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Abstract: PO1590

Reduced Glomerular and Nephron Injury due to Albumin Knockout in the Heavily Nephrotic, Polymerization-Defective GBM Laminin B2-Del44 Mutant Mice

Session Information

Category: Genetic Diseases of the Kidneys

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Funk, Steven Daniel, Washington University Department of Medicine, Division of Nephrology, Saint Louis, Missouri, United States
  • Miner, Jeffrey H., Washington University Department of Medicine, Division of Nephrology, Saint Louis, Missouri, United States
Background

Increased proteinuria is associated with adverse outcomes in chronic renal disease. Much evidence indicates that increased albumin filtration through the glomerular filtration barrier exacerbates nephron injury, but in vivo evidence is conflicting. Although it was previously shown that Nagase analbuminemic rats exhibit little or no increase in renal injury following multiple insults, Alport mice lacking albumin were previously shown to have dramatically increased lifespan with delayed injury to glomeruli and nephron epithelium.

Methods

We mated CRISPR-mediated, albumin-knockout mice with laminin B2-Del44 mice, which exhibit heavy albuminuria, but delayed foot process effacement and fibrosis. Mice were monitored until their natural deaths or euthanized at 9, 3, or 10 months for analyses. Plasma was analyzed for BUN. Glomeruli were analyzed by electron microscopy to determine foot process effacement. Nephron epithelium was analyzed by immunofluorescent microscopy to determine status of injury markers.

Results

Albumin-Del44 double mutant mice exhibited a significantly increased lifespan (6-month vs 9-month average), with significantly reduced BUN at all ages. Similar to Alport mice, foot process effacement in albumin-Del44 double mutant mice was decreased at yonger ages. Nephron tubule epithelium exhibited reduced KIM-1 expression at early ages, indicating delayed injury.

Conclusion

Similar to Alport mice, the absence of albumin in Lamb2-Del44 mice resulted in increased lifespan with delayed renal injury. These data support a significant role of albumin in nephron injury in murine models of nephrotic syndrome.

Funding

  • NIDDK Support