Serum fetuin-A in nondialyzed patients with diabetic nephropathy: Relationship with coronary artery calcification

Background. Fetuin-A is the most potent circulating inhibitor of calcium phosphorus precipitation and, possibly, an important mediator of insulin resistance. Methods. In order to determine the role of fetuin-A in the high coronary artery calcification (CAC) burden seen in nondialyzed individuals with diabetic nephropathy (DN), post-hoc analyses of data collected from a cross-sectional study of 88 patients with type 2 diabetes mellitus was done [age, 40-65 years; normoalbuminuria, N = 30 (Latinos); DN, N = 58 (Latinos and African Americans)]. Results. The serum levels of fetuin-A were significantly higher among Latinos with DN when compared to either African Americans with DN or Latino diabetics with normoalbuminuria. Upon adjusting the data for race/ethnicity, there was a strong, direct relationship between serum fetuin-A levels and the CAC score (r = 0.22, P = 0.038) in the study cohort; however, a strong interaction between the nephropathy status and relationship of serum fetuin-A levels with CAC score was present (DN: r = 0.36, P = 0.006; diabetic controls, r = 0.0, P = 0.98). Among individuals with DN, the significance of the association persisted even after controlling the data for other predictors of CAC (partial r = 0.33, P = 0.018). Furthermore, there was a significant direct relationship between serum fetuin-A and serum triglycerides (partial r = 0.27, P = 0.01) and albumin (partial r = 0.30, P = 0.005), and an inverse relationship with glomerular filtration rate (r = -0.24, P = 0.03). Conclusion. This first study in early stages of diabetic chronic kidney disease shows that the role of serum fetuin-A may be far more complex than previously described. During predialysis stage of DN, there is a direct relationship between serum fetuin-A levels and CAC score. The reasons for this association in the presence of nephropathy are unclear, but may be secondary to proatherogenic insulin resistance.