Histologic versus molecular diagnosis of BK polyomavirus-associated nephropathy: a shifting paradigm?

Although discovered in 1970 the BK virus infections had no significant clinical impact until the emergence of BK virus-associated allograft nephropathy (BKPVAN). Escalating clinical challenges required better diagnostic tools and delineation of uniform criteria for diagnosis. In recent years, the widespread use of real-time PCR for measuring viral loads has confirmed that BK viruria and viremia are consistently identified before the development of overt nephritis. The identification of this viruria-viremia-nephritis sequence has provided tools for screening renal transplant patients and the possibility of earlier intervention with improved outcomes. Analysis of current clinical trends indicates that despite the fact that a positive renal biopsy is the "gold standard" for the diagnosis of BKPVAN, clinical interventions often are based on the surrogate markers of the disease rather than on tissue diagnosis. This is conceptually supported by the fact that early BKPVAN is focal and liable to tissue sampling errors. Strong arguments remain, however, in favor of retaining the requirement for tissue evaluation in patients who are suspected of having BKPVAN. BKPVAN selectively affects the graft and is likely to occur in a background of immune and/or nonimmune renal injury. A renal biopsy is necessary to exclude other pathologic processes (e.g., acute rejection) that could coexist with BKPVAN or be the main cause of allograft dysfunction. Evaluation of a renal biopsy for the purpose of staging is important for prognosis and is also of paramount importance for the rational assessment of therapeutic success.