CYCLOSPORINE-INDUCED NEPHROTOXICITY IN DEOXYCORTICOSTERONE-NACL TREATED RATS

This study tested the hypothesis that the adverse effects of cyclospor ine (Cy) are accelerated in animals with induced hypertension. Four gr oups of rats were unilaterally nephrectomized at 5 weeks of age. Two w eeks later, two of these groups received implantations of Silastic str ips impregnated with deoxycorticosterone acetate (DOCA) and were maint ained on 1% saline (DOCA-NaCl); the other two groups served as sham co ntrols. Daily injections of Cy (20 mg/kg) were given to one DOCA-NaCl and one control group. During the initial 3 days, the Cy/DOCA-NaCl tre ated rats displayed a significant increase in systolic arterial pressu re (SAP), but their SAP did not increase significantly thereafter. Cy/ DOCA-NaCl treatment caused severe nephrotoxicity 18 days after initiat ion of treatment, but neither cyclosporine nor DOCA-NaCl treatment alo ne resulted in morphological renal damage. In Cy/DOCA-NaCl rats, the i nterstitial spaces between renal tubules were dramatically increased i n size and contained abundant bundles of collagenous fibres, deposits of immunoreactive laminin, and infiltrates of mononuclear cells. In a second experiment, bilateral renal denervation prior to treatment did not lessen the Cy-induced renal damage. These results indicate that in the DOCA-NaCl rat, Cy treatment damages the renal cortex in a pattern similar to that observed in humans treated chronically with Cy. Furth er, the results indicate that an absence of renal innervation does not decrease the nephrotoxic effects of Cy in this rapid onset model.