Urine Growth Differentiation Factor-15 is Not an Independent Biomarker of Cardio-Renal Interactions in Patients with Heart Failure

Introduction Growth differentiation factor-15 (GDF-15) is a stress-responsive biomarker that is elevated in patients with heart failure (HF) and carries prognostic value. However, conditions other than HF can increase levels, making plasma concentration non-specific for HF. In diabetic patients, urinary GDF-15 has been associated with worse kidney function, but its role in HF remains unknown. Therefore, we sought to determine if urinary GDF-15 might provide unique cardio-renal information in patients with HF. Hypothesis Urinary GDF-15 will be associated with diuretic efficiency and survival, independently of plasma GDF-15. Methods GDF-15 was measured in 171 patients with heart failure treated with IV diuretics in the outpatient setting. Pre and post diuretic spot urinary GDF-15 (n=166) was measured using the Mesoscale Assay platform (MesoScale Diagnostics, Gaithersburg, MD, USA). Urinary GDF-15 was normalized to urine creatinine. Diuretic efficiency was defined as sodium excretion per doubling of loop diuretic dose. Results Plasma GDF-15 was weakly correlated with pre-diuretic urinary GDF-15 (r= 0.21, p=0.019) and modestly correlated with post-diuretic urinary GDF-15 (r=0.50, p Conclusion Plasma, but not urinary, GDF-15 was independently associated with diuretic efficiency and survival. This suggests that urinary GDF-15 does not provide specific cardio-renal information, likely because it is mainly filtrated from plasma rather than produced in the kidney.