Renal apoptosis parallels ceramide content after prolonged ureteral obstruction in the neonatal rat

Obstructive nephropathy, the primary cause of renal insufficiency in infant s, is characterized by progressive renal apoptosis. Ceramide is a sphingoli pid known to stimulate apoptosis in the kidney. We investigated the effects of unilateral ureteral obstruction (UUO) on endogenous renal ceramide cont ent and apoptosis in neonatal and adult rats. Animals were subjected to WO or sham operation on the first day of life and were studied 3-28 days later . Adult rats were similarly treated and then studied 3 or 14 days later. In additional neonatal rats, the obstruction was removed after 5 days, with s tudy at 14 or 28 days. Renal ceramide content was measured by diacylglycero l kinase assay, and apoptosis was determined by the terminal deoxynucleotid yl transferase dUTP nick-end-labeling technique. Renal ceramide content was 50-fold higher in the 3-day neonatal compared with the adult kidney and 10 -fold higher in the 7-day neonatal compared with the adult kidney, but ther e was no additional effect of WO on ceramide content at these ages. However , after 14 or 28 days UUO in the neonate, renal ceramide was elevated compa red with sham or intact opposite kidneys, and renal apoptosis was directly related to ceramide content (r = 0.99, P < 0.001). Moreover, renal ceramide was reduced by relief of obstruction (P < 0.05). There was less apoptosis in the obstructed kidney of the adult than the neonate, and UUO had no effe ct on ceramide content at 14 days in the adult. We conclude that prolonged UUO (at least 14 days duration) increases endogenous renal ceramide in the neonatal but not the adult rat. It is likely that this contributes to the p rolonged renal apoptotic response of the neonatal obstructed kidney.