Efficacy of Urine Asymmetric Dimethylarginine Concentration to Predict Azotemia in Hyperthyroid Cats After Radio-Iodine Treatment

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 (¹³¹I) treatment.

Hypothesis/objectives: To evaluate the potential of serum and urinary metabolites and metabolite ratios to predict post-¹³¹I renal azotemia in hyperthyroid cats.

Animals: Hyperthyroid cats (n = 31), before and (3-12 months) after treatment with ¹³¹I 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 ¹³¹I administration. After ¹³¹I 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-¹³¹I 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-¹³¹I azotemia in hyperthyroid cats becoming euthyroid after ¹³¹I treatment. These findings can aid clinicians in managing owner expectations and modify treatment plans.