Pathology of Resolving Polyomavirus-Associated Nephropathy

Abstract

These authors contributed equally. Control of polyomavirus BK (BKV) is achieved by reducing immunosuppression allowing an effective BKV-specific T-cell response. The morphology of resolving BKV-associated nephropathy (PyVAN) has not been systematically investigated. Ninety-nine surveillance biopsies of 35 patients with BKV viremia treated exclusively by immunosuppression reduction were scored according to Banff criteria and grouped relative to BKV viremia as pre-, increasing, decreasing and post-BKV viremia. Thirty-four of 35 patients (97%) cleared BKV viremia after a median of 9 months posttransplantation. The tubulitis score, extent of tubules with intraepithelial lymphocytes, and intersti-tial inflammation significantly increased from the time of increasing to decreasing viremia. Tubulointerstitial inflammation, to a lower extent, persisted after clearance. The number of SV40þ tubules correlated with the BKV load in plasma, but SV40 immunohis-tochemistry was frequently negative (60%). During decreasing viremia, 31% of PyVAN cases were plasma cell-rich and 40% showed tubular HLA-DR expression. Compared to baseline 1 month posttransplantation, allograft function remained stable or improved in 29/35 patients (83%) after a median follow-up of 48 months. Within 1 year after clearance of BKV viremia, clinical rejection occurred in 2/35 patients (6%). Our data suggest that resolving PyVAN is typically characterized by a self-limiting acute interstitial nephritis, morphologically indistinguishable from interstitial rejection.

Effect of polyoma viremia on 3‐year allograft kidney function

“…Besides a higher incidence of viremia, our patients also presented a higher rate (14.7%) of PyVAN (bx‐proven (6%) and presumptive PyVAN (8.7%). The incidence of SV40 negative in the presumptive PyVAN biopsies, shown here, are consistent with the findings of negative SV40 in 60% of the biopsies and suggests, as mentioned by others that renal biopsies may not be a gold standard to establish the diagnosis of PyVAN in screening programs. This finding is relevant to support the approach of reducing immunosuppression at a specific level of viremia regardless of a renal biopsy.…”

“…The comparison of bx‐proven and presumptive PyVAN showed that resolving presumptive PyVAN still presented inflammatory cells infiltrating the interstitium along with tubulitis. These findings had already been shown by others who demonstrated an increase in intra‐epithelial lymphocytes and interstitial inflammation during the resolving phase of PyVAN, culminating with some degree of tubular atrophy and interstitial fibrosis (IFTA) . The virus‐specific T cells play a major role in elimination of reactivated polyoma virus.…”

“…We used the cross‐reacting antibodies raised against the large T‐antigen of the Simian virus 40 (clone PAb 416; Calbiochem, San Diego, CA, USA) which allows a binary classification: SV‐40 negative or SV‐40 positive. Patients with persistent (2 or more) viremia ≥4 × 10 4 copies/mL without biopsy or with SV40 negative renal biopsies were considered as presumptive PyVAN . The biopsies were revised and re‐classified according to the recent Banff classification of PyV nephropathy .…”

Hemorrhagic cystitis after allogeneic hematopoietic cell transplantation: risk factors, graft source and survival

“…However, in 2 small series delayed platelet engraftment was not found to be a significant variable in the development of HC 21 or in children with severe HC 31 . We also analyzed serum creatinine because of its association with platelet dysfunction 61 and BK virus-induced nephropathy 62, 63 , but observed no relation to risks or severity of HC. Uhm et al found worsening renal function during HC, but concluded that this resulted from concurrent CMV therapy rather than direct nephrotoxic effect of HC 10 .…”

The human polyomavirus BK (BKPyV): virological background and clinical implications

“…If the disease is detected at an early stage, a reduction in the immunosuppression is often enough to clear the BKPyV viremia and stop the progression of disease (129)(130)(131). In a recent histopathological study of 35 patients with PyVAN treated by reduction in immunosuppression alone, 83% of the patients showed stable or improved allograft function 2 years later, while 2 patients (6%) experienced clinical rejection (132). Interestingly, the morphological pattern of resolving PyVAN could not be distinguished from rejection and revealed intraepithelial lymphocytes and interstitial inflammation.…”