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

Abstract

Background: Galectin-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.

Methods: This is an ancillary study of a prospective, observational, multicenter cohort (FROG-ICU). AKI was defined using KDIGO definition.

Results: Two 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 CI_95% [0.74-0.78], p < 0.001. Gal-3 was associated with MAKE (OR 1.80 CI_95% [1.68-1.93], p < 0.001, non-adjusted and OR 1.37 CI_95% [1.27-1.49], p < 0.001, adjusted). The use of Gal-3 improved prediction performance of prediction model including SAPSII, Screat_adm, pNGAL with a NRI of 0.27 CI_95%(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).

Conclusion: Plasma 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.

Keywords: Acute kidney injury; Galectin-3; Major Adverse Kidney Event; Renal biomarker.

Fig. 1

Gal-3 level for MAKE and NO MAKE (A), Gal-3 level for AKI and NO AKI patients (B), Gal-3 level for survivor and non-survivor patients (C). MAKE: Major adverse kidney event, AKI: Acute kidney injury. p value: ns > 0.05, *0.05–0.01; **0.01–0.001; ***< 0.001

Fig. 2

Gal-3, SAPSII, Screat_adm, pNGAL, Gal-3 after adjustment and Screat_adm after adjustment, Gal-3 after adjustment including pNGAL and Screat_adm after adjustment including pNGAL association with MAKE, AKI and Mortality. Gal-3 association was adjusted with gender, age, CKD, vasopressor treatment, SAPS II, Charlson score, Screat_adm and lactate value at admission. For AKI association, Screat was not include in the adjustment model. OR for continuous variables (Gal-3, SAPSII, Screat_adm) were standardized for each 10-unit change, and pNGAL for each 100-fold unit change. *These model do not include Screat_adm. OR, odds ratio; CI, confidence interval; SAPS II, Simplified acute physiology score II; MAKE, Major adverse kidney event; Gal-3, galectin 3; Screat, serum creatinine; CKD, Chronic kidney disease

Fig. 3

ROC curve of Gal-3 prediction performance for MAKE, AKI and mortality. AKI, Acute kidney injury; ROC, receiver operating characteristics; CI, confidence interval; MAKE, Major adverse kidney event

Fig. 4

Prevalence of mortality according to level of Gal3 (tercile stratification) (a). Prevalence of mortality according to Gal3 positive biomarker and AKI positive biomarker (b). Gal-3, galectin 3; AKI, acute kidney injury

Fig. 5

Gal-3 level according to each acute kidney injury (AKI) stage of the KDIGO classification. AKI, acute kidney injury; KDIGO, Kidney Disease Improving Global Outcomes; ns, non-significant. P value: ns: > 0.05, *0.05–0.01; **0.01–0.001; ***> 0.001