Association of significantly elevated serum levels of NGAL and IGFBP4 in patients with diabetic nephropathy

Abstract Background: Diabetic nephropathy (DN) is a kidney-related complication affecting approximately 40% of patients with diabetes. Current DN diagnostic criteria predominantly rely on albuminuria and serum creatinine levels; however, the specificity and reliability of both markers are limited. Hence, reliable biomarkers are required to diagnose and effectively manage DN progression. Methods: Here we investigated the expression level and the association between neutrophil gelatinase-associated lipocalin (NGAL), IGFBP-1, IGFBP-3, and IGFBP-4 in patients with DN and compared it to patients with T2D and control participants. A cohort comprise of 159 individuals (DN = 67) was clinically evaluated and circulatory levels of NGAL, IGFBP1, IGFBP3, and IGFBP4 were determined using ELISA. Results: Levels of circulating NGAL were significantly higher in people with DN compared to people with T2D and non-diabetic groups (92.76 ± 7.5, 57.22 ± 8.7, and 52.47 ± 2.9 mg/L, respectively; p < 0.0001). IGFBP4 showed a similar pattern, where it was highest in people with DN (795.61 ng/ml ±130.7) compared to people with T2D and non-diabetic respectively (374.56 ng/ml ±86.8, 273.06 ng/ml ±27.8, ANOVA p<0.01). Our analysis presents a significant positive correlation between NGAL and IGFBP4 in people with DN (ρ =.620, p <0.005). IGFBP4 also correlated positively with creatinine level and negatively with eGFR, in people with DN supporting its involvement in DN. Conclusion: Our results report the association between the rise in NGAL and IGFBP4 levels in DN and suggest them as potential markers to aid DN diagnosis.