Light and Electron Microscopic Changes in the Kidney of Wistar Rats following Treatment with Cyclosporine A

Abstract

The morphological changes found in kidneys of patients undergoing chronic Cyclosporine A (CSA) treatment could, despite of numerous attempts, not yet be reproduced in reliable experimental models. The purpose of the present investigation was to systematically scan the in vivo fixed kidneys in CSA treated Wistar rats at the light and electron microscopic level. The study revealed changes in the proximal tubules, i.e., inclusion bodies, vacuolization, microcalcifications and regeneration. Some glomeruli displayed a thickening of the parietal sheet of Bowman's capsule. At the electron microscopic level, individual necroses of myocytes in the tunica media of afferent arterioles were observed. Thus, at the ultrastructural level, the kidneys of CSA treated normotensive Wistar rats do reveal morphological changes similar to those occurring in man.

Role for TGF-β in Cyclosporine-Induced Modulation of Renal Epithelial Barrier Function

“…Mechanisms of CsA-induced nephrotoxicity were thought to be hemodynamic in origin, but there is accumulating evidence for a direct tubular effect. CsAinduced tubular damage is not well understood; however, alterations in tubular morphology have been seen in acute studies in rats (2)(3)(4).…”

CyA-Mediated Renal Interstitial and Vascular Lesions in the Rat under Low-Sodium Diet

“…In humans, however, CyA treatment does not increase plasma renin level (16,22), but increases have been observed in plasma prorenin level and hyperplasia of the juxtaglomerular apparatus (16,22 CyA causes necrosis of smooth muscle cells in afferent arterioles and arteriolar hyalinosis in humans (21,37). In rats, necrosis of smooth muscle cells was only observed following treatment with high doses of CyA (8) except SHR (30). In this study, although severe (24,38), these electron-dense fibrous bodies could have been derived from the aggregation of focal dense bodies and/or attachment plaques.…”

“…There have been only a few reports describing the earlier stages of chronic CyA-mediated nephropathy in animals (8,36,42) and CyA toxicity in UNT rats (6,28). In the present study, we performed detailed examination of the earlier changes in chronic CyA-mediated nephropathy with immunohistochemical and electron microscopic techniques in rats including UNT.…”

Nephrotoxicity of Cyclosporine A in the Rat

“…Furthermore, determining the activity of N-acetyl-fl-D-glucosaminidase in the urine in correlation with the tubular activ ities and, additionally, with parameters of re nal function should provide insight into the tubular origin of this enzymuria and its rele vance as an indicator of renal cell integrity. The dosage ( 15,30 or 50 mg/kg • day) and du ration (12 or 24 days) of cyclosporine A ad ministration were chosen according to the re sults of previous studies on kidney histology and enzymuria [2][3][4][5][6]. Their influence as well as the reversibility of the effects after discon tinuation of the drug for 24 days were investi gated here.…”

“…Cyclosporine A has been shown to de crease the activity of mitochondrial succinate dehydrogenase in circumscribed regions of the normal rat kidney [1], In addition, mor phological alterations of the lysosomes in the proximal tubules have been described, includ ing an increase in the number and size of vacu olar structures [2][3][4][5] and of lysosomes at the stage of inclusion or residual bodies [3,4], These alterations are associated with slight re nal dysfunction and moderate enzymuria [2,5,6].…”