title: Morphometrical analysis of glomerular changes induced by cyclosporine in the rat.
abstract: 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)
authors.affiliation: Mario Negri Institute, Pharmacological Research, Ospedali Riuniti di Bergamo, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Perico
authors.forename: A
authors.initials: A
authors.lastname: Remuzzi
authors.forename: O
authors.initials: O
authors.lastname: Imberti
authors.forename: D
authors.initials: D
authors.lastname: Cavallotti
authors.forename: T
authors.initials: T
authors.lastname: Bertani
authors.forename: G
authors.initials: G
authors.lastname: Remuzzi
mesh_terms: 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
chemical_list: D003524:Cyclosporins