Elevated levels of netrin-1 in the serum of patients with diabetic nephropathy: Relationship with renal function and inflammation

Netrin-1, a survival factor, is highly induced and excreted after renal injury in animal experiments. We aimed to research the relationship between serum netrin-1 and parameters of renal tubule function as well as circulating inflammatory cytokines and to evaluate effect factors for netrin-1 in humans with type 2 diabetes mellitus (T2DM) undergoing different levels of albuminuria. In total, 81 T2DM patients were included and divided into three groups according to their amount of 24-h urine albumin excretion (UAE) after receiving consent. Plasma netrin-1, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were quantified by commercially available enzyme-linked immunosorbent assay kits and the data were analyzed to assess whether serum netrin-1 correlates significantly with disease progression. The results showed that plasma netrin-1 level in patients with macroalbuminuria was significantly higher than that in those with microalbuminuria and normoalbuminuria. Plasma netrin-1 level was significantly associated with UAE, estimated glomerular filtration rate (eGFR), IL-6, and TNF-α independently of age, sex, diabetes duration, and glycosylated hemoglobin (HbA1c). However, no correlation was found between netrin-1 and β2-microglobulin (β2-MG). Our studies may suggest that serum netrin-1 concentrations are increased with diabetic nephropathy progression, particularly in patients with macroalbuminuria, which are associated with renal insufficiency and compensatory responses after inflammation.