Corinna Schmitt1, Lubna Raggub1, Silvia Linnenweber-Held2, Ortwin Adams3, Anke Schwarz2, Albert Heim4. 1. Hannover Medical School, Institute of Virology, Carl-Neuberg-Str. 1, 30625 Hannover, Germany; German Centre for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Germany. 2. Hannover Medical School, Department of Nephrology, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. 3. University of Düsseldorf, Institute of Virology, Universitätsstr. 1, 40225 Düsseldorf, Germany. 4. Hannover Medical School, Institute of Virology, Carl-Neuberg-Str. 1, 30625 Hannover, Germany; German Centre for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Germany. Electronic address: heim.albert@mh-hannover.de.
Abstract
BACKGROUND: BK virus associated nephropathy (BKVN) leads to renal allograft dysfunction and loss. However, it is still unclear whether BKV replication in the transplant recipient is a result of reactivation in the recipient's native kidneys or whether BKV originates from the donor kidney. STUDY DESIGN: Urine of 249 donor/recipient pairs was investigated for the presence of BKV-DNA by qPCR before living transplantation (Tx) and consecutively after Tx. In BKV positive samples, the VP1 typing region (TR) and, in case of the presence of sufficient amount of DNA, the complete VP1 gene, the NCCR and a fragment of the Large T-antigen were sequenced and compared between donors and corresponding recipients before and after Tx. RESULTS: In 20 pairs, sequencing of the BKV TR succeeded in donors and corresponding recipients after Tx. The derived sequences were completely identical in donor and post-Tx recipient samples. For comparison, identical TR sequences were detected in only 24% of 1068 randomly assembled pairs. This difference was statistically highly significant (p<0.0001, Fisher's exact test). Furthermore, all VP1, Large T-antigen and NCCR BKV sequences were also identical between donors and corresponding post-Tx recipients. In two of the 20 donor/recipient pairs, VP1 TR sequencing was also successful from the recipient before Tx. In both cases the sequence differed from the sequence detected in donor and recipient after Tx giving further evidence that recipient BKV was replaced by donor BKV after Tx. CONCLUSIONS: Our study for the first time provides evidence of BKV donor origin in renal transplant recipients.
BACKGROUND:BK virus associated nephropathy (BKVN) leads to renal allograft dysfunction and loss. However, it is still unclear whether BKV replication in the transplant recipient is a result of reactivation in the recipient's native kidneys or whether BKV originates from the donor kidney. STUDY DESIGN: Urine of 249 donor/recipient pairs was investigated for the presence of BKV-DNA by qPCR before living transplantation (Tx) and consecutively after Tx. In BKV positive samples, the VP1 typing region (TR) and, in case of the presence of sufficient amount of DNA, the complete VP1 gene, the NCCR and a fragment of the Large T-antigen were sequenced and compared between donors and corresponding recipients before and after Tx. RESULTS: In 20 pairs, sequencing of the BKV TR succeeded in donors and corresponding recipients after Tx. The derived sequences were completely identical in donor and post-Tx recipient samples. For comparison, identical TR sequences were detected in only 24% of 1068 randomly assembled pairs. This difference was statistically highly significant (p<0.0001, Fisher's exact test). Furthermore, all VP1, Large T-antigen and NCCR BKV sequences were also identical between donors and corresponding post-Tx recipients. In two of the 20 donor/recipient pairs, VP1 TR sequencing was also successful from the recipient before Tx. In both cases the sequence differed from the sequence detected in donor and recipient after Tx giving further evidence that recipient BKV was replaced by donor BKV after Tx. CONCLUSIONS: Our study for the first time provides evidence of BKV donor origin in renal transplant recipients.
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