Madsen J K, Zachariae H, Pedersen E B
Research Laboratory of Nephrology and Hypertension, Aarhus University Hospital, Denmark.
Nephrol Dial Transplant. 1997 Mar;12(3):480-4. doi: 10.1093/ndt/12.3.480.
Deterioration of renal function and rise in blood pressure are clinically important side-effects of cyclosporin (CsA) treatment. Calcium antagonists may have a renoprotective effect against CsA nephrotoxicity.
To investigate the effect of the dihydropyridine calcium-channel blocker felodipine on renal haemodynamics, tubular sodium handling, and blood pressure in CsA-treated patients with no primary renal disease, 18 patients with various CsA-treated dermatological diseases were allocated to receive either felodipine 5 mg (extended release tablets) once daily for 4 weeks followed by placebo for 4 weeks, or vice versa, in a prospective, randomized, double-blind study. The patients were investigated before treatment and at the end of each treatment period.
After felodipine, both glomerular filtration rate (GFR) and renal plasma flow (RPF) were significantly higher compared to placebo (89.4 +/- 17.5 (mean +/- SD) vs 79.0 +/- 15.9 ml/min and 412.0 +/- 107.6 vs 326.1 +/- 78.0 ml/min respectively, P < 0.001 for both), and filtration fraction (FF) was lower (0.22 +/- 0.03 vs 0.25 +/- 0.03, P < 0.001). Both systolic and diastolic blood pressure were lower after felodipine compared to placebo (116 +/- 11/71 +/- 7 vs 133 +/- 18/83 +/- 10 mmHg, P < 0.001 for both). Furthermore, proximal output of sodium, i.e. fractional excretion of lithium, was higher after felodipine (26.9 +/- 7.3% vs 20.4 +/- 5.5%, P < 0.001) as well as total sodium excretion (0.33 +/- 0.19 vs 0.19 +/- 0.08 mmol/min, P < 0.001).
It is concluded, that felodipine 5 mg once daily for 4 weeks increased GFR, RPF, and sodium excretion in cyclosporin-treated dermatological patients with no primary renal disease. Furthermore, felodipine lowers blood pressure in these patients. The effects of felodipine may be due to an antagonizing effect against CsA-induced nephrotoxicity.
肾功能恶化和血压升高是环孢素（CsA）治疗的重要临床副作用。钙拮抗剂可能对CsA肾毒性具有肾脏保护作用。
为研究二氢吡啶类钙通道阻滞剂非洛地平对无原发性肾脏疾病的CsA治疗患者的肾脏血流动力学、肾小管钠处理及血压的影响，在一项前瞻性、随机、双盲研究中，将18例接受CsA治疗的各种皮肤病患者分为两组，一组每天服用一次5mg非洛地平（缓释片），共4周，随后服用4周安慰剂；另一组反之。在治疗前及每个治疗期结束时对患者进行检查。
服用非洛地平后，与服用安慰剂相比，肾小球滤过率（GFR）和肾血浆流量（RPF）均显著升高（分别为89.4±17.5（均值±标准差）对79.0±15.9ml/min和412.0±107.6对326.1±78.0ml/min，两者P均<0.001），滤过分数（FF）降低（0.22±0.03对0.25±0.03，P<0.001）。与服用安慰剂相比，服用非洛地平后收缩压和舒张压均降低（116±11/71±7对133±18/83±10mmHg，两者P均<0.001）。此外，服用非洛地平后近端钠排出量，即锂的分数排泄增加（26.9±7.3%对20.4±5.5%，P<0.001），总钠排泄量也增加（0.33±0.19对0.19±0.08mmol/min，P<0.001）。
得出结论，对于无原发性肾脏疾病的接受CsA治疗的皮肤病患者，每天一次服用5mg非洛地平，持续4周，可增加GFR、RPF和钠排泄。此外，非洛地平可降低这些患者的血压。非洛地平的作用可能归因于其对CsA诱导的肾毒性的拮抗作用。
