Kidney Ischemic Injury Genes Expressed After Donor Brain Death Are
Predictive for the Outcome of Kidney Transplantation
D. Kamin ´ ska, K. Kos ´ cielska-Kasprzak, D. Drulis-Fajdasz, A. Halon ´ , W. Polak, P. Chudoba, D. Jan ´ czak,
O. Mazanowska, D. Patrzalek, and M. Klinger
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.
D
ECEASED DONORS are the main source of kidney
allografts in Poland. The results of deceased kidney
transplantation (KTx) largely depend on the extent of
organ injury induced by donor brain death and transplan-
tation procedures. Animal and clinical studies have
shown donor brain death to affect organ quality influenc-
ing the rates of delayed graft function (DGF), acute
rejection episodes (ARE), and kidney graft survival.
1,2
Cold ischemia time, donor creatinine, body mass index,
cardiac death, and age are the most significant factors
associated with DGF.
3
Donor brain death affects gene
expression in kidney allografts indicating the presence of
an early phase inflammatory process during organ re-
trieval.
4
The results of our recent study demonstrated
intense cytokine gene expression in kidney allograft
biopsies after donor brain death that was even higher
than during an acute rejection episode.
5
From the Departments of Nephrology and Transplantation
Medicine (D.K., K.K.-K., D.D.-F., O.M., M.K.), Pathomorphology
(A.H.), and Vascular, General and Transplant Surgery (W.P.,
P.C., D.J., D.P.), Wroclaw Medical University, Wroclaw, Poland.
The study was supported by a research grant from the Polish
Ministry of Science and Higher Education (2 P05B 165 29).
Address reprint requests to Dorota Kamin ´ ska, Department of
Nephrology and Transplantation Medicine, Wroclaw Medical
University, ul. Borowska 213, 50-556 Wroclaw, Poland. E-mail:
dorotakaminska@interia.pl
© 2011 by Elsevier Inc. All rights reserved. 0041-1345/–see front matter
360 Park Avenue South, New York, NY 10010-1710 doi:10.1016/j.transproceed.2011.08.062
Transplantation Proceedings, 43, 2891–2894 (2011) 2891