Abstract
Background: Environmental factors contributing to diabetic kidney disease are incompletely understood. We investigated whether blood cadmium and lead concentrations were associated with the prevalence of diabetic kidney disease, and to what extent lifestyle-related exposures (diet and smoking) contribute to blood cadmium and lead concentrations. Material and methods: In a cross-sectional analysis in 231 patients with type 2 diabetes included in the DIAbetes and LifEstyle Cohort Twente (DIALECT-1), blood cadmium and lead concentrations were determined using inductively coupled plasma mass spectrometry. The associations between diet (derived from food frequency questionnaire), smoking and cadmium and lead were determined using multivariate linear regression. The associations between cadmium and lead and diabetic kidney disease (albumin excretion >30 mg/24 h and/or creatinine clearance <60 mL/min/1.73 m2) were determined using multivariate logistic regression. Results: Median blood concentrations were 2.94 nmol/L (interquartile range (IQR): 1.78–4.98 nmol/L) for cadmium and 0.07 µmol/L (IQR: 0.04–0.09 µmol/L) for lead, i.e., below acute toxicity values. Every doubling of lead concentration was associated with a 1.75 (95% confidence interval (CI): 1.11–2.74) times higher risk for albuminuria. In addition, both cadmium (odds ratio (OR) 1.50 95% CI: 1.02–2.21) and lead (OR 1.83 95% CI: 1.07–3.15) were associated with an increased risk for reduced creatinine clearance. Both passive smoking and active smoking were positively associated with cadmium concentration. Alcohol intake was positively associated with lead concentration. No positive associations were found between dietary intake and cadmium or lead. Conclusions: The association between cadmium and lead and the prevalence of diabetic kidney disease suggests cadmium and lead might contribute to the development of diabetic kidney disease. Exposure to cadmium and lead could be a so far underappreciated nephrotoxic mechanism of smoking and alcohol consumption.
Highlights
Diabetic kidney disease (DKD) is one of the most debilitating complications in patients with type 2 diabetes (T2D) [1]
Effective treatment options are available for reduction of albuminuria, blood pressure control and glycemic regulation, progression of DKD into end-stage kidney disease (ESKD) is still common, underlining the necessity to identify additional mechanisms to target for renoprotection [2,3,4]
Evidence suggests that low blood levels of Cd and/or Pb already have unwarranted effects, as associations have been found between limited Cd and/or Pb blood concentrations and renal tubular defect markers, reduced estimated glomerular filtration rate (eGFR) and/or albuminuria [8,9,10,11,12,13]
Summary
Diabetic kidney disease (DKD) is one of the most debilitating complications in patients with type 2 diabetes (T2D) [1]. Cd and Pb bind to low-molecular-weight proteins, which are freely filtered through the glomerulus and reabsorbed by the proximal tubules, causing primary tubular toxicity [5] This may lead to albuminuria and progressive kidney disease towards ESKD [6]. We investigated whether blood cadmium and lead concentrations were associated with the prevalence of diabetic kidney disease, and to what extent lifestyle-related exposures (diet and smoking) contribute to blood cadmium and lead concentrations. Every doubling of lead concentration was associated with a 1.75 (95% confidence interval (CI): 1.11–2.74) times higher risk for albuminuria Both cadmium (odds ratio (OR) 1.50 95% CI: 1.02–2.21) and lead (OR 1.83 95% CI: 1.07–3.15) were associated with an increased risk for reduced creatinine clearance. Exposure to cadmium and lead could be a so far underappreciated nephrotoxic mechanism of smoking and alcohol consumption
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