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Originally published online as doi:10.2353/ajpath.2009.080939 on July 2, 2009

Published online before print July 2, 2009
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(American Journal of Pathology. 2009;175:500-509.)
© 2009 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2009.080939

Diabetic Albuminuria Is Due to a Small Fraction of Nephrons Distinguished by Albumin-Stained Tubules and Glomerular Adhesions

Patricia M. Kralik*, Yunshi Long*, Ye Song*, Lu Yang{dagger}, Haiyang Wei{ddagger}, Susan Coventry*, Shirong Zheng* and Paul N. Epstein*

From the Departments of Pediatrics,* Pharmacology and Toxicology,{dagger} and Anatomical Sciences and Neurobiology,{ddagger} University of Louisville, Louisville, Kentucky

OVE26 diabetic mice develop severe albuminuria. Immunohistochemical analysis revealed a pattern of intense albumin staining in a small subset of OVE26 tubules. Immunostaining was strikingly heterogeneous; some tubules stained intensely for albumin, but most tubules had weak or no staining. Serial sectioning showed that staining patterns were distinctive for each nephron. Electron microscopy revealed that albumin accumulated in villi and at the base of the brush border. Tubule cell injury, as shown by loss of villi, tubule dilation, and cellular protrusions into the tubule lumen, was unambiguously associated with albumin staining. Examination of albumin staining of proteinuric human kidneys also showed a heterogeneous pattern of staining. Analysis of OVE26 serial sections indicated that all glomeruli connected to albumin-positive tubules were identified by albumin-stained lesions in the tuft that adhered to Bowman’s capsule, implicating this as a critical feature of heavy albumin leakage. These results indicate that albumin accumulation provides a marker of damaged nephrons, and confirm that albumin leakage produces significant tubular damage. This study shows that that formation of sclerotic glomerular adhesions is a critical step leading to severe albuminuria.






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Copyright © 2009 by the American Society for Investigative Pathology.