PREDNISONE ALTERS THE HISTOPATHOLOGY OF CHRONIC CYCLOSPORINE NEPHROPATHY

The effects of prednisone (Pred) and azathioprine (Aza) on a rat model of chronic cyclosporine (CsA) nephropathy were studied. Twenty-four s alt-depleted Sprague-Dawley rats were randomized to four groups: (1) c ontrol; (2) CsA 15 mg/kg; (3) CsA/Aza 5 mg/kg, and (4) CsA/Pred 1 mg/k g. After 4 weeks, functional measurements, including urinary N-acetyl- beta-D-glucosaminidase (NAG) levels, were determined. Semiquantitative grading of cortical and medullary damage was done. Cross-sectional ar eas of medullary thick ascending limbs (mTAL) and collecting ducts (CD ) were determined. Tubulointerstitial injury was equivalent in all CsA groups, but tended to be lowest in the CsA/Pred group. Mean mTAL size in the CsA/Pred group was significantly greater than controls (p = 0. 035). In contrast, mean CD size was not different among all groups. Al l CsA-treated animals had significantly larger hypertrophic mTAL than controls. The degree of hypertrophy was even greater in the CsA/Pred g roup (p = 0.006 vs. the other CsA-treated groups). Mean mTAL size was found to correlate with creatinine clearance, free water reabsorption, and urinary NAG. The percent of hypertrophic mTAL was found to correl ate with creatinine clearance, free water reabsorption, and urinary NA G. This report shows that Pred alters the nephrotoxic effect of CsA, p ermitting a predominantly hypertrophic, rather than atrophic, medullar y response. The extent of hypertrophy, in all CsA-treated groups, corr elated with improved functional parameters, suggesting that at least i n one phase of CsA nephropathy compensatory responses preserve renal f unction.