METHYLPREDNISOLONE RETARDS THE PROGRESSION OF INHERITED POLYCYSTIC KIDNEY-DISEASE IN RODENTS

Polycystic kidney disease in adult laboratory animals and humans is as sociated with enlarged kidneys and a progressive decline of renal func tion, resulting in death from uremia. Interstitial inflammation and fi brosis typically are observed in association with the development of r enal insufficiency. To determine whether amelioration of interstitial inflammation and fibrosis may diminish cyst expansion/kidney enlargeme nt and stabilize renal function, we administered methylprednisolone, a n anti-inflammatory drug with antifibrogenic effects, to mice and rats with hereditary polycystic kidney disease. The experiment was repeate d once for each species. Mice were studied both in America and in Japa n. Weanling male and female mice (DBA/FG pcy/pcy [cystic] and +/+ [nor mal], n = 87 and 20, respectively) and rats (Han:SPRD Cy/+ and +/+, n = 70 and 33, respectively) were administered methylprednisolone (1 to 2 mg/kg/d) in the drinking water for 100 days (mice) or 42 days (rats) . Control animals drank distilled water. In normal DBA +/+ mice, methy lprednisolone had no effect on serum urea nitrogen (SUN) levels, kidne y weight, or kidney/body weight. Untreated male and female mice develo ped cystic kidneys and azotemia to an equal extent. Methylprednisolone administered in America to mice with renal cystic disease decreased k idney weight, kidney/body weight, SUN levels, volume density of cysts, and severity of interstitial fibrosis. In Japan, methylprednisolone d ecreased kidney weight and SUN levels of animals with cystic disease, but the effect on kidney/body weight did not reach statistical signifi cance. In contrast to mice, male rats developed more severe renal cyst ic changes and were more azotemic than female rats. Methylprednisolone administered to male rats with cystic disease decreased SUN levels, k idney weight, kidney/body weight, volume density of cysts, and severit y of interstitial fibrosis. Methylprednisolone had no effect on kidney /body weight or SUN levels in female rats with renal cystic disease. I n normal Han:SPRD (+/+) rats of both sexes, kidney and body weight wer e decreased by methylprednisolone, but kidney/body weight and SUN leve ls were unchanged. On the basis of this study, we conclude that methyl prednisolone decreased the extent of renal enlargement, reduced renal interstitial fibrosis, and preserved kidney function in mice and rats with relatively severe forms of inherited polycystic kidney disease. ( C) 1995 by the National Kidney Foundation, Inc.