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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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RRT requirement in the population over the first week according to the number of HLA-DRB gene alleles.Black bars in the 2 alleles group, gray bars in the 3 alleles group, white bars in the 4 alleles group.
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pone-0035838-g004: RRT requirement in the population over the first week according to the number of HLA-DRB gene alleles.Black bars in the 2 alleles group, gray bars in the 3 alleles group, white bars in the 4 alleles group.

Mentions: HLA-DRB1 genotype analysis was performed in 149 patients because of DNA degradation in 26 samples. This DNA degradation concerned 14% of the RRT group and 17% of the remaining patients. The frequencies of HLA-DRB1 alleles and of the pairs of second HLA-DRB alleles are detailed in Tables S3A and S3B. The partition of HLA-DRB1 alleles was similar in this cohort with severe sepsis and septic shock compared to the reference population (Table S3A) [24]. AKI within 48 hours was not associated with a specific HLA-DRB genotype. The genotyping showing only two HLA-DRB1 alleles was more frequent in severe AKI than in the rest of the population ((9%) and (1%) respectively, p = 0.050) (data not shown), but the sample size was too small to draw a definitive conclusion. Considering the presence of three or four alleles (two HLA-DRB1 and two second HLA-DRB genes or two HLA-DRB1 and one second HLA-DRB gene), their incidence did not differ between patients with severe AKI vs no or mild AKI. Only in patients presenting four alleles, a trend for a less homozygosity in severe AKI group than in "no AKI" or "mild AKI" was found (p = 0.080). In the RRT population during the 1st week, the incidence of 4 alleles was significantly lower than in the group of patients not treated with RRT (p = 0.004) (Figure 4). In addition, within the 117 patients having 4 alleles, incidence of the homozygotie seemed to be further more protective, with a trend for a lower use of RRT in these patients (8.1%) patients compared to heterozygous (20.6%) (p = 0.070). HLA-DRB genotype was never related to inflammatory phenotypes (Figure S1).


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)

RRT requirement in the population over the first week according to the number of HLA-DRB gene alleles.Black bars in the 2 alleles group, gray bars in the 3 alleles group, white bars in the 4 alleles group.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0035838-g004: RRT requirement in the population over the first week according to the number of HLA-DRB gene alleles.Black bars in the 2 alleles group, gray bars in the 3 alleles group, white bars in the 4 alleles group.
Mentions: HLA-DRB1 genotype analysis was performed in 149 patients because of DNA degradation in 26 samples. This DNA degradation concerned 14% of the RRT group and 17% of the remaining patients. The frequencies of HLA-DRB1 alleles and of the pairs of second HLA-DRB alleles are detailed in Tables S3A and S3B. The partition of HLA-DRB1 alleles was similar in this cohort with severe sepsis and septic shock compared to the reference population (Table S3A) [24]. AKI within 48 hours was not associated with a specific HLA-DRB genotype. The genotyping showing only two HLA-DRB1 alleles was more frequent in severe AKI than in the rest of the population ((9%) and (1%) respectively, p = 0.050) (data not shown), but the sample size was too small to draw a definitive conclusion. Considering the presence of three or four alleles (two HLA-DRB1 and two second HLA-DRB genes or two HLA-DRB1 and one second HLA-DRB gene), their incidence did not differ between patients with severe AKI vs no or mild AKI. Only in patients presenting four alleles, a trend for a less homozygosity in severe AKI group than in "no AKI" or "mild AKI" was found (p = 0.080). In the RRT population during the 1st week, the incidence of 4 alleles was significantly lower than in the group of patients not treated with RRT (p = 0.004) (Figure 4). In addition, within the 117 patients having 4 alleles, incidence of the homozygotie seemed to be further more protective, with a trend for a lower use of RRT in these patients (8.1%) patients compared to heterozygous (20.6%) (p = 0.070). HLA-DRB genotype was never related to inflammatory phenotypes (Figure S1).

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