Novel markers in zero-hour kidney biopsies indicate graft quality and clinical outcome.
BACKGROUND
In renal transplantation, allograft biopsies provide valuable diagnostic information indicating adverse allograft outcome posttransplantation. To uncover novel candidate markers characteristic of subtle inflammation and immune activation present during the intraoperative period, we investigated messenger RNA (mRNA) gene expression profiles in renal zero biopsies.


METHODS
Transcription profiles from deceased donors (n=63) and living donors (n=26) were investigated for inflammation-associated markers in zero-hour biopsies by real-time reverse-transcriptase polymerase chain reaction.


RESULTS
We observed a significant induction of the chemokine receptor 7 ligands [C-C motif] ligand 19/21 in the deceased donor group (P<0.001). Additionally, along with the induction of the activation marker CD69 (P<0.01), we further detected significant elevated mRNA levels of the inducible immunoproteasome subunits PSMB8, PSMB9, and PSMB10 (P<0.001, respectively). Candidate markers were further tested for posttransplantation clinical outcomes showing the potential to predict the development of delayed graft function, acute rejection, and renal function after 6 months. For instance, by combining mRNA gene expression profiles with clinical patient data, the analysis revealed high sensitivity (95%) and specificity (84%, area under the curve=0.93) for the prediction of acute rejection.


CONCLUSIONS
Zero-hour biopsies of renal allografts may provide useful information on subclinical pathological changes in the grafted kidney. The identification of CCL19/21 or PSMB8/9/10 makes these molecules particularly suitable as potential candidate targets for therapeutic interventions.
Kotsch
Katja
K
Institute of Medical Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany. katja.kotsch@charite.de
Kunert
Kristina
K
Merk
Vera
V
Reutzel-Selke
Anja
A
Pascher
Andreas
A
Fritzsche
Florian
F
Tullius
Stefan G
SG
Pratschke
Johann
J
D000328:Adult; D015703:Antigens, CD / Q000235:genetics; D001706:Biopsy; D002102:Cadaver; D054415:Chemokine CCL19 / Q000235:genetics; D054421:Chemokine CCL21 / Q000235:genetics; D051799:Delayed Graft Function / Q000276:immunology / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D019409:Interleukin-15 / Q000235:genetics; D007668:Kidney / Q000276:immunology / Q000473:pathology*; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology*; D019520:Living Donors; D046988:Proteasome Endopeptidase Complex / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012086:Reoperation; D014019:Tissue Donors; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D015703:Antigens, CD; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019409:Interleukin-15; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D046988:Proteasome Endopeptidase Complex