*Article* **Lifestyle-Related Exposure to Cadmium and Lead Is Associated with Diabetic Kidney Disease**

**Ilse J. M. Hagedoorn 1,\*, Christina M. Gant 2,3,\*, Sanne v. Huizen 1, Ronald G. H. J. Maatman 4, Gerjan Navis 3, Stephan J. L. Bakker <sup>3</sup> and Gozewijn D. Laverman <sup>1</sup>**


Received: 11 June 2020; Accepted: 28 July 2020; Published: 30 July 2020

**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.

**Keywords:** alcohol; cadmium; diabetic kidney disease; diet; lifestyle related exposures; lead; proteinuria; smoking; type 2 diabetes
