Are low erythropoietin and 1,25-dihydroxyvitamin D levels indicative of tubulo-interstitial dysfunction in diabetes without persistent microalbuminuria?

Aims: To investigate the relationship between Erythropoietin (EPO) and 1,25-dihydroxyvitamin D levels, and tubular damage in patients with diabetes mellitus (DM) without persistent microalbuminuria. Methods: We measured serum EPO and 1,25-dihydroxyvitamin D levels and tubular injury markers such as urinary N-acetyl-β-d-glucosaminidase (NAG) and retinol binding protein (RBP) levels in 41 non-diabetic controls, 40 patients with Type 1 and 40 with Type 2 DM. Results: Median serum EPO levels were lower in Type 1 (2.57 mIU/ml: p < 0.001) and Type 2 DM (5.69 mIU/ml: p = 0.044) than in controls (8.76 mIU/ml), though haemoglobin levels did not differ. Median 1,25-dihydroxyvitamin D levels were lower in Type 1 (41.0 pmol/l: p = 0.001) and Type 2 DM (41.8 pmol/l: p = 0.035) than in controls (56.1 pmol/l), though serum creatinine, calcium, phosphate and PTH levels did not differ. Median RBP excretion was higher in Type 2 DM (0.35 mg/l vs. 0.23 mg/l: p = 0.013) than in controls. Median NAG excretion was higher in Type 1 DM (1079 μmol/h vs.1030 μmol/h: p = 0.048) compared to controls. Conclusions: Tubulo-interstitial damage with low levels of EPO and 1,25-dihydroxyvitamin D occurs early in Type 1 and Type 2 DM before persistent microalbuminuria.