Effect of cyclosporine in rats with reduced renal mass.
The longterm effect of cyclosporine (CyA) on chronic renal failure was studied in female Wistar rats subjected to 4/5 to 5/6 nephrectomy by partial infarction of the left kidney followed by contralateral nephrectomy. CyA was added to a standard rat diet containing 25% protein. Each rat received 14 g of food daily containing 0 (control), 1.2 (group A), 2.4 (group B), or 4.8 (group C) mg CyA. The number of rats that did not survive the whole experimental period of 20 weeks on the CyA containing diets was similar to the control. In the surviving rats no difference between groups could be detected regarding body weight, serum creatinine and creatinine clearance. Proteinuria rose progressively up to 15 weeks in the control group and similarly in groups A and B. Mean proteinuria in group C was about half the control mean at 5-20 weeks. Systolic blood pressure differed little between groups A, B and control, but was significantly lower than control in group C at 10-20 weeks. Histologically groups B and C showed significantly less glomeruli with segmental sclerosis and less hypertensive vasculopathy than groups A and control. Histological signs of tubular CyA toxicity correlated with the doses applied: inclusion bodies were more frequent in all groups while the score of vacuolisation was increased significantly in group C only. In conclusion, CyA appears not to adversely affect or - at moderately toxic dosage - even to slow down progressive glomerular sclerosis in rats with reduced renal mass.
Brunner
F P
FP
Hermle
M
M
Mihatsch
M J
MJ
Thiel
G
G
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003524:Cyclosporins / Q000097:blood / Q000633:toxicity*; D004435:Eating / Q000187:drug effects; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000473:pathology*; D007677:Kidney Function Tests; D009392:Nephrectomy; D009929:Organ Size / Q000187:drug effects; D011507:Proteinuria / Q000139:chemically induced; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D003524:Cyclosporins