Inherited nephropathy of juvenile onset with progressive glomerulonephritis due to alteration of the glomerular basement membrane (collagen IV). In the Samoyed it is caused by a mutation in COL4A5 (X-linked Alport syndrome); in the English Springer Spaniel the described form is autosomal recessive due to a mutation in COL4A4. It produces proteinuria and progression to renal failure in the young animal.

Samoyed: well-characterised X-linked form (Alport model). English Springer Spaniel: less frequent autosomal recessive form. No reliable carrier frequencies are published in large series.

- Persistent proteinuria in the young animal
- Microscopic or macroscopic haematuria
- Polyuria/polydipsia and weight loss
- Vomiting and progressive azotaemia
- In the Samoyed, affected males usually progress to renal failure before one year of age; carrier females may be normal or develop mild or late-onset disease
- In the Springer, progressive renal failure in the young adult

Samoyed nephropathy was identified as a model of X-linked Alport syndrome; Zheng et al. (1994) found the mutation in COL4A5. In the English Springer Spaniel, Nowend et al. (2012) characterised the autosomal recessive basis in COL4A4. Familial nephropathy of the English Cocker Spaniel (COL4A4 c.115A>T) is a distinct entity.

- In the Samoyed, genotype females from affected lines before mating (COL4A5 variant)
- In the Samoyed, a carrier female must not be mated: mating with a clear male produces 50 % carrier daughters and 50 % affected hemizygous sons
- In the Springer, genotype breeding animals with the specific test and do not mate two carriers
- Affected males must not be used as breeding animals
- After a confirmed case, do not repeat the parental mating and communicate the status to the buyer

Differential diagnosis with PLN of the SCWT/Airedale, familial amyloidosis and immune-mediated glomerulonephritis. Renal biopsy shows laminated glomerular basement membrane (Alport syndrome) in the Samoyed; in the Springer, the pattern is that of progressive glomerulonephritis. Determining the inheritance pattern (X-linked Samoyed versus autosomal Springer) is essential for genetic counselling.

1. Zheng K et al. (1994) Canine X chromosome-linked hereditary nephritis: a genetic model for human X-linked hereditary nephritis resulting from a single base mutation in the gene encoding the alpha 5 chain of collagen type IV. Proc Natl Acad Sci USA 91(9):3989-3993. PMID: 8171024
2. Nowend KL et al. (2012) Characterization of the genetic basis for autosomal recessive hereditary nephropathy in the English Springer Spaniel. J Vet Intern Med 26(2):294-301. PMID: 22369189
3. OMIA:001112-9615 (Nephritis, X-linked) y OMIA:002618-9615 (Nephropathy, COL4A4 related).