Abstract
BACKGROUND: Hyperthyroidism can mask concurrent chronic kidney disease in cats, and no accurate biomarkers are available to predict which cats will develop renal azotemia after radioiodine ((131)I) treatment. HYPOTHESIS/OBJECTIVES: To evaluate the potential of serum and urinary metabolites and metabolite ratios to predict post-(131)I renal azotemia in hyperthyroid cats. ANIMALS: Hyperthyroid cats (n = 31), before and (3-12 months) after treatment with (131)I at the Faculty of Veterinary Medicine (Ghent University, Belgium). METHODS: Retrospective study. Optimized and validated feline extraction and analysis protocols were employed for metabolic profiling of urine and serum samples using ultra-high performance liquid chromatography-high-resolution mass spectrometry. A dual strategy of cross-validated univariate and penalized multivariate logistic regression was applied to determine predictivity (i.e., area under the curve [AUC], accuracy, sensitivity, and specificity) of individual biomarkers and panels. RESULTS: All hyperthyroid cats were non-azotemic before (131)I administration. After (131)I treatment, 7 cats became persistently (≥ 2 timepoints) azotemic while 24 remained non-azotemic. Urinary asymmetric dimethylarginine (ADMA) was identified as a pivotal predictor of post-(131)I azotemia in both univariate and multivariate modeling. When employed as a standalone biomarker, an AUC of 0.851, accuracy of 0.903, sensitivity of 0.714, and specificity of 0.958 were achieved. While pre-treatment USG was significantly different (P = 0.002) between both groups, it did not show enhanced prediction over ADMA, nor in multivariate modeling. CONCLUSIONS AND CLINICAL IMPORTANCE: Urinary ADMA can accurately predict post-(131)I azotemia in hyperthyroid cats becoming euthyroid after (131)I treatment. These findings can aid clinicians in managing owner expectations and modify treatment plans.