Serum myeloid-related protein 8/14 complex is associated with microalbuminuria in patients with type 2 diabetes

Abstract

Objectives: Microalbuminuria (MA) is associated independently with cardiovascular risk and progression of renal disease in patients with diabetes and the normal population. MA is an accepted factor for microvascular defects, in particular in patients with diabetes, and is associated with inflammation. Activated transmigrating macrophages are key cells in these inflammatory processes. Based on the theory that myeloid-related protein 8/14 complex (MRP8/14) is secreted by transmigrating macrophages, we hypothesized that MA was accompanied by elevated MRP8/14 and investigated whether MA predicts MRP8/14 in patients with type 2 diabetes. Methods: A total of 86 men with type 2 diabetes were grouped according to urinary albumin excretion in normoalbuminuria and MA. Serum MRP8/14 levels were measured by enzyme-linked immunosorbent assay. Established cardiovascular risk factors were quantified in both groups and compared with urinary albumin excretion. Results: Albuminuria (mg/day) was positively associated with MRP8/14 ( r = 0.34) and systemic blood pressure ( r = 0.33). Patients with type 2 diabetes and MA demonstrated significantly higher MRP8/14 levels than patients with normoalbuminuria [median (interquartile range), 1.24 (0.97–2.28) µg/ml versus 0.97 (0.67–1.35) µg/ml, p < 0.05]. Serum creatinine levels, systolic blood pressure (SBP), very low density lipoprotein levels and the incidence of hypertension and coronary artery disease were significantly higher in the group with MA. Both groups did not differ significantly in other cardiovascular risk factors. MA was an independent predictor of serum MRP8/14 levels ( β = 0.454) as well as SBP ( β = 0.625) and haemoglobin A1c ( β = 0.322). Conclusion: Our data demonstrate that albumin excretion is associated with the process of macrophage activation determined by MRP8/14 levels. These data not only suggest tissue inflammation as a factor for elevated cardiovascular risk in patients with type 2 diabetes, they further point to a role of macrophage activation in this process.