Cadmium-Induced Tubular Dysfunction in Type 2 Diabetes: A Population-Based Cross-Sectional Study

The global prevalence of diabetes, and its major complication, diabetic nephropathy, have reached epidemic proportions. The toxic metal cadmium (Cd) also induces nephropathy, indicated by a sustained reduction in the estimated glomerular filtration rate (eGFR) and the excretion of beta(2)-microglobulin (beta M-2) above 300 mu g/day, which reflects kidney tubular dysfunction. However, little is known about the nephrotoxicity of Cd in the diabetic population. Here, we compared Cd exposure, eGFR, and tubular dysfunction in both diabetics (n = 81) and non-diabetics (n = 593) who were residents in low- and high-Cd exposure areas of Thailand. We normalized the Cd and beta M-2 excretion rates (E-Cd and E-beta 2M) to creatinine clearance (C-cr) as E-Cd/C-cr and E-beta 2M/C-cr. Tubular dysfunction and a reduced eGFR were, respectively, 8.7-fold (p < 0.001) and 3-fold (p = 0.012) more prevalent in the diabetic than the non-diabetic groups. The doubling of E-Cd/C-cr increased the prevalence odds ratios for a reduced eGFR and tubular dysfunction by 50% (p < 0.001) and 15% (p = 0.002), respectively. In a regression model analysis of diabetics from the low-exposure locality, E-beta 2M/C-cr was associated with E-Cd/C-cr (beta = 0.375, p = 0.001) and obesity (beta = 0.273, p = 0.015). In the non-diabetic group, E-beta 2M/C-cr was associated with age (beta = 0.458, p < 0.001) and E-Cd/C-cr (beta = 0.269, p < 0.001). However, after adjustment for age, and body mass index (BMI), E-beta 2M/C-cr was higher in the diabetics than non-diabetics of similar E-Cd/C-cr ranges. Thus, tubular dysfunction was more severe in diabetics than non-diabetics of similar age, BMI, and Cd body burden.

Automated summary

The global prevalence of diabetes and its major complication, diabetic nephropathy, is at an epidemic level. Cadmium exposure can induce kidney damage, but little is known about its nephrotoxicity in the diabetic population. A study compared cadmium exposure, kidney function, and tubular dysfunction in diabetics and non-diabetics in Thailand. The results showed that diabetics had a higher risk of tubular dysfunction and reduced kidney function compared to non-diabetics. Cadmium exposure and beta(2)-microglobulin excretion were associated with kidney damage. Tubular dysfunction was more severe in diabetics even after adjusting for other factors.