Growth differentiation factor-15 (GDF-15) predicts major bleeding, major adverse cardiac events, and mortality in patients with end-stage kidney disease on hemodialysis: findings from the VIVALDI study.

BACKGROUND
Patients with end-stage kidney disease (ESKD) are at high risk of cardiovascular events and bleeding. Optimizing risk assessment of ESKD patients regarding risk of thromboembolism and bleeding complications in comorbid conditions, including atrial fibrillation and coronary heart disease, is challenging. To improve risk prediction we investigated growth differentiation factor-15 (GDF-15), a promising cardiovascular biomarker, and its relation to adverse outcomes.


METHODS
In this prospective multicenter population-based cohort study, GDF-15 was measured in 594 ESKD patients on hemodialysis (median age: 66 years, 38% women), who were followed-up for in median 3.5 years. The association of GDF-15 with major bleeding, arterial thromboembolism, major adverse cardiac events (MACE), and death was analyzed within a competing risk framework. Further, we evaluated the additive predictive value of GDF-15 to cardiovascular and death risk assessment.


RESULTS
GDF-15 levels were 5475ng/L in median (25th-75th percentile: 3964-7533) and independently associated with major bleeding (subdistribution hazard ratio [SHR] 1.31 per double increase, 95%CI 1.00-1.71), MACE (SHR 1.47, 1.11-1.94), and all-cause mortality (SHR 1.58, 1.28-1.95) but not arterial thromboembolism (SHR 0.91, 95%CI 0.61-1.36). Addition of GDF-15 to the HAS-BLED score significantly improved discrimination and calibration for predicting major bleeding (C-statistics increased from 0.61 (95%CI 0.52-0.70) to 0.68 (95%CI 0.61-0.78)). Furthermore, we established an additive predictive value of GDF-15 beyond current risk models for predicting MACE and death.


CONCLUSION
GDF-15 predicts risk of major bleeding, cardiovascular events, and death in ESKD patients on hemodialysis and might be a valuable marker to guide treatment decisions in this challenging patient population.