P1622GROWTH DIFFERENTIATION FACTOR 15: A BIOMARKER WITH HIGH CLINICAL POTENTIAL IN THE EVALUATION OF KIDNEY TRANSPLANT CANDIDATES
Authors: De Cos Gomez Marina , Benito Hernandez Adalberto , Ramos Barron M Angeles , Lopez del Moral Cuesta Covadonga , Mazon Ruiz Jaime , San Segundo Arribas David , Fernandez Fresnedo Gema , Valero San Cecilio Rosalía , Ruiz San Millán Juan Carlos , Rodrigo Emilio 
Published: June 2020

Abstract

Background and Aims
Kidney transplantation results a significant improvement in patient survival. Nevertheless, mortality the first years after transplant remains relatively high, being mostly related to cardiovascular (CV) events. The selection of patients for kidney transplantation includes a general assessment focused on CV status. In spite of that, due to the complexity and heterogeneity of mechanisms leading to vascular disease in this population (not exclusively related to traditional CV risk factors and pathogenesis), this evaluation remains insufficient and not particularly effective. During the last years different strategies have been studied to stratify potential receptors better and optimize organ allocation, including the development of clinical prognostic scores and novel biomarkers.
Growth differentiation factor 15 (GDF-15) is a stress-responsive member of the TGF-β family. Although its mechanism of action is not completely understood, it acts as a cytokine with effects in regulation of inflammation, metabolism and senescence. In the recent years, interest has arisen regarding its use as a biomarker for diagnosis, prognosis and risk stratification in multiple scenarios. Encouraging results have shown its utility as a biomarker of mortality (all cause and CV), heart failure and acute coronary syndrome in different populations. The aim of this work is to assess the utility of GDF-15 to predict survival in kidney transplant candidates.

Method
395 kidney transplant recipients between 2005 and 2015 were included. GDF-15 measurements were performed from stored serum samples obtained pretransplant. The concentration of GDF-15 was analyzed using an enzyme-linked immunosorbent assay (Quantikine, R&D Systems).

Results
Patient characteristics are shown in Table 1. The median GDF-15 was 5331.3 (50.49-16242.3) pg/ml. After a mean of 90.6 ± 41.5 months of follow up 82 (20.8%) patients died. Patients were stratified in tertiles according to GDF-15 levels: low (GDF-15 ≤ 4612.1 pg/ml), medium (GDF-15 4612.1-6296.5 pg/ml) and high risk tertile (GDF-15 &gt; 6296.5 pg/ml). Higher GDF-15 concentrations were significantly associated with mortality: HR 2.16 95%CI (1.14-1.44), p = 0.018 for medium tertile and HR 3.28 95%CI (1.79-6.1), p &lt;0.001 for high risk tertile (Figure 1). After adjusting for age, diabetes, coronary artery disease, peripheral vascular disease, non-renal solid organ transplant and dialysis at the time of transplant, the relation between survival and GDF-15 was significant (HR 2.24 95%CI (1.2-4.16), p = 0.011 for high risk tertile). After adjusting by EPTS (Estimated Post Transplant Survival score) the association with GDF-15 remained significant: HR 3.24 95%CI (1.2-8.8), p = 0.021 for medium risk tertile and HR 4.3 95%CI (1.65-11.54), p = 0.003 for high risk tertile (calculated only in first renal transplants). Mortality at 3 years was 6.9% (27 patients) and it was only related to coronary artery disease and GDF-15 (OR 7.1 95%CI (1.6-32.1), p = 0.01 for high risk tertile) after adjustment.

Conclusion
In our cohort, higher GDF-15 levels were independently associated with mortality in kidney transplant candidates. This study suggests that GDF-15 may be useful in stratifying recipient risk, adding value to the prognostic tools already available in clinical practice. Further work is needed to confirm these findings and elucidate the mechanisms linking this protein with mortality and CV disease in patients with CKD.