Angiotensin-Converting Enzyme 1 as a Predictor of Diabetic Kidney Disease: Clinical Associations and Molecular Docking Data with 1,25(OH)₂D₃

Background: Diabetic kidney disease (DKD) is a significant complication of diabetes mellitus, marked by albuminuria, hypertension, and renal dysfunction. Activation of the renin-angiotensin-aldosterone system (RAAS), particularly via angiotensin-converting enzyme 1 (ACE-1), contributes to disease progression. This study investigates the inhibitory role of vitamin D (1,25(OH)₂D₃) on ACE-1 and explores its interaction in DKD patients. Methodology: A case-control study was conducted with 90 blood samples, comprising 46 male late-stage patients with diabetic kidney disease, and 44 apparently healthy male controls in Al-Najaf, Iraq. Clinical and biochemical parameters, including ACE-1 and 1,25(OH)₂D₃ serum levels, were measured. Correlation and regression analyses were performed. Molecular docking simulations were conducted using AutoDock Vina to evaluate ligand-ACE-1 interactions. Results: Diabetic kidney disease patients exhibited significantly elevated ACE-1 and IL-6 levels, reduced 1,25(OH)₂D₃ levels, and impaired renal function (as indicated by eGFR). The ROC analysis showed that ACE was an excellent diagnostic marker for the discrimination of DKD patients from controls with an AUC of 0.8525 (95% CI: 0.7756–0.9293, p < 0.0001). ACE-1 levels were moderately inversely correlated with 1,25(OH)₂D₃ (r = –0.453, p = 0.0015) and positively correlated with systolic/diastolic blood pressure. Docking analysis revealed that 1,25(OH)₂D₃ exhibited a high binding affinity (–9.2 kcal/mol) and stable interactions with ACE-1, surpassing those of captopril. Conclusion: Angiotensin-converting enzyme 1 overexpression is linked to DKD severity, while 1,25(OH)₂D₃ deficiency exacerbates disease progression. The molecular docking study provides strong evidence that 1,25(OH)₂D₃ may act as a promising inhibitor of ACE-1, suggesting its therapeutic potential in mitigating RAAS-driven renal damage in DKD. These findings warrant further clinical investigation of vitamin D analogs in the management of DKD.