Search

Abstract 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.

Abstract 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.

Abstract 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 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.

Abstract 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.

Abstract 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