Soluble TWEAK plasma levels increase after renal transplantation and associate with the improvement of endothelial function

Abstract

Background: Soluble TWEAK (sTWEAK) and asymmetric dimethyl arginine (ADMA) concentrations have been associated with endothelial function in patients with chronic kidney disease (CKD). We tested the hypothesis that the improvement in endothelial function observed after renal transplantation is directly linked to the normalization of both sTWEAK and ADMA.

Materials and methods: One hundred and seventy-five kidney transplant recipients (71% men; 31·6 ± 9·4 years) were studied immediately before and on the 180th day post-transplantation. At each visit, blood samples were taken to assess circulating levels of sTWEAK and ADMA. Brachial artery endothelium-dependent vasodilatation (FMD) assessments were also performed.

Results: Renal transplantation was followed by an improvement in FMD. This improvement was paralleled by an increase in sTWEAK and a reduction in ADMA after transplantation (P < 0·001 for all). Cross-sectionally, both molecules associated with FMD before as well as after transplantation (P < 0·001 for all). Longitudinally, the changes observed in sTWEAK (β = 0·26, P < 0·001) and ADMA (β = -0·44, P < 0·001) levels were independently associated with the improvement of FMD (r(2) = 0·30).

Conclusions: Renal transplantation is followed by an improvement of FMD that is independently associated with the normalization of both sTWEAK and ADMA concentrations. We identify two surrogate biomarkers of endothelial function with potential as therapeutic targets.

Keywords: ADMA; endothelial function; renal transplantation; sTWEAK.