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Background: In our fetal lamb model of lower urinary tract obstruction, a pressure limited shunt preserves bladder function and renal development. This study investigates the effects on pulmonary histology., Methods: We created obstructive uropathy (OU) in 60-day gestation fetal lambs, ligating the urethra and urachus, and delivering them at term (130-145days). We compared pulmonary histology in 4 groups: group A, OU without shunt; group B, pressure limited shunt; group C, non-valved shunt. Shunts were inserted 3weeks post-obstruction. Group D were normal controls., Results: We compared 27 fetuses: 7 fetuses in group A, 4 fetuses in group B, 2 fetuses in group C, and 14 fetuses in group D. There was no significant difference in lung volume in any group. In group A, there were some areas of atelectasis and incomplete alveolar formation histologically. The alveoli in group A lambs lungs had a predominance of type II cells, whereas group B lambs lungs were lined by type I epithelial cells and were essentially indistinguishable from controls., Conclusions: This study suggests that using a pressure-limited vesico-amniotic shunt in OU may preserve the renal tract and the lungs., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: In our fetal lamb model of lower urinary tract obstruction, a valved shunt preserves bladder function. This study investigates the effects on renal histology., Methods: We created obstructive uropathy (OU) in 60-day gestation fetal lambs, ligating the urethra and urachus, and delivering them at term (130-145days). We compared renal histology in 4 groups: group A-OU without shunt, group B-low-pressure shunt (15-54mmH2O), group C-high-pressure shunt (95-150mmH2O). Shunts were inserted 3weeks post-obstruction. Group D were normal controls., Results: We delivered 32 fetuses from 23 ewes: 13 fetuses in group A (9 survived), 6 fetuses in group B (5 survived), 7 fetuses in group C (5 survived), and 6 fetuses in group D. Histologically, we found renal tubular distention, vacuolated degeneration of tubular epithelial cells in 7 lambs, and cyst formation in 4 lambs in group A. There was renal tubular distention in two lambs, and cyst formation in one lamb in both groups B and C, with vacuolated degeneration of tubular epithelial cells observed in all but 1 lamb in each group., Conclusions: V-A shunting prevents multicystic dysplastic kidney (MCDK). Some lambs have renal tubular distention and vacuolated degeneration of renal tubular epithelial cells., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Introduction: We have previously shown that a vesico-amniotic shunt (V-A shunt) produces fibrotic bladders with poor compliance in normal fetal lambs. We hypothesized that using a ventriculo-peritoneal shunt (V-P shunt) as a V-A shunt in normal bladders may preserve the filling/emptying cycle and normal bladder development., Materials and Methods: The V-A shunting in normal fetal lambs was performed at 74 days of gestation using a V-P shunt (group A) and a free-draining shunt tube (group B). Sham-operated lambs were used as controls (group C). They were all delivered at term (145 days), and the pressure-volume curve, bladder volume, and histologic features of the bladder wall were compared., Result: The mean bladder volume in group B (n = 5), 5 +/- 2.4 mL, was significantly smaller (P < .01) than that in group A (n = 6), 53 +/- 14 mL, and group C (n = 10), 57.3 +/- 12 mL. The bladder wall thickness in group A was 338 + 94.2 microm; group B, 741 +/- 128 microm; and group C, 374 +/- 120 microm. Group B bladders had very poor compliance with thick bladder wall (P < .01). Histologically, group B bladders showed prominent submucosal fibrotic change, but group A bladders were similar to controls., Conclusion: This study shows that a pressure-limited shunt tube for V-A shunting preserves the normal fetal bladder development.

Introduction: In utero shunting (vesico-amniotic shunt) of obstructive uropathy in fetal lambs produces a shrunken, noncompliant bladder. We hypothesized that using a ventriculo-peritoneal shunt for the vesico-amniotic shunt may preserve the filling/emptying cycle and thus normal bladder development., Materials and Methods: We created obstructive uropathy in 60-day gestation fetal lambs, ligating the urethra and urachus. Vesico-amniotic shunting was performed 21 days later using the valve end of a ventriculo-peritoneal shunt (valve shunt) or silastic tubing (nonvalve shunt). They were delivered at term (145 days), and the bladder volume was measured and compared to normal term fetuses. The lambs were sacrificed, and the kidneys and bladder removed for histology., Results: Twenty-seven lambs were shunted. Of 14 valve shunts, 8 were effective. Of 13 nonvalve shunts, 11 were effective. The mean bladder volume was 57 +/- 41 mL with a valve shunt and 8.8 +/- 4.7 mL with a nonvalve shunt (P < .05) (normal term lambs, 65 +/- 18 mL, n = 5). Histology of the shunted bladders showed increased fibrosis in the submucosal and muscle layers. This was less obvious in lambs with a valve shunt., Conclusion: A pressure controlled shunt for fetal obstructive uropathy improves bladder volume but does not prevent bladder wall fibrosis.

Vesico-amniotic shunting of obstructive uropathy in fetal lambs produced a thick-walled, poorly compliant bladder. We report the early histological changes in the obstructed bladder wall. We created an obstructive uropathy in fetal lambs at 60 days gestation by ligating the urethra and urachus. Vesicostomy or vesico-amniotic shunt tube insertion and biopsy of the bladder wall were performed 21 days later. The fetuses were delivered at term (145 days) and the kidneys and bladder sampled for histology. Colloidal iron (Col Fe), and alpha-smooth muscle actin (alpha-SMA) immunohistochemical stains were used for these samples. Seventeen fetuses were shunted with 15 biopsies taken at that time. Six (shunt failure or missed urachal ligation) were excluded. All biopsies taken at shunting had positive Col Fe and alpha-SMA. Term lambs had mild multicystic dysplastic kidney (MCDK) in five, severe MCDK in two, and hydronephrosis in four. All bladders had small volume and were severely fibrotic. Fetal shunt operations 3 weeks after the creation of obstructive uropathy provided partial preservation of renal histology but did not preserve normal bladder histology. We suggest that the high hyaluronic acid synthesis activity or hyperplasia of the myofibroblasts in the dilated fetal bladder wall at the time of shunting results in irreversible damage to the developing bladder muscle and fibrosis.

Purpose: The long-term outcome for children after antenatal intervention for obstructive uropathies is disappointing. We reported that renal dysplastic changes are well established 3 weeks after obstruction in a fetal lamb model. We used this model to explore renal development and bladder function after fetal intervention., Methods: We created an obstructive uropathy in fetal lambs at 60 days gestation by ligating the urethra and urachus. A vesicostomy (female) or urethrostomy (male) were performed 21 days later. The fetuses were killed at term (145 days) and bladder volume and compliance were measured. The urinary tract was processed for histologic examination., Results: Twenty two fetuses were shunted. Nine were miscarried or were still-born. Thirteen survived, and 11 had a successful shunt with a small bladder (8 +/- 5 mL) compared with controls (71 +/- 19 mL) (P < .05). Shunted bladders had poor compliance. Histologically, they had thickened submucosal connective tissue with hypertrophied muscle. Histology of the renal tissue demonstrated relatively well-preserved renal architecture with reduced nephron mass (oligonephronia) in 2 lambs and multicystic dysplastic change in 3. Six (55%) had normal nephrogenesis., Conclusions: In our model, shunt operations after obstructive uropathy fail to preserve bladder function. Shunting ameliorated the development of cystic dysplasia, but half of the lambs had oligonephronia or multicystic dysplastic kidney. These might develop renal failure later in life.

Purpose: It was still unclear how urinary tract obstruction alters normal nephrogenesis and leads to renal dysplasia. The authors created an obstructive uropathy model in fetal lambs and reviewed the pathology of the obstructed kidney to determine the optimal timing for decompression of the obstruction., Methods: Obstructive uropathy was created in fetal lambs at 60 days' gestation by ligating the urethra and urachus. They were delivered 20 to 31 days later by cesarian section. The kidneys were processed for histologic examination., Results: Thirty-four 60-day lambs were operated on. Dysplastic changes were noted in 25 fetuses, and 24 fetuses had cysts in the nephrogenic zone. The cystic components in multicystic dysplastic kidneys (MCDK) are mainly in the proximal tubules., Conclusions: In utero urinary tract obstruction causes reduction of numbers of functioning nephrons and produces cysts in the nephrogenic zone and in the deeper cortex. These cysts and dilated proximal tubules suppress new nephron formation. Twenty days after obstruction, there were early features of dysplasia, but the nephrogenic zones still were present. Early shunting may salvage renal function.