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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.

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Related in: MedlinePlus

Blood highest leukocytes, monocyte HLA-DR, plasma IL-6, IL-10 and MIF levels in AKI groups.No AKI (white diamond), mild AKI (black diamond) and severe AKI (black circle) at day 0, day1 and day2. Mean and standard deviation are represented.
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pone-0035838-g003: Blood highest leukocytes, monocyte HLA-DR, plasma IL-6, IL-10 and MIF levels in AKI groups.No AKI (white diamond), mild AKI (black diamond) and severe AKI (black circle) at day 0, day1 and day2. Mean and standard deviation are represented.

Mentions: The logistic regression exploring associated factors with both "mild" and "severe" AKI included the following variables: SOFA score, number of organ dysfunctions, mechanical ventilation, fluid balance, PT, lactate, norepinephrine infusion, dobutamine infusion. For "mild" AKI, SOFA score at admission (OR [95% CI]  = 1.30 [1.10–1.53] for an increase of 1 unit, p = 0.002) and the number of organ failure at admission (OR [95% CI]  = 1.05 [1.00–1.09] for an increase of 1 organ failure, p = 0.034) were found to be independently associated. For "severe" AKI, only SOFA score at admission (OR [95% CI]  = 1.64 [1.41–1.92] for an increase of 1 unit, p<0.0001) was found to be independently associated.


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)

Blood highest leukocytes, monocyte HLA-DR, plasma IL-6, IL-10 and MIF levels in AKI groups.No AKI (white diamond), mild AKI (black diamond) and severe AKI (black circle) at day 0, day1 and day2. Mean and standard deviation are represented.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0035838-g003: Blood highest leukocytes, monocyte HLA-DR, plasma IL-6, IL-10 and MIF levels in AKI groups.No AKI (white diamond), mild AKI (black diamond) and severe AKI (black circle) at day 0, day1 and day2. Mean and standard deviation are represented.
Mentions: The logistic regression exploring associated factors with both "mild" and "severe" AKI included the following variables: SOFA score, number of organ dysfunctions, mechanical ventilation, fluid balance, PT, lactate, norepinephrine infusion, dobutamine infusion. For "mild" AKI, SOFA score at admission (OR [95% CI]  = 1.30 [1.10–1.53] for an increase of 1 unit, p = 0.002) and the number of organ failure at admission (OR [95% CI]  = 1.05 [1.00–1.09] for an increase of 1 organ failure, p = 0.034) were found to be independently associated. For "severe" AKI, only SOFA score at admission (OR [95% CI]  = 1.64 [1.41–1.92] for an increase of 1 unit, p<0.0001) was found to be independently associated.

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