The pathogenesis of dysplastic kidney in a urinary tract obstruction in the female fetal lamb

Kitagawa, Hiroaki; Pringle, Kevin C.; Zuccolo, J; Stone, Peter; Nakada, Koonosuke; Kawaguchi, Fumio; Nakada, Masahiro; Wakisaka, Munechika; Furuta, Shigeyuki; Koike, Junki; Seki, Yasuji

doi:10.1016/s0022-3468(99)90643-7

Cited by 40 publications

(28 citation statements)

References 12 publications

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“…Anesthesia was maintained using nitrous oxide, oxygen and halothane, as previously described [8]. The surgical techniques used to create obstruction have previously been described [5,6].…”

Section: Methodsmentioning

confidence: 99%

“…We created a model of obstructive uropathy in the fetal lamb and then placed vesico-amniotic shunts to investigate bladder function after this type of intervention. We have shown that this approach results in marked hypertrophy of the bladder wall muscle with severe interstitial fibrosis [5][6][7]. We repeated our obstructive uropathy model in fetal lambs at 60 days gestation and biopsied the bladder wall at the time of shunting to determine the state of the bladder wall at that time and to attempt to define the optimal timing of prenatal treatment for obstructive uropathy in this model.…”

Section: Introductionmentioning

confidence: 99%

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Early bladder wall changes after creation of obstructive uropathy in the fetal lamb

Kitagawa

Pringle²,

Koike

et al. 2006

Pediatr Surg Int

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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.

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“…Anesthesia was maintained using nitrous oxide, oxygen and halothane, as previously described [8]. The surgical techniques used to create obstruction have previously been described [5,6].…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Early bladder wall changes after creation of obstructive uropathy in the fetal lamb

Kitagawa

Pringle²,

Koike

et al. 2006

Pediatr Surg Int

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“…The perioperative management, anesthetic techniques, and operative procedures have been reported previously. 1,7 Male lambs had their penile urethra and urachus ligated with fine SILASTIC tubing (Dow Corning, Midland, MI) of 0.012-inch (0.545 mm) diameter. Female lambs had their bladder neck and urachus ligated with the same materials.…”

Section: Methodsmentioning

confidence: 99%

“…Our previous experiments showed that obstruction of the ureter or urethra in the fetal lamb at 50 or 60 days' gestation produces a severely dysplastic kidney by term. [1][2][3] Many investigators have attempted to bypass the obstruction in utero to salvage the kidney. [4][5][6] Theoretically, bypassing the obstruction will preserve renal function.…”

mentioning

confidence: 99%

Optimal timing of prenatal treatment of obstructive uropathy in the fetal lamb

Kitagawa

Pringle²,

Koike

et al. 2003

Journal of Pediatric Surgery

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“…Kitagawa [8] ligated the urethra and urachus of fetal lambs at 60 and 90 days of gestation and found definite dysplastic changes in the former group, but none in the latter. Wen et al [9] created mild or severe partial UTO in 2-day-old rats.…”

Section: Discussionmentioning

confidence: 99%

Does Intervention in utero Preserve the Obstructed Kidneys of Fetal Lambs? A Radiological and Pathological Study

Sun

Wang²,

Deng³

et al. 2010

Fetal Diagn Ther

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Objective: Ureteropelvic junction obstruction is a common cause of end-stage pediatric nephropathy. Our aim was to investigate whether in utero decompression can influence its development. Methods: A silastic tube was tied around the superior segment of the left ureter to cause partial unilateral obstruction in 22 fetal lambs at 75–85 days of gestation. Three weeks later, tubes were removed in 10 of the fetuses. A single sham procedure was performed on 4 control fetuses. Intravenous pyelography (IVP) and pathological evaluations were conducted in obstructed, decompressed and control subjects. Results: IVP revealed damaged renal function in obstructed subjects. Macroscopically, obstructed kidneys were larger but weighed less and had thinned parenchyma. Microscopy revealed cortical cysts of various sizes and interstitial fibrosis. The number of glomeruli was markedly decreased. In contrast, decompressed kidneys were visualized during IVP, and pathological changes were greatly ameliorated. Conclusions: Relief of obstruction in utero seems to prevent or attenuate development of nephropathy in lambs. Clinical application of this procedure should proceed with caution until further data are obtained.

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The pathogenesis of dysplastic kidney in a urinary tract obstruction in the female fetal lamb

Cited by 40 publications

References 12 publications

Early bladder wall changes after creation of obstructive uropathy in the fetal lamb

Early bladder wall changes after creation of obstructive uropathy in the fetal lamb

Optimal timing of prenatal treatment of obstructive uropathy in the fetal lamb

Does Intervention in utero Preserve the Obstructed Kidneys of Fetal Lambs? A Radiological and Pathological Study

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