Abstract 1273 Poster Session I, Saturday, 5/1 (poster 57)

Background: Maternally administered indomethacin (IND) has been known to cause ductal constriction and right ventricular (RV) failure in the fetus, along with renal failure. RV failure induces a reduction in cardiac output and subsequent decrease in renal blood flow, which may cause renal dysfunction. However, there is no information about the effect of fetal ductal closure on fetal kidney. We therefore examined the effect of fetal ductal constriction on the morphological changes in fetal kidney.

Methods: IND (10mg/kg) was administered to pregnant rats either on the 18th (n = 20) or on the 20th day (n = 20) of pregnancy. All of the fetal rats were studied at 24 hours after administration. Cardiac chambers, renal artery, and ductal arteriosus were studied using the rapid whole-body freezing techniques. Renal histopathological study was also performed.

Results: In the fetal rats administered IND on the 18th day, the ductus arteriosus remained patent and fetal RV volume and wall thickness did not show significant differences from the normal control. However, in the fetal rats administered on the 20th, all of the ductus were closed and the mean fetal RV wall was significantly thicker (+35 %, p<0.001) and RV cavity was significantly smaller (+30 %, p<0.001) compared with those in the normal control. In contrast, in both IND groups, the kidney revealed corticomedullary necrosis characterized by the reduction in the number of glomeruli, the necrosis of proximal and distal tubules, and the expansion of interstitia without changes in the internal diameter of the renal arteries.

Conclusion: In the fetal rats with IND, the histopathological changes in the kidney may not have resulted from the ductal closure but may be caused by the direct effect of maternally administrated IND. This study also suggests that IND may induce renal dysfunction in earlier stage of pregnancy than causing ductal constriction.