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Critical Care

, 19:368

First Online: 19 October 2015Received: 23 July 2015Accepted: 27 September 2015

Abstract

IntroductionTo determine whether single nucleotide polymorphisms SNPs in FAS and related genes are associated with acute kidney injury AKI in patients with acute respiratory distress syndrome ARDS.

MethodsWe studied 401 Caucasian N = 310 and African-American N = 91 patients aged ≥ 13 years with ALI who enrolled in the Fluid and Catheter Treatment Trial FACTT between 2000 and 2005 from 20 North American centers. We genotyped 367 SNPs in 45 genes of the Fas-Fas ligand pathway to identify associations between SNPs in Fas pathway genes and the development of AKI by day 2 after enrollment in FACTT, adapting Acute Kidney Injury Network AKIN criteria. Written informed consent was obtained from participants or legally authorized surrogates in the original FACTT study and available to use for secondary analysis.

ResultsIn Caucasian patients, we identified associations between two SNPs and the incidence of AKI stage 1 and above: rs1050851 and rs2233417; both are found within the gene for nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha NFKBIA. For rs1050851 and rs2233417, the odds ratios ORs were 2.34 95 % confidence interval CI = 1.58–3.46, p = 1.06 × 10, FDR = 0.003 and 2.46 CI = 1.61–3.76, p = 1.81 × 10, FDR = 0.003 for each minor allele, respectively. The associations were stronger still for AKIN stage 2–3 with respective ORs 4.00 CI = 2.10–7.62, p = 1.05 × 10, FDR = 0.003 and 4.03 CI = 2.09–7.77, p = 1.88 × 10, FDR = 0.003 for each minor allele homozygote. We observed no significant association between these SNPs and AKI in the smaller subset of African Americans.

ConclusionIn Caucasian patients with ALI, the presence of minor alleles in two SNPs in NFKBIA was strongly associated with the development of AKI.

Trial registrationNCT00281268. Registered 20-01-2006.

AbbreviationsAKIacute kidney injury

AKINAcute Kidney Injury Network

ALIacute lung injury

ARDSacute respiratory distress syndrome

CVCcentral venous catheter

FACTTFluid and Catheter Treatment Trial

FasLFas ligand

FDRfalse discovery rate

IRIischemia reperfusion injury

LDlinkage disequilibrium

MAFminor allele frequency

MPOmyeloperoxidase

NFKBIAnuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha

ORodds ratio

PACpulmonary artery catheter

Q-Qquantile-quantile

SCrserum creatinine

SNPsingle nucleotide polymorphism

TNFtumor necrosis factor

Electronic supplementary materialThe online version of this article doi:10.1186-s13054-015-1084-5 contains supplementary material, which is available to authorized users.

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Autor: Pavan Bhatraju - Christine Hsu - Paramita Mukherjee - Bradford J. Glavan - Amber Burt - Carmen Mikacenic - Jonathan Himmel

Fuente: https://link.springer.com/







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