Abstract
Immunosuppression with cyclosporine (CYC) results in an early, acute, reversible reduction in renal hemodynamlcs. In an attempt to establish a model for investigating the functional and morphologic effects of ACIN at the single nephron level, renal micropuncture (MP) and ultra-structural (EM) studies were performed in growing male rats (100-140 g). Pair-caged animals were treated with IM injections of CYC (10 or 25 mg/kg/d) or olive oil for 1 week. Daily weight gain was reduced in both treated groups (-32%, n=24, and -44%, n=6, p<.01). Inactin anesthesia (110-120 mg/kg IP) and the hydropenic (HYP) state were maintained throughout MP. Rats given 25 mg/kg CYC were hypothermic and hypotensive; few survived the surgical preparation for MP. Kidneys appeared grossly abnormal with no superficial tubular flow. Kidney gloraerular filtration rate (GFR) was less in the 10 mg/kg CYC treated rats (0.39 ± .07 S.E. ml/min/100 g, n=4), than in a separate group of HYP controls of the same weight (0.56 ± .04 ml/min/100 g, n=5, p<.005). Proximal single nephron GFR was also lower (24.2 ± 1.8 nl/min, n=4) than the controls (34.0 ± 2.6 nl/min, n=9, p<.001). EM studies performed in a group of identically treated rats showed distal tubules with widely dilated lateral intercellular spaces. Proximal tubules had increased intracellular vacuoles. These results agree with observations in human ACIN and demonstrate that this is a useful animal model of ACIN.
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Kaskel, F., Agarwala, S., Partln, J. et al. 1610 MODEL OF ACUTE CYCLOSPORINE-INDUCED NEPHROTOXI CITY (ACIN) IN THE GROWING RAT. Pediatr Res 19, 379 (1985). https://doi.org/10.1203/00006450-198504000-01634
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DOI: https://doi.org/10.1203/00006450-198504000-01634