The significance of borderline changes in kidney allograft biopsies is widely debated. To help resolve this, we studied differences in intrarenal gene expression patterns between early clinical and 3-month protocol biopsies, all of which had borderline histologic changes. The gene expression profiles in training set of patients by microarray analysis and data were validated in a larger cohort using RT-qPCR. There was greater expression of immunity- and inflammation-related genes in the early clinical biopsies compared to the 3-month protocol biopsies with borderline changes. In early clinically manifested borderline changes, graft deterioration within 24 months due to chronic rejection was associated with increased activation of immune, defense, and inflammatory processes. Regression modeling identified higher donor age and expression of macrophage receptor CLEC5A as risk factors for progression. In the 3-month protocol biopsies with borderline changes, graft dysfunction was associated with increased expression of fibrinogen complex transcripts. The discrimination power of fibrinogen was confirmed by cross-validation on two independent cohorts. Thus, our study highlights variations in gene expression between clinical and subclinical borderline changes despite similar histological findings. The data also support a recommendation for frequent patient monitoring, especially in those with borderline changes who received grafts from older donors.

Biomedical Centre Faculty of Medicine in Plzen Charles University Prague Plzen Czech Republic

Department of Clinical and Transplant Pathology Institute for Clinical and Experimental Medicine Prague Czech Republic

Department of Immunogenetics Institute for Clinical and Experimental Medicine Prague Czech Republic

Department of Nephrology and Dialysis Medical University Vienna Vienna Austria

Department of Nephrology Hannover Medical School Hannover Germany

Department of Nephrology Institute for Clinical and Experimental Medicine Prague Czech Republic

Department of Urology Thomayer's Hospital Prague Czech Republic

Institute of Hematology and Blood Transfusion Prague Czech Republic

Institute of Inherited Metabolic Disorders 1st Faculty of Medicine Charles University and General Faculty Hospital Prague Czech Republic

Transplant Laboratory Institute for Clinical and Experimental Medicine Prague Czech Republic

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