The Molecular Phenotype of Six-Week Protocol Biopsies from Human Renal Allografts: Reflections of Prior Injury but Not Future Course.
Michael Mengel, Jessica Chang, Daniel Kayser, Wilfried Gwinner, Anke Schwarz, Gunilla Einecke, Verena Broecker, Konrad Famulski, Declan De Freitas, Luis Hidalgo, Hermann Haller, Banu Sis, Philip Halloran. University of Alberta, Edmonton, Canada; Hannover Medical School, Germany
Background: Protocol biopsies after renal transplantation are considered a surveillance tool for detection of subclinical pathologies at a stage where they are potentially more amenable to therapy.
Design: We assessed the molecular phenotype of 107 six-week protocol biopsies from human renal allografts, using Affymetrix microarrays. Transcript changes were summarized as pathogenesis-based transcript sets (PBTs) reflecting inflammation (T cells, macrophages, IFNG effects) and the injury-repair response of the parenchyma, stroma, and microcirculation – increased (“injury-up”) and decreased (“injury-down”) transcripts.
Results: The molecular changes were highly correlated with each other, even when all rejection and borderline cases were excluded. Inflammation and injury-down PBTs correlated with histologic inflammation and tubulitis, and the inflammation transcripts were greater in kidneys diagnosed as T cell-mediated or borderline rejection. In terms of their molecular phenotype no difference between borderline and T cell mediated rejection was found (figure 1a). Injury-up PBTs did not correlate with histopathology but did correlate with kidney function: thus functional disturbances are represented in transcript changes but not in histopathology. PBT changes correlated with prior delayed graft function. However, there was little difference between live donor kidneys and deceased donor kidneys that had not shown delayed graft function. Molecular changes did not predict future biopsies for clinical indications, rejection episodes, functional deterioration, or allograft loss. Despite the fact that cases with T cell mediated rejection (n=9) were treated and those with borderline (n=20) not, and both showed a similar molecular phenotype, no difference in terms of outcome between these two Banff groups were observed (figure 1b).
Conclusions: Thus while detecting T cell-mediated inflammation, the molecular phenotype of early protocol biopsies mostly reflects the injury-repair response to implantation stresses, and has little relationship to future events and outcomes, independent of any therapeutic intervention.
Category: Kidney (does not include tumors)
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 263, Wednesday Afternoon