Cyclooxygenase‐2 inhibition ameliorates early renal injury in Han:SPRD‐ cy rats with inherited kidney disease

Abstract

Selective cyclooxygenase-2 (COX-2) inhibition appears to be renoprotective in some models of kidney disease, but not in others. The objective of our study was to examine the effects of COX-2 inhibition in a rat model of chronic kidney disease. Four week old Han:SPRD-cy rats were given either a standard rodent diet containing 3mg/kg body weight NS-398 (a selective COX-2 inhibitor) or a control diet with no drug for 7 weeks. Morphometric and immunohistochemical analyses revealed that NS-398 fed animals had reduced renal fibrosis, macrophage infiltration, epithelial cell proliferation and oxidant injury, compared to control fed animals. COX-2 inhibition did not alter the degree of cystic change or creatinine clearance. Kidney disease was associated with higher renal COX-1 and -2 enzyme activities. Treatment with NS398 blunted this increase in enzyme activity only for COX-2 (as indicated by 26% lowerrenal prostaglandin E2 (PGE2), 29% lower 6-keto-prostaglandin F1α (6-keto-PGF1α) and 28% lower total prostanoid production). NS398 decreased urinary excretion of thromboxane B2, PGE2 and 6-keto-PGF1α. In conclusion, COX-2 inhibition reduces the elevated renal COX-2 activity, prostanoid production and attenuates renal injury in this rat model of chronic renal disease. (Supported by funding from the Natural Sciences and Engineering Research Council of Canada)