In utero treatment of urinary tract obstruction is technically feasible and intellectually appealing yet, largely unproven. The long-term objective of this proposal is to study the effects of early partial lower urinary tract obstruction on the kidney. Specifically, this project will measure the endocrine, hemodynamic and functional changes of the fetal kidney in response to partial bladder outlet obstruction and its release in utero. Using a fetal sheep preparation, the fetal urethra will be ligated and the urachus catheterized at 115 days' gestation (term=145 days). By means of a large connector outside the mother, the fetal urine will be drained via the urachal catheter into the amniotic cavity. On the third postoperative day a standardized partial obstruction will be created by using a narrow connector to replace the large one. Obstruction will be continued for either 13 (128 days' gestation) or 23 (138 days' gestation) days and will be released in utero by removing the narrow connector and reconnecting the urachal and amniotic catheters with a large connector. Plasma renin activity, cortisol, catecholamines, renal blood flow, glomerular filtration rate and tubular reabsorption of sodium will be monitored before, during and after obstruction. The endocrine and hemodynamic changes of short-term (first three days) and long-term (after 12 days) obstruction will be compared with controls; the renal function changes will be analyzed as a percentage of controls and the results compared for short (13 days) and long (23 days) periods of obstruction. The renal function changes during recovery from obstruction for 7 vs. 17 days before birth will also be compared. The results will further our understanding of the pathophysiology of prenatal urinary obstruction and will direct further investigation into the management of this
| Bogaert, G A; Kogan, B A; Mevorach, R A et al. (1996) Exogenous endothelin-1 causes renal vasodilation in the fetal lamb. J Urol 156:847-53 |
| Bogaert, G A; Gluckman, G R; Mevorach, R A et al. (1995) Renal preservation despite 35 days of partial bladder obstruction in the fetal lamb. J Urol 154:694-9 |
| Bogaert, G A; Mevorach, R A; Kogan, B A (1994) Renal hemodynamic and functional effects of 10 days' partial urinary obstruction in the fetal lamb. J Urol 152:220-5 |
| Mevorach, R A; Bogaert, G A; Kogan, B A (1994) Role of nitric oxide in fetal lower urinary tract function. J Urol 152:510-4 |
| Bogaert, G A; Kogan, B A; Mevorach, R A (1993) Effects of endothelium-derived nitric oxide on renal hemodynamics and function in the sheep fetus. Pediatr Res 34:755-61 |
| Kim, K M; Kogan, B A; Massad, C A (1992) Acute hemodynamic and endocrinological effects of partial fetal bladder obstruction. J Urol 148:497-502 |
