Putative episodes of T-cell-mediated rejection in patients with sustained BK viruria but no viremia

Background: Polyomavirus BK (BKV) infection characterized by viruria alone is considered to be of little clinical significance, but this issue has not been systematically studied. Methods: We studied 230 patients with sustained viruria from whom multiple samples taken after a median of 877 days (range, 24-2739) showed no progression to viremia or nephropathy. Biopsies satisfying Banff thresholds for inflammation and tubulitis in the presence of viruria but negative for BKV stains were designated as putative T-cell-mediated acute rejection. Results: Compared with no viruria (n=515), sustained viruria was associated with more putative rejection episodes (0.62 vs. 0.33 per patient, P=0.006) and greater incidence of steroid resistance (36.2% vs. 19.6%, P=0.002). Most putative rejection episodes (52.1%) occurred concurrently with viruria, with a minority before (7.8%) or after (40.1%) BKV clearance. Steroid resistance was more frequent in putative rejection with concurrent viruria (48.6%), compared with rejection before (9.1%) or after (26.0%) viral clearance. These observations remained valid even on a separate analysis of patients with BKV load 1E+07 copies per mL or less. As assessed by the slope of reciprocal serum creatinine levels, accelerated deterioration of graft function resulted from rejection episodes occurring more than 2 years after transplantation. Conclusions: These observations indicate that intrarenal viral replication in sustained viruria is frequently associated with putative acute rejection. The implications of this association on the development of immune tolerance deserve further investigation.