Cyclooxygenase-2 up-regulation in reflux nephropathy

Purpose: Reflux nephropathy (RN) is a major cause of end stage renal failure in children and hypertension is a frequent complication. Cyclooxygenase-2 (COX-2) is an enzyme responsible for the prostaglandin synthesis. It has been shown that COX-2 up-regulates renin production leading to renovascular hypertension. We investigate COX-2 expression in the kidneys of children with RN. Materials and Methods: Kidney specimens from 12 patients 2 to 13 years old with severe RN secondary to primary high grade vesicoureteral reflux obtained at the time of nephrectomy and 5 controls were examined. Single labeled imimmohistochemistry was performed with 2 COX-2 antibodies using light and confocal microscopy. Quantification of COX-2 was determined by Western blotting analysis. COX-2 gene expression was evaluated by real-time quantitative reverse transcription polymerase chain reaction. Results: There was a strong COX-2 immunoreactivity in the proximal tubules and tubulointerstitial space in the RN samples compared to controls. Immunoreactive COX-2 protein expression was markedly increased in RN samples compared to controls. Real-time reverse transcription polymerase chain reaction showed a significant increase in COX-2 mRNA expression in the RN samples compared to controls (p <0.05). Conclusions: Over expression of COX-2 in reflux nephropathy suggests that COX-2 may be involved in the pathogenesis of tubulointerstitial damage associated with severe reflux nephropathy.