NGAL and Cystatin C: Two possible early markers of diabetic nephropathy in patients with type 2 diabetes mellitus

Abstract

Introduction. Diabetic nephropathy (DN) is a progressive renal impairment characterized by impaired renal architecture and function and is one of the leading causes of permanent renal impairment. Patients with DN have a high mortality rate, which is primarily due to cardiovascular complications. In everyday practice in the Republic of North Macedonia, serum creatinine, microalbuminuria and glomerular filtration rate are used to detect DN. However, these standard tests do not always allow for detection of initial DN damage. Aim. The aim of this study was to investigate the role of NGAL (in urine) and Cystatin C (in serum) values as adjunctive testing of existing markers (microalbuminuria and creatinine) in unmasking early structural and functional renal impairment in asymptomatic patients with type 2 diabetes mellitus (DM type 2). Methods. This was a prospective, observational (6-month follow-up) study, involving 60 patients aged 35-70 years. The first two groups were patients with diagnosed DM type 2 for a minimum of 5 years, 15 patients diagnosed with DM type 2 with diabetic nephropathy and 15 patients without diabetic nephropathy. The third group consisted of healthy respondents (30). In addition to standard biochemical analyses, the three groups were also examined for body fluid concentrations of NGAL (architect urine NGAL) and Cystatin C (nephelometry), as well as standard biomarkers for renal nephropathy (serum creatinine and microalbumin). Results. The respondents from the three analyzed groups did not differ significantly in terms of gender structure (p=0.71) and age (p=0.068). The study found that (the core values) baseline creatinine, microalbuminuria, NGAL and Cystatin C serum levels were higher in patients diagnosed with DM type 2 and diabetic nephropathy (DN) compared to those with diabetes and without diabetic nephropathy in healthy trials. Also, after 6 months of follow-up, it was proven that in patients diagnosed with DM type 2 and DN all four parameters were higher with confirmed significance unlike the group of patients with DM type 2 without DN. In the group with diabetes and diabetic nephropathy, during the re-evaluation after 6 months of monitoring we registered a non-significant increase in the biomarker NGAL p=0.16), and a significant increase in the biomarker Cystatin C (p=0.016). There was a statistically significant correlation between baseline creatinine values and baseline control values of Cystatin C (p<0.0001), creatinine and NGAL values after a 6-month re-evaluation (p=0.014), all of which were positive. The correlation between the two biomarkers NGAL and Cystatin C were statistically insignificant in the first measurements (p=0.160), and were significant and direct positive on the second measurements, after 6 months (r=0.536, p=0.039). The two markers changed in direct proportion to the serum, with the increasing of one marker in the serum. Also, the other biomarker increased, and vice versa. Conclusion. NGAL and Cystatin C, biomarkers of renal impairment, are correlated with decreased renal function in patients with DM type 2, suggesting that NGAL and Cystatin C may be used as adjunctive tests to existing ones (creatinine and microalbuminuria) to unmask early renal dysfunction.