THE LONG-TERM COURSE OF CYCLOSPORINE-ASSOCIATED CHRONIC NEPHROPATHY
THE LONG-TERM COURSE OF CYCLOSPORINE-ASSOCIATED CHRONIC NEPHROPATHY
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DOI：
10.1038/ki.1988.38
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发表时间：
1988-02-01
影响因子：
19.6
通讯作者：
PERLROTH, MG
中科院分区：
文献类型：
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作者：
MYERS, BD;SIBLEY, R;PERLROTH, MG
我们评估了37例心脏移植受者接受环孢素（CsA）治疗12至24个月的慢性肾损伤。24例接受硫唑嘌呤治疗超过24个月的心脏移植受者作为对照。尽管心脏功能相当，但CsA治疗组的GFR降低，为47 . ±. 3比94。+-。4ml/min/1.73m2（P < 0.001）。CsA治疗还与肾血管阻力（RVR）显著升高、蛋白尿、动脉高血压和肾内非活性原肾素向活性肾素转化受损相关。与CsA相关的组织学变化包括闭塞性小动脉病伴坏死小动脉壁中蛋白质物质沉积，以及相关的肾小管间质损伤。少数肾小球表现为缺血性塌陷或硬化。面积周长分析显示其余肾小球增大，系膜显著扩张。在CsA减量或停药的48个月期间（N = 15），纵向检查显示持续性低滤过，RVR逐渐升高，尿蛋白较重。在6名患者的肾组织第二次取样时观察到进一步的组织病理学恶化，实验组的3名成员发展为终末期肾病。我们的结论是，连续CsA治疗超过12个月会导致慢性肾微血管损伤，很少是可逆的，并可能进行性。
We evaluated a chronic renal injury in 37 cardiac transplant recipients treated for 12 to 24 months with cyclosporine (CsA). Twenty-four cardiac transplant recipients treated with azathioprine for more than 24 months served as controls. Despite equivalent cardiac performance, GFR in those treated with CsA was depressed, 47 .+-. 3 versus 94 .+-. 4 ml/min/1.73 m2 (P < 0.001). CsA therapy was also associated with significant elevation of renal vascular resistance (RVR), proteinuria, arterial hypertension, and impaired intrarenal conversion of inactive prorenin to active renin. Histopathological changes associated with CsA included an obliterative arteriolopathy with deposition of proteinaceous material in necrotic arteriolar walls, and associated tubulointerstitial damage. A minority of glomerbuli exhibited either ischemic collapse or sclerosis. Area perimeter analysis revealed enlargement of the remaining glomeruli with significant expansion of the mesangium. Longitudinal examination over a 48 month period (N = 15) during which CsA was reduced in dosage or withdrawn revealed persistent hypofiltration, increasingly elevated RVR and heavier protein urid. Further histopathological deterioration was observed when renal tissue was sampled a second time in six patients, and three members of the experimental group developed end-stage renal disease. We conclude that continuous CsA therapy for more than 12 months causes a chronic injury to renal microvessels that is rarely reversible and potentially progressive.