The effect of rapamycin on renal function in the rat: a comparative study with cyclosporine.
Male adult Sprague-Dawley rats were treated for 14 days with either rapamycin (RAP, 1.5 mg/kg/d i.p.) in carboxymethylcellulose (RAP/CMC) or polyethyleneglycol (RAP/PEG), cyclosporine (CsA, 15 mg/kg/d by gavage) or with the appropriate drug vehicles. Biochemical indices of renal function and integrity were determined throughout the experimental period, at the end of which the rats were killed and kidneys examined histologically. All animals gained weight at a similar rate to untreated animals except those treated with RAP; RAP/PEG animals were lighter on day 14 compared with day 0 values, whilst RAP/CMC animals were lighter only in comparison with CMC-only controls on day 14. Significant increases in urinary flow rate (UFR) were found in each drug treatment group. RAP/CMC, RAP/PEG and CsA caused mild renal functional impairment, but only with CsA was there a significant reduction in 51Cr-EDTA clearance. Significant enzymuria, resulting from drug but not vehicle administration, was observed only in the CsA-treatment group. Increased plasma and urinary glucose levels, elevated in all drug-treatment groups, were related to increased UFR. Kidneys of RAP-treated rats appeared normal, whereas mild, focal, acute tubular necrosis was evident in all CsA-tested animals. Pancreases of all drug-treated animals were histologically normal.
Department of Clinical Biochemistry, University of Aberdeen, U.K.
P H
PH
Whiting
B J
BJ
Adam
J
J
Woo
N U
NU
Hasan
A W
AW
Thomson
D000118:Acetylglucosaminidase / Q000652:urine; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D016572:Cyclosporine / Q000097:blood / Q000494:pharmacology*; D006029:Glycosuria / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D008297:Male; D011090:Polyenes / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D020123:Sirolimus; D005723:gamma-Glutamyltransferase / Q000652:urine
D001786:Blood Glucose; D007166:Immunosuppressive Agents; D011090:Polyenes; D016572:Cyclosporine; D005723:gamma-Glutamyltransferase; D000118:Acetylglucosaminidase; D020123:Sirolimus