Neuregulin 4 in correlation with flow mediated dilatation and transcranial Doppler in assessment of endothelial dysfunction in type 2 diabetic kidney disease patients

Abstract Background Endothelial dysfunction plays a central role in the pathophysiology of diabetic kidney disease (DKD), leading to systemic vascular complications. Neuregulin 4 (Nrg4) has emerged as a novel marker with potential vascular protective properties, and its dysregulated expression may lead to vascular damage. Aim Assess the correlation between Nrg4, flow-mediated dilatation (FMD%), and parameters of cerebral hemodynamics in type 2 DKD patients to evaluate endothelial dysfunction. Methods A cross-sectional study included 120 participants, comprising 40 proteinuric type 2 diabetic patients, 40 nonproteinuric patients, and 40 controls. CBC, HbA1c, lipid profile, serum creatinine, albumin-to-creatinine ratio (ACR), and Nrg4 were measured. FMD, pulsatility index (PI), and breath-holding index (BHI) of the middle cerebral artery were assessed. Results Proteinuric diabetics showed significantly lower Nrg4 and FMD (1.13 ± 0.41 ng/mL; 6.08 ± 1.78%) compared with nonproteinuric (3.07 ± 0.80 ng/mL; 11.23 ± 1.68%) and controls (10.05 ± 2.44 ng/mL; 16.13 ± 0.97%) ( p < 0.001). The proteinuric group showed significantly higher baseline PI and lower BHI (0.93 ± 0.12 and 0.30 ± 0.07) compared with the nonproteinuric group (0.67 ± 0.06 and 0.52 ± 0.05) and controls (0.55 ± 0.03 and 0.90 ± 0.13), respectively ( p < 0.001). Nrg4 showed positive correlations with FMD ( r = 0.971) and BHI ( r = 0.955), with p < 0.001. Nrg4 correlates negatively with PI ( r = -0.917, p < 0.001). Conclusion Reduced Nrg4 levels, along with impaired FMD and altered cerebral hemodynamics, may serve as markers of endothelial dysfunction and be associated with vascular abnormalities in patients with DKD.