Hereditary glomerular nephropathy with breed predisposition, characterised by persistent proteinuria and hypoalbuminemia progressing to chronic kidney failure. It appears in the Irish Soft Coated Wheaten Terrier (SCWT) and, with much more limited molecular evidence, in the Airedale Terrier. In the SCWT, a risk haplotype on CFA1 has been identified with variants in genes of the glomerular filtration barrier (NPHS1 and KIRREL2). Inheritance is complex, with incomplete penetrance modulated by environmental factors.

Predisposition in the Irish Soft Coated Wheaten Terrier and the Airedale Terrier. The disease is considered relatively frequent in the SCWT, with a mean onset described at around 6.3 ± 2.0 years (Littman 2013); no reliable figures for carriers of the risk haplotype in large series are published.

- Persistent proteinuria with a high urine protein/creatinine ratio (UPC)\n- Hypoalbuminemia\n- Oedema and ascites\n- Weight loss\n- Polydipsia/polyuria\n- Intermittent vomiting and hypertension\n- Progression to chronic kidney failure

PLN in the SCWT was recognised as a familial entity with complex inheritance. In 2013, Littman and colleagues carried out a genome-wide association study in 62 dogs and delimited a candidate region on chromosome 1, in which they identified missense substitutions in NPHS1 (nephrin) and KIRREL2 (Neph3/filtrin) associated with a risk haplotype; homozygotes had a very high risk of PLN. In the same study, an affected Airedale Terrier homozygous for both substitutions was identified; the molecular association in the Airedale has not been confirmed in large series.

- Test SCWT breeding animals with the panel available for the risk variants, and interpret the result with caution because of the incomplete penetrance\n- Do not mate two homozygotes for the risk haplotype\n- With a family history of PLN, monitor the urine protein/creatinine ratio (UPC) throughout the reproductive life\n- A carrier can be mated with a low-risk animal and the offspring intended for breeding must be tested\n- Prioritise breeding animals with normal UPC and without risk variants\n- In the Airedale Terrier, base the breeding decision on UPC monitoring and family history, given the scarce molecular evidence

Differential diagnosis with immune-mediated glomerulopathies (LESG, membranoproliferative), familial amyloidosis (Shar-Pei, Akita) and other hereditary nephropathies. Renal biopsy shows glomerulosclerosis with deposits and, in the SCWT, a thickened basement membrane pattern. Monitor UPC annually in predisposed breeds; hypertension control and a low-protein renal diet slow deterioration.

1. Littman MP et al. (2013) Glomerulopathy and mutations in NPHS1 and KIRREL2 in soft-coated Wheaten Terrier dogs. Mamm Genome 24(3-4):119-126. PMID: 23325127
2. Vaden SL et al. (2013) Familial renal disease in soft-coated wheaten terriers. J Vet Emerg Crit Care 23(2):174-183. PMID: 23461660