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

      Highlights

      • Galectin-3 was associated with renal dysfunction, renal tubular damage and myocardial injury in acute heart failure.
      • Higher Galctin-3 levels predicted in-hospital adverse events and higher 1-year mortality rates.
      • Galectin-3 may help to identify patients at higher risk for cardiorenal adverse events and worse prognoses.

      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.

      Key Words

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      References

        • Damman K
        • Valente MA
        • Voors AA
        • O'Connor CM
        • van Veldhuisen DJ
        • Hillege HL
        Renal impairment, worsening renal function, and outcome in patients with heart failure: an updated meta-analysis.
        Eur Heart J. 2014; 35: 455-469
        • Parikh CR
        • Puthumana J
        • Shlipak MG
        • Koyner JL
        • Thiessen-Philbrook H
        • McArthur E
        • et al.
        Relationship of kidney injury biomarkers with long-term cardiovascular outcomes after cardiac surgery.
        J Am Soc Nephrol. 2017; 28: 3699-3707
        • Sawhney S
        • Marks A
        • Fluck N
        • Levin A
        • Prescott G
        • Black C.
        Intermediate and long-term outcomes of survivors of acute kidney injury episodes: a large population-based cohort study.
        Am J Kidney Dis. 2017; 69: 18-28
        • Legrand M
        • Rossignol P.
        Cardiovascular consequences of acute kidney injury.
        N Engl J Med. 2020; 382: 2238-2247
        • de Boer RA
        • Voors AA
        • Muntendam P
        • van Gilst WH
        • van Veldhuisen DJ.
        Galectin-3: a novel mediator of heart failure development and progression.
        Eur J Heart Fail. 2009; 11: 811-817
        • Dang Z
        • MacKinnon A
        • Marson LP
        • Sethi T.
        Tubular atrophy and interstitial fibrosis after renal transplantation is dependent on galectin-3.
        Transplantation. 2012; 93: 477-484
        • Prud'homme M
        • Coutrot M
        • Michel T
        • Boutin L
        • Genest M
        • Poirier F
        • et al.
        Acute kidney injury induces remote cardiac damage and dysfunction through the galectin-3 pathway.
        JACC Basic Transl Sci. 2019; 4: 717-732
        • Maisel AS
        • Wettersten N
        • van Veldhuisen DJ
        • Mueller C
        • Filippatos G
        • Nowak R
        • et al.
        Neutrophil gelatinase-associated lipocalin for acute kidney injury during acute heart failure hospitalizations: the AKINESIS Study.
        J Am Coll Cardiol. 2016; 68: 1420-1431
        • Horiuchi YU
        • Wettersten N
        • Veldhuisen DJV
        • Mueller C
        • Filippatos G
        • Nowak R
        • et al.
        Potential utility of cardiorenal biomarkers for prediction and prognostication of worsening renal function in acute heart failure.
        J Card Fail. 2020; 27: 533-541
        • Mehta RL
        • Kellum JA
        • Shah SV
        • Molitoris BA
        • Ronco C
        • Warnock DG
        • et al.
        Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury.
        Crit Care. 2007; 11: R31
        • Khwaja A.
        KDIGO clinical practice guidelines for acute kidney injury.
        Nephron Clin Pract. 2012; 120: c179-c184
        • Haase M
        • Bellomo R
        • Devarajan P
        • Schlattmann P
        • Haase-Fielitz A
        • Group NM-aI.
        Accuracy of neutrophil gelatinase-associated lipocalin (NGAL) in diagnosis and prognosis in acute kidney injury: a systematic review and meta-analysis.
        Am J Kidney Dis. 2009; 54: 1012-1024
        • Wettersten N
        • Horiuchi Y
        • van Veldhuisen DJ
        • Mueller C
        • Filippatos G
        • Nowak R
        • et al.
        B-type natriuretic peptide trend predicts clinical significance of worsening renal function in acute heart failure.
        Eur J Heart Fail. 2019; 21: 1553-1560
        • Metra M
        • Cotter G
        • Davison BA
        • Felker GM
        • Filippatos G
        • Greenberg BH
        • et al.
        Effect of serelaxin on cardiac, renal, and hepatic biomarkers in the Relaxin in Acute Heart Failure (RELAX-AHF) development program: correlation with outcomes.
        J Am Coll Cardiol. 2013; 61: 196-206
        • de Boer RA
        • Lok DJ
        • Jaarsma T
        • van der Meer P
        • Voors AA
        • Hillege HL
        • et al.
        Predictive value of plasma galectin-3 levels in heart failure with reduced and preserved ejection fraction.
        Ann Med. 2011; 43: 60-68
        • Felker GM
        • Fiuzat M
        • Shaw LK
        • Clare R
        • Whellan DJ
        • Bettari L
        • et al.
        Galectin-3 in ambulatory patients with heart failure: results from the HF-ACTION study.
        Circ Heart Fail. 2012; 5: 72-78
        • Felker GM
        • Lee KL
        • Bull DA
        • Redfield MM
        • Stevenson LW
        • Goldsmith SR
        • et al.
        Diuretic strategies in patients with acute decompensated heart failure.
        N Engl J Med. 2011; 364: 797-805
        • Endre ZH
        • Walker RJ
        • Pickering JW
        • Shaw GM
        • Frampton CM
        • Henderson SJ
        • et al.
        Early intervention with erythropoietin does not affect the outcome of acute kidney injury (the EARLYARF trial).
        Kidney Int. 2010; 77: 1020-1030
        • Pickering J
        • Endre Z.
        The metamorphosis of acute renal failure to acute kidney injury.
        Basic Nephrol Acute Kidn Inj. 2012; 6: 125-150
        • Lee DS
        • Austin PC
        • Rouleau JL
        • Liu PP
        • Naimark D
        • Tu JV.
        Predicting mortality among patients hospitalized for heart failure: derivation and validation of a clinical model.
        JAMA. 2003; 290: 2581-2587
        • Felker GM
        • Leimberger JD
        • Califf RM
        • Cuffe MS
        • Massie BM
        • Adams Jr, KF
        • et al.
        Risk stratification after hospitalization for decompensated heart failure.
        J Card Fail. 2004; 10: 460-466
        • O'Connor CM
        • Hasselblad V
        • Mehta RH
        • Tasissa G
        • Califf RM
        • Fiuzat M
        • et al.
        Triage after hospitalization with advanced heart failure: the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) risk model and discharge score.
        J Am Coll Cardiol. 2010; 55: 872-878
        • WFt Peacock
        • T De Marco
        • Fonarow GC
        • Diercks D
        • Wynne J
        • Apple FS
        • et al.
        Cardiac troponin and outcome in acute heart failure.
        N Engl J Med. 2008; 358: 2117-2126
        • Chen SC
        • Kuo PL.
        The role of galectin-3 in the kidneys.
        Int J Mol Sci. 2016; 17: 565
        • Horiuchi YU
        • Wettersten N
        • Veldhuisen DJV
        • Mueller C
        • Filippatos G
        • Nowak R
        • et al.
        Potential utility of cardiorenal biomarkers for prediction and prognostication of worsening renal function in acute heart failure.
        J Card Fail. 2021; 27: 533-541
        • Schmidt-Ott KM.
        Neutrophil gelatinase-associated lipocalin as a biomarker of acute kidney injury: where do we stand today?.
        Nephrol Dial Transplant. 2011; 26: 762-764
        • Westermann D
        • Neumann JT
        • Sorensen NA
        • Blankenberg S.
        High-sensitivity assays for troponin in patients with cardiac disease.
        Nat Rev Cardiol. 2017; 14: 472-483
        • Thygesen K
        • Alpert JS
        • Jaffe AS
        • Chaitman BR
        • Bax JJ
        • Morrow DA
        • et al.
        Fourth universal definition of myocardial infarction (2018).
        Circulation. 2018; 138: e618-e651
        • Bagshaw SM
        • Hoste EA
        • Braam B
        • Briguori C
        • Kellum JA
        • McCullough PA
        • et al.
        Cardiorenal syndrome type 3: pathophysiologic and epidemiologic considerations.
        Contrib Nephrol. 2013; 182: 137-157
        • Martin-Lorenzo M
        • Gonzalez-Calero L
        • Ramos-Barron A
        • Sanchez-Nino MD
        • Gomez-Alamillo C
        • Garcia-Segura JM
        • et al.
        Urine metabolomics insight into acute kidney injury point to oxidative stress disruptions in energy generation and H2S availability.
        J Mol Med (Berl). 2017; 95: 1399-1409
        • Hromadka M
        • Seidlerova J
        • Suchy D
        • Rajdl D
        • Lhotsky J
        • Ludvik J
        • et al.
        Myocardial fibrosis detected by magnetic resonance in systemic sclerosis patients: relationship with biochemical and echocardiography parameters.
        Int J Cardiol. 2017; 249: 448-453
        • van Kimmenade RR
        • Januzzi Jr, JL
        • Ellinor PT
        • Sharma UC
        • Bakker JA
        • Low AF
        • et al.
        Utility of amino-terminal pro-brain natriuretic peptide, galectin-3, and apelin for the evaluation of patients with acute heart failure.
        J Am Coll Cardiol. 2006; 48: 1217-1224
        • Shah RV
        • Chen-Tournoux AA
        • Picard MH
        • van Kimmenade RR
        • Januzzi JL.
        Galectin-3, cardiac structure and function, and long-term mortality in patients with acutely decompensated heart failure.
        Eur J Heart Fail. 2010; 12: 826-832