Renal Tubular Dysgenesis in Twin-Twin Transfusion Syndrome

Oberg, Kerby C.; Pestaner, Joseph P.; Bielamowicz, Lisa; Hawkins, Edith P.

doi:10.1007/s100249900086

Cited by 44 publications

(39 citation statements)

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“…Thus, the reduction in proximal tubular density seems to be a selective effect of NH on the kidney. An interesting finding in the NH cases was FAH staining of Bowman's capsule, which has also been observed in proximal tubular dysgenesis in the twin-twin transfusion syndrome (16). When the proximal tubule fails to develop, the embryologically related parietal epithelium of Bowman's capsule seems to express FAH ectopically.…”

Section: Resultsmentioning

confidence: 69%

“…One section of each was stained with hematoxylin and eosin (H&E) and Perl's Prussian blue for detection of ferric iron. Using previously reported immunohistochemistry techniques (14), kidney sections were stained for epithelial membrane antigen (EMA; antihuman monoclonal mouse epithelial membrane antigen, Dako Corporation, Carpinteria, CA), which is an antigen known to be confined to the distal tubular epithelium (15), and fumarylacetoacetate hydrolase (FAH; monoclonal antibody kindly provided by RM Tanguay, Quebec Canada), which is confined to the proximal tubular epithelium (16,17), and liver sections were stained for AGT (anti-human angiotensinogen polyclonal rabbit serum, Sigma Chemical Co.-Aldrich, St. Louis, MO) and for human IgG (VECTASTAIN ABC kit for Human IgG, Vector Laboratories, Burlingame, CA). Sections were counterstained with hematoxylin.…”

Section: Methodsmentioning

confidence: 99%

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Relationship of Proximal Renal Tubular Dysgenesis and Fetal Liver Injury in Neonatal Hemochromatosis

2010

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Renal tubular dysgenesis has been reported in isolated cases of neonatal hemochromatosis (NH). We hypothesized that fetal liver injury in NH impairs proximal renal tubular development via impaired hepatic angiotensinogen (AGT) elaboration. Morphometric analyses were performed of postmortem liver and kidney sections of cases of proven NH and postconception age-matched controls for renal proximal tubule density, hepatocyte mass, and hepatic AGT expression. Proximal tubule density was markedly reduced in NH cases, although they showed a spectrum from mild to severe paucity. Hepatic AGT expression was markedly reduced in NH cases and correlated closely with reduced hepatocyte mass. A linear relationship was established between hepatic AGT expression and the degree of renal tubular dysgenesis suggesting that there is a relationship between them. Our results demonstrate that there is a spectrum of kidney pathology in patients with NH including a large proportion of cases with severe proximal tubular dysgenesis. Hepatic synthetic failure resulting in insufficient production of AGT to support renal tubular development is the likely mechanism of kidney disease in NH. (Pediatr Res 67: [188][189][190][191][192][193] 2010) N eonatal hemochromatosis (NH) is defined by the presence in newborns of liver disease in association with pathologic siderosis of various organs and tissues in a pattern similar to hereditary hemochromatosis (1). NH has also been called "neonatal iron storage disease" and "perinatal hemochromatosis" on the basis of these unique pathologic findings. NH is invariably associated with severe liver injury, which evidently is initiated during fetal life (2). Current thinking is that gestational alloimmune hepatocyte injury is involved in the pathogenesis of most or all cases of NH (3,4).Several clinical observations date the onset of liver injury in NH to midgestation. One such observation is the postmortem finding of renal tubular dysgenesis reported in five neonates with NH (5-7). The hallmark histopathologic findings of renal tubular dysgenesis are paucity or absence of proximal tubules and the absence of necroinflammatory disease that could otherwise account for tubular loss. The proximal tubules in this condition appear short and poorly developed, with reduced convolution leading to reduced number of tubular profiles in histologic sections (8). These findings suggest that renal development has been arrested at 20-to 25-wk gestation. Assuming that failed renal development in renal tubular dysgenesis associated with NH is the result of or a complication of fetal liver injury, the finding dates the liver injury in these cases to around 20-wk gestation (9). That raises the question of whether renal development is affected in more cases of NH than is reflected in the meager case reports. In addition, the mechanism by which fetal liver injury leads to a rather specific pattern of failed development in the kidney deserves to be addressed. Renal tubular development is dependent on an intact renin-ang...

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Section: Resultsmentioning

confidence: 69%

Section: Methodsmentioning

confidence: 99%

Relationship of Proximal Renal Tubular Dysgenesis and Fetal Liver Injury in Neonatal Hemochromatosis

2010

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“…2C to F), consistent with diminished expression of mFuc-TIX (CD15 synthase) and uromodulin (uromucoid, Tamm-Horsfall glycoprotein), which are proximal and distal tubule-specific markers, respectively ( Fig. 3A and C) (25,35,48). To test the hypothesis that this tubular dysgenesis was caused by apoptotic tubular epithelial cell death, we carried out TUNEL assays to detect fragmented nuclear DNA in the kidneys of heterozygous and homozygous mutant neonatal mice.…”

Section: Resultsmentioning

confidence: 81%

MafB Is Essential for Renal Development and F4/80 Expression in Macrophages

Moriguchi

Hamada

Morito

et al. 2006

Molecular and Cellular Biology

199

255

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MafB is a member of the large Maf family of transcription factors that share similar basic region/leucine zipper DNA binding motifs and N-terminal activation domains. Although it is well known that MafB is specifically expressed in glomerular epithelial cells (podocytes) and macrophages, characterization of the null mutant phenotype in these tissues has not been previously reported. To investigate suspected MafB functions in the kidney and in macrophages, we generated mafB/green fluorescent protein (GFP) knock-in null mutant mice. mafB homozygous mutants displayed renal dysgenesis with abnormal podocyte differentiation as well as tubular apoptosis. Interestingly, these kidney phenotypes were associated with diminished expression of several kidney disease-related genes. In hematopoietic cells, GFP fluorescence was observed in both Mac-1-and F4/80-expressing macrophages in the fetal liver. Interestingly, F4/80 expression in macrophages was suppressed in the homozygous mutant, although development of the Mac-1-positive macrophage population was unaffected. In primary cultures of fetal liver hematopoietic cells, MafB deficiency was found to dramatically suppress F4/80 expression in nonadherent macrophages, whereas the Mac-1-positive macrophage population developed normally. These results demonstrate that MafB is essential for podocyte differentiation, renal tubule survival, and F4/80 maturation in a distinct subpopulation of nonadherent mature macrophages.

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“…40 In our cohort, the incidence of impaired renal function is similar between donors and recipients as reported by some 40 but not all studies, which rather indicate a higher proportion of donors affected. 12 Donor kidneys present tubular dysgenesis and ischemic glomerules compatible with chronic hypoperfusion whereas lesions in recipients are compatible with hypertensive glomerulopathies; 9,41,42 renal histopathology data were not available in this study. The rate of patent ductus arteriosus requiring ligation is elevated in the donors.…”

Section: Discussionmentioning

confidence: 90%

Blood pressures in newborns with twin–twin transfusion syndrome

Mercanti

Boivin

et al. 2011

J Perinatol

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Objective: In addition to unbalanced flow through placental anastomoses, evidence suggests that transfer of circulating vasoactive elements from the donor to the recipient contribute to the pathological process of twin-twin transfusion syndrome (TTTS). The objective of this study was to test the hypothesis that TTTS recipients have higher blood pressure (BP) at birth than donors.Study Design: Chart review of all TTTS infants born from 1996 to 2007 with both twins alive X24 h (51 pairs; average gestational age 30 ± 3 weeks).Results: Both systolic and diastolic neonatal BPs were significantly higher in recipients. When expressed relative to predicted BP for birth weight (BW), BP were lower than expected in donors and higher in recipients.Conclusions: Data indicate that TTTS recipients have BP significantly higher than donors and than BP expected for BW. The long-term impact of these early hemodynamic perturbations remains to be determined.

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Renal Tubular Dysgenesis in Twin-Twin Transfusion Syndrome

Cited by 44 publications

References 46 publications

Relationship of Proximal Renal Tubular Dysgenesis and Fetal Liver Injury in Neonatal Hemochromatosis

Relationship of Proximal Renal Tubular Dysgenesis and Fetal Liver Injury in Neonatal Hemochromatosis

MafB Is Essential for Renal Development and F4/80 Expression in Macrophages

Blood pressures in newborns with twin–twin transfusion syndrome

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