Molecular biomarker candidates of acute kidney injury in zero-hour renal transplant needle biopsies.
The aim of this study was to assess gene expression levels of four biomarker candidates [lipocalin 2 (LCN2), the kidney injury molecule 1 (HAVCR1), netrin 1, and the cysteine-rich, angiogenic inducer, 61] in the tubulointerstitial and the glomerular compartment of zero-hour kidney biopsies in order to predict developing delayed graft function (DGF). Thirty-four needle kidney biopsy samples of deceased donors were manually microdissected. Relative gene expression levels were determined by real-time RT-PCR. For the validation of the biomarker candidates, we calculated a mixed model comparing kidneys with DGF, primary function and control samples from the healthy parts of tumor nephrectomies. Significant biomarker candidates were analyzed together with donor age in multivariable regression models to determine the prognostic value. Expression levels of LCN2 and HAVCR1 in the tubulointerstitium were significantly upregulated in the DGF group (LCN2: fold change = 3.78, P = 0.031 and HAVCR1: fold change = 3.44, P = 0.010). Odds ratios of both genes could not reach significance in the multivariable model together with donor age. The area under the curve of the receiver operating characteristic ranges between 0.75 and 0.83. LCN2 and HAVCR1 gene expression levels in zero-hour biopsies show potential to act as early biomarkers for DGF.
Korbély
Reka
R
Department of Nephrology, KH Elisabethinen, Linz, Austria.
Wilflingseder
Julia
J
Perco
Paul
P
Kainz
Alexander
A
Langer
Robert M
RM
Mayer
Bernd
B
Oberbauer
Rainer
R
D058186:Acute Kidney Injury / Q000097:blood; D000209:Acute-Phase Proteins; D000328:Adult; D015415:Biomarkers / Q000097:blood*; D001706:Biopsy; D055515:Cysteine-Rich Protein 61 / Q000097:blood*; D051799:Delayed Graft Function / Q000235:genetics / Q000473:pathology; D005260:Female; D006084:Graft Rejection / Q000378:metabolism; D006085:Graft Survival / Q000235:genetics; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D016030:Kidney Transplantation / Q000473:pathology*; D007684:Kidney Tubules / Q000378:metabolism*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood*; D016015:Logistic Models; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000097:blood*; D000075388:Netrin-1; D011518:Proto-Oncogene Proteins / Q000097:blood*; D011991:Receptors, Virus / Q000097:blood*; D014019:Tissue Donors; D025521:Tumor Suppressor Proteins / Q000097:blood*
D000209:Acute-Phase Proteins; D015415:Biomarkers; C501848:CCN1 protein, human; D055515:Cysteine-Rich Protein 61; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D008562:Membrane Glycoproteins; C000617351:NTN1 protein, human; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D011991:Receptors, Virus; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1