Morphometrical analysis of glomerular changes induced by cyclosporine in the rat.
Functional and morphologic techniques were used to study the renal changes induced by a long-term exposure of normal rats to cyclosporine A (CsA), as well as their potential reversibility. CsA treatment for 3 months resulted in a significant (P less than 0.01) reduction of glomerular filtration rate (GFR) as compared with vehicle-treated animals. Histological examination of the kidneys showed mild glomerular damage characterized by ischemic lesions, increased mesangial matrix, and intracapillary hypercellularity in the CsA-treated group, but not in the vehicle-treated group. Proximal tubular abnormalities and limited areas of interstitial fibrosis were also present in the CsA group. A complete reconstruction of glomerular corpuscle was used to evaluate the consequence of CsA-induced renal ischemia on capillary tuft volume. The results showed that in rats administered CsA for 3 months glomerular volume distribution was shifted toward small glomeruli. Prolongation of CsA administration for 5 months did not result in a further decrease in GFR, and was associated with the appearance of a subset of glomeruli that became larger than normal. We have also investigated whether, once established, CsA-induced renal injury is reversible. In rats that were administered CsA for 3 months and then treatment discontinued for 2 months, GFR returned to pretreatment values and partial reversibility of morphologic changes was observed. Morphometric analysis showed that 2 months after withdrawal of CsA, glomerular volume distribution was almost comparable to that observed in vehicle-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Perico
N
N
Mario Negri Institute, Pharmacological Research, Ospedali Riuniti di Bergamo, Italy.
Remuzzi
A
A
Imberti
O
O
Cavallotti
D
D
Bertani
T
T
Remuzzi
G
G
D000818:Animals; D003524:Cyclosporins / Q000633:toxicity*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D003524:Cyclosporins