Falkenhain M E, Cosio F G, Sedmak D D
Department of Internal Medicine, The Ohio State University, Columbus 43210, USA.
Transplantation. 1996 Aug 15;62(3):364-70. doi: 10.1097/00007890-199608150-00011.
Cyclosporine (CsA) causes both acute and chronic nephrotoxicity. The goal of the present studies was to examine the nature of the chronic renal pathologic lesions of CsA nephrotoxicity and to determine whether these lesions progress with prolonged exposure to the drug. With this purpose, we examined large sections of kidneys obtained at autopsy from 15 heart transplant recipients, 7 liver transplant recipients, and 10 nontransplanted controls. Tissue sections were examined blindly by light microscopy, histomorphometry, and color computer image analysis. With increasing time following transplantation, there was a progressive increase in renal arteriolar hyalinosis and in the percentage of glomeruli demonstrating global sclerosis. In addition, there was a statistically significant relationship between arteriolar hyalinosis and global glomerulosclerosis (r=0.61, P<0.003). The percentage of glomeruli with focal glomerulosclerosis was also increased in transplant recipients followed for more than 80 days. The kidneys of heart and liver recipients who died less than 80 days after transplantation, that is, those patients who received no CsA or low doses of CsA, demonstrated significantly more interstitial fibrosis than the kidneys of control individuals. Furthermore, there was no significant increase in the amount of renal interstitial fibrosis in allograft recipients followed for prolonged periods of time. There were no significant relationships between the severity of renal pathologic changes and serum creatinine or systemic blood pressure levels. In conclusion, non-renal transplant recipients demonstrate renal damage that affects primarily the preglomerular arterioles and results in glomerular obliteration. This renal damage increases in relation to the time of exposure to CsA and in relation to the total dose of CsA that the patient receives. These renal structural changes are not reflected initially in changes in glomerular filtration rate, as determined by serum creatinine.
环孢素（CsA）可导致急性和慢性肾毒性。本研究的目的是检查CsA肾毒性慢性肾脏病理损害的性质，并确定这些损害是否会随着药物暴露时间的延长而进展。为此，我们检查了15例心脏移植受者、7例肝脏移植受者和10例非移植对照者尸检时获取的肾脏大体标本。组织切片通过光学显微镜、组织形态计量学和彩色计算机图像分析进行盲法检查。随着移植后时间的增加，肾小动脉玻璃样变性以及呈现全球性硬化的肾小球百分比逐渐增加。此外，小动脉玻璃样变性与全球性肾小球硬化之间存在统计学显著相关性（r = 0.61，P < 0.003）。随访超过80天的移植受者中，伴有局灶性肾小球硬化的肾小球百分比也增加。移植后不到80天死亡的心脏和肝脏受者（即未接受CsA或接受低剂量CsA的患者）的肾脏，与对照个体的肾脏相比，间质纤维化明显更多。此外，长期随访的同种异体移植受者肾间质纤维化量没有显著增加。肾脏病理改变的严重程度与血清肌酐或全身血压水平之间没有显著相关性。总之，非肾移植受者表现出主要影响肾小球前小动脉并导致肾小球闭塞的肾损害。这种肾损害随着CsA暴露时间以及患者接受的CsA总剂量的增加而加重。这些肾脏结构变化最初并未反映在血清肌酐所测定的肾小球滤过率变化中。
