Association of donor inflammation- and apoptosis-related genotypes and delayed allograft function after kidney transplantation.
BACKGROUND
Delayed renal allograft survival (delayed graft function [DGF]) after deceased donor kidney transplantation is associated with an increased risk of allograft loss. Inflammatory response and apoptosis are associated with increased risk of DGF.


METHODS
Cross-sectional study.


METHODS
We first recruited 616 recipients of kidneys from 512 deceased kidney donors, and donor DNA was genotyped. These recipients, who were included in a prospective cohort study of 9 transplant centers in the Delaware Valley region, had their DGF outcome obtained through medical record abstraction. We then identified the recipient (n = 349) of the contralateral deceased kidney donor, if not part of the cohort, through the US Renal Data System registry. The final cohort consisted of 965 recipients of deceased donor kidneys from 512 donors.


METHODS
Donor single-nucleotide polymorphisms in genes for tumor necrosis factor alpha (TNF), transforming growth factor beta1 (TGFB1), interleukin 10 (IL10), p53 (TP53), and heme oxygenase 1 (HMOX1).


RESULTS
DGF, defined as the need for dialysis therapy in the first week posttransplantation. Secondary outcomes included acute rejection and estimated glomerular filtration rate.


METHODS
Information for DGF, acute rejection, and estimated glomerular filtration rate for recipients in the Delaware Valley Cohort was obtained through medical record abstraction. For other recipients, information for DGF was obtained from United Network for Organ Sharing forms and Centers for Medicare & Medicaid Services claims in the US Renal Data System registry.


RESULTS
No association was detected between the TGFB1, IL10, TP53, and HMOX1 genes and DGF. The G allele of the TNF polymorphism rs3093662 was associated with DGF in an adjusted analysis (odds ratio, 1.85 compared with A allele; 95% confidence interval, 1.16 to 2.96; P = 0.01). However, this association did not achieve statistical significance after adjusting for multiple comparisons.


CONCLUSIONS
Inadequate sample size for infrequent genotypes and multiple comparisons.


CONCLUSIONS
Because of the low frequency of donor single-nucleotide polymorphisms of interest, a larger sample size and replication are necessary to confirm these findings on the association of donor genotypes with DGF.
Israni
Ajay K
AK
Department of Medicine, Hennepin County Medical Center, University of Minnesota, Minneapolis, MN, USA.
Li
Na
N
Cizman
Bojana B
BB
Snyder
Jon
J
Abrams
John
J
Joffe
Marshall
M
Rebbeck
Timothy
T
Feldman
Harold I
HI
D000328:Adult; D000483:Alleles; D017209:Apoptosis; D001706:Biopsy; D003430:Cross-Sectional Studies; D004247:DNA / Q000235:genetics*; D003691:Delaware / Q000453:epidemiology; D051799:Delayed Graft Function / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers / Q000235:genetics*; D005838:Genotype; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D006085:Graft Survival / Q000235:genetics; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015994:Incidence; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D016030:Kidney Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D013997:Time Factors; D014019:Tissue Donors; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D005819:Genetic Markers; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D016753:Interleukin-10; D004247:DNA; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1