A multicentre study of acute kidney injury in severe sepsis and septic shock: association with inflammatory phenotype and HLA genotype.
<h4>Background</h4>To investigate the association between severity of acute kidney injury (AKI) and outcome, systemic inflammatory phenotype and HLA genotype in severe sepsis.<h4>Methodology/principal findings</h4>Prospective multicenter observational study done in 4 intensiv...
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oai:doaj.org-article:767187ad0aff4486a10f24d308589d222021-11-18T07:16:16ZA multicentre study of acute kidney injury in severe sepsis and septic shock: association with inflammatory phenotype and HLA genotype.1932-620310.1371/journal.pone.0035838https://doaj.org/article/767187ad0aff4486a10f24d308589d222012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22701553/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>To investigate the association between severity of acute kidney injury (AKI) and outcome, systemic inflammatory phenotype and HLA genotype in severe sepsis.<h4>Methodology/principal findings</h4>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).<h4>Conclusions</h4>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.Didier PayenAnne-Claire LukaszewiczMatthieu LegrandEtienne GayatValérie FaivreBruno MegarbaneElie AzoulayFabienne FieuxDominique CharronPascale LoiseauMarc BussonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 6, p e35838 (2012) |
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Medicine R Science Q |
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Medicine R Science Q Didier Payen Anne-Claire Lukaszewicz Matthieu Legrand Etienne Gayat Valérie Faivre Bruno Megarbane Elie Azoulay Fabienne Fieux Dominique Charron Pascale Loiseau Marc Busson A multicentre study of acute kidney injury in severe sepsis and septic shock: association with inflammatory phenotype and HLA genotype. |
| description |
<h4>Background</h4>To investigate the association between severity of acute kidney injury (AKI) and outcome, systemic inflammatory phenotype and HLA genotype in severe sepsis.<h4>Methodology/principal findings</h4>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).<h4>Conclusions</h4>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. |
| format |
article |
| author |
Didier Payen Anne-Claire Lukaszewicz Matthieu Legrand Etienne Gayat Valérie Faivre Bruno Megarbane Elie Azoulay Fabienne Fieux Dominique Charron Pascale Loiseau Marc Busson |
| author_facet |
Didier Payen Anne-Claire Lukaszewicz Matthieu Legrand Etienne Gayat Valérie Faivre Bruno Megarbane Elie Azoulay Fabienne Fieux Dominique Charron Pascale Loiseau Marc Busson |
| author_sort |
Didier Payen |
| title |
A multicentre study of acute kidney injury in severe sepsis and septic shock: association with inflammatory phenotype and HLA genotype. |
| title_short |
A multicentre study of acute kidney injury in severe sepsis and septic shock: association with inflammatory phenotype and HLA genotype. |
| title_full |
A multicentre study of acute kidney injury in severe sepsis and septic shock: association with inflammatory phenotype and HLA genotype. |
| title_fullStr |
A multicentre study of acute kidney injury in severe sepsis and septic shock: association with inflammatory phenotype and HLA genotype. |
| title_full_unstemmed |
A multicentre study of acute kidney injury in severe sepsis and septic shock: association with inflammatory phenotype and HLA genotype. |
| title_sort |
multicentre study of acute kidney injury in severe sepsis and septic shock: association with inflammatory phenotype and hla genotype. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/767187ad0aff4486a10f24d308589d22 |
| work_keys_str_mv |
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