Galectin-3, Acute Kidney Injury and Myocardial Damage in Patients With Acute Heart Failure

Abstract

Background: Galectin-3, a biomarker of inflammation and fibrosis, can be associated with renal and myocardial damage and dysfunction in patients with acute heart failure (AHF).

Methods and results: We retrospectively analyzed 790 patients with AHF who were enrolled in the AKINESIS study. During hospitalization, patients with galectin-3 elevation (> 25.9 ng/mL) on admission more commonly had acute kidney injury (assessed by KDIGO criteria), renal tubular damage (peak urine neutrophil gelatinase-associated lipocalin [uNGAL] > 150 ng/dL) and myocardial injury (≥ 20% increase in the peak high-sensitivity cardiac troponin I [hs-cTnI] values compared to admission). They less commonly had ≥ 30% reduction in B-type natriuretic peptide from admission to last measured value. In multivariable linear regression analysis, galectin-3 was negatively associated with estimated glomerular filtration rate and positively associated with uNGAL and hs-cTnI. Higher galectin-3 was associated with renal replacement therapy, inotrope use and mortality during hospitalization. In univariable Cox regression analysis, higher galectin-3 was associated with increased risk for the composite of death or rehospitalization due to HF and death alone at 1 year. After multivariable adjustment, higher galectin-3 levels were associated only with death.

Conclusions: In patients with AHF, higher galectin-3 values were associated with renal dysfunction, renal tubular damage and myocardial injury, and they predicted worse outcomes.

Keywords: acute heart failure; acute kidney injury; galectin-3; myocardial injury; prognosis; renal tubular damage.

Fig. 1.

Levels of galectin-3 and adverse events. A, Galectin-3 and biomarker defined endpoints. Patients with admission values of Gal-3 > 25.9 ng/mL less commonly had BNP ≥ 30% decrease and more commonly had hs-cTnI ≥ 20% increase and peak uNGAL > 150 ng/dL than those with Gal-3 ≤ 25.9 ng/mL (P < 0.05 for all). B, Galectin-3 and acute kidney injury. The incidence of AKI was higher in patients with Gal-3 > 25.9 ng/mL than those with Gal-3 ≤ 25.9 ng/mL (P < 0.05). C, Galectin-3 and in-hospital clinical endpoints. Renal-replacement therapy, inotrope use and in-hospital death were more frequently observed in patients with Gal-3 > 25.9 ng/mL (P < 0.05). AKI, acute kidney injury; BNP, B-type natriuretic peptide; Gal-3, galectin 3; hs-cTnI, high-sensitivity cardiac troponin I; uNGAL, urine neutrophil gelatinase-associated lipocalin.

Fig. 2.

Relationship between galectin-3 and other biomarkers. Standardized beta-coefficient (β) of biomarkers for eGFR, uNGAL, BNP, and hs-cTnI in multivariable linear regression models are shown. AUCs of the first 3 days of hospitalization were used for biomarkers (eGFR, uNGAL, BNP, hs-cTnI, and urine creatinine). For eGFR, factors included in the model were age, gender, race, heart rate, systolic blood pressure, history of CAD, PCI, CABG, and dyslipidemia, smoking, ACE inhibitors, hemoglobin, edema, rales, furosemide dose during the first 3 days of hospitalization, Gal-3, uNGAL, BNP, and hs-cTnI. For uNGAL, factors included in the model were age, gender, history of PCI, hemoglobin, edema, furosemide dose during the first 3 days, Gal-3, BNP, hs-cTnI, eGFR, and urine creatinine. For BNP, factors included in the model were age, gender, systolic blood pressure, body mass index, history of CAD, CABG, COPD, and diabetes mellitus, beta-blocker, hemoglobin, rales, jugular vein distention, Gal-3, uNGAL, hs-cTnI, eGFR, and urine creatinine. For hs-cTnI, factors included in the model were age, gender, heart rate, body mass index, history of CAD and COPD, diuretics use on admission, rales, hemoglobin, furosemide dose during the first 3 days, Gal-3, uNGAL, BNP, and eGFR. In multivariable linear regression analysis for eGFR, VIFs of Gal3, uNGAL, BNP and hs-cTnI were 1.23, 1.17, 1.24, and 1.27, respectively. For uNGAL, VIFs of Gal3, BNP, hs-cTnI and eGFR were 1.51, 1.26, 1.21, and 1.64, respectively. For BNP, VIFs of Gal3, uNGAL, hs-cTnI, and eGFR were 1.61, 1.56, 1.12, and 1.66, respectively. For hs-cTnI, VIFs of Gal3, uNGAL, BNP, and eGFR were 1.55, 1.20, 1.29, and 1.74, respectively. ACE-I, angiotensin-converting-enzyme inhibitor; BNP, B-type natriuretic peptide; CABG, coronary artery bypass grafting; CAD, coronary artery disease; COPD, chronic obstructive pulmonary disease; eGFR, estimated glomerular filtration rate; Gal-3, galectin 3; hs-cTnI, high sensitivity cardiac troponin I; PCI, percutaneous coronary intervention; uNGAL, urine neutrophil gelatinase-associated lipocalin; VIF, variance inflation factor.

Fig. 3.

Galectin-3 and clinical outcomes. Patients with Gal-3 > 25.9 ng/mL on admission had higher incidence of the composite of death or readmission due to heart failure and mortality within 1 year (P = 0.01 for the composite endpoint; P < 0.01 for mortality; P = 0.875 for HF rehospitalization).