Histologic versus Molecular Diagnosis of BK Polyomavirus–Associated Nephropathy

Abstract

Although discovered in 1970 the BK virus infections had no significant clinical impact until the emergence of BK virusassociated 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.

Antibody Responses to Recombinant Polyomavirus BK Large T and VP1 Proteins in Young Kidney Transplant Patients

“…Moreover, LT is conveniently detectable in the nuclei of renal tubular epithelial cells with activated BKV replication and precedes the late gene expression of agnoprotein or the capsid protein VP1 (24,34,44,45). In fact, positive immunohistochemistry detecting intranuclear LT has been established as the standard confirmatory assay for the diagnosis of PVAN in renal allograft biopsies (5,18,28,37,40). The lower-antibody response despite its relative abundance suggests differences in immunogenicity.…”

Aggressive Immunosuppression Minimization Reduces Graft Loss Following Diagnosis of BK Virus-Associated Nephropathy

“…There are other limitations of this study. First, given the evolution of BKVAN screening and histologic classification over time, not every patient had quantitative PCR monitoring, biopsy scoring, or prior screening for BKVAN; thus, these characteristics were not included in this analysis despite their proven value (8,9,19). We attempted to account for these deficiencies by examining BKVAN outcomes segregated into separate eras and found that there was no difference in outcomes between eras on univariate or multivariate analysis.…”

“…Although the biopsy findings at diagnosis are proposed to be a predictive tool for assessing prognosis (18,19), quantitative assessments of viral load at diagnosis have generally not been predictive of outcomes. To date, there has not been an assessment of clinical risk factors for disease progression or a comparison of immunosuppression withdrawal strategies.…”

Changing Kidney Allograft Histology Early Posttransplant: Prognostic Implications of 1-Year Protocol Biopsies

“…Borderline inflammatory changes were considered to be an acute rejection. Polyoma-associated nephropathy (PVAN) was diagnosed by the presence of BK virus DNA in the allograft biopsy by in situ hybridization (15,16).…”