Growth Differentiation Factor 15: A Biomarker with High Clinical Potential in the Evaluation of Kidney Transplant Candidates

Abstract

Kidney transplantation implies a significant improvement in patient survival. Nevertheless, early mortality after transplant remains high. Growth differentiation factor 15 (GDF-15) is a novel biomarker under study as a mortality predictor in multiple scenarios. The aim of this study is to assess the utility of GDF-15 to predict survival in kidney transplant candidates. For this purpose, 395 kidney transplant recipients with pretransplant stored serum samples were included. 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 with higher GDF-15 levels (high risk tertile) had a doubled risk of mortality after adjustment by clinical characteristics (p = 0.009). After adjustment by EPTS (Estimated Post Transplant Survival score) the association remained significant for medium hazards ratios (HR) 3.24 95%CI (1.2-8.8), p = 0.021 and high risk tertiles HR 4.3 95%CI (1.65-11.54), p = 0.003. GDF-15 improved the prognostic accuracy of EPTS at 1-year (ΔAUC = 0.09, p = 0.039) and 3-year mortality (ΔAUC = 0.11, p = 0.036). Our study suggests an independent association between higher GDF-15 levels and mortality after kidney transplant, adding accuracy to the EPTS score, an established risk prediction model currently used in kidney transplant candidates.

Keywords: early mortality; growth differentiation factor 15; kidney transplantation; pretransplant assessment; survival.

Figure 1

Unadjusted Kaplan–Meier estimates of patient survival according to growth differentiation factor 15 (GDF-15) tertiles.

Figure 2

ROC curves based on predicted probability of logistic regression with EPTS, GDF-15 tertiles and EPTS + GDF-15 tertiles. (a) 1-year mortality prediction: AUC EPTS 0.81 CI95% (0.67–0.89) vs. AUC EPTS + GDF-15 0.90 CI95% (0.81–0.94), ΔAUC = 0.09 (p = 0.039), AUC EPTS vs. AUC GDF-15 0.766 CI95% (0.71–0.81), ΔAUC = 0.04 (p = 0.55). (b) 3-year mortality prediction: AUC EPTS 0.73 CI95% (0.59–0.82) vs. AUC EPTS + GDF-15 0.83 CI95% (0.71–0.90), ΔAUC = 0.11 (p = 0.036), AUC EPTS vs. AUC GDF-15 0.77 CI95% (0.71–0.82), ΔAUC = 0.04 (p = 0.56). (c) 5-year mortality prediction: AUC EPTS 0.69 CI95% (0.56–0.78) vs. AUC EPTS + GDF-15 0.74 CI95% (0.61–0.83), ΔAUC = 0.06 (p = 0.22), AUC EPTS vs. AUC GDF-15 0.69 CI95% (0.62–0.74), ΔAUC = 0.002 (p = 0.98). EPTS: estimated post transplant survival; GDF-15: growth differentiation factor 15.