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.

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.