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Background: Plasma total magnesium concentration (tMg) is a prognostic indicator in cats with chronic kidney disease (CKD), shorter survival time being associated with hypomagnesemia. Whether this risk factor is modifiable with dietary magnesium supplementation remains unexplored., Objectives: Evaluate effects of a magnesium-enriched phosphate-restricted diet (PRD) on CKD-mineral bone disorder (CKD-MBD) variables., Animals: Sixty euthyroid client-owned cats with azotemic CKD, with 27 and 33 allocated to magnesium-enriched PRD or control PRD, respectively., Methods: Prospective double-blind, parallel-group randomized trial. Cats with CKD, stabilized on a PRD, without hypermagnesemia (tMg >2.43 mg/dL) or hypercalcemia (plasma ionized calcium concentration, (iCa) >6 mg/dL), were recruited. Both intention-to-treat and per-protocol (eating ≥50% of study diet) analyses were performed; effects of dietary magnesium supplementation on clinicopathological variables were evaluated using linear mixed effects models., Results: In the per-protocol analysis, tMg increased in cats consuming a magnesium-enriched PRD (β, 0.25 ± .07 mg/dL/month; P < .001). Five magnesium supplemented cats had tMg >2.92 mg/dL, but none experienced adverse effects. Rate of change in iCa differed between groups (P = .01), with decreasing and increasing trends observed in cats fed magnesium-enriched PRD and control PRD, respectively. Four control cats developed ionized hypercalcemia versus none in the magnesium supplemented group. Log-transformed plasma fibroblast growth factor-23 concentration (FGF23) increased significantly in controls (β, 0.14 ± .05 pg/mL/month; P = .01), but remained stable in the magnesium supplemented group (β, 0.05±.06 pg/mL/month; P =.37)., Conclusions and Clinical Importance: Magnesium-enriched PRD is a novel therapeutic strategy for managing feline CKD-MBD in cats, further stabilizing plasma FGF23 and preventing hypercalcemia., (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Microscopic nephrocalcinosis is a common pathological feature of chronic kidney disease (CKD) in cats. Detection of macroscopic nephrocalcinosis using ultrasonography and its implications remain unexplored., Objectives: Identify risk factors associated with ultrasound-diagnosed nephrocalcinosis and evaluate the influence of nephrocalcinosis on CKD progression., Animals: Thirty-six euthyroid client-owned cats with CKD., Methods: Prospective cohort study. Cats with CKD with and without ionized hypercalcemia were enrolled for renal ultrasonography. Cats were categorized according to the presence or absence of ultrasound-diagnosed nephrocalcinosis. Binary logistic regression was performed to identify nephrocalcinosis risk factors. The influence of nephrocalcinosis on CKD progression was assessed using linear mixed models., Results: Ultrasound-diagnosed nephrocalcinosis was evident in 61% of CKD cats overall, with increased prevalence (81%) in those with hypercalcemia. At enrollment, higher blood ionized calcium concentration (odds ratio [OR], 1.27 per 0.1 mg/dL; P = .01), plasma phosphate concentration (OR, 1.16 per 0.1 mg/dL; P = .05), plasma creatinine concentration (OR, 1.29 per 0.1 mg/dL; P = .02) and alanine aminotransferase activity (OR, 2.08 per 10 U/L; P = .04) were independent nephrocalcinosis risk factors. The rate of change in log-transformed fibroblast growth factor-23 differed significantly between groups (P = .04). Cats with CKD and nephrocalcinosis had increasing plasma creatinine concentrations (.03 ± .01 mg/dL/month; P = .04) and phosphate concentrations (.06 ± .02 mg/dL/month; P < .001) and decreasing body weight (.02 ± .01 kg/month; P < .001) over time., Conclusions and Clinical Importance: Nephrocalcinosis is prevalent in cats with CKD, especially in those with hypercalcemia. This pathological feature appears to be associated with CKD progression in cats., (© 2024 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Identification of nephrocalcinosis in cats with chronic kidney disease (CKD) is of clinical interest but the ability of ultrasonography to detect nephrocalcinosis is uncertain., Objectives: To compare ultrasonography, micro-computed tomography (μCT) and histopathology for identification of nephrocalcinosis., Animals: Twelve kidneys from 7 euthyroid client-owned cats with CKD., Methods: Descriptive study. Renal ultrasonography was performed ante-mortem for nephrocalcinosis detection. Kidneys were grouped based on nephrocalcinosis: present, suspected, or absent. When cats died, necropsy was performed. Renal tissue was evaluated using μCT for macroscopic nephrocalcinosis, and nephrocalcinosis volume-to-kidney tissue ratio (macro-VN:KT) and sagittal nephrocalcinosis area-to-kidney tissue ratio (macro-AN:KT) were calculated. Each kidney subsequently was bisected longitudinally, formalin-fixed, and paraffin-embedded for microscopic nephrocalcinosis assessment using von Kossa and Alizarin red staining with AN:KT (VK-micro-AN:KT and AR-micro-AN:KT) quantified using ImageJ. Data are presented as median (range). Relationships between macroscopic and microscopic AN:KT were assessed using Spearman's correlation., Results: Nephrocalcinosis by ultrasonography was considered to be absent in 3, suspected in 3, and present in 5 kidneys; 1 kidney had nephrolithiasis with nephrocalcinosis. The macro-VN:KT was 0.001%, 0.001%, and 0.019%, and the macro-AN:KT was 0.08%, 0.30%, and 1.47%, respectively. Histologically, VK-micro-AN:KT was 0.21%, 2.85%, and 4.56%, and AR-micro-AN:KT was 1.73%, 5.82%, and 8.90% for kidneys where ultrasonographic macro-nephrocalcinosis was absent, suspected, or present, respectively. A strong correlation was identified between macroscopic (macro-AN:KT) and microscopic (VK-micro-AN:KT) nephrocalcinosis (r s  = 0.76; P = .01)., Conclusions and Clinical Importance: Ultrasonographically diagnosed nephrocalcinosis correlates well with macroscopic and microscopic nephrocalcinosis at necropsy despite their separation in time., (© 2024 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Cats presenting with upper urinary tract uroliths (UUTUs) and ureteral obstruction ("obstructive UUTU") are typically younger than cats with idiopathic CKD that often have incidental nephroliths., Hypothesis: Cats with upper urinary tract urolith have 2 clinical phenotypes; a more aggressive phenotype at risk of obstructive UUTU at a young age and a more benign phenotype in older cats, with reduced risk of obstructive UUTU., Objectives: Identify risk factors for UUTU and for obstructive UUTU., Animals: Eleven thousand four hundred thirty-one cats were referred for care over 10 years; 521 (4.6%) with UUTU., Methods: Retrospective VetCompass observational cross-sectional study. Multivariable logistic regression models were performed to identify risk factors for a diagnosis of UUTU vs no UUTU and additionally, obstructive UUTU vs nonobstructive UUTU., Results: Risk factors for UUTU included female sex (odds ratio [OR] 1.6, confidence interval [CI] 1.3-1.9; P < .001), British shorthair, Burmese, Persian, Ragdoll or Tonkinese (vs non-purebred ORs 1.92-3.31; P < .001) breed and being ≥4 years (ORs 2.1-3.9; P < .001). Risk factors for obstructive UUTU were female sex (OR 1.8, CI 1.2-2.6; P = .002), having bilateral uroliths (OR 2.0, CI 1.4-2.9; P = .002) and age, with the odds of obstructive UUTU increasing as age at diagnosis of UUTU decreased (≥12 years, reference category; 8-11.9 years, OR 2.7, CI 1.6-4.5; 4-7.9 years, OR 4.1, CI 2.5-7.0; 0-3.9 years, OR 4.3, CI 2.2-8.6; P < 0.001)., Conclusions and Clinical Importance: Cats diagnosed with UUTU at a younger age have a more aggressive phenotype with higher risk of obstructive UUTU compared to cats over 12 years of age diagnosed with UUTU., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Ionized calcium concentration ([iCa]) is more sensitive for detecting calcium disturbances than serum total calcium concentration but literature on ionized hypercalcemia in cats is limited. Urolithiasis is a possible adverse consequence of hypercalcemia., Hypothesis/objectives: To describe clinical details of diagnoses associated with ionized hypercalcemia in cats and association with urolithiasis., Animals: Cats (238) seen between 2009 and 2019 at a referral hospital with [iCa] above the normal reference interval., Methods: Observational cross-sectional study. Signalment, serum biochemical and imaging findings were reviewed for cats with ionized hypercalcemia considered to be clinically relevant (>1.41 mmol/L). Data were summarized by cause of hypercalcemia (i.e., diagnosis)., Results: Diagnoses for the 238 cats with [iCa] >1.41 mmol/L included: acute kidney injury (AKI; 13%), malignancy-associated (10.1%), idiopathic hypercalcemia (IHC; 10.1%), chronic kidney disease/renal diet-associated (8.4%), iatrogenic (5.5%), primary hyperparathyroidism (2.1%), vitamin D toxicity (2.1%) and granulomatous disease (1.7%). In 112 cases (47.1%), no cause for ionized hypercalcemia could be determined (n = 95), hypercalcemia was transient (n = 12), or the cat was juvenile (<1 year; n = 5). Urolithiasis was identified in 83.3% of AKI, 72.7% of iatrogenic, 61.1% of CKD/renal diet-associated and 50% of IHC cases that were imaged (<50% for other diagnoses). Diagnoses with a high proportion of concurrent total hypercalcemia included primary hyperparathyroidism (100%), vitamin D toxicity (100%), malignancy-associated (71.4%), granulomatous disease (66.7%) and IHC (65.2%)., Conclusions and Clinical Importance: Ionized hypercalcemia was most commonly associated with kidney diseases, neoplasia or IHC. The proportion of urolithiasis cases varied by diagnosis., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Hypothyroidism is a commonly diagnosed endocrinopathy in dogs. This study aimed to investigate the frequency and risk factors for diagnosis of hypothyroidism in UK primary-care practice. Dogs diagnosed with hypothyroidism were identified by searching electronic patient records of primary-care practices participating in VetCompass. A cohort study design estimated one-year (2016) period prevalence and incidence risk for hypothyroidism. Multivariable binary logistic regression models were used to evaluate associations between demographic risk factors and hypothyroidism., Results: From 905,553 dogs, 2,105 dogs were recorded with diagnosed hypothyroidism in 2016; 359 incident and 1,746 pre-existing, giving an annual prevalence of 0.23% (95% CI 0.22-0.24) and annual incidence risk of 0.04% (95% CI 0.04-0.04). Multivariable logistic regression identified 24 predisposed and nine protected breeds. Standard Doberman pinscher (odds ratio [OR] = 17.02, 95% CI 12.8-22.64), Tibetan terrier (11.25, 95% CI 8.27-15.32) and boxer (10.44, 95% CI 8.66-12.58) breeds showed high predisposition. Pug (OR 0.29, 95% CI 0.09-0.89), Yorkshire terrier (OR 0.38, 95% CI 0.24-0.59), Shih-tzu (OR 0.38, 95% CI 0.23-0.64) and Jack Russell terrier (OR 0.40, 95% CI 0.29-0.54) were the most protected breeds. Overall, being a purebred dog, being insured, having bodyweight above the breed-sex mean, increasing age, being neutered and rising adult bodyweight also showed increased odds being a dog living with a diagnosis of hypothyroidism., Conclusions: Several strong breed predispositions for diagnosis of hypothyroidism were identified that can assist with disorder prioritisation in ongoing efforts to improve breed health. Other risk factors were also identified that can assist veterinary surgeons during clinical work-up of suspected cases. Identification of novel evidence for protected breeds provides useful information for research into genetic mechanisms., (© 2022. The Author(s).)

Background: Hypercalcemia is associated with chronic kidney disease (CKD) in cats, but studies assessing the physiologically relevant ionized calcium fraction are lacking., Objectives: To describe the prevalence and incidence rate of ionized hypercalcemia, and to explore predictor variables to identify cats at risk of ionized hypercalcemia in a cohort of cats diagnosed with azotemic CKD., Animals: One hundred sixty-four client-owned cats with azotemic CKD., Methods: Variables independently associated with ionized hypercalcemia at diagnosis of azotemic CKD were explored by binary logistic regression. Cats that were normocalcemic at diagnosis of azotemic CKD were followed over a 12-month period or until ionized hypercalcemia occurred and baseline predictor variables for ionized hypercalcemia explored using Cox proportional hazards and receiver operating characteristic curve analysis., Results: Ionized hypercalcemia (median, 1.41 mmol/L; range, 1.38-1.68) was observed in 33/164 (20%) cats at diagnosis of azotemic CKD and was associated with male sex, higher plasma total calcium and potassium concentrations, and lower plasma parathyroid hormone concentrations. Twenty-five of 96 initially normocalcemic (26%) cats followed for minimum 90 days developed ionized hypercalcemia (median, 1.46 mmol/L; range, 1.38-1.80) at a median of 140 days after diagnosis of azotemic CKD (incidence rate, 0.48 per feline patient-year). Only body condition score was independently associated with incident ionized hypercalcemia., Conclusions and Clinical Importance: The occurrence of ionized hypercalcemia is high in cats with CKD. Continued monitoring of blood ionized calcium concentrations is advised., (© 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

New discoveries relating to phosphorus homeostasis include the hormones fibroblast growth factor-23 and klotho produced by bone and kidney. These hormones, together with novel understanding of how calcium and phosphate ions are carried in colloidal form as calciprotein particles, have changed our view of how phosphorus is regulated. Recognition that high dietary intake of inorganic forms of phosphorus in humans is a risk factor for both cardiovascular and renal diseases have led to re-examination of the impact of inorganic sources of phosphorus in prepared cat foods on renal health. Data suggest that when homeostatic mechanisms lead to proximal tubular (S3 segment) phosphate concentrations exceeding 3.25 mmol/L for a significant part of the day, tubular stress and structural kidney damage ensues. Recent experimental rodent studies support the concept that calciprotein particles form in the proximal tubule at these prevailing phosphate concentrations and trigger proximal tubular damage. Long-term feeding studies in cats suggest that carefully formulated prepared diets containing 1 g/Mcal of inorganic phosphorus (in the form of sodium tripolyphosphate or potassium monophosphate and pyrophosphate), resulting in estimated tubular phosphate concentrations < 2.5 mmol/L can be fed to healthy adult cats without detectable adverse effects on renal health., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., (© 2021 The Authors. Journal of Small Animal Practice published by John Wiley & Sons Ltd on behalf of British Small Animal Veterinary Association.)

Background: Nephrocalcinosis is a pathological feature of chronic kidney disease (CKD). Its pathophysiological implications for cats with CKD are unexplored., Objectives: Identify nephrocalcinosis risk factors and evaluate its influence on CKD progression and all-cause mortality., Animals: Fifty-one euthyroid client-owned cats with International Renal Interest Society (IRIS) stages 2-3 azotemic CKD., Methods: Retrospective cohort study. Histopathological kidney sections were assessed for nephrocalcinosis (von Kossa stain). Nephrocalcinosis severity was determined by image analysis (ImageJ). Ordinal logistic regressions were performed to identify nephrocalcinosis risk factors. The influence of nephrocalcinosis on CKD progression and mortality risk were assessed using linear mixed model and Cox regression, respectively. Cats were categorized by their owner-reported time-averaged phosphate-restricted diet (PRD) intake, where PRD comprised ≥50%, 10-50%, or none of food intake., Results: Nephrocalcinosis was rated as mild-to-severe in 78.4% and absent-to-minimal in 21.6% of cases. Higher baseline plasma total calcium concentration (tCa; odds ratio [OR] = 3.07 per 1 mg/dL; P = .02) and eating a PRD (10%-50%: OR = 8.35; P = .01; ≥50%: OR = 5.47; P = .01) were independent nephrocalcinosis risk factors. Cats with absent-to-minimal nephrocalcinosis had increasing plasma creatinine (0.250 ± 0.074 mg/dL/month; P = .002), urea (5.06 ± 1.82 mg/dL/month; P = .01), and phosphate (0.233 ± 0.115 mg/dL/month; P = .05) concentrations over a 1-year period, and had shorter median survival times than cats with mild-to-severe nephrocalcinosis., Conclusion and Clinical Importance: Higher plasma tCa at CKD diagnosis and PRD intake are independently associated with nephrocalcinosis. However, nephrocalcinosis is not associated with rapid CKD progression in cats., (© 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Derangements in mineral metabolism are one of the main entities in chronic kidney disease-mineral and bone disorder (CKD-MBD). This is the second of a two-part review of the physiology and pathophysiology of calcium homeostasis in feline CKD-MBD. While dysregulation in calcium homeostasis is known to contribute to the development of vascular calcification in CKD, evidence characterising the relationship between serum calcium concentration and nephrocalcinosis and nephrolithiasis is limited. Recently, fibroblast growth factor 23 (FGF23) and α-Klotho have gained increased research interest and been shown to be important biomarkers for the prediction of CKD progression in human patients. However, conflicting evidence exists on their role in calcium homeostasis and vascular and soft tissue calcification. This review details the pathophysiology of calcium disorders associated with CKD-MBD and its implications on vascular and soft tissue mineralisation in human and feline patients. Further prospective studies investigating the clinical consequences of calcium disturbances in cats with CKD are warranted and this may provide additional insight into the pathophysiology of feline CKD-MBD., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Mineral derangements are a common consequence of chronic kidney disease (CKD). Despite the well-established role of phosphorus in the pathophysiology of CKD, the implications of calcium disturbances associated with CKD remain equivocal. Calcium plays an essential role in numerous physiological functions in the body and is a fundamental structural component of bone. An understanding of calcium metabolism is required to understand the potential adverse clinical implications and outcomes secondary to the (mal)adaptation of calcium-regulating hormones in CKD. The first part of this two-part review covers the physiology of calcium homeostasis (kidneys, intestines and bones) and details the intimate relationships between calcium-regulating hormones (parathyroid hormone, calcitriol, fibroblast growth factor 23, α-Klotho and calcitonin) and the role of the calcium-sensing receptor., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: There is a lack of evidence-based guidelines on perioperative insulin administration and fasting time in diabetic dogs. The aim of this study was to compare two protocols with respect to intraoperative changes in blood glucose (BG) concentrations compared to preoperative values., Methods: Thirty-two dogs were included. Dogs of group AM (n = 15) underwent anaesthesia in the morning after 12 hours fasting and received half their usual insulin dose, while dogs of group PM (n = 17) had surgery in the afternoon after 6 hours fasting and received their usual insulin dose; BG was measured before premedication (baseline), after anaesthetic induction, every 30 minutes throughout surgery, at extubation and after anaesthetic recovery. The occurrence of intraoperative complications was recorded., Results: There were no differences between groups in perioperative changes in BG over time, and in the proportion of dogs experiencing complications. Common complications were hypotension (53 per cent of dogs in either groups), hyperglycaemia (67 and 65 per cent in groups AM and PM) and hyperkalaemia (20 and 11 per cent in groups AM and PM)., Conclusions: Either protocols may be used in diabetic dogs undergoing anaesthesia. The occurrence of hyperkalaemia in the study population supports routine intraoperative monitoring of blood potassium concentration., (© 2021 British Veterinary Association.)

Cushing's syndrome is an endocrine disease in dogs that negatively impacts upon the quality-of-life of affected animals. Cushing's syndrome can be a challenging diagnosis to confirm, therefore new methods to aid diagnosis are warranted. Four machine-learning algorithms were applied to predict a future diagnosis of Cushing's syndrome, using structured clinical data from the VetCompass programme in the UK. Dogs suspected of having Cushing's syndrome were included in the analysis and classified based on their final reported diagnosis within their clinical records. Demographic and clinical features available at the point of first suspicion by the attending veterinarian were included within the models. The machine-learning methods were able to classify the recorded Cushing's syndrome diagnoses, with good predictive performance. The LASSO penalised regression model indicated the best overall performance when applied to the test set with an AUROC = 0.85 (95% CI 0.80-0.89), sensitivity = 0.71, specificity = 0.82, PPV = 0.75 and NPV = 0.78. The findings of our study indicate that machine-learning methods could predict the future diagnosis of a practicing veterinarian. New approaches using these methods could support clinical decision-making and contribute to improved diagnosis of Cushing's syndrome in dogs.

Objectives: The aims of this study were to report the postoperative incidence of subcutaneous ureteral bypass (SUB)-associated bacteriuria and risk factors in a large population of UK cats, to identify the commonly implicated isolates in these cases and to report associations of positive postoperative urine cultures with device occlusion or a need for further surgery., Methods: Electronic clinical records were reviewed to identify cats with ureteral obstruction that underwent unilateral or bilateral SUB implantation between September 2011 and September 2019. In total, 118 client-owned cats were included in the study population. Information recorded included signalment, history, surgical and biochemical factors, urinalysis and culture results. Multivariable logistic regression was performed to identify variables associated with a positive postoperative culture., Results: In total, 10 cats (8.5%) had a positive postoperative culture within 1 month postsurgery and 28 cats (23.7%) within 1 year postsurgery. Cats with a positive preoperative culture were significantly more likely to have a positive culture within 6 months postoperatively (odds ratio [OR] 4.09, 95% confidence interval [CI] 1.18-14.18; P  = 0.026). Of the 14 cats with a positive preoperative culture, six (42.9%) returned a positive culture within 1 year postoperatively, and in four cases (66.7%) the same isolate was identified. Cats with a higher end-anaesthetic rectal temperature were significantly less likely to return a positive culture within 3 months (OR 0.398, 95% CI 0.205-0.772; P  = 0.006) postsurgery. Cats culturing positive for Escherichia coli at any time point (OR 4.542, 95% CI 1.485-13.89; P  = 0.008) were significantly more likely to have their implant removed or replaced., Conclusions and Relevance: Perioperative hypothermia and preoperative positive culture were independent predictors of a postoperative positive culture and this should be taken into consideration when managing these cases. Positive postoperative culture rates were higher than have previously been reported.

Background: Hypercalcemia is commonly observed in cats with azotemic chronic kidney disease (CKD). Dietary phosphate restriction is considered standard of care but may contribute to the development of hypercalcemia. The optimal dietary management strategy for these cats is unclear., Objectives: To describe the effect of feeding a moderately phosphate-restricted diet (MP; 1.5 g/Mcal phosphorus; Ca : P ratio, 1.3) to cats with concurrent azotemic CKD and ionized hypercalcemia., Animals: Client-owned cats with ionized hypercalcemia (ionized calcium [iCa] concentration >1.4 mmol/L) at diagnosis of CKD (n = 11; baseline hypercalcemics) or after CKD diagnosis while eating a phosphate-restricted clinical renal diet (0.8 g/Mcal phosphorus; Ca : P ratio, 1.9; n = 10; RD hypercalcemics)., Methods: Changes in variables over time, after starting MP at visit 1, were assessed using linear mixed model analysis within each group of cats. Data are reporte as median [25th, 75th percentiles]., Results: At visit 1, iCa was 1.47 [1.42, 1.55] mmol/L for baseline hypercalcemics and 1.53 [1.5, 1.67] mmol/L for RD hypercalcemics. Blood iCa decreased (P < .001) when RD hypercalcemics were fed MP, with iCa <1.4 mmol/L in 8/10 cats after 2.2 [1.8, 3.7] months. Plasma phosphate concentrations did not change. In contrast, the baseline hypercalcemic group overall showed no change in iCa but a decrease in plasma phosphate concentration during 8.8 [5.5, 10.6] months on the MP diet, although 4/11 individual cats achieved iCa <1.4 mmol/L by 3.4 [1.0, 6.2] months., Conclusions and Clinical Importance: Attenuation of dietary phosphate restriction could result in normalization of iCa in cats that develop hypercalcemia while eating a clinical renal diet., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC. on behalf of the American College of Veterinary Internal Medicine.)

Background: Dietary phosphate restriction improves survival in cats with chronic kidney disease (CKD). However, feeding a phosphate-restricted diet may disrupt calcium homeostasis leading to hypercalcemia in some cats., Objectives: To identify risk factors associated with increasing plasma total calcium (tCa) concentration after transition to a phosphate-restricted diet and to explore its role in CKD-mineral and bone disorder (CKD-MBD) in cats., Animals: Seventy-one geriatric (≥9 years) euthyroid client-owned cats with International Renal Interest Society (IRIS) stage 2 to 3 azotemic CKD., Methods: Retrospective cross-sectional cohort study. Changes in plasma tCa concentration in the first 200 days of diet transition were assessed using linear regression. Binary logistic regressions were performed to identify risk factors for increasing calcium concentration. Changes in clinicopathological variables associated with CKD-MBD over time were explored using linear mixed model and generalized linear mixed model analyses., Results: Lower baseline plasma potassium (odds ratio [OR] = 1.19 per 0.1 mmol/L decrease; P = .003) and phosphate (OR = 1.15 per 0.1 mmol/L decrease; P = .01) concentrations remained independent risk factors for increasing plasma tCa concentration. Plasma creatinine (β = .069 ± .029 mg/dL; P = .02), symmetric dimethylarginine (β = .64 ± .29 μg/dL; P = .03), phosphate (β = .129 ± .062 mg/dL; P = .04), and ln[FGF23] (β = .103 ± .035 pg/mL; P = .004) concentrations had significantly increased rates of change in cats with increasing plasma tCa concentration over time., Conclusion and Clinical Importance: Lower plasma potassium or phosphate concentrations or both at the time of transition of cats with CKD to a phosphate-restricted diet are independently associated with increased risk of an increase in plasma tCa concentration. Increasing plasma tCa concentration is associated with progression of CKD., (© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC. on behalf of the American College of Veterinary Internal Medicine.)

Background: Novel methods to aid identification of dogs with spontaneous Cushing's syndrome are warranted to optimize case selection for diagnostics, avoid unnecessary testing, and ultimately aid decision-making for veterinarians., Hypothesis/objectives: To develop and internally validate a prediction tool for dogs receiving a diagnosis of Cushing's syndrome using primary-care electronic health records., Animals: Three hundred and ninety-eight dogs diagnosed with Cushing's syndrome and 541 noncase dogs, tested for but not diagnosed with Cushing's syndrome, from a cohort of 905 544 dogs attending VetCompass participating practices., Methods: A cross-sectional study design was performed. A prediction model was developed using multivariable binary logistic regression taking the demography, presenting clinical signs and some routine laboratory results into consideration. Predictive performance of each model was assessed and internally validated through bootstrap resampling. A novel clinical prediction tool was developed from the final model., Results: The final model included predictor variables sex, age, breed, polydipsia, vomiting, potbelly/hepatomegaly, alopecia, pruritus, alkaline phosphatase, and urine specific gravity. The model demonstrated good discrimination (area under the receiver operating curve [AUROC] = 0.78 [95% CI = 0.75-0.81]; optimism-adjusted AUROC = 0.76) and calibration (C-slope = 0.86). A tool was developed from the model which calculates the predicted likelihood of a dog having Cushing's syndrome from 0% (score = -13) to 96% (score = 10)., Conclusions and Clinical Importance: A tool to predict a diagnosis of Cushing's syndrome at the point of first suspicion in dogs was developed, with good predictive performance. This tool can be used in practice to support decision-making and increase confidence in diagnosis., (© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Hypertension is a common problem, particularly in older cats. Hypertension secondary to a concurrent disease is the most common form of hypertension in cats, particularly in association with chronic kidney disease or hyperthyroidism. However, idiopathic hypertension may account for up to 24% of cases. Any form of persistent hypertension risks target organ damage (TOD), therefore measurement of blood pressure is vital in at-risk cats to identify occult hypertension before TOD occurs. This article addresses when and how to perform blood pressure measurement in cats, TOD that has been documented in this species, and our evidence basis for treating hypertension., Competing Interests: Disclosure R.F. Geddes has a consultancy agreement with Boehringer Ingelheim., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Clinical signs and consequences of Cushing's syndrome are likely to impact upon a dog's life. Quantification of this impact on a dog's health-related quality-of-life (HRQoL) could contribute to optimized disease management., Hypothesis/objectives: To develop a novel HRQoL tool to aid assessment of dogs with Cushing's syndrome and to evaluate factors that impact upon dogs living with this disease., Animals: Two hundred and ten dogs with Cushing's syndrome and 617 dogs without Cushing's syndrome., Methods: Cross-sectional study design. Dog owners answered questions relating to the HRQoL of their dogs which were refined to develop the final tool. The tool was analyzed for reliability, validity, and interpretability, including Cronbach's alpha and principal components analysis. Factors impacting upon the HRQoL of dogs with Cushing's syndrome were assessed using appropriate nonparametric tests., Results: The tool was refined from 32 questions to 19 and showed good internal consistency (α = .83). Owners rated questions related to "owner impact" as more important and those related to demeanor as less important. There was a positive correlation between the tool score of dogs with Cushing's syndrome and owner's assessment of their dog's quality-of-life (r = .41, P < .001). Dogs currently on treatment with trilostane had a statistically better HRQoL (.33, interquartile range [IQR] .23-.44) than those not receiving trilostane (.36, IQR .33-.54, P = .04)., Conclusions and Clinical Importance: The developed tool quantifies the HRQoL of dogs with Cushing's syndrome and could assist clinicians in the clinical assessment of dogs with Cushing's syndrome., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

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., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

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 (τ b  = 0.14; P = 0.31; n = 33), but significant positive correlation was evident within individual responders over time (within-subject correlation coefficient [r within ], 0.83; 95% confidence interval [CI], 0.63-0.92). Calcitonin correlated negatively over time with plasma ALP (r within , -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., (Copyright © 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

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., (Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

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., (Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

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., (Copyright © 2013 by the American College of Veterinary Internal Medicine.)

Objective: To review the human and veterinary literature on the role of phosphorus in the pathophysiology of chronic kidney disease (CKD) and to explore why control of plasma phosphorus concentration is an important goal in the management of patients with this disease., Data Sources: Human and veterinary studies, reviews, clinical reports, textbooks, and recent research findings focused on phosphate homeostasis and CKD patient management., Human Data Synthesis: Recent studies using rodent models and human patients with CKD have focused on trying to elucidate the role of the phosphatonins, predominantly fibroblast growth factor-23, in phosphate homeostasis and the pathophysiology of secondary renal hyperparathyroidism (SRHP). Fibroblast growth factor-23 is now considered to be a key regulator of plasma phosphorus concentration in people but has only recently been investigated in companion animal species., Veterinary Data Synthesis: Cross-sectional studies of naturally occurring CKD in dogs and cats have shown hyperphosphatemia and SRHP to be highly prevalent and associated with increased morbidity and mortality in these patients. Experimental studies of surgically induced renal impairment in the dog and cat, and cases of naturally occurring CKD have emphasized the ability of renal care diets to modify plasma phosphorus and parathyroid hormone concentrations. Evidence from these studies indicates that maintaining plasma phosphorus concentrations to within the International Renal Interest Society targets for CKD patients improves survival time and reduces clinical manifestations of hyperphosphatemia and SRHP., Conclusions: The maintenance of plasma phosphorus concentrations in to within the International Renal Interest Society targets is recommended in management of CKD patients. The discovery of the phosphatonins has improved understanding of the mechanisms involved in phosphorus homeostasis and SRHP and may lead to improved ability to monitor and manage these patients., (© Veterinary Emergency and Critical Care Society 2013.)

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., (Copyright © 2013 by the American College of Veterinary Internal Medicine.)

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., (Copyright © 2013 by the American College of Veterinary Internal Medicine.)

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.