Key result
Patients with chronic kidney disease exhibited significantly higher multivariable-adjusted median levels of ADMA (0.54 vs 0.25 μmol/L, p<0.0001) and other endothelial biomarkers compared to controls.
Why the study?
Are multiple endothelial dysfunction biomarkers associated with the presence and severity of chronic kidney disease?
Case-Control (n=402)
Are multiple endothelial dysfunction biomarkers associated with the presence and severity of chronic kidney disease?
Absolute Event Rate: 0.54% vs 0.25%
p-value: p=<0.0001
Multiple pathways of endothelial dysfunction, including nitric oxide, inflammation, and thrombosis, are significantly and independently associated with the presence and severity of chronic kidney disease.
Supports endothelial dysfunction in CKD; hypothesis-generating for ADMA as biomarker, should not yet change practice.
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.
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Chen et al. (2015) conducted a case-control in Chronic Kidney Disease (n=402). Chronic kidney disease vs. Controls without CKD was evaluated on Multivariable-adjusted median ADMA level (μmol/L) (p=<0.0001). Patients with chronic kidney disease exhibited significantly higher multivariable-adjusted median levels of ADMA (0.54 vs 0.25 μmol/L, p<0.0001) and other endothelial biomarkers compared to controls.
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