Date: Monday, June 13, 2016
Session Time: 4:30pm-6:00pm
Presentation Time: 4:54pm-5:06pm
Location: Veterans Auditorium
Introduction Integrity of the microvasculature is critical for long term survival after solid organ transplantation. We hypothesize that biomarkers of endothelial injury and repair are early predictors of chronic rejection. Preliminary evidence suggests that angiogenic markers are associated with cardiac allograft vasculopathy. We investigate if angiogenic markers measured 12 months after renal transplantation can predict late allograft dysfunction.
Methods Levels of 17 angiogenic proteins and donor specific HLA-antibodies (DSA) were measured by mulitanalyte profiling 12 months after renal transplantation in sera of 152 recipients. 45 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 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 post-transplant 33 patients switched to dual therapy, including 13 with mTOR inhibitors.
Results 5-year death-censored graft survival was 100% in the control group and 79.2% in the progressors. Follistatin, a promoter of tubular regeneration, was significantly increased (median(IQR) = 1146(1060) vs 826(1341) in controls, p=0.033) in recipients with progressive renal dysfunction. Also the angiogenic and pro-inflammatory factors PLGF (median(IQR) = 16(37) vs 10(26) resp, p=0.019) and VEGF-C (median(IQR) = 276(372) vs 183(274) resp, p=0.029) were increased in the progressors, independent of treatment regimen. Remaining biomarkers including endothelin1, FGF1/2 and VEGF-A showed no association 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.
Conclusion Increased levels of VEGF-C, PLGF and Follistatin 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 and may have the potential to identify patients with progressive renal dysfunction at early times post-transplant.
CITATION INFORMATION: Dreyer G, de Fijter J, Briscoe D, Daly K, Reinders M. Levels of VEGF-C, PLGF and Follistatin at 12 Months Post Transplantation Are Associated with Increased Risk for Long Term Progressive Renal Dysfunction. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:Dreyer G, Fijter Jde, Briscoe D, Daly K, Reinders M. Levels of VEGF-C, PLGF and Follistatin at 12 Months Post Transplantation Are Associated with Increased Risk for Long Term Progressive Renal Dysfunction. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/levels-of-vegf-c-plgf-and-follistatin-at-12-months-post-transplantation-are-associated-with-increased-risk-for-long-term-progressive-renal-dysfunction/. Accessed May 31, 2020.
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