Interrelationship of Multiple Endothelial Dysfunction Biomarkers with Chronic Kidney Disease

Abstract

The interrelationship of multiple endothelial biomarkers and chronic kidney disease (CKD) has not been well studied. We measured asymmetric dimethylarginine (ADMA), L-arginine, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), von Willebrand factor (vWF), flow-mediated dilation (FMD), and nitroglycerin-induced dilation (NID) in 201 patients with CKD and 201 community-based controls without CKD. Multivariable analyses were used to examine the interrelationship of endothelial biomarkers with CKD. The multivariable-adjusted medians (interquartile ranges) were 0.54 (0.40, 0.75) in patients with CKD vs. 0.25 (0.22, 0.27) μmol /L in controls without CKD (p<0.0001 for group difference) for ADMA; 67.0 (49.6, 86.7) vs. 31.0 (27.7, 34.2) μmol/L (p<0.0001) for L-arginine; 230.0 (171.6, 278.6) vs. 223.9 (178.0, 270.6) ng/mL (p=0.55) for sICAM-1; 981.7 (782.6, 1216.8) vs. 633.2 (507.8, 764.3) ng/mL (p<0.0001) for sVCAM-1; 47.9 (35.0, 62.5) vs. 37.0 (28.9, 48.0) ng/mL (p=0.01) for sE-selectin; 1320 (1044, 1664) vs. 1083 (756, 1359) mU/mL (p=0.008) for vWF; 5.74 (3.29, 8.72) vs. 8.80 (6.50, 11.39)% (p=0.01) for FMD; and 15.2 (13.5, 16.9) vs. 19.1 (17.2, 21.0)% (p=0.0002) for NID, respectively. In addition, the severity of CKD was positively associated with ADMA, L-arginine, sVCAM-1, sE-selectin, and vWF and inversely associated with FMD and NID. Furthermore, FMD and NID were significantly and inversely correlated with ADMA, L-arginine, sVCAM-1, sE-selectin, and vWF. In conclusion, these data indicate that multiple dysfunctions of the endothelium were present among patients with CKD. Interventional studies are warranted to test the effects of treatment of endothelial dysfunction on CKD.

Associations of Plasma Nitrite, l-Arginine and Asymmetric Dimethylarginine With Morbidity and Mortality in Patients With Necrotizing Soft Tissue Infections

“…We decided a priori to adjust for potential confounders (age, sex, comorbidities, and SAPS II) that most likely affect disease severity and mortality. It has previously been shown that kidney function has an impact on the nitrite, l -arginine, and ADMA levels in plasma ( 32 ), and this is confirmed in this study because there was a significant correlation between the biomarker levels and the creatinine levels. An adjustment for this was done as urine output and blood urea nitrogen levels are included in the SAPS II.…”

Omega 3 Polyunsaturated Fatty Acids Improve Endothelial Dysfunction in Chronic Renal Failure: Role of eNOS Activation and of Oxidative Stress

“…Besides, reduced vascular NO availability in this setting has been described in association with enhanced generation of oxygen free radicals by NADPH oxidases [ 9 , 10 ]. In addition, other factors including increased concentrations of the NOS inhibitor asymmetric dimethylarginine (ADMA) can contribute to endothelial dysfunction during renal failure [ 11 ].…”

Clinical Effects of Topiroxostat on Renal and Endothelial Function in A Patient with Chronic Kidney Disease and Hyperuricemic Arteriolopathy: A Case Report

“…In this regard, UA has been shown to promote proliferation of vascular smooth muscle cells and reduce nitric oxide, resulting in endothelial dysfunction [ 19 ]. On the other hand, Chen et al [ 20 ] reported an interrelationship between multiple markers and pathways, leading to impaired endothelial function in patients with CKD. Given these relationships, there seems to be a pathological triangle between hyperuricemia, CKD, and endothelial dysfunction.…”