[1514] Reduced Angiotensinogen in Neonatal Hemochromatosis Leads to Impaired Development of Proximal Renal Tubules and Compensitory Glomerular Changes.

David Azar, Silvana Bonilla, Deirdre Amaro, Peter Whitington, Henry Krous. University of California, San Diego; Northwestern University Feinberg School of Medicine, Chicago, IL; Rady Children's Hospital, San Diego, CA

Background: Neonatal hemochromatosis (NH) is associated with severe liver injury and extrahepatic tissues siderosis. Renal tubular dysgenesis (RTD) is characterized by paucity or absence of proximal renal tubules (PRTs) leading to late onset oligohydramniosis. While five cases of concurrent NH and RTD have been reported, more recently Bonilla et al. showed a larger number of NH patients have reduced PRTs with a correlation between hepatocyte density, hepatic angiotensinogen (AGT) expression, and PRT density. The current study aims to support these results, confirming the correlation between AGT expression and PRT density as well as exploring glomerulocystic change and expression of Fumarylacetoacetate hydrolase (FAH), a PRT specific marker, within the glomerular epithelium as compensatory/metaplastic changes to accommodate for lost PRT function.
Design: Liver and kidney sections from four NH cases and four gestational age-matched controls were examined. Hepatocyte and glomeruli counts and the degree of glomerular cystic change were determined from H+E sections. Immunohistochemically stained sections were assessed to determine hepatic AGT expression, PRT density (FAH), and renal distal tubule density (EMA). FAH staining of glomerular epithelium was also evaluated. A correlation between hepatocyte volume, AGT expression, and PRT density was sought.
Results: NH cases showed reduced hepatocyte volume(P=0.02), AGT expression(P=0.02), and PRT density(P=0.0007) compared to the age-matched controls, with no difference in distal tubules(P=0.26). AGT expression was correlated to hepatocyte volume(R2=0.85) and PRT density(R2=0.81). One NH case and all control cases showed no glomerulocystic change and no glomerular FAH staining. Two NH cases with moderately reduced PRTs showed mild glomerulocystic change and occasional glomerular FAH staining. The remaining NH case, with the fewest PRTs, showed moderate glomerulocystic change and a higher density of glomerular FAH staining.
Conclusions: A spectrum of renal pathology is seen in NH patients including reduced PRTs. Fetal liver damage with decreased AGT synthesis is the likely mechanism leading to RTD in NH. Glomeruli in cases with reduced PRTs demonstrate glomerulocystic changes and FAH staining of the glomerular epithelium, possibly in compensation for lost PRT function.
Category: Liver & Pancreas

Wednesday, March 2, 2011 9:30 AM

Poster Session V # 182, Wednesday Morning


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