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Inflammation in the setting of chronic allograft dysfunction post‐kidney transplant: phenotype and genotype
Author(s) -
Israni Ajay K.,
Leduc Robert,
Jacobson Pamala A.,
Wildebush Winston,
Guan Weihua,
Schladt David,
Matas Arthur J.,
Oetting William S.
Publication year - 2013
Publication title -
clinical transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 76
eISSN - 1399-0012
pISSN - 0902-0063
DOI - 10.1111/ctr.12074
Subject(s) - medicine , single nucleotide polymorphism , snp , concomitant , kidney transplantation , cohort , gastroenterology , genotype , immunology , kidney , gene , biology , genetics
Background Chronic allograft dysfunction ( CGD ) is a common outcome in kidney transplants, but its pathogenesis is unclear. We investigated the CGD phenotype and single‐nucleotide polymorphisms ( SNP s) associated with CGD . Method This prospective study enrolled 2336 transplants from seven transplant centers in North America. CGD was defined as a >25% rise in serum creatinine relative to a three‐month post‐transplant baseline, requiring a kidney biopsy. We genotyped 2724 SNP s in the initial 979 transplants, which form the test cohort. Results CGD occurred 11.2 times per 100 person‐years at a median of 509 ± 387 days from the three‐month baseline. CGD was independently associated with death‐censored, allograft failure, in an adjusted analysis [ HR =20.6 (11.8–35.8, p < 0.001)]. Among 366 transplant recipients with CGD , 91% had inflammation on biopsy scores. 94 (26%) had inflammatory changes consistent with a diagnosis of concomitant acute rejection. SNP s in FM 06 and FM 03, potential drug metabolism genes, were associated with CGD , after accounting for multiple testing. Conclusion CGD phenotype with concomitant inflammation is associated with increased risk of allograft failure. SNP s associated with CGD in novel drug metabolism and transport genes, will be validated in subsequent transplants.