Risk factors and implications associated with ultrasound-diagnosed nephrocalcinosis in cats with chronic kidney disease.

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.

Detection of nephrocalcinosis using ultrasonography, micro-computed tomography, and histopathology in cats.

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 (rs = 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.

Risk factors for upper urinary tract uroliths and ureteral obstruction in cats under referral veterinary care in the United Kingdom.

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.

Ionized hypercalcemia in 238 cats from a referral hospital population (2009-2019).

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.

Frequency, breed predispositions and other demographic risk factors for diagnosis of hypothyroidism in dogs under primary veterinary care in the UK.

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.

Ionized hypercalcemia in cats with azotemic chronic kidney disease (2012-2018).

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.

New concepts in phosphorus homeostasis and its impact on renal health with particular reference to the cat.

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.

Risk factors and implications associated with renal mineralization in chronic kidney disease in cats.

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.

A feline-focused review of chronic kidney disease-mineral and bone disorders - Part 2: Pathophysiology of calcium disorder and extraosseous calcification.

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.

A feline-focused review of chronic kidney disease-mineral and bone disorders - Part 1: Physiology of calcium handling.

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.

Comparison of two protocols for insulin administration and fasting time in diabetic dogs anaesthetised for phacoemulsification: A prospective clinical trial.

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.

Machine-learning based prediction of Cushing's syndrome in dogs attending UK primary-care veterinary practice.

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.

The effect of attenuating dietary phosphate restriction on blood ionized calcium concentrations in cats with chronic kidney disease and ionized hypercalcemia.

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.

Factors associated with positive urine cultures in cats with subcutaneous ureteral bypass system implantation.

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.

Risk factors associated with disturbances of calcium homeostasis after initiation of a phosphate-restricted diet in cats with chronic kidney disease.

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 (ß = .069 ± .029 mg/dL; P = .02), symmetric dimethylarginine (ß = .64 ± .29 µg/dL; P = .03), phosphate (ß = .129 ± .062 mg/dL; P = .04), and ln[FGF23] (ß = .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.

Development and internal validation of a prediction tool to aid the diagnosis of Cushing's syndrome in dogs attending primary-care practice.

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.

Hypertension: Why Is It Critical?

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.

Development and evaluation of a health-related quality-of-life tool for dogs with Cushing's syndrome.

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.

The role of phosphorus in the pathophysiology of chronic kidney disease.

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.