Evaluation of serum cystatin C and chromogranin A as markers of nephropathy in patients with Type 2 diabetes mellitus

Nephropathy is a significant cause of morbidity and mortality in patients with diabetes mellitus (DM). The condition is characterized by persistent albuminuria and years of progressive renal structural changes associated with decline in the glomerular filtration rate (GFR). This study evaluates whether serum concentrations of the endogenous markers of GFR, cystatin C and chromogranin A could be used as indicators of nephropathy in 77 patients with Type 2 DM. On the basis of early morning urine microalbumin:creatinine ratio, patients were divided into patients without diabetic nephropathy (DN) who were normoalbuminuric (n=27) and patients with DN who were microalbuminuric (n=8) or macroalbuminuric (n=42). Patients with reduced GFR or elevated serum cystatin C did not show the expected increase in serum chromogranin A. Twenty-six percent of the patients with normoalbuminuria and 6%, of those with DN had serum chromogranin A below the detection limit of the assay (<2 U/L). In patients with DN, serum chromogranin A showed significant correlation with serum cystatin C, but not with serum creatinine and creatinine clearance. Serum cystatin C and creatinine showed poor correlation with duration of DM and HbA(1c). Serum cystatin C and creatinine were significantly higher in patients with DN than in normoalbuminuric patients. Serum cystatin C showed significant correlation with serum creatinine (rs=0.45, p=0.002), but not with creatinine clearance (rs=-0.23, p=0.17) in patients with DN. Four of nine patients with creatinine clearance between 50 and 80 mL/min had increased (<greater than or equal to>1.4 mg/L) serum cystatin C compared with only two patients with increased serum creatinine concentration. Twenty of 50 (40%) patients with DN had elevated serum cystatin C compared with 6 of 50 (12%) with elevated serum creatinine. If microalbuminuria is regarded as the "gold-standard" test, serum cystatin C has a sensitivity of 40% and specificity of 100% for the detection of DN. However, further studies are required to confirm the usefulness of serum cystatin C estimation as a screening test and as an early indicator and predictor of the development of DN.