Hypoxia Inducible Factor-1 Alpha as a Diagnostic Marker in Early Diabetic Nephropathy

Background: Research on the diagnostic utility of hypoxia-inducible factor-1 alpha (HIF-1α) as an indicator of diabetic kidney disease (DKD) in the Indian population is lacking. We aimed to assess the relationship between the circulating HIF-1α levels and serum creatinine in individuals with DKD. Methods: This observational, analytical case–control study enrolled 80 patients (40 cases and 40 controls) with diabetes mellitus stratified according to serum creatinine (≥1.4 mg/dL and ≤1.4 mg/dL). Data on glycated hemoglobin (HbA1c) and serum creatinine levels were collected. HIF-1α levels were estimated using enzyme-linked immunosorbent assay, and for estimated glomerular filtration rate (eGFR), the chronic kidney disease epidemiology collaboration formula was utilized. Group comparisons were performed using an independent t -test and analysis of variance. Pearson correlation, receiver operating characteristic (ROC) curve analysis, multivariable logistic regression, and multiple linear regression were used to assess associations and diagnostic performance. Results: Circulating HIF-1α levels were significantly higher in cases compared to controls (4.88 ± 2.16 vs. 3.25 ± 0.83 ng/mL, P < 0.001). HIF-1α showed a moderate positive correlation with serum creatinine ( r = 0.436, P < 0.001) and an inverse correlation with eGFR ( r = −0.440, P < 0.001). ROC analysis demonstrated moderate diagnostic accuracy (area under the curve = 0.747; 95% confidence interval: 0.635–0.859), with 60% sensitivity and 92.5% specificity at a cutoff > 4.214 ng/mL. In multiple linear regression analysis, HIF-1α was independently and inversely associated with eGFR after adjustment for age, sex, and HbA1c (β = −5.36; P < 0.001). Conclusions: Circulating HIF-1α levels are significantly associated with markers of renal dysfunction in diabetic patients and may serve as a potential adjunct biomarker of early renal impairment. No significant association was observed between HIF-1α and HbA1c.