Elevated plasma Galectin-3 is associated with major adverse kidney events and death after ICU admission

L Boutin,C E Chadjichristos,M Legrand,E Gayat,F Dépret,M Sadoune,A Mebazaa

doi:10.1186/s13054-021-03878-x

Abstract

BackgroundGalectin-3 (Gal-3) is a proinflammatory and profibrotic protein especially overexpressed after Acute Kidney Injury (AKI). The early renal prognostic value of Gal-3 after AKI in critically ill patients remains unexplored. The objective was to evaluate the prognostic value of plasma level of Gal-3 for Major Adverse Kidney Events (MAKE) and mortality 30 days after ICU admission across AKI stages.MethodsThis is an ancillary study of a prospective, observational, multicenter cohort (FROG-ICU). AKI was defined using KDIGO definition.ResultsTwo thousand and seventy-six patients had a Gal-3 plasma level measurement at ICU admission. Seven hundred and twenty-three (34.8%) were females and the median age was 63 [51, 74] years. Eight hundred and seven (38.9%) patients developed MAKE, 774 (37.3%) had AKI and mortality rate at 30 days was 22.4% (N = 465). Patients who developed MAKE had higher Gal-3 level at admission compared to patients without (30.2 [20.8, 49.2] ng/ml versus 16.9 [12.7, 24.3] ng/ml, p < 0.001, respectively. The area under the receiver operating characteristic curve of Gal-3 to predict MAKE was 0.76 CI95% [0.74–0.78], p < 0.001. Gal-3 was associated with MAKE (OR 1.80 CI95% [1.68–1.93], p < 0.001, non-adjusted and OR 1.37 CI95% [1.27–1.49], p < 0.001, adjusted). The use of Gal-3 improved prediction performance of prediction model including SAPSII, Screatadm, pNGAL with a NRI of 0.27 CI95%(0.16–0.38), p < 0.001. Median Gal-3 was higher in non-survivors than in survivors at 30 days (29.2 [20.2, 49.2] ng/ml versus 18.8 [13.3, 29.2] ng/ml, p < 0.001, respectively).ConclusionPlasma levels of Gal-3 were strongly associated with renal function, with an increased risk of MAKE and death after ICU admission.Trial registration ClinicalTrials.gov NCT01367093. Registered on 6 June 2011.Graphical abstract

Highlights

Galectin-3 (Gal-3) is a proinflammatory and profibrotic protein especially overexpressed after Acute Kidney Injury (AKI)
Collection of patient data Upon admission, demographics, body mass index, presence of sepsis or septic shock, type of intensive care unit (ICU) admission, organ dysfunction and severity scores (Sequential Organ Failure Assessment [SOFA] [11], Simplified Acute physiology score [SAPS II] [12]), preexisting comorbidities treated within the past year, past medical history, laboratory values, admission urine output, as well as organ support were recorded
S6A, S7B, S9A) and after excluding patients with CHF or CKD (Additional file 1: Fig. S13). In this cohort study, Gal-3 was associated with Major Adverse Kidney Events (MAKE) and all its components

Summary

Introduction

Galectin-3 (Gal-3) is a proinflammatory and profibrotic protein especially overexpressed after Acute Kidney Injury (AKI). The objective was to evaluate the prognostic value of plasma level of Gal-3 for Major Adverse Kidney Events (MAKE) and mortality 30 days after ICU admission across AKI stages. In a model of sepsis (i.e., caecal ligature and puncture), Gal-3 was associated with the risk of AKI and its pharmacological blockage using modified citrus pectin prevented sepsis-associated AKI [9]. These translational data suggest that Gal-3 could play a role both in the development of renal damage and remote organs damage after AKI. The objectives of this study were to evaluate the association between plasma Gal-3 level at intensive care unit (ICU) admission with Major Adverse Kidney Events (MAKE), and mortality at day 30

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