Young E W, Ellis C N, Messana J M, Johnson K J, Leichtman A B, Mihatsch M J, Hamilton T A, Groisser D S, Fradin M S, Voorhees J J
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor.
Kidney Int. 1994 Oct;46(4):1216-22. doi: 10.1038/ki.1994.387.
The impact of long-term cyclosporin therapy on kidney structure and function was evaluated in psoriasis patients with normal baseline renal function. Patients received cyclosporin at an average dose 3.9 mg/kg/day for up to three years and underwent serial kidney biopsies and measurements of iothalamate clearance and serum creatinine concentration. Kidney biopsy specimens (assessed on a scale of 0 to 4 where 0 = normal and 4 = severe) from 19 cyclosporin-treated patients as compared to 38 age-matched transplant donors showed increased interstitial fibrosis (1.9 +/- 0.2 vs. 0.3 +/- 0.1, P < 0.0001) and tubular atrophy (1.6 +/- 0.2 vs. 0.3 +/- 0.1, P < 0.0001) at one year. Eleven patients had a second biopsy after an additional two years of cyclosporin treatment demonstrating additional interstitial fibrosis (1.8 +/- 0.2 to 2.4 +/- 0.3, P = 0.002) and tubular atrophy (1.4 +/- 0.2 to 1.9 +/- 0.2, P = 0.053), and the onset of cyclosporin-associated arteriolopathy (0 to 0.5 +/- 0.2, P = 0.02). Quantitative digital morphometric analysis of trichrome-stained specimens also showed increased interstitial fibrosis (22.5 +/- 1.5 to 32.0 +/- 2.0% of interstitial area, P = 0.0008). Iothalamate clearance declined at an average rate of -3.1 ml/min/1.73 m2 per year (95% CI -5.8, -0.3) during the period of cyclosporin treatment. The slope of reciprocal serum creatinine declined by -0.06 dl/mg per year (95% CI -0.08, -0.04). Chronic cyclosporin treatment of otherwise healthy psoriasis patients is associated with progressive renal structural injury and reduced glomerular filtration rate.
在基线肾功能正常的银屑病患者中评估了长期环孢素治疗对肾脏结构和功能的影响。患者接受平均剂量为3.9毫克/千克/天的环孢素治疗，最长达三年，并接受了系列肾脏活检以及碘肽酸盐清除率和血清肌酐浓度的测量。与38名年龄匹配的移植供体相比，19名接受环孢素治疗患者的肾脏活检标本（按0至4分进行评估，0分 = 正常，4分 = 严重）显示，一年时间质纤维化增加（1.9±0.2对0.3±0.1，P < 0.0001）和肾小管萎缩增加（1.6±0.2对0.3±0.1，P < 0.0001）。11名患者在接受另外两年的环孢素治疗后进行了第二次活检，结果显示间质纤维化进一步增加（从1.8±0.2至2.4±0.3，P = 0.002）和肾小管萎缩进一步增加（从1.4±0.2至1.9±0.2，P = 0.053），并且出现了环孢素相关的小动脉病变（从0至0.5±0.2，P = 0.02）。对三色染色标本进行的定量数字形态计量分析也显示间质纤维化增加（从间质面积的22.5±1.5%至32.0±2.0%，P = 0.0008）。在环孢素治疗期间，碘肽酸盐清除率平均每年下降-3.1毫升/分钟/1.73平方米（95%可信区间-5.8，-0.3）。血清肌酐倒数的斜率每年下降-0.06分升/毫克（95%可信区间-0.08，-0.04）。对原本健康的银屑病患者进行慢性环孢素治疗会导致进行性肾脏结构损伤和肾小球滤过率降低。
