Background: Hyperthyroid cats are at risk of developing azotemic chronic kidney disease (CKD) and diagnostic tools currently used to screen for CKD in hyperthyroid cats are either unreliable or impractical.Hypothesis: Urine N-acetyl-b-D-glucosaminidase index (NAG i ) is a good biomarker for azotemic CKD in hyperthyroid cats.Animals: Twenty-four newly diagnosed nonazotemic hyperthyroid cats and 10 healthy cats. Methods: All cats were evaluated for hyperthyroidism at baseline. Hyperthyroid cats were treated with methimazole and reevaluated once euthyroid. At the end of the study, cats were divided into 3 groups: healthy cats, nonazotemic, and azotemic euthyroid cats. Baseline group characteristics were compared to predict azotemic CKD. The influence of treatment on NAG i was evaluated.Results: Baseline NAG i was significantly different among groups (P 5 .004). Azotemic cats had a higher median value (13.12 U/g) when compared with healthy cats (1.38 U/g). With NAG i 42.76 U/g, negative and positive predictive values for development of azotemia were 77.7 and 50%, whereas the combination of a urine specific gravity (USG) 1.035 and T 4 47.80 mg/dL enhanced predictive values to 88.9 and 83.3%, respectively. NAG i values decreased significantly over time in treated nonazotemic cats.Conclusions and Clinical Relevance: Baseline NAG i did not differentiate azotemic from nonazotemic euthyroid cats. NAG i could be used to assess renal function during medical therapy allowing the clinician to adjust methimazole dosage accordingly. The combination of USG and T 4 could optimize identification of appropriate candidates for permanent treatment of hyperthyroidism.