A retrospective study on epidemiology and management of canine cystine uroliths in one part of Norway from 2015 to 2020.

BACKGROUND: Urinary tract problems are a common complaint in small animal medicine and urolithiasis is considered to be an important cause of urinary tract disease in dogs. In this study the main aim was to investigate whether the occurrence of cystine urolithiasis increased during a five-year period. A second aim was to evaluate possible risk-factors as breed, age and gender. This study also evaluated how urine specific gravity, pH and level of cystine in urine responded to preventive strategies. Medical records of dogs with urolithiasis presented at nine Norwegian animal clinics and one animal hospital between 2015 and 2020 were retrospectively reviewed. RESULTS: The incidence of cystine uroliths increased significantly during the five study years (R2 = 0.72, P = 0.0199). Dogs with cystine uroliths were significantly younger (5.0 years (n = 84, 95% CI [4.4-5.6])) when they were diagnosed with cystine uroliths compared to dogs with other types of uroliths (8.1 years (n = 255, 95% CI[7.8-8.5]) P < < 0.0001). Cystine levels in urine were increased in 93% of the dogs with cystine urolithiasis. Cystinuria decreased significantly after neutering (P < 0.0001). Breeds most commonly affected with cystine urolithiasis in this study were Staffordshire bull terrier, Danish Swedish farmdog and Chihuahua. CONCLUSIONS: The results from this study supports a suggested genetic basis for cystine urolithiasis as described in previous studies. Neutering is considered an important part of preventing reoccurrence since cystine values decreased significantly after neutering.

Genetics and epidemiology of hypothyroidism and symmetrical onychomadesis in the Gordon setter and the English setter.

BACKGROUND: Hypothyroidism is one of the most common endocrine disorders, whereas symmetrical onychomadesis is a rare claw disease in the general dog population. The aims of this study were to estimate the prevalence of hypothyroidism and symmetrical onychomadesis in a birth cohort of 291 Gordon setters at eight years of age. Further, to describe the age at diagnosis of hypothyroidism in the 68 Gordon setters and 51 English setters included in the DLA study. Finally, to elucidate potential associations between dog leukocyte antigen (DLA) class II and hypothyroidism and/or symmetrical onychomadesis in the Gordon setter and the English setter. RESULTS: In the birth cohort of eight years old Gordon setters, 2.7 % had hypothyroidism and 8.9 % had symmetrical onychomadesis, but only one out of these 291 dogs (0.3 %) had both diseases. Mean age at diagnosis of hypothyroidism for dogs included in the DLA study was 6.4 years (95 % CI: 5.6-7.2 years) in the Gordon setters and 7.7 years (95 % CI: 7.2-8.2 years) in the English setters. The DLA alleles most associated with hypothyroidism in the Gordon setter and English setter were DLA-DQB1*00201 (OR = 3.6, 95 % CI: 2.1-6.4, p < 0.001) and DLA-DQA1*00101 (OR = 2.9, 95 % CI: 1.3-6.6, p < 0.001), respectively. In the Gordon setter, the haplotype DLA-DRB1*01801/DQA1*00101/DQB1*00802 was significantly associated with both symmetrical onychomadesis (OR = 2.9, 95 % CI: 1.7-5.2, p < 0.001) and with protection against hypothyroidism (OR = 0.3, 95 % CI: 0.2-0.5, p < 0.001). CONCLUSION: Hypothyroidism is a complex disease where DLA genes together with other genes may be involved in the pathogenesis of the disease. In the Gordon setter, one DLA haplotype that was associated with protection against hypothyroidism was also associated with symmetrical onychomadesis. These findings indicate that closely linked genes, instead of or together with the DLA genes themselves, may be associated with hypothyroidism and symmetrical onychomadesis. In a breed where several autoimmune diseases are prevalent all possible associations between DLA genes and actual diseases need to be investigated before DLA is considered used as a tool for marker-assisted selection.

DLA class II alleles are associated with risk for canine symmetrical lupoid onychodystrophy [corrected](SLO).

Symmetrical lupoid onychodystrophy (SLO) is an immune-mediated disease in dogs affecting the claws with a suggested autoimmune aethiology. Sequence-based genotyping of the polymorphic exon 2 from DLA-DRB1, -DQA1, and -DQB1 class II loci were performed in a total of 98 SLO Gordon setter cases and 98 healthy controls. A risk haplotype (DRB1*01801/DQA1*00101/DQB1*00802) was present in 53% of cases and 34% of controls and conferred an elevated risk of developing SLO with an odds ratio (OR) of 2.1. When dogs homozygous for the risk haplotype were compared to all dogs not carrying the haplotype the OR was 5.4. However, a stronger protective haplotype (DRB1*02001/DQA1*00401/DQB1*01303, OR = 0.03, 1/OR = 33) was present in 16.8% of controls, but only in a single case (0.5%). The effect of the protective haplotype was clearly stronger than the risk haplotype, since 11.2% of the controls were heterozygous for the risk and protective haplotypes, whereas this combination was absent from cases. When the dogs with the protective haplotype were excluded, an OR of 2.5 was obtained when dogs homozygous for the risk haplotype were compared to those heterozygous for the risk haplotype, suggesting a co-dominant effect of the risk haplotype. In smaller sample sizes of the bearded collie and giant schnauzer breeds we found the same or similar haplotypes, sharing the same DQA1 allele, over-represented among the cases suggesting that the risk is associated primarily with DLA-DQ. We obtained conclusive results that DLA class II is significantly associated with risk of developing SLO in Gordon setters, thus supporting that SLO is an immune-mediated disease. Further studies of SLO in dogs may provide important insight into immune privilege of the nail apparatus and also knowledge about a number of inflammatory disorders of the nail apparatus like lichen planus, psoriasis, alopecia areata and onycholysis.