Renal Dysfunction Is a Stronger Determinant of Systemic Neutrophil Gelatinase–Associated Lipocalin Levels Than Myocardial Dysfunction in Systolic Heart Failure

Abstract

Background Neutrophil gelatinase–associated lipocalin (NGAL) is released by renal tubular cells in response to inflammation and injury. Recent studies have demonstrated that NGAL is up-regulated in cardiomyocytes within the failing myocardium. However, the overall relationship between systemic NGAL levels and myocardial structure and performance has not been established. Methods and Results We measured systemic NGAL levels in 130 subjects with chronic systolic heart failure (HF) and comprehensive echocardiographic evaluation, as well as 69 subjects with acute decompensated systolic HF and hemodynamic evaluation. In the chronic HF cohort, higher plasma NGAL levels were modestly associated with increasing age ( r = 0.18; P = .035), higher New York Heart Association functional class (rank sums: P = .022) and impaired renal function (eGFR: r = −0.53; P < .0001; cystatin C: r = 0.60; P < .0001). Plasma NGAL levels were modestly associated with indices of diastolic dysfunction (mitral E/Ea: r = 0.27; P = .002; LAVi: r = 0.25; P = .011; tricuspid E/Ea: r = 0.20; P = .029), but not after adjustment for renal function ( P > .10 for all). In Cox proportional hazards analysis, plasma NGAL predicted cardiac death or transplantation after adjustment for age, gender, left ventricular ejection fraction, and mitral E/Ea (hazard ratio 1.68, 95% confidence interval 1.08–2.57; P = .022), but not after adjustment for renal function ( P = .83). In the acute HF cohort, we did not observe any relationship between NGAL and hemodynamic indices, but NGAL strongly correlated with renal function. Conclusions Systemic NGAL levels are largely determined by underlying impairment of renal rather than myocardial function. Our findings did not support any prognostic significance or relationship between systemic NGAL levels and indices of cardiac structure and function after adjustment for underlying renal function.