The author declares no conflict of interest.
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State of the Art Review
Kidney diseases caused by glomerular basement membrane type IV collagen defects in dogs
Article first published online: 6 MAR 2013
DOI: 10.1111/vec.12031
© Veterinary Emergency and Critical Care Society 2013
Issue
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Journal of Veterinary Emergency and Critical Care
Volume 23, Issue 2, pages 184–193, March/April 2013
Additional Information
How to Cite
Lees, G. E. (2013), Kidney diseases caused by glomerular basement membrane type IV collagen defects in dogs. Journal of Veterinary Emergency and Critical Care, 23: 184–193. doi: 10.1111/vec.12031
Publication History
- Issue published online: 8 APR 2013
- Article first published online: 6 MAR 2013
- Manuscript Accepted: 2 FEB 2013
- Manuscript Received: 19 APR 2012
- Abstract
- Article
- References
- Cited By
Keywords:
- Alport syndrome;
- chronic kidney disease;
- hereditary nephritis;
- proteinuria
Abstract
Objective
To review the pathogenesis, as well as the clinical and pathologic features of canine glomerular diseases caused by genetic type IV collagen defects.
Data Sources
Original studies and review articles from human and veterinary medical fields.
Human Data Synthesis
Presence in glomerular basement membranes (GBM) of a network composed of α3.α4.α5 heterotrimers of type IV collagen is required to maintain structure and function of glomerular capillary walls.
Veterinary Data Synthesis
Hereditary nephropathy (HN) is the most commonly used name for kidney diseases that occur in dogs due to genetic type IV collagen abnormalities. To date, 4 different collagen IV gene mutations have been identified in dogs with HN; 2 are COL4A5 mutations that cause X-linked HN (XL-HN), and 2 are COL4A4 mutations that cause autosomal recessive HN (AR-HN). Affected males with XL-HN and affected males and females with AR-HN develop juvenile-onset kidney disease manifested by proteinuria typically starting at 3–6 months of age and followed by progressive kidney disease leading to terminal failure usually at 6–24 months of age. Carrier female dogs with XL-HN also develop proteinuria starting at 3–6 months of age, but progressive disease causing kidney failure is uncommon until they are >5 years old. The distinctive pathologic lesions of HN are extensive multilaminar splitting and thickening of the GBM, as demonstrated by electron microscopy, and abnormal type IV collagen α-chain content of basement membranes, as demonstrated by immunolabeling. Identification of the underlying gene mutations has permitted genetic testing and selective breeding practices that currently are minimizing HN in breeds known to be at risk.
Conclusions
Canine HN is a rare disease that should be considered whenever a dog exhibits a juvenile-onset kidney disease characterized partly by proteinuria, but highly specialized methods are required to pursue a definitive diagnosis.