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Impaired renal function and development in Belgrade rats.

Tania Veuthey¹, Dana Hoffmann, Vishal S Vaidya

¹Dept. of Genetics & Complex Diseases, Harvard School of Public Health, 665 Huntington Ave., Boston, MA 02115. wessling@hsph.harvard.edu.

American Journal of Physiology. Renal Physiology

|November 15, 2013

Summary

This summary is machine-generated.

Belgrade rats with a divalent metal transporter 1 (DMT1) mutation exhibit severe kidney disease, including glomerular nephritis and end-stage renal disease, due to impaired renal development and function.

Keywords:

DMT1 iron deficiency anemia kidney renal development

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Transcutaneous Assessment of Renal Function in Conscious Rodents

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Published on: March 26, 2016

Area of Science:

Nephrology
Iron Metabolism
Genetics

Background:

Divalent metal transporter 1 (DMT1) is crucial for intestinal iron absorption.
The role of DMT1 in kidney function, particularly in iron handling and filtration, is not well understood.
Belgrade rats possess a disabling mutation in the DMT1 gene.

Purpose of the Study:

To investigate the physiological and morphological consequences of DMT1 deficiency in the kidneys of Belgrade rats.
To characterize the role of DMT1 in renal function and development.

Main Methods:

Physiological assessments including creatinine clearance measurements.
Analysis of urinary biomarkers for kidney injury (albumin, fibrinogen, kidney injury molecule-1).
Morphological examination of renal tissues and assessment of nephrogenesis.
Measurement of nonheme iron and transferrin levels in kidney and urine.

Main Results:

Belgrade rats exhibited premature mortality, glomerular nephritis, and chronic end-stage renal disease.
Renal morphology showed sclerosis and fibrosis by 15 weeks, with significantly reduced creatinine clearance.
Elevated urinary biomarkers indicated substantial kidney injury.
Delayed nephrogenesis was observed in Belgrade rat pups, linked to low iron status and fetal growth restriction.
While kidney iron levels were unchanged, urinary iron and transferrin were elevated.

Conclusions:

DMT1 plays a critical role in kidney development and function, impacting iron reabsorption and glomerular filtration.
DMT1 deficiency leads to severe renal pathology and compromised renal metabolism.
These findings highlight DMT1's importance beyond intestinal iron absorption, extending to renal health.