Fibrosis with inflammation at one year predicts transplant functional decline.
Lack of knowledge regarding specific causes for late loss of kidney transplants hampers improvements in long-term allograft survival. Kidney transplants with both interstitial fibrosis and subclinical inflammation but not fibrosis alone after 1 year have reduced survival. This study tested whether fibrosis with inflammation at 1 year associates with decline of renal function in a low-risk cohort and characterized the nature of the inflammation. We studied 151 living-donor, tacrolimus/mycophenolate-treated recipients without overt risk factors for reduced graft survival. Transplants with normal histology (n = 86) or fibrosis alone (n = 45) on 1-year protocol biopsy had stable renal function between 1 and 5 years, whereas those with both fibrosis and inflammation (n = 20) exhibited a decline in GFR and reduced graft survival. Immunohistochemistry confirmed increased interstitial T cells and macrophages/dendritic cells in the group with both fibrosis and inflammation, and there was increased expression of transcripts related to innate and cognate immunity. Pathway- and pathologic process-specific analyses of microarray profiles revealed that potentially damaging immunologic activities were enriched among the overexpressed transcripts (e.g., Toll-like receptor signaling, antigen presentation/dendritic cell maturation, IFN-γ-inducible response, cytotoxic T lymphocyte-associated and acute rejection-associated genes). Therefore, the combination of fibrosis and inflammation in 1-year protocol biopsies associates with reduced graft function and survival as well as a rejection-like gene expression signature, even among recipients with no clinical risk factors for poor outcomes. Early interventions aimed at altering rejection-like inflammation may improve long-term survival of kidney allografts.
Park
Walter D
WD
Department of Surgery, Division of Transplantation Surgery, Mayo Clinic, Rochester, Minnesota, USA.
Griffin
Matthew D
MD
Cornell
Lynn D
LD
Cosio
Fernando G
FG
Stegall
Mark D
MD
D000328:Adult; D001706:Biopsy; D015331:Cohort Studies; D005260:Female; D005355:Fibrosis; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000502:physiology; D006084:Graft Rejection / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000473:pathology* / Q000503:physiopathology; D016030:Kidney Transplantation / Q000473:pathology / Q000502:physiology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009393:Nephritis / Q000150:complications* / Q000473:pathology* / Q000503:physiopathology; D011237:Predictive Value of Tests; D011379:Prognosis
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