Factors influencing the development of Multicystic Dysplastic Kidney (MCDK) following urinary tract obstruction in the fetal lamb.

BACKGROUND: Creating obstructive uropathy (OU) during glomerulogenesis in the fetal lamb results in multicystic dysplastic kidney (MCDK) at term. We explored this using immunohistochemical techniques. METHOD: OU was created in fetal lambs at 60-day gestation, ligating the urethra and urachus. The kidneys of MCDK lambs, 60-day gestation fetal lambs, full-term lamb (145 days), term sham-operated lambs, and adult ewes were evaluated by HE staining, and immunohistochemistry with paired box genes 2 (PAX2) and CD10. RESULTS: Multiple cysts were found in the MCDK model. CD10 was expressed in proximal tubular epithelial cells, glomerular epithelial cells, and medullary stromal cells in the kidneys of 60-day gestation fetal lambs and full-term lambs and adult ewes. PAX2 expression was found in ureteric buds, C- and S-shaped bodies, epithelial cells of collecting ducts, and Bowman's capsule of fetal kidneys at 60-day gestation, but only in the collecting ducts of full-term fetal lambs and adult ewes. Both CD10 and PAX2 were expressed in the cystic epithelial cells of the MCDK model. DISCUSSION: PAX2 expression in cystic epithelial cells suggests that cyst formation is associated with disturbed down-regulation of PAX2 in the nephrogenic zone epithelial cells during the renal development in the OU model.

Cryopreservation of paediatric ovarian tissue with an updated version of the Edinburgh criteria for appropriate patient selection.

RESEARCH QUESTION: Are the revised patient selection criteria for fertility preservation of children and adolescents appropriate? DESIGN: A retrospective and prospective observational cohort study implemented at a university hospital approved for fertility preservation by an academic society. The characteristics of children and the process of fertility preservation consultation were investigated. Mortality, the longitudinal course of the endocrine profile and the menstrual cycle were confirmed in patients who underwent ovarian tissue cryopreservation (OTC) before the age of 18 years. RESULTS: Of the 74 children and adolescents referred for a fertility preservation consultation, 40 (54.1%) had haematological disease, which included patients with rare diseases. The mean age of patients was 11.1 ± 4.3 years (median 12 years, range 1-17 years). In accordance with the revised criteria, 31 (41.9%) patients had their ovarian tissue cryopreserved. Two out of 31 had complications after surgery (infection and drug allergy) and one patient with leukaemia (3.2%) had minimum residual disease on the extracted ovarian tissue. Of the 14 patients (>12 years) who completed treatment, 12 (85.7%) had primary ovarian insufficiency (POI) more than a year after treatment. Two out of 31 (6.5%) died because of recurrence of their underlying disease (median 28 months, range 0-60 months). Oocyte cryopreservation, as an additional and salvage fertility preservation treatment, was suggested to five patients with biochemical status POI (procedures pending). CONCLUSION: The primary disease and patients' ages varied in fertility preservation for children and adolescents. Our patient selection criteria might be appropriate over a short follow-up period.

Survey of understanding and awareness of fertility preservation in pediatric patients: Is conversation about fertility preservation unpleasant for pediatric patients?

Objective: To verify understanding and awareness of fertility preservation (FP) in pediatric patients undergoing FP treatments. Methods: A questionnaire survey was conducted before and after explanation of fertility issues and FP treatments for patients 6-17 years old who visited or were hospitalized for the purpose of ovarian tissue cryopreservation (OTC) or oocyte cryopreservation (OC), or sperm cryopreservation between October 2018 and April 2022. This study was approved by the institutional review board at St. Marianna University School of Medicine (No. 4123, UMIN000046125). Result: Participants in the study comprised 36 children (34 girls, 2 boys). Overall mean age was 13.3 ± 3.0 years. The underlying diseases were diverse, with leukemia in 14 patients (38.9%), brain tumor in 4 patients (11.1%). The questionnaire survey before the explanation showed that 19 patients (52.8%) wanted to have children in the future, but 15 (41.7%) were unsure of future wishes to raise children. And most children expressed some degree of understanding of the treatment being planned for the underlying disease (34, 94.4%). Similarly, most children understood that the treatment would affect their fertility (33, 91.7%). When asked if they would like to hear a story about how to become a mother or father after FP which including information of FP, half answered "Don't mind" (18, 50.0%). After being provided with information about FP treatment, all participants answered that they understood the adverse effects on fertility of treatments for the underlying disease. Regarding FP treatment, 32 children (88.9%) expressed understanding for FP and 26 (72.2%) wished to receive FP. "Fear" and "Pain" and "Costs" were frequently cited as concerns about FP. Following explanations, 33 children (91.7%) answered "Happy I heard the story" and no children answered, "Wish I hadn't heard the story". Finally, 28 of the 34 girls (82.4%) underwent OTC and one girl underwent OC. Discussion: The fact that all patients responded positively to the explanations of FP treatment is very informative. This is considered largely attributable to the patients themselves being involved in the decision-making process for FP. Conclusions: Explanations of FP for children appear valid if age-appropriate explanations are provided.

The triangular cord ratio and the presence of a cystic lesion in the triangular cord. Suggested new ultrasound findings in the early diagnosis of Biliary Atresia.

BACKGROUND: In biliary atresia (BA), the ultrasonic triangular cord (TC) sign is positive at ≥ 3 mm, but sometimes there is BA even if it is ≤ 3 mm. For improving the ultrasonographic diagnosis, we have established a new evaluation, adding the ratio of the anterior/posterior thickness (TC ratio) in the hyperechoic area and the presence of a cystic lesion in the triangular cord (TCC). METHODS: We examined 24 cases of suspected BA who demonstrated acholic stools from 2006 to 2020. We retrospectively reviewed the timing of ultrasonographic diagnosis, the gallbladder diameter, gallbladder mucosal irregularity, the TC sign, TCC, and the TC ratio. RESULTS: In the BA group (n = 10) vs the Non-BA group (n = 14), the age at ultrasonography was 75 ± 41.7 vs. 81 ± 39.1 days (p = 0.72), the gallbladder diameter was 12.1 ± 9.7 vs. 24.2 ± 6.96 mm (p = 0.02), irregularity of gallbladder mucosa was 7 cases vs. 1 case (p < 0.01), and TC sign was 3.9 ± 1.3 vs. 2.0 ± 0.49 mm (p = 0.01), respectively. TCC was observed in 8/10 cases in the BA group and none in the Non-BA group (p < 0.01). TC ratio was 3.40 ± 0.68 (BA group) and 1.59 ± 0.41 (Non-BA group) (p < 0.01). CONCLUSION: The ultrasonic TC ratio improves the diagnostic accuracy of BA. TCC is a specific finding in the BA group.

Muscle imbalance as a cause of scoliosis: a study in a fetal lamb abdominal wall defect model.

BACKGROUND: We created abdominal wall defects (AWD) in fetal lambs to investigate possible causes of scoliosis. METHODS: We incised the upper abdominal wall (including Rectus) in 60-day gestation fetal lambs, from the midline to either the right (Group A) or left (Group B) costal margin, in 14 lambs carried by 7 ewes. They were delivered by cesarean section at term (about 145 days). Scoliosis was evaluated by anterio-posterior X-rays, determining the Cobb angle. RESULTS: Four fetuses in Group A and 3 in Group B survived. There were 3 successful AWD lambs Group A and 2 in Group B. One lamb in each group survived with the AWD covered with a thick capsule. The convexity of spinal curve was the direction of scoliosis. Right scoliosis was only seen in the 4 Group A lambs. Left scoliosis was only seen in Group B lambs (2/3, 67%). The mean Cobb angle was 41.7 ± 11.5° in Group A and in Group B the Cobb angles were 59.6o and 60.6°. Overall, 4/5 lambs with organ prolapse (80%) and both lambs without organ prolapse had scoliosis. CONCLUSION: Muscle imbalance may contribute to the development of scoliosis in a fetal lamb AWD model.

The Expression of Transcription Factors in Fetal Lamb Kidney.

(1) Background: Renal development involves frequent expression and loss of transcription factors, resulting in the activation of genes. Wilms' tumor 1 (WT1), hepatocyte nuclear factor-1-beta (HNF1ß), and paired box genes 2 and 8 (Pax2 and Pax8) play an important role in renal development. With this in vivo study, we examined the period and location of expression of these factors in renal development. (2) Methods: Fetal lamb kidneys (50 days from gestation to term) and adult ewe kidneys were evaluated by hematoxylin and eosin staining. Serial sections were subjected to immunohistochemistry for WT1, HNF1ß, Pax2, and Pax8. (3) Results: Pax2, Pax8, and HNF1ß expression was observed in the ureteric bud and collecting duct epithelial cells. We observed expression of WT1 alone in metanephric mesenchymal cells, glomerular epithelial cells, and interstitial cells in the medullary rays and Pax8 and HNF1ß expression in tubular epithelial cells. WT1 was highly expressed in cells more proximal to the medulla in renal vesicles and in C- and S-shaped bodies. Pax2 was expressed in the middle and peripheral regions, and HNF1ß in cells in the region in the middle of these. (4) Conclusions: WT1 is involved in nephron development. Pax2, Pax8, and HNF1ß are involved in nephron maturation and the formation of peripheral collecting ducts from the Wolffian duct.

Surgical management of unilateral oophorectomy for ovarian tissue cryopreservation in high-risk children and adolescents with varied backgrounds.

PURPOSE: Fertility preservation (FP) for children is still challenging due to an information gap. In particular, there is little information about the surgical aspects of ovarian tissue cryopreservation (OTC) for children. In the present study, the appropriateness of preoperative management and the criteria of our cases were investigated with the aim of establishing a safe OTC procedure. METHODS: A total of 25 girls who underwent OTC from November 2015 through May 2020 were retrospectively analyzed with IRB approval. RESULTS: The median age of the patients was 13 (1-17) years. The medical indications were varied (e.g., leukemia, lymphoma, brain tumor), and included rare diseases. Seventeen cases (68%) underwent OTC during chemotherapy or radiotherapy, and 21 (84%) had comorbidities. All cases underwent ovarian tissue retrieval (OTR) with laparoscopy, and the median operating time was 64 (36-97) min, with little bleeding. Although two had complications, all patients started treatment on schedule. The median WBC and CRP increases a day after OTR were 0 (- 4400 to + 5200)/µl and 0.21 (- 0.2 to 0.87) mg/dl, respectively, with no complications. CONCLUSION: As long as the preoperative criteria are met, OTC could be possible even for children with a severe blood condition. In such cases, the degrees of the WBC and CRP elevations are useful to assess surgical infection.

Therapeutic effectiveness of costal cartilage grafting into both anterior and posterior walls for laryngotracheal reconstruction in acquired subglottic stenosis.

BACKGROUND: We have reviewed the surgical procedures performed and outcomes for low-birth-weight infants with acquired subglottic stenosis. METHODS: The gestational age at birth, birth weight, age at Laryngotracheal reconstruction, and therapeutic outcome over the past 26 years were reviewed. Laryngotracheal reconstruction was initially performed by costochondral grafting involving only the anterior wall for the first operation, but since 2010 a costal cartilage was also inserted into the posterior wall of the cricoid cartilage using the BENSON pylorus spreader to split the cartilage. RESULTS: There were 21 patients. The mean gestational age was 29.6 weeks, the mean birth weight was 1127 g, and the first surgery was performed at a mean age of 37.0 ± 21.8 months. Extubation was possible in 11 of 21 patients (52.3%) after the first surgery and in 7 of 7 patients after re-operation. The total extubation rate reached 100% (18/18) excluding three patients (one who suffered sudden death, and two who were lost to follow-up). CONCLUSION: Sufficient dilatation of the subglottic space could not be achieved by costochondral grafting involving the anterior wall alone. The extubation rate was improved by dilatation of the posterior wall and the insertion of costal cartilage into both the anterior and posterior walls.

Differences in post-operative complications after reconstruction for congenital biliary dilatation in a single institution-Roux-en-Y hepaticojejunostomy versus hepaticoduodenostomy.

BACKGROUND: The standard surgical procedure for congenital biliary dilatation (CBD) consists of excision of extrahepatic bile duct and Roux-en-Y hepaticojejunostomy (HJ). However, alternative reconstructive operations for CBD includes hepaticoduodenostomy (HD). We compared postoperative complications and therapeutic outcomes of these two operations at our institution. METHODS: From 1981 to 2009, there were 23 traceable patients who underwent operation for CBD, They were divided into an HJ Group (n = 15) and an HD Group (n = 8). Demographic and outcome data were compared. RESULTS: There were no significant differences in postoperative complications (cholangitis, pancreatitis, and anastomotic stenosis) and current blood test data (AST, ALT, Total Bilirubin, Direct Bilirubin, Amylase) between the two groups. Current abdominal pain and carcinogenesis were not observed in either group. Intrahepatic stones occurred in one patient in each group, both > 25 years post-operation. CONCLUSION: HD is considered to be an acceptable reconstruction method compared to HJ, based on our results. There has been a suggestion that inadequate diversion in HD might increase the risk of cholangiocarcinoma. To date, in this series, that has not happened.

Risk factors influencing ascending testis after laparoscopic percutaneous extraperitoneal closure for pediatric inguinal hernia and hydrocele.

BACKGROUND: We investigated the risk factors influencing ascending testis following laparoscopic percutaneous extraperitoneal closure (LPEC) for inguinal hernia or hydrocele. METHODS: Boys undergoing LPEC between 2014 and 2018 had their medical records and operative movies reviewed. Group A patients required orchiopexy after LPEC. Group B patients did not. Their baseline characteristics were reviewed. The path of the LPEC needle (not crossing the spermatic duct at first circuit [Not Crossing]), whether the second entry of the LPEC needle was different from the first hole (Different Hole), peritoneal injury requiring re-ligation (Re-ligation), and hematoma (Hematoma) were evaluated. The quantitative factors of significant difference were set as a cut-off value. RESULTS: There were 5 patients (7 sides) in Group A and 162 patients (237 sides) in Group B. Birth weight was lower in Group A (p = 0.035). Not Crossing was 7 sides (100%) in Group A and 97 sides (41%) in Group B (p = 0.002). Hematoma was 2 sides (29%) in Group A and 11 sides (5%) in Group B (p = 0.047). Cut-off value of birth weight was 932 g (AUC 0.78). CONCLUSION: Birth weight < 932 g and operative findings (not crossing over the spermatic duct on the first circuit and hematoma) indicated an increased risk of ascending testis after LPEC.

The vacuum treatment for the pectus excavatum thickened subcutaneous fat of the chest wall and is effective in preteenagers.

PURPOSE: We report effects of treatment for pectus excavatum (PE) with a Vacuum Bell (VB). MATERIALS AND METHODS: Fifteen patients (13 males and 2 females) undergoing VB therapy over 6 years, aged 6-17 years (mean: 11.1 years), were divided into two Groups: Group 1 (G1), preteenagers (< 13 years); Group 2 (G2), teenagers (≧ 13 years). We retrospectively recorded changes in depth of depression and the Haller index. RESULTS: The depth of depression reduced in 93.3% of 15 patients (mean; 8.7 mm). Minimal change occurred in the Haller index but the subcutaneous fat thickened significantly (11/15 patients). The improvement rate on elevation of the chest wall was better in G1 than G2 (G1: 54.0% vs G2: 51.3%). CONCLUSION: The maximum depth of depression improved in PE patients as a result of thickening of subcutaneous fat. VB is most effective in preteenagers with PE.

A new approach using image analysis to assess pulmonary hypoplasia in the fetal lamb diaphragmatic hernia model.

BACKGROUND: In congenital diaphragmatic hernia (CDH), there is pulmonary hypoplasia (PH) and also pulmonary vascular and bronchial abnormalities. Few studies have investigated bronchial maldevelopment in CDH. We evaluated bronchial area (BA) by bronchography in a fetal lamb DH model to develop a measure of PH. METHODS: We created DH in fetal lambs at 75 days gestation, delivering by cesarean section and killing them at term (DH, n = 12). Normal term fetuses provided controls (C, n = 5). We measured total lung volume (TLV) and performed barium bronchography. Using image analysis, BA, total lung area (TLA) and bronchial area/lung area ratio (B/L ratio) were calculated. Student's T test (p < 0.05; significant) and Spearman's correlation coefficient were performed. RESULTS: TLV (ml) was 133.3 ± 41.2 in DH and 326 ± 22.5 in C (p = 0.0000001). TLA (cm2) was 78.8 ± 17.4 in DH and 107.1 ± 10.3 in C (p = 0.006). BA (cm2) was 39.6 ± 11.9 in DH and 52.2 ± 7.7 in C (p = 0.019). The B/L ratio was 0.45 ± 0.06 in DH and 0.49 ± 0.05 in C (p = 0.28). There are correlations in DH between TLV and TLA (r = 0.79), TLV and BA (r = 0.73) and in C between TLV and TLA (r = 0.97) and TLV and BA (r = 0.67). CONCLUSION: It may be possible to assess PH on fetal MRI, given the correlation between TLV and TLA, and TLV and BA.

The role of the ureteric bud in the development of the ovine fetal kidney.

BACKGROUND: The kidney develops from an intimate interaction between the ureteric bud and the metanephric mass. We attempted to differentially stain the derivatives of the ureteric bud and the metanephric mass in ovine fetuses. METHODS: After appropriate approval, 47 fetal lambs' kidneys at 50 (4), 60 (6), 70 (5), 80 (4), 100 (10), 110 (8), 145 (10) days' gestation (term is 140-145 days) were obtained. After confirming the pregnancy, the sheep were anesthetized, and the fetuses sacrificed. The fetal kidneys were prepared for histological examination, using immunostaining for ß-catenin, Laminin, CK34ßE12, CK7, E-cadherin, and EMA. RESULTS: In the nephrogenic zone, positive staining was only seen for ß-catenin and Laminin. Areas with linear ß-catenin expression increased with increasing gestational age, whereas cytoplasmic granular expression in the nephrogenic zone diminished. At 50 days, Laminin-positive cells appeared in the ureteric bud epithelial cells, but not in the proximal tubule epithelium. They were found only in the immature collecting duct at 60 days. CONCLUSION: We have shown that the distribution of ß-catenin and Laminin positive-stained cells initially appearing in the ureteric bud changes with gestational age. Further studies may help inform the optimal timing of fetal shunt insertion in obstructive uropathy.

Evaluation of alveolar epithelial cells in the sheep model of congenital diaphragmatic hernia: Type 1 alveolar epithelial cells and histopathological image analysis.

BACKGROUND: There are few reports comparing type 1 alveolar epithelial cell development with histopathological image analysis. We investigated these as indicators of maturity in fetal lambs' lungs in a congenital diaphragmatic hernia (CDH) model. METHODS: We created left CDH in 4 fetal lambs at 75 or 76days' gestation (Group A). Controls were 5 sham-operated lambs (Group B); both groups delivered at term. The right lower lung lobe (RLL) and left lower lobe (LLL) were sampled. Using histopathological image analysis, alveoli/air sacs count (AC), alveoli/air sacs area percentage (AP), average area (AA), total area (TA), and perimeter (PM) were determined. We also evaluated total lung volumes, radial alveolar count (RAC), and Type 1 alveolar epithelial cells ratio (AT1 ratio), which we previously reported. Regression analysis was performed, with p<0.05 considered significant. RESULTS: RLL and LLL AT1 ratio and LLL RAC in Group A were lower than in Group B. There are no significant differences demonstrated by histopathological image analysis. In Group A, the AT1 ratio in the LLL was lower than in the RLL. There were no differences between LLL and RLL in Group B. CONCLUSION: AT1 ratio was superior to the other indicators evaluating lung maturity.

Does a large abdominal wall defect affect lung growth?

BACKGROUND/PURPOSE: Respiratory distress in babies with large abdominal wall defects suggests a relationship to decreased diaphragmatic movement. We evaluated pulmonary development in a fetal lamb gastroschisis model. METHODS: We created gastroschisis in 25 fetal lambs at 60days gestation (group A). Controls were 14 nonoperated lambs. (Group B) were all delivered at term. Lung volume, histology, and type 1 (AT1)/type 2 (AT2) cell ratios (AT1 ratio) were determined. We subdivided group A, comparing lambs with a large defect and scoliosis [group A (S)] with the remainder [group A (NS)]. RESULTS: Twenty-five lambs survived (11 fetuses in group A and 14 fetuses in group B). Lung volume in group A (S) was less than in group A (NS) (p<0.05). The AT1 ratio in group A was lower than in group B (p<0.01), without any difference in radial alveolar counts (RACs) or alveolar growth, and no association between scoliosis and alveolar differentiation. CONCLUSION: Gastroschisis in a sheep model reduces the AT1 ratio but not the RAC. Severe scoliosis affects lung volume but not the AT1 ratio, suggesting reduced diaphragmatic movement in fetuses with large abdominal defects.

Relation between amount of bile ducts in portal canal and outcomes in biliary atresia.

BACKGROUND: There is no good prognostic indicator for biliary atresia (BA). We reviewed liver biopsies taken during the initial procedure to find a prognostic marker. METHODS: Thirty-two BA cases underwent Kasai operation from 1976 to 2009. We compared two groups at 1, 3, and 9 years. Group A required liver transplantation or died. Group B survived with their native liver. Biopsies were analyzed for liver fibrosis, portal-central vein bridging (P-C bridging), ductal plate malformation (DPM) and the number of the bile ducts in portal canal/measured surface area of the portal canal (BDP ratio). Statistical comparisons of the multiple data were evaluated by Mann-Whitney U test, Student's t test and Pearson's Chi-square test. Regression analysis with P < 0.05 was considered significant. RESULTS: BDP ratios (/mm(2)) were 2.4 ± 1.5 in Group A1 (n = 9) vs 4.6 ± 2.4 in Group B1 (n = 23) (P = 0.01); 2.6 ± 1.4 in Group A3 (n = 14) vs 5.1 ± 2.5 in Group B3 (n = 18) (P < 0.01), 3.0 ± 2.2 in Group A9 (n = 15) vs 4.9 ± 2.5 in Group B9 (n = 15) (P < 0.05). There was no significant difference in any other finding. CONCLUSION: The BDP ratio is a sound prognostic indicator in BA.

Pressure limited vesico-amniotic shunt allows normal lung growth in a fetal lamb model of obstructive uropathy.

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.

Are there reliable indicators predicting post-operative complications in acute appendicitis?

PURPOSE: To clarify the predictors of post-operative complications of pediatric acute appendicitis. METHODS: The medical records of 485 patients with acute appendicitis operated on between January 2006 and November 2014 were retrospectively reviewed. Age, sex, preoperative WBC, CRP, and appendix maximum short diameter on diagnostic imaging (AMSD) were compared retrospectively with the complications group (Group C) vs the non-complication group (Group NC) by Student's T test, Fisher exact test and Multivariate analysis. Regression analysis with p less than 0.01 was considered significant. We analyzed the most recent 314 laparoscopic appendectomy patients similarly. RESULTS: Complications were found in 29 of the 485 appendectomies (6.0%). Comparing Group C to Group NC, preoperative WBC (×10(3)/µl) 16.4 ± 5.6 vs 14.1 ± 4.1 (p < 0.01), CRP (mg/dl) 8.3 ± 7.1 vs 3.3 ± 4.6 (p < 0.01), AMSD (mm) was 12.1 ± 3.7 vs 9.9 ± 2.8 (p < 0.01). The CRP was significantly different by Multivariate analysis, but the WBC and AMSD wasn't. The results following laparoscopic appendicectomy data were identical. CONCLUSION: Preoperative WBC, CPR and AMSD all indicated an increased risk of complications. If WBC (/µl) >16,500, CRP >3.1 mg/dl and AMSD >11.4 mm, complications increased sixfold.

Can a pressure-limited V-A shunt for obstructive uropathy really protect the kidney?

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.