TLR4 mRNA levels as tools to estimate risk for early posttransplantation kidney graft dysfunction.
BACKGROUND
The participation of Toll-like receptor (TLR) 4, an innate immunity receptor, has been previously demonstrated in the pathogenesis of acute renal injury. We aimed to investigate whether messenger RNA (mRNA) levels of TLR4 and its adapter molecule, myeloid differentiation primary response gene (MYD) 88, are associated with delayed graft function (DGF) and could be used as biomarkers of its occurrence.


METHODS
TLR4 and MYD88 gene mRNA levels were evaluated with real-time polymerase chain reaction, in preimplantation biopsies (n=89) and first day posttransplantation samples of urine (n=67) and blood (n=80) from graft recipients and analyzed according to donor type (living or deceased) and DGF occurrence.


RESULTS
Expression levels of both genes were higher in biopsies from deceased donors than from living donors (P<0.001 for both) but did not differ between deceased-donor kidney transplants with and without DGF; in urine, TLR4 expression levels were higher in patients with prolonged DGF (DGF lasting >14 days) (P=0.05, compared with cases without DGF); in blood, lower mRNA levels of TLR4 and MYD88 predicted pDGF occurrence with an accuracy of 86% and 87%, respectively.


CONCLUSIONS
The expression levels of TLR4 and MYD88 were higher in kidneys from deceased donors than from living donors. Lower levels of expression of both genes in blood were associated with DGF occurrence. The prediction of prolonged DGF by low TLR4 and MYD88 expression levels in blood with a greater the 85% accuracy was the most important finding of this study.
Instituto de Imunogenética-Associação Fundo de Incentivo à Pesquisa, São Paulo, Brazil.
Vinicius
V
Andrade-Oliveira
Erika F
EF
Campos
Amador
A
Goncalves-Primo
Patricia C
PC
Grenzi
Jose O
JO
Medina-Pestana
Helio
H
Tedesco-Silva
Maria
M
Gerbase-DeLima
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D051799:Delayed Graft Function / Q000175:diagnosis / Q000209:etiology / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007668:Kidney / Q000276:immunology / Q000378:metabolism*; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology; D019520:Living Donors; D008875:Middle Aged; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000097:blood / Q000378:metabolism* / Q000652:urine; D060888:Real-Time Polymerase Chain Reaction; D018570:Risk Assessment; D012307:Risk Factors; D012680:Sensitivity and Specificity; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000097:blood / Q000235:genetics*; D016896:Treatment Outcome
D015415:Biomarkers; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4