Urinary Neutrophil Gelatinase-Associated Lipocalin as an early marker for diagnosis of diabetic nephropathy in T2DM patients and its correlation to albumin creatinine ratio

Abstract

Background:The presence of micro albuminuria is considered as the earliest indicator or warning signal to renal and cardiovascular disease in patients with T2DM, associated with significant glomerular damage. In addition, the early structure damage in both tubular structure and glomerular may be present in normal albuminuria. So there is a need to find biomarkers that help in identification the patients at risk of the disease. The appearance of NGAL in the urine of patients may indicate early glomerular injury, and this has been demonstrated at earlier stage than the appearance of microalbuminuria.Objectives were to evaluate Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL) as an early marker for diagnosis of diabetic nephropathy in T2DM patients and its correlation to albumin creatinine ratio. Methods:The study was conducted on 84 subjects, from (18- 80 years old), 45 (53.5%) were males and 39 (46.4%) were females (table 3), with mean age (58.18 ± 13.98) They were collected from Endocrinology and nephrology clinic after a written consent was taken from the patients at Zagazig University Hospital. The subjects were divided into 4 groups according to KDIGO guide lines, Classification of albuminuria (2012): Group (1): 21 healthy control subjects of comperative group and sex. Group (2):          21 T2DM patient with normoalbuminuria (albuminuria<30 mg/g). Group (3):       21 T2DM patient with microalbuminuria (albuminuria 30-300 mg/g). Group (4):   21 T2DM patient with macroalbuminuria (albuminuria >300 mg/g). All subjects of this study were be subjected to the following: Estimation of GFR, Albumin, creatinine ratio in urine and Measurement of urinary neutrophil gelatinase associated lipocalin in urine. Results:Our study showed that that urinary NGAL is higher in diadetic patients compared with non-diabetic controls with high significant difference (p < 0.0000). Also, there was high significant difference between diabetic groups on comaparison as regades urinary NGAL level between Gr III (microalbuminuria) (180.86 ±38.16 ng/ml) and Gr IV (macroalbuminuria) (354.24 ±99.12ng/ml) than Gr II (normoalbuminuria) (20.01±1.89 ng/ml) with high significant difference (r = -5.668, P = 0.000).  Our study showed that Gr IV (macroalbuminuria) had higher NGAL level (354.24 ±99.12ng/ml) in comparison to Gr II (normoalbuminuria) (20.01±1.89ng/ml), Gr III (microalbuminuria) (180.86 ±38.16ng/ml), and Gr I (control) (3.18±1.64ng/ml). We found GFR was high in G1 (normoalbuminuric patients) (115.42 ± 12.52) than control group (107.53 ± 6.59) (p =0.055).  NGAL was high in G1 (normoalbuminuric patients) (20.01±1.89) than control group (3.18±1.64). So, Urinary NGAL can be considered as a promising early marker for DN as we found a high level of NGAL in normoalbuminuric patients, especially those with long-standing DM, uncontrolled diabetes, and dyslipidemia. Conclusion:urinary NGAL was higher in cases with macroalbuminuria than microalbuminuria and normoalbuminuria. Urine NGAL can be used as an early biomarker for DN as we found a high level of NGAL in normoalbuminuric patients, especially those with long-standing DM, uncontrolled diabetes, and dyslipidemia. These results suggest a possible role of urinary NGAL to be promising new biomarker with the ability to reflect renal damage and impairment.