THE INFLUENCE OF INDOMETHACIN ON NEONATAL RENAL FUNCTION

Abstract

Transient renal dysfunction has been observed in premature infants receiving indomethacin (indo) to inhibit prostaglandin (PG) synthesis and hence constrict their patent ductus arteriosus. The present study was designed to evaluate in 14 newborn lambs the influence of high (7.5 mg/kg) and low (0.2 mg/kg) doses of indo. on renal blood flow (RBF), glomerular filtration rate (GFR), and urine flow (V). The latter indices of renal function were studied by 1311-hippuran and 14C-inulin clearances in conscious, chronically instrumented lambs over a 24-hour period. Both indo. doses reduced RBF significantly at 4 hours (high 12.4 ± 1.2 (SE), low-12.8 ± 1.0 ml/kg/min) but only high-dose animals were significantly lower than the control group at 12 (8.2 ± 0.8, p < 0.025) and 24 hours (6.5 ± 0.9, p < 0.001). PGE levels, determined by radioimmunoassay, Correlated directly with alterations in RBF. GFR was unaltered in all groups. Urine flow was significantly lower than in the control group at 24 hrs. only in the high-dose indo. group (0.08 ± 0.2 vs 0.15 ± 0.1 cc/kg/min, p < 0.025). Filtration fraction rose significantly at 12 hrs. in both indo. groups. Thus, these data suggest that the renal dysfunction observed transiently in some human prematures may be dose-related and support the need to carefully monitor renal function in continued clinical applications of a pharmacological approach to constriction of the ductus arteriosus.