Serum arylhydrocarbon receptor transactivating activity is elevated in type 2 diabetic patients with diabetic nephropathy

Aims/Introduction Evidence is emerging that exposure to persistent organic pollutants (POPs) is a risk factor for obesity-related diseases and for diabetes mellitus (DM). We found that POPs could be measured by a cell-based arylhydrocarbon receptor (AhR)-dependent reporter assay. We tested if serum AhR transactivating (AHRT) activities are a risk factor for diabetic nephropathy in people with type 2 diabetes. Materials and Methods We enrolled diabetic patients with normoalbuminuria (n=36), microalbuminuria (n=29), macroalbuminuria (n=8) and end-stage renal disease (n=31). Sera were tested for their AHRT activities, which were standardized by an AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and expressed as TCDD equivalents (TCDDeqpmol/L). Results Mean serum AHRT activities were higher in patients with microalbuminuria (40.1 +/- 7.1pmol/L), macroalbuminuria (37.4 +/- 5.5pmol/L) and end-stage renal disease (59.1 +/- 20.0pmol/L) than in subjects with normoalbuminuria (12.7 +/- 5.4pmol/L; P<0.05 for all comparisons). Serum AhR ligands showed a correlation with estimated glomerular filtration rate (eGFR; r=-0.663, P<0.001), serum creatinine level (r=0.635, P<0.001), systolic blood pressure (r=0.223, P=0.026), glycated hemoglobim (r=0.339, P<0.001) and diabetic duration (r=0.394, P<0.001). In a multiple regression analysis, diabetic nephropathy was found to be an independent risk factor for higher AHRT activity after controlling for the confounding factors. Conclusions The present findings suggest serum AHRT activity, thus serum AhR ligands, is a risk factor for diabetic nephropathy. Further studies are required to clarify if an accumulation of POPs in the body is causally related to diabetic nephropathy.