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.

Systemic Neutrophil Gelatinase-Associated Lipocalin Alterations in Chronic Pancreatitis: A Multicenter, Cross-Sectional Study

“…Combining NGAL with other potential mechanistic markers such as IL-17 may improve accuracy for CP compared with controls or AP/RAP ( 36 , 37 ). Urine NGAL is currently being investigated as a biomarker for acute kidney injury ( 38 , 39 ), diabetic nephropathy, or diabetic kidney disease ( 40 , 41 ), and others are working on ways to test plasma NGAL using automated assays ( 42 ). Because we did not see differences in NGAL levels in the urine, urine NGAL may be specific to kidney injury and not CP.…”

“…There is conflicting evidence on whether NGAL promotes insulin resistance or counteracts diabetes ( 44 , 45 ). However, several studies suggest NGAL is elevated in diabetes associated with microvascular complications (neuropathy and nephropathy) ( 40 , 41 , 46 ). Here, NGAL levels were higher in subjects with both CP and diabetes compared with CP alone, although we were unable to compare with a control group with diabetes because of a limitation in the PROCEED study design.…”

Potential Role of N-Cadherin in Diagnosis and Prognosis of Diabetic Nephropathy

“…DN patients were identified based on elevated Albumin-to-creatinine ratio (ACR) in a spot urine sample in accordance with the American Diabetes Association criteria ( 33 ). Patients’ exclusion criteria included: 1) Non-diabetic kidney disease, 2) Chronic liver disease, 3) Heart failure, 4) Current/recent infection, 5) Acute/chronic inflammatory disease, 6) Allergic condition, 7) Autoimmune disease, 8) Malignancy, 9) Patients with T1D and 10) ESRD ( 34 ).…”

Identification of ferroptosis-related genes as potential diagnostic biomarkers for diabetic nephropathy based on bioinformatics

“…It is characterized by progressive renal impairment, deterioration of glomerular filtration rate (GFR), elevated serum creatinine level (SCR), hypertension, and high mortality ( Giralt-López et al, 2020 ; Zhou et al, 2022 ). However, the specificity and reliability of these two indicators are limited ( Ali et al, 2022 ). In recent years, researchers have explored various biomarkers and molecular pathways associated with the development and progression of DN ( Pentyala et al, 2015 ; Liang et al, 2022 ).…”