A multicentre study of acute kidney injury in severe sepsis and septic shock: association with inflammatory phenotype and HLA genotype.
BACKGROUND
To investigate the association between severity of acute kidney injury (AKI) and outcome, systemic inflammatory phenotype and HLA genotype in severe sepsis.


RESULTS
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.
Department of Anesthesiology and Critical Care, Lariboisière Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France. dpayen1234@orange.fr
Didier
D
Payen
Anne-Claire
AC
Lukaszewicz
Matthieu
M
Legrand
Etienne
E
Gayat
Valérie
V
Faivre
Bruno
B
Megarbane
Elie
E
Azoulay
Fabienne
F
Fieux
Dominique
D
Charron
Pascale
P
Loiseau
Marc
M
Busson
D058186:Acute Kidney Injury / Q000097:blood* / Q000209:etiology*; D005838:Genotype; D006684:HLA-DR Antigens / Q000097:blood / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood; D015233:Models, Statistical; D011446:Prospective Studies; D018805:Sepsis / Q000150:complications / Q000503:physiopathology*; D012772:Shock, Septic / Q000150:complications / Q000503:physiopathology*
D006684:HLA-DR Antigens; D015850:Interleukin-6; D008263:Macrophage Migration-Inhibitory Factors; D016753:Interleukin-10