Kidney Damage in Diabetics Exposed to Cadmium and Lead: The Emergent Role for β2-Microglobulin

Elevated levels of circulating β2-microglobulin (β2M) are linked to an increased risk of developing hypertension and hyperglycemia. The mechanism of this association, however, remains unclear. One hypothesis which has recently gained traction is that environmental pollutants, particularly cadmium (Cd) and lead (Pb), by inducing kidney tubular cell toxicity, promote the development and progression of diabetic kidney disease. Herein, we analyzed data from a Thai cohort of 72 diabetics and 65 non-diabetic controls who were chronically exposed to low levels of Cd and Pb. Serum concentrations of β2M inversely correlated with the estimated glomerular filtration rate (eGFR) (r = −0.265), and directly with age (r = 0.200), fasting plasma glucose (r = 0.210) and systolic blood pressure (r = 0.229). The prevalence odds ratio (POR) for hyperglycemia increased 7.7% per every 1-year increase in age (p = 0.004), and increased 3.9-fold, 3.1-fold, and 3.7-fold in those with serum β2M levels ≥ 5 mg/L (p = 0.002), Cd/Pb exposure category 2 (p = 0.021), and category 3 (p = 0.014), respectively. The POR for hypertension was increased 2.9-fold, 3-fold, and 4-fold by hyperglycemia (p = 0.011), Cd/Pb exposure category 2 (p = 0.050) and category 3 (p = 0.008). The POR for albuminuria was increased 3.5-fold by hyperglycemia (p = 0.005). In conclusion, albuminuria was particularly pronounced in diabetics who have serum β2M above 5 mg/dL plus chronic exposure to low-dose Cd and Pb.