Recovery after relief of fetal urinary obstruction: morphological, functional and molecular aspects

Edouga, Didier; Hugueny, Brigitte; Gasser, Bernard; Bussières, Laurence; Laborde, Kathleen

doi:10.1152/ajprenal.2001.281.1.f26

Cited by 40 publications

(29 citation statements)

References 34 publications

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“…Relief of the obstruction could partially reverse PAX2 expression. Consistent with our finding, Edouga et al found that the shunting procedure could reverse the expression of PAX2 completely in the obstructed bladder outlet of kidneys from sheep fetuses (13). Nevertheless, there were differences between our results and theirs.…”

Section: Discussionsupporting

confidence: 88%

Does Intervention in Utero Preserve the Obstructed Kidneys of Fetal Lambs? A Histological, Cytological, and Molecular Study

et al. 2009

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Ureteropelvic junction obstruction is a common cause of end-stage nephropathy in children. Our aim was to investigate whether relief of obstruction in utero can alleviate the development of nephropathy. A silastic tube was tied around the left superior segment ureter to induce unilateral partial ureteral obstruction in 22 fetal sheep at 75-85 d of gestation. Three weeks later, the tubes were removed to relieve the obstruction in 10 of the 22 lambs. A sham operation was performed on four fetuses (the control). At birth, the lambs were killed, and their kidneys were removed to study the changes in histology, podocytes, and expression of paired-box 2 (PAX2) and VEGF. In the obstructed kidneys, we observed cysts of various sizes in the cortex, fibrosis in the interstitial tissue, much decreased number of glomeruli, severe podocyte foot process fusion, and markedly increased PAX2 and decreased VEGF expressions. However, relief of obstruction preserved the number of glomeruli, significantly increased VEGF expression, reduced fusion of the podocyte foot processes, and restored expression of PAX2 to some extent. Thus, relief of obstruction in utero may prevent or attenuate the development of nephropathy in lambs. (1)]. At present, infants suffering from UPJO are either simply followed up or given surgical treatment based on hydronephrosis grade or renal function condition. However, Murer et al (2) found that the recovery from renal function injury even after the relief of UPJO was not assured in some children. Intervention in utero may help these patients. Chevalier et al (3) found that the relief of obstruction markedly reduced tubular atrophy and interstitial fibrosis in developing kidneys. However, Josephson et al (4) found that renal damage persisted despite very early efforts to remove obstruction. Because there is no consistent evidence linking recovery from renal damage to relief of UPJO in utero in humans, we decided to study this issue in fetal lambs.Podocytes are needed to maintain normal renal function; yet, they are easily injured by various abnormal situations. To our knowledge, changes in podocytes in obstructed kidneys have rarely been studied.Paired-box 2 (PAX2) is an important regulatory factor that functions early in the development of the kidney, and is restricted to the developing kidney. In damaged kidneys, PAX2 expression seems to be related to the proliferation of cystic renal epithelia, which is common in obstructed kidneys. VEGF is needed to maintain the renal blood vessel system. Decrease in VEGF will lead to fibrosis, another very common condition in obstructed kidneys.In this study, whether the relief of UPJO in utero in lambs would attenuate the development of nephropathy was investigated by observing changes in histology, podocytes, and expression of PAX2 and VEGF in kidneys after ureteral obstruction relief in utero. MATERIALS AND METHODSSevere unilateral partial ureteral obstruction was produced in 22 sheep fetuses at 75-85 d of gestation. In brief, open hysterotomy was perfo...

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Section: Discussionsupporting

confidence: 88%

Does Intervention in Utero Preserve the Obstructed Kidneys of Fetal Lambs? A Histological, Cytological, and Molecular Study

et al. 2009

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“…Scheme of fetal sheep gestation, from conception to birth, with timing of sham and obstructed group operations and analyses of urinary bladders. To place these procedures in relation to upper renal tract development, the percent glomerular complement of the developing sheep metanephric kidney is also shown (adapted from results in Edouga et al 46 ).…”

Section: Bladder Weight Protein and Dna Measurementmentioning

confidence: 99%

Urinary Outflow Obstruction Increases Apoptosis and Deregulates Bcl-2 and Bax Expression in the Fetal Ovine Bladder

Thiruchelvam

Nyírády

Peebles

et al. 2003

The American Journal of Pathology

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During organogenesis, net growth of tissues is determined by a balance between proliferation, hypertrophy, and apoptotic death. Human fetal bladder outflow obstruction is a major cause of end-stage renal failure in children and is associated with complex pathology in the kidney and lower urinary tract. Experimental manipulation of the fetal sheep urinary tract has proved informative in understanding the pathobiology of congenital obstructive uropathy. In this study we used an ovine model of fetal bladder outflow obstruction to examine effects on apoptotic cell death in the developing urinary bladder. While 30 days of obstruction in utero between 75 and 105 days gestation resulted in overall growth of the fetal bladder as assessed by weight, protein, and DNA measurements, we found that apoptosis, as assessed by in situ end-labeling, was up-regulated in fetal bladder detrusor muscle and lamina propria cells and that this was accompanied by a down-regulation of the anti-death protein Bcl-2 and an up-regulation of the pro-death protein Bax. Moreover, activated caspase-3, an effector of apoptotic death, was increased in obstructed bladders. This is the first study to define altered death in an experimental fetal model of bladder dysmorphogenesis. We speculate that enhanced apoptosis in detrusor smooth muscle cells is part of a remodeling response during compensatory hyperplasia and hypertrophy. Conversely, in the lamina propria, an imbalance between death and proliferation leads to a relative depletion of cells.

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“…At 70 d of gestation, ewes were subjected to surgery under general anesthesia as described previously (20). A laparotomy was performed on the ewe to gain access to the fetuses.…”

Section: Fetal Compensatory Renal Growthmentioning

confidence: 99%

“…As nephrogenesis continues after birth in these species, studies were carried out in neonate animals, at the end of the nephrogenesis process and in a different setting, ex utero. One study performed in the ewe (15), a species in which nephrogenesis is very similar to humans (20) and ends before birth, showed that for the first time, renal compensatory growth was associated with an increase in nephron number, although insufficient to fully compensate for the missing kidney. The authors speculated that removing one kidney at a time when nephrogenesis is more active may have resulted in activation of unknown genes and prolonged nephrogenesis, allowing additional nephrons endowment.…”

mentioning

confidence: 99%

Compensatory renal growth after unilateral or subtotal nephrectomy in the ovine fetus

et al. 2013

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Background:Clinical and experimental studies show that unilateral (1/2Nx) and subtotal nephrectomy (5/6Nx) in adults result in compensatory renal growth without formation of new nephrons. During nephrogenesis, the response to renal mass reduction has not been fully investigated. Methods: Ovine fetuses underwent 1/2Nx, 5/6Nx, or sham surgery (sham) at 70 d of gestation (term: 150 d), when nephrogenesis is active. At 134 d, renal function was determined, fetuses were killed, and kidneys were further analyzed at the cellular and molecular levels. Additional fetuses subjected to 5/6Nx were killed at 80 and 90 d of gestation to investigate the kinetics of the renal compensatory process. results: At 134 d, in 1/2Nx, a significant increase in kidney weight and estimated glomerular number was observed. In 5/6Nx, the early and marked catch-up in kidney weight and estimated glomerular number was associated with a striking butterfly-like remodeling of the kidney that developed within the first 10 d following nephrectomy. In all groups, in utero glomerular filtration rates were similar. conclusion: Compensatory renal growth was observed after parenchymal reduction in both models; however, the resulting compensatory growth was strikingly different. After 5/6Nx, the remnant kidney displayed a butterfly-like remodeling, and glomerular number was restored.

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Recovery after relief of fetal urinary obstruction: morphological, functional and molecular aspects

Cited by 40 publications

References 34 publications

Does Intervention in Utero Preserve the Obstructed Kidneys of Fetal Lambs? A Histological, Cytological, and Molecular Study

Does Intervention in Utero Preserve the Obstructed Kidneys of Fetal Lambs? A Histological, Cytological, and Molecular Study

Urinary Outflow Obstruction Increases Apoptosis and Deregulates Bcl-2 and Bax Expression in the Fetal Ovine Bladder

Compensatory renal growth after unilateral or subtotal nephrectomy in the ovine fetus

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