Limits...
A multicentre study of acute kidney injury in severe sepsis and septic shock: association with inflammatory phenotype and HLA genotype.

Payen D, Lukaszewicz AC, Legrand M, Gayat E, Faivre V, Megarbane B, Azoulay E, Fieux F, Charron D, Loiseau P, Busson M - PLoS ONE (2012)

Bottom Line: The VDI did not differ between groups of AKI.HLA-DRB genotyping showed a significantly lower proportion of 4 HLA-DRB alleles among patients requiring renal replacement therapy (RRT) (58%) than in patients with severe AKI who did not receive RRT (84%) (p = 0.004).Presence of 4 alleles of HLA-DRB in severe AKI patients seems associated with a lower need of RRT.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology and Critical Care, Lariboisière Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France. dpayen1234@orange.fr

ABSTRACT

Background: To investigate the association between severity of acute kidney injury (AKI) and outcome, systemic inflammatory phenotype and HLA genotype in severe sepsis.

Methodology/principal findings: Prospective multicenter observational study done in 4 intensive care units in two university hospitals. Severe sepsis and septic shock patients with at least 2 organ failures based on the SOFA score were classified: 1) "no AKI", 2) "mild AKI" (grouping stage 1 and 2 of AKIN score) and 3) "severe AKI" (stage 3 of AKIN score). Sequential measurements: The vasopressor dependency index (VDI; dose and types of drugs) to evaluate the association between hemodynamic status and the development of early AKI; plasma levels of IL-10, macrophage migration inhibitory factor (MIF), IL-6 and HLA-DR monocyte expression. Genotyping of the 13 HLA-DRB1 alleles with deduction of presence of HLA-DRB3, -DRB4 and -DRB5 genes. We used multivariate analysis with competitive risk model to study associations. Overall, 176 study patients (146 with septic shock) were classified from AKIN score as "no AKI" (n = 43), "mild AKI" (n = 74) or "severe AKI" (n = 59). The VDI did not differ between groups of AKI. After adjustment, "mild and severe AKI" were an independent risk factor for mortality (HR 2.42 95%CI[1.01-5.83], p = 0.048 and HR 1.99 95%CI[1.30-3.03], p = 0.001 respectively). "Severe AKI" had higher levels of plasma IL-10, MIF and IL-6 compared to "no AKI" and mild AKI (p<0.05 for each), with no difference in mHLA-DR at day 0. HLA-DRB genotyping showed a significantly lower proportion of 4 HLA-DRB alleles among patients requiring renal replacement therapy (RRT) (58%) than in patients with severe AKI who did not receive RRT (84%) (p = 0.004).

Conclusions: AKI severity is independently associated with mortality and plasma IL-10, MIF or IL-6 levels. Presence of 4 alleles of HLA-DRB in severe AKI patients seems associated with a lower need of RRT.

Show MeSH

Related in: MedlinePlus

Analysis of mortality according to AKI severity. A.Mortality curves according to AKI severity from day 2 to day 28. B. Univariate and multivariate analysis of the association between mortality and AKI. (*) indicates results using competitive risk regression models (analyses adjusted on SOFA-II, age, sex, diabetes and cancer) of mortality risk.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3368929&req=5

pone-0035838-g002: Analysis of mortality according to AKI severity. A.Mortality curves according to AKI severity from day 2 to day 28. B. Univariate and multivariate analysis of the association between mortality and AKI. (*) indicates results using competitive risk regression models (analyses adjusted on SOFA-II, age, sex, diabetes and cancer) of mortality risk.

Mentions: Patients with "severe AKI" had a significantly higher mortality rate at day 28 (40.7%) compared to patients with mild AKI (26%) or no AKI (12%) (p = 0.001) (Figure 2a). The multivariate analysis (Figure 2b) using competitive risks model as an independent factor of mortality after adjusting for age, gender, presence of diabetes and cancer and the SOFA score, excluding the renal item showed differences for "severe AKI" versus "no AKI" or "mild" AKI (Hazard Ratio (HR) 2.27 CI 1.30-3.97; p = 0.004). In absence of adjustment, "mild AKI" versus no AKI (HR 2.42 CI 1.01-5.83; p = 0.048) were significant and "severe AKI" versus "mild AKI" was closed to the significance (HR 1.74 CI 0.97-3.12; p = 0.061).


A multicentre study of acute kidney injury in severe sepsis and septic shock: association with inflammatory phenotype and HLA genotype.

Payen D, Lukaszewicz AC, Legrand M, Gayat E, Faivre V, Megarbane B, Azoulay E, Fieux F, Charron D, Loiseau P, Busson M - PLoS ONE (2012)

Analysis of mortality according to AKI severity. A.Mortality curves according to AKI severity from day 2 to day 28. B. Univariate and multivariate analysis of the association between mortality and AKI. (*) indicates results using competitive risk regression models (analyses adjusted on SOFA-II, age, sex, diabetes and cancer) of mortality risk.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3368929&req=5

pone-0035838-g002: Analysis of mortality according to AKI severity. A.Mortality curves according to AKI severity from day 2 to day 28. B. Univariate and multivariate analysis of the association between mortality and AKI. (*) indicates results using competitive risk regression models (analyses adjusted on SOFA-II, age, sex, diabetes and cancer) of mortality risk.
Mentions: Patients with "severe AKI" had a significantly higher mortality rate at day 28 (40.7%) compared to patients with mild AKI (26%) or no AKI (12%) (p = 0.001) (Figure 2a). The multivariate analysis (Figure 2b) using competitive risks model as an independent factor of mortality after adjusting for age, gender, presence of diabetes and cancer and the SOFA score, excluding the renal item showed differences for "severe AKI" versus "no AKI" or "mild" AKI (Hazard Ratio (HR) 2.27 CI 1.30-3.97; p = 0.004). In absence of adjustment, "mild AKI" versus no AKI (HR 2.42 CI 1.01-5.83; p = 0.048) were significant and "severe AKI" versus "mild AKI" was closed to the significance (HR 1.74 CI 0.97-3.12; p = 0.061).

Bottom Line: The VDI did not differ between groups of AKI.HLA-DRB genotyping showed a significantly lower proportion of 4 HLA-DRB alleles among patients requiring renal replacement therapy (RRT) (58%) than in patients with severe AKI who did not receive RRT (84%) (p = 0.004).Presence of 4 alleles of HLA-DRB in severe AKI patients seems associated with a lower need of RRT.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology and Critical Care, Lariboisière Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France. dpayen1234@orange.fr

ABSTRACT

Background: To investigate the association between severity of acute kidney injury (AKI) and outcome, systemic inflammatory phenotype and HLA genotype in severe sepsis.

Methodology/principal findings: Prospective multicenter observational study done in 4 intensive care units in two university hospitals. Severe sepsis and septic shock patients with at least 2 organ failures based on the SOFA score were classified: 1) "no AKI", 2) "mild AKI" (grouping stage 1 and 2 of AKIN score) and 3) "severe AKI" (stage 3 of AKIN score). Sequential measurements: The vasopressor dependency index (VDI; dose and types of drugs) to evaluate the association between hemodynamic status and the development of early AKI; plasma levels of IL-10, macrophage migration inhibitory factor (MIF), IL-6 and HLA-DR monocyte expression. Genotyping of the 13 HLA-DRB1 alleles with deduction of presence of HLA-DRB3, -DRB4 and -DRB5 genes. We used multivariate analysis with competitive risk model to study associations. Overall, 176 study patients (146 with septic shock) were classified from AKIN score as "no AKI" (n = 43), "mild AKI" (n = 74) or "severe AKI" (n = 59). The VDI did not differ between groups of AKI. After adjustment, "mild and severe AKI" were an independent risk factor for mortality (HR 2.42 95%CI[1.01-5.83], p = 0.048 and HR 1.99 95%CI[1.30-3.03], p = 0.001 respectively). "Severe AKI" had higher levels of plasma IL-10, MIF and IL-6 compared to "no AKI" and mild AKI (p<0.05 for each), with no difference in mHLA-DR at day 0. HLA-DRB genotyping showed a significantly lower proportion of 4 HLA-DRB alleles among patients requiring renal replacement therapy (RRT) (58%) than in patients with severe AKI who did not receive RRT (84%) (p = 0.004).

Conclusions: AKI severity is independently associated with mortality and plasma IL-10, MIF or IL-6 levels. Presence of 4 alleles of HLA-DRB in severe AKI patients seems associated with a lower need of RRT.

Show MeSH
Related in: MedlinePlus