Разработка и валидация стандартизированной технологии IVD для скрининга хронической болезни почек на основе сравнительного анализа методов определения протеинурии

Background. Chronic kidney disease (CKD) is a global public health problem. Proteinuria screening plays a key role in its early detection; however, variability in results due to differences in methods and equipment hinders standardization of diagnostics.

Objective. Development and optimization of standardized in vitro diagnostic (IVD) technology for CKD screening based on a comparative analysis of the accuracy, reproducibility, and clinical significance of urine protein determination methods.

Materials and methods. A prospective study of 43 patient urine samples was conducted. Protein concentration was determined using three analyzers: Aution Max AX-4030 (semi-quantitative dry chemistry method), Belur-600 (pyrogallol red, PGR), and AU480 (Beckman Coulter, pyrogallol red/molybdate). Urine and serum creatinine level was determined using the AU480 (Jaffe method, IDMS-standardized). Reproducibility, bias, correlation, and regression analyses were assessed. Glomerular filtration rate (GFR) was calculated using the CKD-EPI, MDRD, and Cockcroft-Gault formulas.

Results. All methods demonstrated high reproducibility (CV < 3.5%). A systematic overestimation of results on the AU480 analyzer by an average of 15–20% compared to the Belur-600 and Aution Max was detected, especially in the low protein concentration range (0–0.99 g/L; p < 0.05). Aution Max demonstrated 100% sensitivity at the clinically relevant urinary protein-to-creatinine ratio threshold of 150 mg/L. A strong inverse correlation between the protein-to-creatinine (P/Cr) ratio and GFR (r=-0.78–-0.81; p<0.001) confirmed the diagnostic value of the P/Cr ratio. The highest agreement in CKD staging was observed between the CKD-EPI and MDRD formulas (88% complete stage agreement).

Conclusion. Based on these results, a standardized two-stage IVD screening technology for CKD was developed. The algorithm includes an initial, highly sensitive screening using Aution Max, followed by confirmation and quantification of proteinuria by determining the P/Cr ratio in urine using a biochemical analyzer (preferably AU480) and calculating GFR using the CKD-EPI formula. To ensure the accuracy and comparability of results, the use of a single platform and reagents within a single laboratory is critical.