Levels of VEGF-C, PLGF and Follistatin at 12 months post trans­plan­tation are associated with increased risk for long term pro­gressive renal dysfunction

G.J. Dreyer, H.J.W. de Fijter, D.M. Briscoe, K.P. Daly, M.E.J. Reinders

Chair(s): dr. Marije C. Baas, nefroloog, Radboudumc, Nijmegen & dr. Dries E. Braat, chirurg, LUMC

Thursday 10 march 2016

15:00 - 15:10h at Zaal 1 & 2

Categories: Parallelsessie (klinisch)

Parallel session: Parallelsessie XII - Klinisch

The integrity of the microvasculature is critical for long term survival following solid organ transplantation. We hypothesize that biomarkers of endothelial injury and repair are early predictors of chronic rejection, and preliminary evidence suggests that angiogenic biomarkers are associated with chronic cardiac allograft vasculopathy. Here we investigate if angiogenic markers measured 12 months after renal transplantation can predict late allograft dysfunction.

Levels of 17 angiogenic proteins and anti-HLA donor specific antibodies (DSA) were measured by mulitanalyte profiling 12 months after renal transplantation in sera of 152 recipients. Forty-five patients had progressive renal dysfunction,defined as at least 20 ml/min/1.73m2 eGFR loss between year 1 and 5 (mean baseline eGFR 54±22 ml/min/1.73m2), and 107 control patients had stable renal function (mean baseline eGFR 48±15 ml/min/1.73m2). All patients had low to standard immunological risk and started on triple therapy with calcineurin inhibitors. Six months after transplantation 33 patients switched to dual therapy, including 13 with mTOR inhibitors.

The 5-year death-censored graft survival was 100% in the control group and 79.2% in the progressor group. Follistatin, a promoter of tubular regeneration, was significantly increased (median(IQR) = 1146(1060) vs. 826 (1341) in controls, p=0.033) 12 months after transplantation in recipients with progressive renal dysfunction. Also, the angiogenic and pro-inflammatory factors PLGF (median(IQR) = 16(37) vs. 10(26) in controls, p=0.019) and VEGF-C (median(IQR) = 276(372) vs. 183(274) in controls, p=0.029) were increased in the progressors, independent of treatment regimen. The remaining biomarkers including endothelin1, FGF1/2 and VEGF-A showed no associations with loss of renal function. In total, 46 patients had allograft rejection. Late, but not early rejection, was associated with progressive renal decline at 5 years (OR 3.15, 95%CI 1.27–7.81, p 0.013). De novo DSAs were found in 22 patients (14.5%), however no association with biomarkers was found.

Increased levels of VEGF-C, PLGF and Follistatin at 12 months post-transplant were associated with progressive renal dysfunction at 5 years. These specific biomarkers have been reported to play important roles in (lymph)angiogenesis and inflammation. These markers have potential to identify patients with progressive renal dysfunction at early times post-transplant.