Impaired Renal Function in Belgrade rats

VEUTHEY TANIA V; WESSLING-RESNICK MARIANNE

Conferencia; Seminar at Department of Genetics and Complex Diseases; 2013

Belgrade rats carry a disabling mutation in the iron transporter DMT1. Although DMT1 plays a major role in intestinal iron absorption, the transporter is also highly expressed in kidney, where its function remains unknown. The goal of this study was to characterize renal physiology of Belgrade rats. Male Belgrade rats died prematurely with ~50% survival at 20 weeks of age. Necropsy results indicate that renal failure was the major cause of death. By 15 weeks of age, Belgrade rats displayed thickening of glomerular membrane and collagen deposits in tubules and glomeruli. This altered renal morphology was associated with sclerosis and fibrosis. Creatinine clearance was significantly lower compared with heterozygote littermates. Urinary biomarkers of kidney injury, including albumin, fibrinogen and Kim-1, were significantly elevated. Belgrade rat kidney non-heme iron levels were not different from controls but urinary iron excretion was higher. Morphological studies show that nephrogenesis is delayed in Belgrade rat pups due to their low iron status and fetal growth restriction. Defects in renal development underlie the renal injury and compromised renal metabolism observed in adult b/b rats. Thus, DMT1 function plays a key role in kidney structure and function.