BK Virus Infection Is Associated with Hematuria and Renal Impairment in Recipients of Allogeneic Hematopoetic Stem Cell Transplants

Abstract

BK virus (BKV) is an important pathogen and cause of nephropathy in renal transplant recipients, but its significance following hematopoetic stem cell transplantation (HSCT) is less well described. We measured blood and urine BKV in 124 allogeneic HSCT patients (67 had undergone prior HSCT [surveillance cohort]; 57 were monitored from transplant day 0 [prospective cohort]). BK viruria was manifest in 64.8% of the patients; 16.9% developed viremia. In the prospective cohort, the median time from transplantation to BK viremia development (128 days) was longer than for viruria (24 days; P < 0.0001). Among clinical factors (gender, disease, transplant type, alemtuzumab use, CMV viremia, GVHD, donor HLA C7 allele), only CMV viremia was more common in patients with BKV infection (P ≤ 0.04). There was a direct relationship between blood and urine BKV levels and the occurrence, and degree, of hematuria (P ≤ 0.03). Finally, BKV infection was analyzed along with other clinical factors in relation to the development of post-HSCT renal impairment. On multivariate analysis, only BK viremia (P = 0.000002) and alternative-donor transplantation (P = 0.002) were independent predictors of development of post-HSCT renal impairment, with BK viremia associated with a median 1.62 mg/dL rise in creatinine from the pre-transplant baseline. Among eight patients in the surveillance cohort with BK viremia, two developed biopsy-proven BKV nephropathy requiring hemodialysis. Investigation of whether prophylaxis against, or treatment of, BKV in the post-HSCT setting mitigates the associated morbidities, especially kidney injury, warrants prospective evaluation.

Brincidofovir for Polyomavirus-Associated Nephropathy After Allogeneic Hematopoietic Stem Cell Transplantation

“…6 Reducing immunosuppression usually is not feasible in these patients due to ongoing GVHD, and the majority of HSC transplant recipients reported to have PVAN eventually required dialysis. 4,10 …”

“…Even so, BK viremia has been implicated in kidney failure and PVAN after HSC transplantation in at least 2 studies. 10,11 In another study in HSC transplant recipients, 3 of 20 kidney biopsy specimens showed evidence of PVAN, a sign that this complication might be more prevalent than previously thought. 12 All 3 patients had BK viremia, and the pathology findings showed diffuse interstitial inflammation and tubulitis.…”

Investigation of BK and JC Virus DNA Positivities by Real-Time Polymerase Chain Reaction in Immunosuppressive Patients

“…O'Donnell ve ark. 'nın (13) hematopoetik kök hücre nakli yapıl-mış 124 hastada BK virüs varlığını araştırdıkları çalışmada tüm hastaların %64.8'inde BK virüri-si %16.9'unda BK viremisi saptanmıştır. Lösemi tanılı hastaların %63.4'ünde (45/71) BK virüri-si; %'18.3'ünde (13/71) BK viremisi; multiple myelom tanısı alan hastaların %33'ünde BKV DNA'sı tespit etmişlerdir.…”

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

“…In vitro studies examining BKPyV replication found that A771726 inhibited BKPyV replication, but that this was closely connected to the significant cytostatic effects triggered by pyrimidine depletion (139,150). There are several case reports presenting favourable outcomes in both adult (151)(152)(153)(154) and paediatric kidney transplant patients (155), but also reports where some patients experienced graft function deterioration (156,157). Of note, no difference in clearance of viremia was found between patients maintained at a high (>40 lg/mL) or low dose (<40 lg/mL) (149).…”