Relationship of proximal renal tubular dysgenesis and fetal liver injury in neonatal hemochromatosis

Pediatr Res. 2010 Feb;67(2):188-93. doi: 10.1203/PDR.0b013e3181c2df69.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensinogen / metabolism
  • Autopsy
  • Case-Control Studies
  • Down-Regulation
  • Female
  • Gestational Age
  • Hemochromatosis / embryology*
  • Hemochromatosis / metabolism
  • Hemochromatosis / pathology
  • Humans
  • Immunohistochemistry
  • Kidney Tubules, Proximal / abnormalities*
  • Kidney Tubules, Proximal / metabolism
  • Kidney Tubules, Proximal / pathology
  • Liver / embryology*
  • Liver / metabolism
  • Liver / pathology
  • Liver Diseases / embryology*
  • Liver Diseases / metabolism
  • Liver Diseases / pathology
  • Pregnancy

Substances

  • Angiotensinogen