title: Kidney ischemic injury genes expressed after donor brain death are predictive for the outcome of kidney transplantation.
abstract: The results of deceased donor kidney transplantation largely depend on the extent of organ injury induced by brain death and the transplantation procedure. In this study, we analyzed the preprocurement intragraft expression of 29 genes involved in apoptosis, tissue injury, immune cell migration, and activation. We also assessed their influence on allograft function. Before flushing with cold solution we obtained 50 kidney core biopsies of deceased donor kidneys immediately after organ retrieval. The control group included 18 biopsies obtained from living donors. Gene expression was analyzed with low-density arrays (Taqman). LCN2/lipocalin-2 is considered a biomarker of kidney epithelial ischemic injury with a renoprotective function. HAVCR1/KIM-1 is associated with acute tubular injury. Comparison of deceased donor kidneys to control organs revealed a significantly higher expression of LCN2 (8.0-fold P=.0006) and HAVCR1 (4.7-fold, P<.0001). Their expressions positively correlated with serum creatinine concentrations after 6 months after transplantation: LCN2 (r=.65, P<.0001), HAVCR1 (r=.44, P=.006). Kidneys displaying delayed graft function and/or an acute rejection episode in the first 6 months after showed higher LCN2 expression compared to event-free ones (1.7-fold, P=.027). A significantly higher increase in expression of TLR2 (5.2-fold), Interleukin (IL) 18 (4.6-fold), HMGB1 (4.1-fold), GUSB (2.4-fold), CASP3 (2.0-fold) FAS (1.8-fold), and TP53 (1.6-fold) was observed among deceased donor kidneys compared with the control group. Their expression levels were not related to clinical outcomes: however, they showed significant correlations with one another (r>.6, P<.0001). We also observed a slightly reduced expression of IL10 (0.6-fold, P=.004). Our data suggested that increased LCN2 and HAVCR1 expression observed in the kidneys after donor brain death were hallmarks of the organ injury process. LCN2 expression level in retrieved kidneys can predict kidney transplantation outcomes.
authors: Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland. dorotakaminska@interia.pl
authors: D
authors: D
authors: Kamińska
authors: K
authors: K
authors: Kościelska-Kasprzak
authors: D
authors: D
authors: Drulis-Fajdasz
authors: A
authors: A
authors: Hałoń
authors: W
authors: W
authors: Polak
authors: P
authors: P
authors: Chudoba
authors: D
authors: D
authors: Jańczak
authors: O
authors: O
authors: Mazanowska
authors: D
authors: D
authors: Patrzałek
authors: M
authors: M
authors: Klinger
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics; D000328:Adult; D001926:Brain Death; D051799:Delayed Graft Function / Q000235:genetics; D005260:Female; D015870:Gene Expression; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D007511:Ischemia / Q000235:genetics*; D007668:Kidney / Q000098:blood supply* / Q000293:injuries*; D016030:Kidney Transplantation / Q000009:adverse effects; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics; D019520:Living Donors; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D008875:Middle Aged; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D011991:Receptors, Virus / Q000235:genetics; D014019:Tissue Donors
chemical_list: D000209:Acute-Phase Proteins; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D011991:Receptors, Virus