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Protein-losing nephropathy (PLN) — Airedale Terrier and Irish Soft Coated Wheaten Terrier

Renal / urinario · Dog

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.

Inheritance pattern	Polygenic/complex, associated with a risk haplotype on CFA1; the risk is greatest in homozygotes. Incomplete penetrance, modulated by environmental factors.
Gene / Mutation	Irish Soft Coated Wheaten Terrier: risk haplotype on CFA1 with missense variants in NPHS1 (nephrin; Gly→Arg in the fibronectin type 3 domain) and KIRREL2 (Neph3/filtrin; Pro→Arg in a proline-rich region). It has not been determined whether one or both variants are causal. Airedale Terrier: one affected dog homozygous for both substitutions in the original study; limited molecular evidence. PMID 23325127.
Penetrance	Incomplete and age-dependent penetrance: a dog homozygous for the risk haplotype may not develop the disease. Environmental and comorbid factors (e.g. protein-losing enteropathy, hypertension) modulate the clinical expression.
Code	qrtr
Turnaround time	10 days
Price	52,60 €

Incidence

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.

Breeder management

- 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

Specialist notes

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.

References

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

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