+/-18 ml/min; placebo: 40+/-16 ml/min; P=0.05) and RPF (felodipine: 225+/-77 ml/min; placebo: 175+/-48 ml/min; P<0.01). No difference was found in FF. Felodipine lowered BP significantly. No differences were found with regard to duration of primary anuria, hospitalization time, number of rejection episodes, plasma creatinine day 7 post-transplant, or treatment doses of CsA.
It is concluded that in renal transplant recipients treated with CsA, felodipine significantly increased both GFR and RPF 3 months after transplantation when compared with placebo, despite a concomitant lowering of BP. A possible antagonizing affect of felodipine against CsA-induced nephrotoxicity in these patients is suggested.
由于具有血管舒张作用，钙拮抗剂可能对肾移植中出现的环孢素（CsA）诱导的肾毒性及血压（BP）升高具有肾脏保护作用。
为评估钙拮抗剂非洛地平在环孢素治疗期间对肾功能和血压的影响，在一项随机、双盲、安慰剂对照的平行两组研究中，对79例接受CsA治疗的肾移植受者在移植后的前3个月进行了调查。在移植前及研究期间每天给予非洛地平（缓释片，10毫克）或安慰剂。患者在移植后4 - 6周和10 - 12周进行了两次评估。通过持续输注技术测量肾血浆流量（RPF）和肾小球滤过率（GFR）。根据锂清除率评估肾小管功能。
移植后6周，非洛地平使RPF显著升高[非洛地平：219±70毫升/分钟；安慰剂：182±56毫升/分钟（均值±1标准差）；P = 0.03]。在GFR、滤过分数（FF）、肾小管钠处理或钠排泄方面未发现差异。非洛地平显著降低血压。移植后12周，非洛地平使GFR显著升高（非洛地平：49±18毫升/分钟；安慰剂：40±16毫升/分钟；P = 0.05）和RPF（非洛地平：225±77毫升/分钟；安慰剂：175±48毫升/分钟；P < 0.01）。FF方面未发现差异。非洛地平显著降低血压。在原发性无尿持续时间、住院时间、排斥反应发作次数、移植后第7天的血浆肌酐或CsA治疗剂量方面未发现差异。
得出结论，在接受CsA治疗的肾移植受者中，与安慰剂相比，非洛地平在移植3个月后显著增加了GFR和RPF，尽管同时降低了血压。提示非洛地平对这些患者中CsA诱导的肾毒性可能具有拮抗作用。
