Assessment of Beta-2 Microglobulin, serum creatinine and creatinine clearance in chronic kidney disease patients in KwaZulu-Natal

Abstract

Background: Chronic kidney disease (CKD) is a major and escalating global health burden, affecting 8-16% of the population and disproportionately impacting low and middle-income countries such as South Africa. KwaZulu-Natal, in particular, bears a high CKD prevalence, with 67% of patients hypertensive, 24% diabetic, and 23% HIV-positive in this cohort. Conventional biomarkers like serum creatinine (sCr) are late indicators of renal dysfunction, often rising only after substantial nephron loss. Beta-2 microglobulin (B2M), a low molecular weight protein filtered by the kidneys and independent of muscle mass, may provide earlier detection of kidney impairment and improved risk stratification, but its clinical utility remains underexplored in routine clinical practice and in African populations. Aims and Objectives: This study aimed to assess the clinical utility of B2M, alongside serum creatinine and creatinine clearance, for the diagnosis and staging of CKD in KwaZulu Natal. The specific objectives were: (1) to evaluate the association between B2M levels and leading CKD aetiologies (hypertension, diabetes and HIV); and (2) to determine the correlation between B2M levels and estimated glomerular filtration rate (eGFR) calculated with the CKDEPI 2021 equation. Materials and Methods: A retrospective cross-sectional study was performed on 173 CKD patients (53% female, mean age 54.3±15.8 years) from the Clinical Medicine Research Laboratory, University of KwaZulu-Natal. Serum samples were analysed for B2M concentrations using enzyme-linked immunosorbent assay (ELISA). Clinical and biochemical data, including sCr and eGFR, were extracted from laboratory databases. Participants were stratified by key comorbidities (hypertension, diabetes, and human immunodeficiency virus). Statistical methods included descriptive statistics, ANOVA, bivariate and multivariable regression, and correlation analysis to explore associations between biomarkers, CKD stages, and clinical variables. Results: B2M concentrations demonstrated a distinctive J-shaped distribution across CKD stages: elevated in Stage 1 (mean 0.19±0.32 μg/mL), dipping in Stage 2 (0.12±0.21 μg/mL), and rising sharply in Stage 3 (0.30±0.41 μg/mL) and Stage 4 (0.52±0.46 μg/mL) (p = 0.032). B2M showed a robust inverse correlation with eGFR (r = -078, p = 0.001), particularly in ii hypertensive (r = -0.20, p = 0.034) and diabetic (r = -0.36, p = 0.021) subgroups. By contrast, serum creatinine showed significant increases only at advanced stages of CKD. Multivariable regression confirmed CKD stages 3-4 as independent predictors of higher B2M after adjusting for demographic and clinical covariates. B2M was not significantly influenced by sex or muscle mass. HIV-positive patients exhibited higher B2M, but without a significant correlation to eGFR. The overall pattern supports B2M as a more sensitive marker for early nephron stress and risk stratification in multi-morbid cohorts. Conclusion: B2M is a sensitive, early-stage biomarker for CKD in KwaZulu-Natal, outperforming sCr in early detection and disease monitoring, particularly among hypertensive and diabetic patients. Its independence from demographic confounders and strong association with CKD severity support its integration into local diagnostic pathways. Routine B2M testing could enable earlier intervention, improved risk stratification, and optimisation of outcomes in high-risk, resource-constrained settings. Further research is warranted to validate B2M’s predictive value and cost-effectiveness in larger, prospective cohorts and to define its role in multi-marker diagnostic panels.