Jørgen Frøkiær

Aim:  Cisplatin induced acute renal failure has previously been associated with decreased urinary prostaglandin E2 excretion and reduced aquaporin 2 expression in kidney collecting duct. In this study we examined the expression of cyclooxygenase-1 and 2 as well as aquaporin 2 and the Na-K-2Cl cotransporter in kidneys from rats with cisplatin induced acute renal failure. Methods:  Rats were treated with either cisplatin or saline and followed for 5 days. Kidneys were dissected into 3 zones and prepared for immunoblotting, quantitative PCR and immunohistochemistry. Renal content and urinary prostaglandin E2 excretion was measured. Results:  Cisplatin treatment was associated with polyuria and a significant decreased creatinine clearence. Inner medullary prostaglandin E2 content and urinary prostaglandin E2 excretion was decreased in cisplatin treated rats. Quantitative polymerase chain reaction and semiquatitative immunoblotting demonstrated that cisplatin treatment reduced cyclooxygenase-2, aquaporin 2 and Na-K-2Cl cotransporter abundance in the different kidney zones, whereas no change in cyclooxygenase-1 was observed. Results were confirmed by immunohistochemistry. Conclusion:  Cyclooxygenase-2 expression is decreased in inner medulla and cortex. Consistent with this urinary prostaglandin E2 levels were reduced. These data suggest that downregulation of cyclooxygenase-2 is responsible for impaired de novo generation of vasodilatory prostaglandins which may play an important role for the cisplatin induced renal vasoconstriction and development of nephropathy.