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Growth Differentiation Factor 15 Is a New Biomarker for Survival and Renal Outcomes in Light Chain (AL) Amyloidosis

Efstathios Kastritis, Ioannis Papassotiriou, Giampaolo Merlini, Paolo Milani, Evangelos Terpos, Marco Basset, Athanasios Akalestos, Francesca Russo, Erasmia Psimenou, Filia Apostolakou, Maria Roussou, Maria Gavriatopoulou, Evangelos Eleutherakis Papaiakovou, Despina Fotiou, Dimitrios C. Ziogas, Elektra Papadopoulou, Constantinos Pamboucas, Meletios A. Dimopoulos and Giovanni Palladini

Key points

  • GDF-15 levels is a new prognostic factor for survival in AL amyloidosis and their reduction after therapy are associated with better outcome

  • GDF-15 level is probably the strongest predictor for renal outcomes in patients with AL amyloidosis

Abstract

Growth differentiation factor-15 (GDF-15) improves prognostication in patients with cardiovascular disorders in addition to conventional cardiac markers (NT-proBNP, troponins) and has shown prognostic value in patients with renal diseases. In patients with AL amyloidosis cardiac involvement is the major determinant of prognosis and cardiac markers define prognosis, while biomarkers of renal involvement stratify renal risk. We explored the prognostic importance of serum levels of GDF-15 in patients with AL amyloidosis, in two independent cohorts. The prognostic value of GDF-15 levels was initially evaluated in a cohort of 107 consecutive patients with previously untreated patients with AL amyloidosis from Athens, Greece and was then validated in a second cohort of 202 consecutive previously untreated patients from Pavia, Italy. High GDF-15 levels were associated with a higher risk of early death and poor overall survival independently of NT-proBNP and hsTnT or hsTnI levels. At 6 months landmark, reduction of GDF-15 levels ≥25% was associated with improved outcome. GDF-15 levels ≥4000 pg/ml were associated with a high risk for progression to dialysis, independently of renal risk defined by eGFR and proteinuria, in both cohorts; failure to reduce GDF-15 below these levels was associated with increased risk at either 3 or 6 months landmark, independently of the established renal response or progression criteria. In conclusion GDF-15 has prognostic implications for different outcomes in patients with AL and adds prognostic information independent to cardiac and renal risk biomarkers.

  • Submitted December 5, 2017.
  • Accepted January 18, 2018.