B-031 Validation of a Novel Fully Automated Immunoassay for Symmetric Dimethylarginine (SDMA)

Abstract Background Accurate kidney function measurement is crucial for managing acute kidney injury (AKI) and chronic kidney disease (CKD). Traditional biomarkers like creatinine and cystatin C (CysC) have limitations. Creatinine levels are influenced by factors like muscle mass, diet, and hydration, leading to inaccurate results, particularly in patients with atypical body compositions. The inclusion of race in creatinine-based equations has also raised concerns about underestimating kidney dysfunction in black individuals. CysC, while less affected by race, can still be influenced by extrarenal factors and may miss early kidney dysfunction. Symmetric dimethylarginine (SDMA) is a promising new biomarker, offering more accurate kidney function assessment as it is less affected by extrarenal factors. However, current SDMA testing methods, like liquid chromatography-tandem mass spectrometry (LC-MS), are time-consuming and impractical for routine clinical use. This study evaluates the performance of the IDEXX SDMA® Test, an automated immunoassay for SDMA, comparing it with LC-MS and establishing reference intervals using over 700 samples. This method could improve kidney disease diagnosis, enabling earlier interventions and better patient outcomes. Methods Serum samples were analyzed on the IDEXX SDMA® Test, a high-throughput, competitive, homogeneous enzyme immunoassay run on a Beckman Coulter AU5800 chemistry auto analyzer (Beckman Coulter, Brea, CA). The IDEXX SDMA® reagent kits, calibrator kit, and low and high control kits were used for the analysis. The reference interval was established using 611 samples from the Association for Diagnostics & Laboratory Medicine (ADLM, formerly AACC) Universal Sample Bank. Results The SDMA immunoassay test demonstrated a limit of detection (LOQ) of 5 µg/dL and an analytical measurement range (AMR) of 5–100 µg/dL. Inter-assay precision was acceptable, with a coefficient of variation (CV) of <20% and <10% at healthy (10 µg/dL) and abnormal (46 µg/dL) concentrations, respectively. Intra-assay precision also met acceptable standards, with a CV <10% across the healthy and abnormal range. Sample stability testing demonstrated that SDMA is stable in human serum for 7 days at 4°C, -20°C, and 25°C. Interference studies for hemolysis, lipemia, icterus, and drugs showed no significant effects on SDMA measurement. Hemolysis at 500 mg/dL did not cause significant interference, and lipemic and icteric interference were minimal. Drug interference was absent within therapeutic ranges, and no cross-reactivity with ADMA and MMA was observed up to 40 µg/dL. The IDEXX SDMA® immunoassay was compared to LC-MS/MS using 730 serum samples, showing strong correlation (R = 0.97) and confirming method agreement. The reference interval was established, per CLSI EP28-A3, as 8.2–15.4 µg/dL using 611 samples from the ADLM Universal Sample Bank. Conclusion In conclusion, we validated a novel SDMA immunoassay (IDEXX SDMA®), established its reference interval, and confirmed its comparability to LC-MS. The use of the ADLM universal sample bank to establish reference intervals further strengthens the clinical relevance of this assay. With its high throughput and potential to serve as a more specific biomarker for kidney function, this immunoassay could enhance patient outcomes in cases of kidney dysfunction by making results more readily available for routine care.