[Establishment of a new rat model of chronic cyclosporine A nephrotoxicity].
OBJECTIVE
To establish a new rat model of chronic cyclosporine A nephrotoxicity and explore its features.


METHODS
Totally 24 male SD rats were equally randomized divided into 3 groups: sham-adrenalectomized (sham-ADX) group, ADX group and ADX plus cyclosporine A (CsA) group. Rats in ADX and CsA group first underwent adrenalectomy, followed by the administration of placebo or dexamethasone, respectively. Rats in sham-ADX group received sham adrenalectomy and distilled water as control. Six weeks later, all rats were sacrificed and the following indicators were evaluated: urine protein excretion, creatinine clearance, aldosterone level in serum and urine, aldosterone level and its synthase CYP11B2 gene expression in kidney, serum natrium and potassium, urine natrium and potassium excretion, and tubulointerstitial fibrosis by masson trichrome stain.


RESULTS
In ADX and CsA group, serum and urine aldosterone were undetectable on the second post-operative day, with other observations including natriuresis, hyponatremia, decreased urine potassium excretion, and hyperpotassemia, suggesting that adrenals were removed intact and the adrenalectomy was successful. Rats in CsA group showed increased urine protein, decreased creatinine clearance and tubulointerstitial fibrosis, suggesting that a model of chronic CsA nephrotoxicity was successfully established. At the endpoint, serum potassium, serum aldosterone, urine potassium and urine aldosterone excretion partially retrieved. Natrium in serum and urine was not significant different between ADX group/CsA group and sham-ADX group. Local renal aldosterone and its gene expression were remarkably upregulated.


CONCLUSIONS
We successfully established a new rat model of chronic CsA nephrotoxicity by adrenalectomy without low sodium diet. After adrenalectomy, local renal aldosterone in kidney may compensate for circulatory aldosterone deficit to maintain electrolyte balance.
Sun
Qiao-ling
QL
Graduate School, CAMS and PUMC, Beijing 100730, China.
Chen
Yi-pu
YP
Rui
Hong-liang
HL
D058186:Acute Kidney Injury / Q000139:chemically induced*; D000315:Adrenalectomy; D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D016572:Cyclosporine / Q000633:toxicity*; D004195:Disease Models, Animal; D007166:Immunosuppressive Agents / Q000633:toxicity; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D007166:Immunosuppressive Agents; D000450:Aldosterone; D016572:Cyclosporine