Methylprednisolone retards the progression of inherited polycystic kidney disease in rodents.
Polycystic kidney disease in adult laboratory animals and humans is associated with enlarged kidneys and a progressive decline of renal function, resulting in death from uremia. Interstitial inflammation and fibrosis typically are observed in association with the development of renal insufficiency. To determine whether amelioration of interstitial inflammation and fibrosis may diminish cyst expansion/kidney enlargement and stabilize renal function, we administered methylprednisolone, an anti-inflammatory drug with antifibrogenic effects, to mice and rats with hereditary polycystic kidney disease. The experiment was repeated once for each species. Mice were studied both in America and in Japan. Weanling male and female mice (DBA/FG pcy/pcy [cystic] and +/+ [normal], 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, methylprednisolone had no effect on serum urea nitrogen (SUN) levels, kidney weight, or kidney/body weight. Untreated male and female mice developed cystic kidneys and azotemia to an equal extent. Methylprednisolone administered in America to mice with renal cystic disease decreased kidney weight, kidney/body weight, SUN levels, volume density of cysts, and severity of interstitial fibrosis. In Japan, methylprednisolone decreased kidney weight and SUN levels of animals with cystic disease, but the effect on kidney/body weight did not reach statistical significance. In contrast to mice, male rats developed more severe renal cystic changes and were more azotemic than female rats. Methylprednisolone administered to male rats with cystic disease decreased SUN levels, kidney weight, kidney/body weight, volume density of cysts, and severity of interstitial fibrosis. Methylprednisolone had no effect on kidney/body weight or SUN levels in female rats with renal cystic disease. In normal Han:SPRD (+/+) rats of both sexes, kidney and body weight were decreased by methylprednisolone, but kidney/body weight and SUN levels were unchanged. On the basis of this study, we conclude that methylprednisolone 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.
Gattone
V H
VH
Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City 66160-7400.
Cowley
B D
BD
Barash
B D
BD
Nagao
S
S
Takahashi
H
H
Yamaguchi
T
T
Grantham
J J
JJ
D000818:Animals; D001806:Blood Urea Nitrogen; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use*; D051379:Mice; D008811:Mice, Inbred DBA; D009393:Nephritis / Q000188:drug therapy; D009929:Organ Size / Q000187:drug effects; D007690:Polycystic Kidney Diseases / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D014511:Uremia / Q000209:etiology
D008775:Methylprednisolone