Rapamycin preserves renal function compared with cyclosporine A after ischemia/reperfusion injury.
OBJECTIVE
To determine the effect of cyclosporine and rapamycin administration on renal function after ischemia/reperfusion injury (I/R). Cyclosporine A has known nephrotoxic effects. Thus, cyclosporine therapy subsequent to I/R injury may further exacerbate graft dysfunction. Rapamycin is a newer agent that suppresses the immune system by a different mechanism.


METHODS
Male Wistar rats (250 g) were anesthetized, and the suprarenal aorta was clamped for 40 minutes. The right kidney was removed. After recovery, the rats were divided into four groups: group 1, controls, no ischemia and no treatment (n = 10); group 2, ischemia with no treatment (n = 8); group 3, ischemia plus rapamycin (0.17 mg/kg/day gavage, n = 8); and group 4, ischemia plus cyclosporine A (30 mg/kg/day intraperitoneally, n = 9). The glomerular filtration rate was measured 5 to 7 days after I/R injury using urinary iohexol clearance. Data are expressed as the mean +/- SEM, and intergroup comparisons were made using one-way analysis of variance.


RESULTS
The mean GFR value for the controls (no ischemia, no treatment) was 1.23 +/- 0.08 mL/min; for group 2 (ischemia, no treatment), it was 1.05 +/- 0.10 mL/min; for group 3 (ischemia plus rapamycin) 1.06 +/- 0.14 mL/min; and for group 4 (ischemia plus cyclosporine A) 0.44 +/- 0.06 mL/min (P <0.05 versus the other three groups). The mean arterial pressure was significantly lower in the ischemic rats treated with cyclosporine A (P <0.05 versus the other three groups).


CONCLUSIONS
After I/R injury, rapamycin may preserve renal function compared with cyclosporine treatment, because it does not have a direct vasoconstrictor effect on the renal microcirculation.
Inman
Sharon R
SR
Department of Biomedical Sciences, Ohio University College of Osteopathic Medicine, Athens, Ohio 45701, USA.
Davis
Nancy A
NA
Olson
Kristen M
KM
Lukaszek
Victoria A
VA
McKinley
Marc R
MR
Seminerio
Jennifer L
JL
D000818:Animals; D019703:Calcineurin / Q000502:physiology; D016572:Cyclosporine / Q000633:toxicity*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007511:Ischemia / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control; D016030:Kidney Transplantation; D008297:Male; D009392:Nephrectomy; D011183:Postoperative Complications / Q000139:chemically induced / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000503:physiopathology*; D020123:Sirolimus / Q000633:toxicity*; D009927:Tissue and Organ Procurement
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D019703:Calcineurin; D020123:Sirolimus