Soluble TWEAK plasma levels as a novel biomarker of endothelial function in patients with chronic kidney disease.
OBJECTIVE
Recently, we showed that soluble TNF-like weak inducer of apoptosis (sTWEAK) plasma levels are diminished in hemodialysis patients and had additive effects with IL-6 on survival. Because sTWEAK plasma level has been associated with the presence of chronic kidney disease (CKD) and cardiovascular disease, we hypothesized that in patients with CKD, sTWEAK levels may relate to the increased prevalence of endothelial dysfunction that usually accompanies the decline of estimated GFR (eGFR).


METHODS
We studied 295 patients with different stages of nondiabetic CKD (52% male; age 47 +/- 12 yr), testing the association between sTWEAK plasma levels and CKD stage and the relationship between flow-mediated dilation (FMD) and sTWEAK concentrations. Fifty-five healthy volunteers (51% male; age 47 +/- 11 yr) served as matched control subjects.


RESULTS
A gradual decrease in FMD was observed as eGFR decreased. Compared with healthy control subjects, sTWEAK plasma levels were diminished in all stages of CKD and correlated strongly with eGFR. FMD levels were associated with sTWEAK concentrations in univariate analysis. This association persisted after multivariate adjustment for eGFR levels, high-sensitivity C-reactive protein, diastolic BP, and sTWEAK, all of which were found to be significant and independent contributors to FMD.


CONCLUSIONS
A decline in eGFR is accompanied by gradual reductions in sTWEAK plasma levels. Because sTWEAK strongly and independently correlated with FMD, our study suggests novel links between sTWEAK and endothelial dysfunction in patients with CKD.
Yilmaz
Mahmut Ilker
MI
Department of Nephrology, Gülhane School of Medicine, Ankara, Turkey.
Carrero
Juan Jesús
JJ
Ortiz
Alberto
A
Martín-Ventura
Jose Luis
JL
Sonmez
Alper
A
Saglam
Mutlu
M
Yaman
Halil
H
Yenicesu
Mujdat
M
Egido
Jesús
J
Blanco-Colio
Luis Miguel
LM
D000328:Adult; D017209:Apoptosis / Q000502:physiology; D015415:Biomarkers / Q000097:blood*; D000074049:Cytokine TWEAK; D042783:Endothelial Cells / Q000473:pathology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D015995:Prevalence; D012044:Regression Analysis; D012079:Renal Circulation / Q000502:physiology; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000453:epidemiology / Q000473:pathology*; D048069:Tumor Necrosis Factors / Q000097:blood*
D015415:Biomarkers; D000074049:Cytokine TWEAK; C109743:TNFSF12 protein, human; D048069:Tumor Necrosis Factors