Cadmium, active smoking and renal function deterioration in patients with type 2 diabetes

Background: Cadmium is an established nephrotoxin, present in cigarette smoke. We investigated the hazards of cadmium concentration and smoking status on renal function deterioration. We furthermore discerned whether the association of cadmium concentration with renal function deterioration is attributable to smoking status. Methods: Prospective analyses were performed in data of 226 patients of the DIAbetes and LifEstyle Cohort Twente-1 (DIALECT). Cadmium concentrations were determined from EDTA whole-blood. Smoking status was determined via a self-administered questionnaire. Renal function deterioration was defined as need for renal replacement therapy or a persistent decline of ≥30% in estimated glomerular filtration rate from baseline for at least 3 months. Multivariable Cox regression models were performed to calculate hazard ratios (HRs) for the association between smoking status, cadmium concentration and renal function deterioration. Results: Median (interquartile range) whole-blood cadmium was 2.9 (1.9–5.1) nmol/L. Active smokers had significantly higher cadmium [7.4 (3.3–11.7) nmol/L] compared with never smokers [2.6 (1.6–4.2) nmol/L] and former smokers [2.8 (1.8–4.8) nmol/L]. During median follow-up for 6 (4–8) years, renal function deterioration occurred in 60 persons (27%). Both cadmium and active smoking were associated with an increased hazard for renal function deterioration [HR 1.37, 95% confidence interval (95% CI) 1.06–1.78 and 3.77, 95% CI 1.72–8.29, respectively]. In a multivariable model with both smoking status and cadmium concentration included, active smokers have an increased risk for renal function deterioration (HR 3.00, 95% CI 1.22–7.40), while the association between cadmium and renal function deterioration lost statistical significance (HR 1.16, 95% CI 0.87–1.54). Conclusions: Active smoking is associated with progressive kidney disease in type 2 diabetes. The association between cadmium concentration and renal function deterioration in large part determined by smoking status. Extensive assessment of smoking status may be useful in patients with type 2 diabetesat high risk of kidney damage