Prospective Measurement of BK Virus Blood and Urine Levels, and Associations with Morbidity, in Recipients of Allogeneic Hematopoetic Stem Cell Transplants.

BK virus (BKV) is an important pathogen and cause of nephropathy in recipients of renal transplants, but its clinical significance in patients following hematopoetic stem cell transplantation (HSCT) is less well described. Over a 10 month period we prospectively measured BKV (by quantitative PCR) in the blood and urine of 103 patients who had undergone previous allogeneic HSCT [HLA-identical donor (n = 58), alternative donor (HLA-mismatched-related, matched-unrelated, or cord) (n = 45)] and who were receiving inpatient or outpatient post-transplant care. The median time from transplantation to the last follow-up virus sampling was 422 days (range = 12 to 3456 days), and the cohort included patients undergoing transplants as early as 1998 through 2007. BK viruria was manifest at any time during the period of measurement in 62% of the patients. Only 16% (16/103) developed BK viremia. All patients with BK viremia also had detectable BK viruria. In 38 patients who underwent BKV monitoring beginning immediately after transplant, development of BK viruria was an early phenomenon (median 26 days post-transplant, range = 4 to 274 days), while BK viremia occurred later (median 157 days post-transplant, range = 62 to 323 days). More recipients of alternative donor transplants compared to HLA-identical transplants developed BK viruria (75% vs 53%, P = 0.03) and BK viremia (24% vs 9%, P = 0.02). Given the tropism of BKV for the genitourinary tract and its association with hemorrhagic cystitis, urinalyses from all patients were analyzed for the presence and number of red blood cells (RBCs). Those patients with microscopic hematuria (81/103) had significantly higher levels of urinary BKV than patients without hematuria (P < 0.001), and there was a suggestion that the degree of hematuria was directly related to the amount of urinary virus, since a subset of patients with more pronounced hematuria (> 5 RBCs per high-powered microscopic field) had higher levels of urinary BKV than those with only small numbers of urinary RBCs (P = 0.06). Blood BKV levels were not associated with hematuria. The presence of BK viremia and/or viruria were not significantly associated with renal function, as measured by the mean serum creatinine, although 2/16 patients with BK viremia developed biopsy proven BKV interstitial nephritis, with one requiring hemodialysis. In summary, BK viruria is a common early finding in patients undergoing allogeneic HSCT, especially in those who do not have HLA-identical donors. Our data support the claim that BKV urinary infection is associated with hematuria post-HSCT. BK viremia occurs later and less commonly. Investigation of a larger number of patients is warranted to establish the incidence of and risk factors for BKV nephropathy in the allogeneic HSCT setting.