The inverse association of glomerular function and urinary β2-MG excretion and its implications for cadmium health risk assessment

Abstract

Urinary β2-microgroblin (β2-MG) excretion levels above 300 μg/g creatinine are used to indicate defective tubular reabsorption. Arguably, increased urinary β2-MG excretion could also reflect glomerular filtration rate decline. Thus, we investigated an association between urinary β2-MG and estimated glomerular filtration rate (eGFR). We studied 527 subjects, aged 30-87 years (mean 51.2), who lived in a rural area of Thailand polluted with cadmium (Cd). Of this cohort, 10.3% had urinary Cd levels <2 μg/g creatinine and 53.5% had urinary Cd levels ≥5 μg/g creatinine. Half (53.1%) of the participants had urinary β2-MG levels ≥ 300 μg/g creatinine, and 11.6% had low GFR, defined as eGFR <60 mL/min/1.73 m². Lower eGFR values were associated with older age (β = -0.568, P < 0.001), higher urinary β2-MG (β = -0.170, P < 0.001), higher urinary Cd (β = -0.103, P = 0.005) and diabetes (β = 0.074, P = 0.032). An inverse association between eGFR and urinary β2-MG was evident in subjects with low GFR (β = -0.332, P = 0.033), but not in those with GFR >90 mL/min/1.73 m² (β = -0.008, P = 0.896). These findings suggested Cd-induced nephron loss and reduced tubular reabsorption in low eGFR subjects. Urinary β2-MG levels <300 μg/g creatinine were associated with 4.66 (95% CI: 1.92, 11.32) fold increase in the POR for low GFR, compared with urinary β2-MG levels <100 μg/g creatinine. Findings in the present study cast doubt on a cut-off value for urinary β2-MG, while lending support to the notion that elevated urinary β2-MG excretion could indicate a fall of GFR.

Keywords: Cadmium; Chronic kidney disease; Estimated glomerular filtration rate; Health risk assessment; Tubular dysfunction; β2-microglobumin.