Neumayer H H, Gellert J, Luft F C
Department of Medicine and Nephrology University of Erlangen-Nürnberg, Germany.
Ren Fail. 1993;15(3):353-8. doi: 10.3109/08860229309054944.
A growing body of evidence supports the notion that calcium antagonists exert a renal protective effect. Calcium antagonists may play an important future role in renal hemodynamics related to their reversal of renal vasoconstrictors. Calcium antagonists are also capable of blocking intracellular calcium overload induced by various types of ischemia or toxic stimuli. Features such as these may be of substantial value in ameliorating acute renal insufficiency secondary to renal ischemia, iodinated radiographic contrast media, or the administration of various nephrotoxic drugs. The latter includes agents such as the aminoglycoside antibiotics, cyclosporine A, and the cancer chemotherapeutic agent cisplatin. Recent prospective, controlled studies from our group indicate that calcium antagonists protected against postischemic acute renal failure in the setting of cadaveric renal transplantation. Moreover, in a prospective, randomized, controlled clinical trial, we were able to demonstrate that the prophylactic use of nitrendipine reduced the decrease in GFR in patients receiving radiographic contrast agents. Such protection may extend to favorably influencing the course of chronic renal insufficiency, particularly when the latter is complicated by hypertension. Seven putative mechanisms have been proposed by which calcium antagonists may ameliorate the decline in GFR associated with renal insufficiency. These are: (a) reduction in blood pressure per se, (b) reduction in renal hypertrophy, (c) modulation of mesangial traffic of macromolecules, (d) reduction in metabolic activity in remnant renal tissue, (e) amelioration of uremic nephrocalcinosis, (f) reduction of pressure-induced calcium entry into vessel walls, and (g) reduction of free radical formation. Experimental investigations in rats with reduced renal mass, desoxycorticosterone-induced hypertension, or chronic angiotensin II infusion, and in spontaneously hypertensive rats support such a view.
越来越多的证据支持钙拮抗剂具有肾脏保护作用这一观点。钙拮抗剂可能通过逆转肾血管收缩剂，在肾脏血流动力学方面发挥重要的未来作用。钙拮抗剂还能够阻断由各种类型的缺血或毒性刺激所诱导的细胞内钙超载。诸如此类特性在改善继发于肾缺血、碘化造影剂或各种肾毒性药物给药后的急性肾功能不全方面可能具有重大价值。后者包括诸如氨基糖苷类抗生素、环孢素A以及癌症化疗药物顺铂等药物。我们小组最近的前瞻性对照研究表明，在尸体肾移植情况下，钙拮抗剂可预防缺血后急性肾衰竭。此外，在一项前瞻性、随机、对照临床试验中，我们能够证明预防性使用尼群地平可减少接受造影剂患者的肾小球滤过率（GFR）下降。这种保护作用可能会延伸至对慢性肾功能不全病程产生有利影响，尤其是当后者并发高血压时。已经提出了七种可能的机制，通过这些机制钙拮抗剂可能改善与肾功能不全相关的GFR下降。这些机制是：（a）血压本身的降低，（b）肾肥大的减轻，（c）大分子物质在系膜中的转运调节，（d）残余肾组织代谢活性的降低，（e）尿毒症性肾钙质沉着症的改善，（f）压力诱导的钙进入血管壁的减少，以及（g）自由基形成的减少。对肾质量减少、脱氧皮质酮诱导的高血压或慢性输注血管紧张素II的大鼠以及自发性高血压大鼠进行的实验研究支持了这一观点。
