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

Flowchart of the enrolled septic patients with different AKI severity and outcome.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3368929&req=5

pone-0035838-g001: Flowchart of the enrolled septic patients with different AKI severity and outcome.

Mentions: This study involved patients from 4 Intensive Care Units in Paris, France, including 2 medical and 2 surgical ICUs. Patients fulfilling the criteria of severe sepsis or septic shock defined according to the ACCP/SCCM consensus conference [15] and having at least two organ failures defined by the SOFA (sequential organ failure assessment) score (value >1 for each organ failure were considered) [16] were included between January 2004 and December 2005. Patients with chronic renal failure were excluded (Figure 1). Epidemiological characteristics and common past medical events were collected. Use of vasopressors, inotropes, hydrocortisone, activated protein C, insulin, fluid loading, and renal replacement therapy (RRT) were recorded. Mortality was assessed at the 28th day after enrolment. Patients who died during the first 48 hrs were excluded from this study, considering the time-evolution too short to meet the criteria for AKI definition (Figure 1) [17].


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)

Flowchart of the enrolled septic patients with different AKI severity and outcome.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0035838-g001: Flowchart of the enrolled septic patients with different AKI severity and outcome.
Mentions: This study involved patients from 4 Intensive Care Units in Paris, France, including 2 medical and 2 surgical ICUs. Patients fulfilling the criteria of severe sepsis or septic shock defined according to the ACCP/SCCM consensus conference [15] and having at least two organ failures defined by the SOFA (sequential organ failure assessment) score (value >1 for each organ failure were considered) [16] were included between January 2004 and December 2005. Patients with chronic renal failure were excluded (Figure 1). Epidemiological characteristics and common past medical events were collected. Use of vasopressors, inotropes, hydrocortisone, activated protein C, insulin, fluid loading, and renal replacement therapy (RRT) were recorded. Mortality was assessed at the 28th day after enrolment. Patients who died during the first 48 hrs were excluded from this study, considering the time-evolution too short to meet the criteria for AKI definition (Figure 1) [17].

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