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Published ahead of print on October 9, 2009
Clin J Am Soc Nephrol 4: 1716-1723, 2009
© 2009 American Society of Nephrology
doi: 10.2215/CJN.02760409
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Chronic Kidney Disease

Soluble TWEAK Plasma Levels as a Novel Biomarker of Endothelial Function in Patients with Chronic Kidney Disease

Mahmut Ilker Yilmaz*, Juan Jesús Carrero{dagger}, Alberto Ortiz{ddagger}, Jose Luis Martín-Ventura{ddagger}, Alper Sonmez§, Mutlu Saglam||, Halil Yaman, Mujdat Yenicesu*, Jesús Egido{ddagger}, and Luis Miguel Blanco-Colio{ddagger}

Departments of * Nephrology, § Endocrinology, || Radiology, and Biochemistry, Gülhane School of Medicine, Ankara, Turkey; {dagger} Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; and {ddagger} Vascular and Renal Research Laboratory, Fundacion Jimenez Diaz, Autonoma University, Madrid, Spain

Correspondence: Dr. Luis M. Blanco-Colio,Vascular Research Laboratory, Fundación Jiménez Díaz, Avenida Reyes Católicos 2, 28040, Madrid, Spain. Phone: 34-915504800; Fax: 31-915442636; E-mail: lblanco{at}fjd.es

Background and objectives: 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).

Design, setting, participants, & measurements: 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.






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