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Background/purpose: We aimed to determine whether the profile of matrix metalloproteinase (MMP) activity in fetal urine correlates with the degree of kidney damage in the setting of congenital obstructive uropathy., Methods: Fetal lambs underwent either a sham operation or creation of a complete urinary tract obstruction. Necropsies were performed before term, when urinary MMP profiling was performed by zymography; and kidney damage was assessed histologically by multiple semiquantitative analyses and histomorphometric measurements., Results: There was a significant correlation between inner medullary thickness and MMP-9 (P = .005) and 63-kd MMP-2 (P = .019) activities. In like manner, the only MMPs associated with kidney fibrosis were MMP-9 and 63-kd MMP-2. Matrix metalloproteinase-9 activity was a highly significant independent predictor of the total combined kidney fibrosis score (P < .001) as well as of higher fibrosis grades in each of 6 kidney areas analyzed (all with P < .01). The activity of 63-kd MMP-2 correlated significantly with higher fibrosis in select areas., Conclusions: In a fetal ovine model, urinary MMP activity correlates with the degree of kidney damage. The presence of MMP-9 (in particular) and that of 63-kd MMP-2 are independent predictors of severity. Prenatal urinary MMP profiling may enhance patient stratification and counseling in the setting of congenital obstructive uropathy., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background/purpose: Flow of a fluid through a collapsible tube is under the influence of various factors including the external compressing pressure. Because the intraabdominal pressure may compress the ureter, an experimental study has been planned to determine and compare the normal intraabdominal and renal pelvic pressures and the alterations in renal pelvic pressure in response to the increments in intraabdominal pressure in the rabbits., Methods: Eight adult rabbits were used for the experiment. Under general anesthesia, an urethral catheter, a nasogastric tube, and an intraperitoneal catheter were placed to measure intravesical (IVP), intragastric (IGP), and intraabdominal pressures (IAP), respectively. Intracranial pressure monitorization catheter was placed into the renal pelvis to monitor intrapelvic pressure (IPP). Basal pressure measurements have been recorded. The pressures have been recorded in every 5 minutes, and IAP has been increased gradually about 3 to 4 cm of water pressure in every step for 30-minute periods., Results: Increases in the intrapelvic pressure values have been significantly higher than the increases in the IAP (P < .001). A significant correlation has been found between IPP and IAP (P = .000, r = 0.866). By using linear regression analysis the relationship has been found to be IPP = 7.303 + 1.985 (IAP). Intragastric pressure values have been higher compared with IAP values (P < .001), whereas intravesical pressures have not differed from IAP (P > .05)., Conclusions: Elevations in IAP results in augmented increases in the IPP. Poiseuille and Laplace Laws suggest this augmented increase to resemble proximal ureteric obstruction. Increases in IAP may simulate proximal ureteric obstruction and may take part in the pathogenesis of hydronephrosis. J Pediatr Surg 36:901-904., (Copyright 2001 by W.B. Saunders Company.)

Background: If creating an obstructive uropathy early in glomerulogenesis produces MCDK (Multicystic Dysplastic Kidney), then a very early obstruction may produce Potter's Syndrome (PS) with oligohydramnios., Methods: Fetal lambs at 50 days' gestation underwent urethral and urachal ligation using fine SILASTIC (Dow Corning, Midland, MI) tubing and were delivered by cesarean section at 145 days' gestation. At the time of death, kidney weight, length, and lung volumes were measured. These samples were examined histologically. Urinary sodium, chloride, potassium, and osmolarity also were measured. These were compared with normal-term fetuses., Results: One ewe miscarried. Two of 3 of 50-day obstructive uropathy lambs survived. The 2 survivors had dysplastic kidneys. One with large gastroschisis did not have PS but the other had renal, pulmonary, and chest wall hypoplasia. Both male lambs had undescended testes with a large bladder. Kidney weights were 2 g in the PS lamb and 16 g in controls. Lung volume was 84 mL in the PS lamb and 340 mL in controls. The lamb's face was compressed and the fetus was hydropic. Urine sodium, potassium, and osmolarity levels were higher than that of controls., Conclusions: This is the first successful model ligating the penile urethra and urachus in a 50-day lamb. The authors' previous 60-day model did not have PS, but an earlier obstructive uropathy caused MCDK with PS.

Is the renal dysplasia (RD) commonly seen in babies with urinary tract obstruction a developmental consequence of the obstruction or is it an associated embryologic malformation? We produced complete unilateral ureteral obstruction in six 58- to 66-day old lamb fetuses by clipping a silastic ring on the ureter. Three fetuses survived to term. All obstructed kidneys were not only grossly hydronephrotic but dysplastic by histologic criteria; ie, parenchymal disorganization, primitive epithelial structures, and marked fibrosis. The contralateral unobstructed control kidneys were normal. The changes were similar to those seen in the human neonate with obstruction and RD, suggesting that in this model RD was caused by obstruction to the flow of urine early in fetal development.