Frequency and risk factors for naturally occurring Cushing's syndrome in dogs attending UK primary-care practices.

OBJECTIVES: To estimate the frequency and risk factors for Cushing's syndrome in dogs under UK primary veterinary care. MATERIALS AND METHODS: Dogs with Cushing's syndrome were identified by searching electronic patient records of primary-care veterinary practices. Pre-existing and incident cases of Cushing's syndrome during 2016 were included to estimate the 1-year period prevalence. Incident cases were used to estimate the annual incidence and to identify demographic risk factors for the diagnosis of Cushing's syndrome in dogs, through multivariable logistic regression. RESULTS: Analysis included 970 pre-existing and 557 incident cases of Cushing's syndrome from a population of 905,544 dogs. The estimated 1-year period prevalence for Cushing's syndrome in dogs under veterinary care was 0.17% (95% confidence interval 0.16 to 0.18) and incidence was 0.06% (95% confidence interval 0.05 to 0.07). In multivariable logistic regression modelling, the Bichon frise (odds ratio=6.17, 95% confidence interval 4.22 to 9.00), Border terrier (5.40, 95% confidence interval 3.66 to 7.97) and Miniature schnauzer (3.05, 95% confidence interval 1.67 to 5.57) had the highest odds of Cushing's syndrome. The Golden retriever (0.24, 95% confidence interval 0.06 to 0.98) and Labrador retriever (0.30, 95% confidence interval 0.17 to 0.54) were the most protected breeds. Increasing age, bodyweight greater than the breed-sex mean and being insured also showed increased odds of Cushing's syndrome. CLINICAL SIGNIFICANCE: As Cushing's syndrome is predominately diagnosed and managed in primary-care practice, this study provides valuable new information of its epidemiology in this setting. Demographics reported are supportive of previous work and additional novel associations identified, such as the Border terrier, could enhance the index of suspicion for veterinarians.

Associations between single nucleotide polymorphisms in the calcium sensing receptor and chronic kidney disease-mineral and bone disorder in cats.

Feline chronic kidney disease (CKD) is associated with high variability in severity of CKD-mineral and bone disorder (CKD-MBD). The calcium sensing receptor (CaSR) regulates circulating parathyroid hormone (PTH) and calcium concentrations. Single nucleotide polymorphisms (SNPs) in the CaSR are associated with severity of secondary renal hyperparathyroidism and total calcium concentrations in human patients receiving haemodialysis. The objective of this study was to explore associations between polymorphisms in the feline CaSR (fCaSR) and biochemical changes observed in CKD-MBD. Client owned cats (≥9years) were retrospectively included. SNP discovery was performed in 20 cats with azotaemic CKD and normal or dysregulated calcium concentrations. Non-pedigree cats (n=192) (125 with azotaemic CKD and 66 healthy), Persians (n=40) and Burmese (n=25) were genotyped for all identified SNPs using KASP. Biochemical parameters from the date of CKD diagnosis or from first visit to the clinic (healthy cats) were used. Associations between genotype and ionized calcium, total calcium, phosphate, PTH and FGF-23 were performed for non-pedigree cats using logistic regression. Sequence alignment against the fCaSR sequence revealed eight novel exonic SNPs. KASP genotyping had high accuracy (99.6%) and a low failure rate (<6%) for all SNPs. Allele frequencies varied between breeds. In non-pedigree cats, one synonymous SNP CaSR:c.1269G>A was associated with logPTH concentration (adjusted for plasma creatinine concentration), with a recessive model having the best fit (G/G vs A/A-G/A, P=0.031). Genetic variation in the fCaSR is unlikely to explain the majority of the variability in presence and severity of CKD-MBD in cats.

Calcitonin Response to Naturally Occurring Ionized Hypercalcemia in Cats with Chronic Kidney Disease.

BACKGROUND: Hypercalcemia is commonly associated with chronic kidney disease (CKD) in cats. OBJECTIVES: To explore the calcitonin response to naturally occurring ionized hypercalcemia in cats with azotemic CKD, and to assess the relationship of plasma calcitonin with ionized calcium, alkaline phosphatase (ALP), and urinary calcium excretion. ANIMALS: Thirty-three client-owned cats with azotemic CKD and ionized hypercalcemia from first opinion practice. METHODS: Cohort study. Calcitonin was measured with an immunoradiometric assay in heparinized plasma. Simple correlations were assessed with Kendall's rank correlation, and the within-subject correlations of calcitonin with ionized calcium and other clinicopathological variables were calculated with a bivariate linear mixed effects model. RESULTS: Calcitonin concentrations above the lower limit of detection (>1.2 pg/mL; range, 1.7-87.2 pg/mL) were observed in 11 of 33 hypercalcemic cats (responders). Blood ionized calcium concentration did not differ significantly between responders (median, 1.59 [1.46, 1.66] mmol/L) and nonresponders (median, 1.48 [1.43, 1.65] mmol/L; P = 0.22). No evidence was found for calcitonin and ionized calcium to correlate between cats (τb = 0.14; P = 0.31; n = 33), but significant positive correlation was evident within individual responders over time (within-subject correlation coefficient [rwithin ], 0.83; 95% confidence interval [CI], 0.63-0.92). Calcitonin correlated negatively over time with plasma ALP (rwithin , -0.55; 95% CI, -0.79 to -0.16). CONCLUSIONS AND CLINICAL IMPORTANCE: Calcitonin does not appear to have an important role in calcium metabolism in cats with CKD.

The Effect of Moderate Dietary Protein and Phosphate Restriction on Calcium-Phosphate Homeostasis in Healthy Older Cats.

BACKGROUND: Dietary phosphate and protein restriction decreases plasma PTH and FGF-23 concentrations and improves survival time in azotemic cats, but has not been examined in cats that are not azotemic. HYPOTHESIS: Feeding a moderately protein- and phosphate-restricted diet decreases PTH and FGF-23 in healthy older cats and thereby slows progression to azotemic CKD. ANIMALS: A total of 54 healthy, client-owned cats (≥ 9 years). METHODS: Prospective double-blinded randomized placebo-controlled trial. Cats were assigned to test diet (protein 76 g/Mcal and phosphate 1.6 g/Mcal) or control diet (protein 86 g/Mcal and phosphate 2.6 g/Mcal) and monitored for 18 months. Changes in variables over time and effect of diet were assessed by linear mixed models. RESULTS: A total of 26 cats ate test diet and 28 cats ate control diet. There was a significant effect of diet on urinary fractional excretion of phosphate (P = 0.045), plasma PTH (P = 0.005), and ionized calcium concentrations (P = 0.018), but not plasma phosphate, FGF-23, or creatinine concentrations. Plasma PTH concentrations did not significantly change in cats fed the test diet (P = 0.62) but increased over time in cats fed the control diet (P = 0.001). There was no significant treatment effect of the test diet on development of azotemic CKD (3 of 26 (12%) test versus 3 of 28 (11%) control, odds ratio 1.09 (95% CI 0.13-8.94), P = 0.92). CONCLUSIONS AND CLINICAL IMPORTANCE: Feeding a moderately protein- and phosphate-restricted diet has effects on calcium-phosphate homeostasis in healthy older cats and is well tolerated. This might have an impact on renal function and could be useful in early chronic kidney disease.

Relationship between Plasma Fibroblast Growth Factor-23 Concentration and Survival Time in Cats with Chronic Kidney Disease.

BACKGROUND: Fibroblast growth factor-23 (FGF-23) and parathyroid hormone (PTH) are commonly increased in cats with azotemic chronic kidney disease (CKD). Both are predictors of survival time in human patients, but these relationships have not previously been examined in the cat. OBJECTIVES: To investigate the relationship between plasma FGF-23 and PTH concentrations at diagnosis of CKD in cats with survival time and with disease progression over 12 months. ANIMALS: 214 azotemic, client-owned cats (≥9 years). METHODS: Retrospective study: Biochemical and urinary variables at diagnosis of azotemic CKD, including plasma FGF-23 and PTH concentrations were assessed as predictors of survival time (all-cause mortality) using Cox regression, and as predictors of CKD progression over 12 months using logistic regression. RESULTS: In the final multivariable Cox regression model, survival was negatively associated with plasma creatinine (P = .002) and FGF-23 concentrations (P = .014), urine protein-to-creatinine ratio (P < .001) and age (P < .001). Survival was positively associated with PCV (P = .004). In the final multivariable logistic regression model, independent predictors of CKD progression included logFGF-23 and age. Neither plasma phosphate nor PTH was found to be an independent predictor of survival time or of CKD progression. CONCLUSIONS AND CLINICAL IMPORTANCE: Plasma FGF-23 concentration is a novel prognostic indicator in cats with CKD, independent of other factors including plasma creatinine and phosphate concentrations. Further work is required to assess if FGF-23 contributes directly to CKD progression, but regardless these findings may make FGF-23 a useful biomarker for predicting poorer outcomes in cats with CKD.

The effect of feeding a renal diet on plasma fibroblast growth factor 23 concentrations in cats with stable azotemic chronic kidney disease.

BACKGROUND: Fibroblast growth factor 23 (FGF-23) is a phosphatonin, which is increased in cats with azotemic CKD. Dietary phosphate restriction decreases FGF-23 concentrations in humans and rodents, but this relationship has not previously been examined in the cat. OBJECTIVES: To investigate the effect of feeding renal diet on plasma FGF-23 concentrations in cats with stable azotemic CKD. ANIMALS: Azotemic, client-owned cats (≥ 9 years); 33 cats ate renal diet (RD group) and 11 cats did not eat renal diet (comparator group) over 28-56 days. METHODS: Retrospective longitudinal study: Plasma FGF-23, PTH, and phosphate concentrations were measured at baseline and after 28-56 days. Cats in the RD group were classified as hyperphosphatemic (HP) or normophosphatemic (NP) based on the International Renal Interest Society targets for plasma phosphate concentration. Nonparametric tests were performed. RESULTS: In the HP group (n = 15), feeding renal diet was associated with a significant decrease in plasma phosphate (P = .001), PTH (P = .007), and FGF-23 (P = .008), but not creatinine concentrations (P = .91). In the NP group (n = 18), feeding renal diet was associated with a significant decrease in plasma FGF-23 (P = .006), but not phosphate (P = .48), PTH (P = .35), or creatinine concentrations (P = .10). No significant changes were seen in any parameters in the comparator group during the study period. CONCLUSIONS AND CLINICAL IMPORTANCE: Feeding renal diet is associated with reductions in plasma FGF-23 concentrations in hyper- and normophosphatemic cats with stable azotemic CKD, suggesting that dietary phosphate restriction may enable cats with CKD to maintain normal plasma phosphate concentrations in association with lower plasma FGF-23 concentrations.

Fibroblast growth factor 23 (FGF-23) concentrations in cats with early nonazotemic chronic kidney disease (CKD) and in healthy geriatric cats.

BACKGROUND: Fibroblast growth factor (FGF-23) has an important role in phosphate regulation. Its clinical relevance in cats with CKD has not been explored previously. HYPOTHESIS/OBJECTIVES: The study objectives were (1) to determine whether FGF-23 concentrations are increased in nonazotemic cats, cats which developed azotemia within 12 months of screening compared with cats that remained non-azotemic, and (2) to evaluate the relationships between FGF-23 and PTH and FGF-23 and glomerular filtration rate (GFR). ANIMALS: Sixty-two healthy client-owned geriatric cats, 14 of which developed azotemia during the 12-month follow-up period. METHODS: Healthy nonazotemic cats were recruited prospectively into the study and followed for 12 months. At the study end-point, cats were categorized into 3 groups according to plasma creatinine concentration. PTH, FGF-23, and additional biochemical variables were evaluated at baseline and after 12 months. GFR was measured by a corrected slope-intercept iohexol clearance method. RESULTS: FGF-23 concentrations at baseline were found to be significantly increased in cats that developed azotemia (P = .001) compared with cats that did not develop azotemia. A significant positive relationship was identified between FGF-23 and PTH, whereas the relationship between FGF-23 and GFR was negative. CONCLUSIONS AND CLINICAL IMPORTANCE: FGF-23 concentrations predicted development of azotemia in geriatric cats. Positive relationships between FGF-23 and PTH suggest an association between FGF-23 and renal secondary hyperparathyroidism.

Fibroblast growth factor 23 in feline chronic kidney disease.

BACKGROUND: Fibroblast growth factor 23 (FGF-23) is a phosphaturic hormone involved in the pathogenesis of secondary renal hyperparathyroidism (SRHP) in humans. There are no published studies examining feline FGF-23. OBJECTIVES: Validation of a method for FGF-23 quantification in feline plasma and assessment of the associations among plasma FGF-23, PTH, creatinine, and phosphate concentrations in cats with chronic kidney disease (CKD). ANIMALS: One hundred nonazotemic and azotemic geriatric (>9 years) client-owned cats. METHODS: Retrospective cross-sectional study: Cats were categorized into 4 groups: control group (plasma creatinine (Cr) ≤2.0 mg/dL), stage 2 (Cr 2.1-2.8 mg/dL), stage 3 (Cr 2.9-5.0 mg/dL), stage 4 (Cr >5.0 mg/dL). Stages 2 and 3 were further subdivided based on International Renal Interest Society targets for plasma phosphate concentration (PO4 ): stage 2a (PO4 ≤4.5 mg/dL), stage 2b (PO4 >4.5 mg/dL), stage 3a (PO4 ≤5 mg/dL), stage 3b (PO4 >5 mg/dL). Plasma FGF-23 concentrations were measured by a human intact FGF-23 ELISA. Descriptive statistics and linear regression were performed. RESULTS: The ELISA demonstrated acceptable precision, reproducibility, and specificity. Plasma FGF-23 concentrations increased with increasing plasma creatinine concentrations and were significantly different between all groups (P < .008). Plasma FGF-23 concentrations were significantly higher in cats in stage 2b than stage 2a (P = .008) and in stage 3b than in stage 3a (P = .012). Phosphate, log creatinine, total calcium, log parathyroid hormone, and packed cell volume were all independent predictors of FGF-23. CONCLUSIONS AND CLINICAL IMPORTANCE: FGF-23 concentrations increase with increasing stage of feline CKD and might be a marker or mediator of feline SRHP.

Survey of pet owners' expectations of surgical practice within first opinion veterinary clinics in Great Britain.

OBJECTIVES: The expectations of small animal pet owners in Great Britain were evaluated on a number of issues regarding aseptic practice and clinical management and compared with final year veterinary students' assessment of actual veterinary practice. MATERIALS AND METHODS: A survey was completed by 328 small animal pet owners and 56 veterinary practices in Great Britain. Questions from the pet owner survey related to expectations and opinions on a number of surgical issues and questions from the veterinary surgeon survey examined veterinary practice in relation to the same issues. Comparisons were made to determine whether there were any differences between pet owner expectations and veterinary student assessment of actual practice of small animal first opinion clinics. RESULTS: In the majority of issues examined there was a significant mismatch between client expectation and provisions made. Of particular importance was the discrepancy regarding the use of surgical gloves and administration of analgesia. CLINICAL SIGNIFICANCE: These results suggest that attempts should be made to understand and improve the disparity that exists between small animal pet owners and veterinary surgeons in Great Britain.