BK virus-associated nephropathy (BKVAN) is the leading cause of infection-related graft loss in renal transplantation. The lack of sensitivity of transplant biopsy in the diagnosis of BKVAN (30% of false negative results) is responsible for treatment delay and progression toward irreversible graft scarring. Early diagnosis of BKVAN is therefore a major challenge to improve its poor outcome. We aimed to improve the performance of graft biopsy in the diagnosis of BKVAN through detection of BKV in renal tissue with highly sensitive quantitative polymerase chain reaction (PCR).

In situ BKV PCR assay was retrospectively performed in 79 biopsies from 27 kidney transplant recipients with medical history of positive BK viremia. Biopsies from BKVAN kidney transplant recipients (BKVAN group, n=12) were compared to biopsies from recipients with self-limited BK viremia (sl-BKV group, n=15). Both groups were remarkably similar in terms of epidemiological and clinical characteristics, with the exception of a greater frequency of ureteral stenting in the BKVAN group. Immunosuppression was similarly reduced based on a stepwise local algorithm in the two groups.

In the BKVAN group, the in situ BKV specific PCR was positive in all diagnostic biopsies of BKVAN (7.1±2.3 log BK virus/million of cells). Eight patients of the BKVAN group had previously undergone a graft biopsy because of the detection of BKV in the blood. Strikingly, in situ BKV PCR was already positive in 5 of them (62.5%) 7.1±5.5 months before the diagnosis of overt BKVAN, with a mean viral load of 5.2±1.3 log/million of cells. By contrast, in the sl-BKV group, the 18 biopsies performed following the detection of BKV in the blood remained constantly negative throughout the follow-up (13.3±12.1 months). In addition, the 20 biopsies performed before BK viremia turned positive in both groups (screening/for cause n=10, pre-transplant n=10) were all negative.

In the settings of a newly diagnosed BK viremia, in situ BK virus detection using PCR provides a significant sensitivity gain for early diagnosis of BKVAN as compared with conventional histological criteria. Our study suggests that subclinical presence of BKV within the graft should be considered as an early stage of BKVAN and should lead to a prompt and significant reduction of immunosuppression.

« Back to 2013 American Transplant Congress