Abstract
<title>Abstract</title> <p>Background Endothelial dysfunction is significantly influence the pathophysiology of diabetic kidney disease (DKD), which leads to systemic vascular complications. Neuregulin 4 (Nrg4) is a novel marker with potential vascular protective properties, and its dysregulated expression may leads to vascular damage, so we aimed to assess the correlation between Nrg4, flow mediated dilatation (FMD), and parameters of cerebral hemodynamics in type 2 DKD patients to evaluate endothelial dysfunction. Methods 120 participants were enrolled, comprising 40 proteinuric type 2 diabetic patients, 40 nonproteinuric, and 40 controls. Laboratory investigations were measured (CBC, Nrg4, serum creatinine, HBA1C, albumin creatinine ratio (ACR), lipid profile, and fasting blood glucose). Endothelial dysfunction was evaluated by FMD and transcranial Doppler (breath-holding index (BHI) and pulsatility index (PI)). 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 control groups (p < 0.001). Transcranial Doppler parameters were impaired in diabetics, especially those with proteinuria (PI, 0.93 ± 0.12; BHI, 0.30 ± 0.07) compared to nonproteinuric (PI, 0.67 ± 0.06; BHI, 0.52 ± 0.05) and control groups (p < 0.001). Nrg4 correlated positively with FMD (r = 0.971) and BHI (r = 0.955) with p < 0.001. Nrg4 correlates negatively with PI (p < 0.001, r = -0.917). Conclusion Reduced Nrg4, in conjunction with impaired FMD and cerebral hemodynamics, a potential measures to assess endothelial dysfunction in DKD patients, a key contributor of vascular complications.</p>