Deray G, Le Hoang P, Cacoub P, Hornych A, Legrand S, Aupetit B, Zogbi F, Landault C, Carayon A, Baumelou A
Department of Nephrology, CHU Pitié-Salpêtrière, Paris, France.
Am J Nephrol. 1988;8(4):298-304. doi: 10.1159/000167604.
Animals and humans undergoing treatment with ciclosporin (CS) show a reversible increase in renal vascular resistance and a decrease in glomerular filtration rate. The causes of these abnormalities have not yet been established. We evaluated the effects of a 1-week treatment with CS on creatinine clearance, renal arachidonic acid metabolites, plasma renin activity (PRA), plasma aldosterone levels, urinary excretion and plasma levels of catecholamines in 7 patients with idiopathic uveitis. We show that CS treatment induces a significant (p less than 0.05) decrease in creatinine clearance (from 132 +/- 0.5 to 108 +/- 8 ml/min); urinary 6-keto-PGF1 excretion (from 17.8 +/- 4.9 to 10.9 +/- 3.3 ng/mmol creatinine), urinary thromboxane B2 excretion (from 7.0 +/- 1.0 to 3.6 +/- 0.9 ng/mmol creatinine), upright PRA (from 4.2 +/- 0.9 to 2.3 +/- 0.8) and supine PRA (from 2.0 +/- 0.5 to 1.1 +/- 0.3). We found no change in plasma aldosterone levels and plasma levels and urinary excretion of catecholamines. We suggest that the reversible renal vasoconstriction observed in patients treated with CS may be induced by inhibition of renal prostacyclin synthesis. In this setting inhibition of PRA and angiotensin II formation may impair autoregulation of effective filtration pressure and therefore glomerular filtration rate.
接受环孢素(CS)治疗的动物和人类表现出肾血管阻力可逆性增加以及肾小球滤过率降低。这些异常的原因尚未明确。我们评估了CS为期1周的治疗对7例特发性葡萄膜炎患者的肌酐清除率、肾花生四烯酸代谢产物、血浆肾素活性(PRA)、血浆醛固酮水平、儿茶酚胺的尿排泄及血浆水平的影响。我们发现CS治疗可导致肌酐清除率显著降低(p<0.05)(从132±0.5降至108±8 ml/分钟);尿6-酮-前列环素F1排泄量(从17.8±4.9降至10.9±3.3 ng/mmol肌酐)、尿血栓素B2排泄量(从7.0±1.0降至3.6±0.9 ng/mmol肌酐)、立位PRA(从4.2±0.9降至2.3±0.8)及卧位PRA(从2.0±0.5降至1.1±0.3)。我们未发现血浆醛固酮水平以及儿茶酚胺的血浆水平和尿排泄有变化。我们认为,接受CS治疗的患者中观察到的可逆性肾血管收缩可能是由肾前列环素合成受抑制所致。在此情况下,PRA及血管紧张素II生成受抑制可能会损害有效滤过压的自身调节,进而影响肾小球滤过率。