BK polyomavirus-associated nephropathy(BKPyVAN)is a common cause of allograft failure.However,differentiation between BKPyVAN and type I T cell-mediated rejection(TCMR)is challenging when simian virus 40(SV40)staining...BK polyomavirus-associated nephropathy(BKPyVAN)is a common cause of allograft failure.However,differentiation between BKPyVAN and type I T cell-mediated rejection(TCMR)is challenging when simian virus 40(SV40)staining is negative,because of the similarities in histopathology.This study investigated whether donor-derived cell-free DNA(ddcfDNA)can be used to differentiate BKPyVAN.Target region capture sequencing was applied to detect the ddcfDNAs of 12 recipients with stable graft function,22 with type I TCMR,21 with proven BKPy VAN,and 5 with possible Py VAN.We found that urinary ddcfDNA levels were upregulated in recipients with graft injury,whereas plasma ddcfDNA levels were comparable for all groups.The median urinary concentrations and fractions of ddcfDNA in proven BKPyVAN recipients were significantly higher than those in type I TCMR recipients(10.4 vs.6.1 ng/mL,P<0.001 and 68.4%vs.55.3%,P=0.013,respectively).Urinary ddcfDNA fractions(not concentrations)were higher in the BKPyVAN-pure subgroup than in the BKPyVAN-rejection-like subgroup(81.30%vs.56.64%,P=0.025).With a cut-off value of 7.81 ng/m L,urinary ddcf DNA concentrations distinguished proven BKPyVAN from type I TCMR(area under the curve(AUC)=0.848,95%confidence interval(95%CI):0.734 to 0.963).These findings suggest that urinary ddcf DNA is a non-invasive biomarker which can reliably differentiate BKPy VAN from type I TCMR.展开更多
基金the Science and Technology Department of Zhejiang Province(No.2019C03029)the Bethune Charitable Foundation(No.G-X-2019-0101-12)+1 种基金the National Natural Science Foundation of China(Nos.81870510,81770719,81770752,and 81370851)the Zhejiang Provincial Natural Science Foundation of China(No.LQ18H050002)。
文摘BK polyomavirus-associated nephropathy(BKPyVAN)is a common cause of allograft failure.However,differentiation between BKPyVAN and type I T cell-mediated rejection(TCMR)is challenging when simian virus 40(SV40)staining is negative,because of the similarities in histopathology.This study investigated whether donor-derived cell-free DNA(ddcfDNA)can be used to differentiate BKPyVAN.Target region capture sequencing was applied to detect the ddcfDNAs of 12 recipients with stable graft function,22 with type I TCMR,21 with proven BKPy VAN,and 5 with possible Py VAN.We found that urinary ddcfDNA levels were upregulated in recipients with graft injury,whereas plasma ddcfDNA levels were comparable for all groups.The median urinary concentrations and fractions of ddcfDNA in proven BKPyVAN recipients were significantly higher than those in type I TCMR recipients(10.4 vs.6.1 ng/mL,P<0.001 and 68.4%vs.55.3%,P=0.013,respectively).Urinary ddcfDNA fractions(not concentrations)were higher in the BKPyVAN-pure subgroup than in the BKPyVAN-rejection-like subgroup(81.30%vs.56.64%,P=0.025).With a cut-off value of 7.81 ng/m L,urinary ddcf DNA concentrations distinguished proven BKPyVAN from type I TCMR(area under the curve(AUC)=0.848,95%confidence interval(95%CI):0.734 to 0.963).These findings suggest that urinary ddcf DNA is a non-invasive biomarker which can reliably differentiate BKPy VAN from type I TCMR.
