Clinical usefulness of BK virus plasma quantitative PCR to prevent BK virus associated nephropathy

Abstract

Summary The present study investigated the clinical usefulness of plasma real‐time polymerase chain reaction (PCR) (plasma‐PCR) in the prevention of BK virus‐associated nephropathy (BKVAN). First, we investigated the diagnostic value of plasma BK‐PCR, urine BK‐PCR, and urine cytology for the prediction of BKVAN retrospectively. Then we designed a prospective study of regular plasma‐PCR monitoring and pre‐emptive immunosuppression (IS) reduction based on the result. In the retrospective cohort, the prevalence of BKVAN was 3.7% (14/379) and the positive rate of decoy cells, urine‐PCR (>1 × 1010 copies/ml), and plasma‐PCR (>1 × 104 copies/ml) was 18.6%, 11.1%, and 5.5%, respectively. Plasma‐PCR was superior to urine‐PCR or urine cytology in specificity and positive predictive value for detection of BKVAN. In prospective study, regular monitoring of plasma‐PCR detected significant BKV viremia in 8.3% (12/145) and BKVAN in 1 patient (0.6%). After IS reduction, BKV viremia was eliminated in 91.6% (11/12) within 103 days (25–254). In patients with viremia, the frequency of acute rejection did not increase and allograft function did not differ significantly compared with those in patients without viremia during the first year post‐transplant (P > 0.05, in both). Plasma‐PCR is useful to predict an increased risk for BKVAN, and regular monitoring is effective to prevent the development of BKVAN.

Transient versus Persistent BK Viremia and Long-Term Outcomes after Kidney and Kidney–Pancreas Transplantation

“…Because there is no universal definition for transient BK viremia, we chose a 3-month interval for viral clearance to reduce the possibility of false positive tests. Because BKV loads$10,000 copies/ml have been suggested as a predictor of BKVAN (1,(8)(9)(10), we subclassified our population into high and low VLs using a 10,000-copy/ml cutoff.…”

“…This finding suggests the possibility that mechanisms other than direct tissue invasion by the BK virus may be responsible for graft dysfunction or that sampling error for BK viral particles occurred. Others have suggested that any VL.10,000 copies/ml suggests a presumptive or emerging BKVAN (1,(8)(9)(10).…”

“…No patient showed recurrence of BK viremia after clearance for 3 consecutive months. The intensity of BK infection was defined according to the duration of viremia (from the onset until clearance) and the peak BK viral load (VL) as follows: transient low viremia, presence of BKV in the blood for less than 3 months with peak VL,10,000 copies/ml; transient high viremia, presence of BKV in blood for less than 3 months with peak VL$10,000 copies/ml; persistent low viremia, presence of BKV in blood for more than 3 months with peak VL,10,000 copies/ml; and persistent high viremia, presence of BKV in blood for more than 3 months with peak VL$10,000 copies/ml (1,(8)(9)(10).…”

Association of BK Virus Titers With Lymphocyte Count in Renal Transplant Patients

“…In addition, BKV screenings were performed whenever there was an impairment in a renal function test. Viremia was defined by detection of BKV-DNA at any level in plasma [6,7]. We retrospectively monitored lymphocyte count, creatinine, and tacrolimus/cyclosporine/mTOR inhibitors levels during the same time period as the BKV screening.…”

Nation-wide measure of variability in HCMV, EBV and BKV DNA quantification among centers involved in monitoring transplanted patients

“…Virological monitoring of transplanted patients is based on standardized protocols for genome quantification, in order to apply clinical cut-offs in pre-emptive approaches for disease prevention [12][13][14][15]. performed [11,16].…”