EXPRESS: Longitudinal evaluation of discordant symmetric dimethylarginine and creatinine as markers of glomerular filtration rate in radioiodine-treated hyperthyroid cats

OBJECTIVES: To determine the frequency and clinical significance of discordant serum symmetric dimethylarginine (SDMA) and creatinine concentrations relative to glomerular filtration rate (GFR) in mature and senior hyperthyroid cats treated with radioactive iodine (RAI). Further, to compare the sensitivity and specificity of two SDMA upper reference limits (>14 and ≥18 µg/dL) and creatinine (≥175 µmol/l) for detecting decreased GFR and evaluate the intra-individual variability of both biomarkers. METHODS: A prospective longitudinal study of 27 client-owned hyperthyroid cats receiving low-dose RAI therapy. At baseline, one, six, and 12 months post-RAI, cats were evaluated for thyroid status, GFR, SDMA, and creatinine concentrations. Discordance was defined as one renal biomarker exceeding its reference interval with the other within/below reference range, using laboratory and age-specific SDMA reference intervals. In euthyroid cats, sensitivity, specificity, and predictive values of SDMA/creatinine for decreased GFR and intra-individual variability were determined. RESULTS: Discordance between SDMA and creatinine ranged from 10%-75%, and was highest with the SDMA limit >14 µg/dL. SDMA-GFR discordance exceeded creatinine-GFR discordance at all time points and was highest at baseline, when all cats were hyperthyroid. In euthyroid cats at 12 months, SDMA >14 µg/dL was more sensitive (83%) but less specific (50%) for decreased GFR than SDMA ≥18 µg/dL (sensitivity 50%, specificity 71%) and creatinine (sensitivity 50%, specificity 85%). Intra-individual variability was similar for both biomarkers (~15%). CONCLUSIONS AND CLINICAL RELEVANCE: Discordant SDMA and creatinine concentrations are frequent in older hyperthyroid cats and are influenced by thyroid status and SDMA reference limits, complicating interpretation. The SDMA limit ≥18 µg/dL improves specificity for decreased GFR and is more appropriate for senior cats. SDMA concentrations of 15-18 µg/dL are less likely to reflect true GFR reduction when creatinine is normal; therefore, non-renal influences such as hyperthyroidism should be considered and ongoing monitoring of renal parameters is recommended.