The Natural History of BK Polyomavirus and the Host Immune Response After Stem Cell Transplantation.

BACKGROUND: BK polyomavirus (BKPyV) is associated with symptomatic hemorrhagic cystitis after hematopoietic cell transplantation (HCT). Little is known about the host immune response, effectiveness of antiviral treatment, or impact of asymptomatic replication on long-term kidney function. METHODS: In children and young adults undergoing allogeneic HCT, we quantified BKPyV viruria and viremia (pre-HCT and at Months 1-4, 8, 12, and 24 post-HCT) and tested associations of peak viremia ≥10 000 or viruria ≥109 copies/mL with estimated kidney function (glomerular filtration rate, eGFR) and overall survival at 2 years posttransplant. We examined the factors associated with viral clearance by Month 4, including BKPyV-specific T cells by enzyme-linked immune absorbent spot at Month 3 and cidofovir use. RESULTS: We prospectively enrolled 193 participants (median age 10 years) and found that 18% had viremia ≥10 000 copies/mL and 45% had viruria ≥109 copies/mL in the first 3 months post-HCT. Among the 147 participants without cystitis (asymptomatic), 58 (40%) had any viremia. In the entire cohort and asymptomatic subset, having viremia ≥10 000 copies/mL was associated with a lower creatinine/cystatin C eGFR at 2 years post-HCT. Viremia ≥10 000 copies/mL was associated with a higher risk of death (adjusted hazard ratio, 2.2; 95% confidence interval, 1.1-4.2). Clearing viremia was associated with detectable BKPyV-specific T cells and having viremia <10 000 copies/mL, but not cidofovir exposure. CONCLUSIONS: Screening for BKPyV viremia after HCT identifies asymptomatic patients at risk for kidney disease and reduced survival. These data suggest potential changes to clinical practice, including prospective monitoring for BKPyV viremia to test virus-specific T cells to prevent or treat BKPyV replication.

Outcomes Among Children Who Received a Kidney Transplant in the United States From a Hepatitis B Core Antibody-Positive Donor, 1995-2010.

BACKGROUND: Accepting kidneys for transplant from donors with a history of hepatitis B virus infection may increase the availability of organs for those with end-stage kidney disease. In adult recipients, kidney transplants from hepatitis B virus core antibody-positive donors have resulted in favorable graft and patient survival rates. However, pediatric organ transplant recipients have developing immune systems and a higher risk of infectious complications than adults. Accordingly, little is known about the outcomes of children who have received a kidney transplant from a hepatitis B virus core antibody-positive donor. METHODS: We included 11 898 children ≤18 years of age who received a first kidney transplant in the United States between January 1, 1995, and December 31, 2010, and who were recorded in the Scientific Registry of Transplant Recipients. We examined differences in graft and patient survival rates among children who received a kidney transplant from a hepatitis B virus core antibody-positive donor. RESULTS: There were 199 children (1.7%) who received a kidney transplant from a hepatitis B virus core antibody-positive donor. More than 80% of these transplants occurred in recipients who were hepatitis B virus core antibody and surface antigen negative. After a median follow-up of 7.9 years, there were no significant differences in the adjusted graft (hazard ratio [HR], 1.03 [95% confidence interval (CI), 0.80-1.31]) or patient (HR, 1.12 [95% CI, 0.73-1.73]) survival rates according to donor core antibody status. CONCLUSIONS: It may be acceptable, on a case-by-case basis, to consider hepatitis B virus core antibody-positive donors for kidney transplants to seroprotected children with end-stage kidney disease.

The Noninvasive Urinary Polyomavirus Haufen Test Predicts BK Virus Nephropathy in Children After Hematopoietic Cell Transplantation: A Pilot Study.

BACKGROUND: After hematopoietic cell transplantation (HCT), polyoma-BK virus is associated with hemorrhagic cystitis and also with polyomavirus nephropathy (PVN). However, the true burden of post-HCT PVN is unknown because kidney biopsies are avoided due to their bleeding risk. The novel, noninvasive urinary PV-Haufen test detects PVN in kidney transplant recipients with greater than 95% positive/negative predictive values. We hypothesized that the detection of PV-Haufen in voided urine samples-a positive PV-Haufen test-was also clinically significant after HCT. METHODS: We examined 21 suitable urine samples from 14 patients (median age, 15 years; 71.4% male) who were selected from repositories for having varying degrees of BK viremia (range, 0-1.0 × 10 copies/mL), hemorrhagic cystitis (present/absent), and data on kidney function. Urine samples were obtained at a median of 88 days post-HCT. RESULTS: The PV-Haufen were detected in 5 of 14 patients (35.7%) and 7 of 21 (33.3%) urine samples, with histologic confirmation of PVN in 1 autopsy specimen. After a median of 285 days post-HCT, patients with PV-Haufen had an increased risk of dialysis-dependent renal failure (P < 0.05). All 3 dialysis-dependent patients had PV-Haufen and died. The presence of urinary PV-Haufen was not significantly correlated with hemorrhagic cystitis. From the 16 urines collected during BK viremia, 43.8% were PV-Haufen-positive, and 56.2% were negative. The PV-Haufen were not present in the 5 urines from patients without concomitant BK-viremia. CONCLUSIONS: In this proof-of-concept study, a positive PV-Haufen test was only seen in some patients with BK viremia and was not associated with hemorrhagic cystitis. The detection of PV-Haufen suggests underlying PVN with an increased risk of kidney failure and dialysis.