Development and validation of a standardized IVD technology for screening for chronic kidney disease based on a comparative analysis of proteinuria determination methods
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.Schmidt I.O., Vlasova O.L., Guseinov R.G., Beshtoev A.Kh., Malyshev E.A., Lelyavina T.A.
Keywords
chronic kidney disease
screening
proteinuria
in vitro diagnostics (IVD)
automated analyzers
protein/creatinine ratio
glomerular filtration rate
standardization
About the Authors
Inna O. Shmidt – Researcher, St. Petersburg St. Luke’s Clinical Hospital. Address: 46 Chugunnaya St., St. Petersburg, 194044. https://orcid.org/0000-0003-0653-6757Olga L. Vlasova – Doctor of Physics and Mathematics, Researcher, Peter the Great St. Petersburg Polytechnic University, Institute of Biomedical Systems and Biotechnology,
Higher School of Biomedical Systems and Technology. Address: Bldg. 1A 11 Khlopin St., St. Petersburg, 194021. A. E-mail: vlasova_ol@spbstu.ru
https://orcid.org/0000-0002-9590-703X
Ruslan G. Guseinov – Cand.Sci. (Med.), Deputy Chief Physician for Research, St. Petersburg St. Luke’s Clinical Hospital. Address: 46 Chugunnaya St., St. Petersburg, 194044; E-mail: rusfa@yandex.ru. https://orcid.org/0000-0001-9935-0243
Akhmed Kh. Beshtoev – Researcher, St. Petersburg St. Luke’s Clinical Hospital. Address: 46 Chugunnaya St., St. Petersburg, 194044; Tel.: +7 (812) 576-11-08;
E-mail: akhmed.beshtoev@gmail.com. https://orcid.org/0009-0004-6436-3860
Egor A. Malyshev – Researcher, St. Petersburg St. Luke’s Clinical Hospital. Address: 46 Chugunnaya St., St. Petersburg, 194044; Tel.: +7 (812) 576-11-08;
e-mail: malyshevyegor@gmail.com. https://orcid.org/0000-0001-6294-6182
Tatyana A. Lelyavina – Dr.Sci. (Med.), Leading Researcher, Research Department of Microcirculation and Miocardial Metabolism, Almazov National Medical Research Center. Address: 2 Akkuratov St., St. Petersburg, 197341; e-mail: tatianalelyavina@mail.ru. https://orcid.org/0000-0002-1834-4982
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