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

Abstract

Background: Diabetic nephropathy (DN) is a type of progressive kidney disease affecting approximately 40% of patients with diabetes. Current DN diagnostic criteria predominantly rely on albuminuria and serum creatinine (sCr) levels. However, the specificity and reliability of both markers are limited. Hence, reliable biomarkers are required for early diagnosis to effectively manage DN progression. Methods: In this study, a cohort of 159 individuals were clinically evaluated and the plasma levels of NGAL, IGFBP-1, IGFBP-3, and IGFBP-4 were determined using Multiplexing Assays. Additionally, the association between the plasma levels of NGAL, IGFBP-1, IGFBP-3, and IGFBP-4 in patients with DN were compared to those in patients with T2D without kidney disease and control participants. Results: Circulating level of 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). IGFBP-4 showed a similar pattern, where it was highest in people with DN (795.61 ng/ml ±130.7) compared to T2D and non-diabetic people (374.56 ng/ml ±86.8, 273.06 ng/ml ±27.8 respectively, ANOVA p < 0.01). The data from this study shows a significant positive correlation between NGAL and IGFBP-4 in people with DN (ρ =.620, p < 0.005). IGFBP-4 also correlated positively with creatinine level and negatively with eGFR, in people with DN supporting its involvement in DN. Conclusion: The data from this study shows a parallel increase in the plasma levels of NGAL and IGFBP-4 in DN. This highlights the potential to use these markers for early diagnosis of DN.