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 recipients of renal transplants, but its clinical significance in patients (pts) following hematopoetic stem cell transplantation (HSCT) is less well described. Over a 16 month period we prospectively measured BKV in the blood and urine of 124 pts who had undergone allogeneic HSCT [HLA-identical donor (n = 70), alternative-donor (HLA-mismatched-related, matched-unrelated, or cord) (n = 54)] between 1998–2007 and who were receiving in- or outpatient post-transplant care. Most pts (73%) received alemtuzumab-containing regimens. BK viruria was manifest at some time in 64.8% of pts; 16.9% developed BK viremia. All pts with BK viremia also had viruria. BK viruria developed at a median time post-HSCT of 24 d (range 3–138 d), while viremia was detected at a significantly longer median time of 128 d (range 62–307 d) (P<0.0001). Among clinical factors (disease, transplant type, alemtuzumab use, CMV viremia, GVHD, HLA C locus status), only CMV viremia was significantly more common in pts with BK viruria and viremia. Given the association of BKV with hemorrhagic cystitis, urinalyses from all pts were analyzed for the presence and number of red blood cells. There was a direct relationship between higher median and maximum levels of urinary BKV with both an increased occurrence, and greater degree, of microscopic hematuria (P<0.03). BK viremia was also associated with the development 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 = 0.000001) and undergoing an alternative-donor transplant (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. Two pts with BK viremia developed biopsy-proven BKV nephropathy, with both requiring hemodialysis. In summary, BK viruria is a common early finding in pts undergoing allogeneic HSCT, and higher urinary BKV levels are directly related to increased hematuria. BK viremia occurs later and less commonly, is associated with hematuria, and is an independent predictor of worsening renal function post-HSCT. Investigation of whether prophylaxis against, or treatment of, BKV in the post-HSCT setting mitigates the associated morbidities, especially kidney injury, warrants prospective evaluation. BK virus (BKV) is an important pathogen and cause of nephropathy in recipients of renal transplants, but its clinical significance in patients (pts) following hematopoetic stem cell transplantation (HSCT) is less well described. Over a 16 month period we prospectively measured BKV in the blood and urine of 124 pts who had undergone allogeneic HSCT [HLA-identical donor (n = 70), alternative-donor (HLA-mismatched-related, matched-unrelated, or cord) (n = 54)] between 1998–2007 and who were receiving in- or outpatient post-transplant care. Most pts (73%) received alemtuzumab-containing regimens. BK viruria was manifest at some time in 64.8% of pts; 16.9% developed BK viremia. All pts with BK viremia also had viruria. BK viruria developed at a median time post-HSCT of 24 d (range 3–138 d), while viremia was detected at a significantly longer median time of 128 d (range 62–307 d) (P<0.0001). Among clinical factors (disease, transplant type, alemtuzumab use, CMV viremia, GVHD, HLA C locus status), only CMV viremia was significantly more common in pts with BK viruria and viremia. Given the association of BKV with hemorrhagic cystitis, urinalyses from all pts were analyzed for the presence and number of red blood cells. There was a direct relationship between higher median and maximum levels of urinary BKV with both an increased occurrence, and greater degree, of microscopic hematuria (P<0.03). BK viremia was also associated with the development 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 = 0.000001) and undergoing an alternative-donor transplant (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. Two pts with BK viremia developed biopsy-proven BKV nephropathy, with both requiring hemodialysis. In summary, BK viruria is a common early finding in pts undergoing allogeneic HSCT, and higher urinary BKV levels are directly related to increased hematuria. BK viremia occurs later and less commonly, is associated with hematuria, and is an independent predictor of worsening renal function post-HSCT. Investigation of whether prophylaxis against, or treatment of, BKV in the post-HSCT setting mitigates the associated morbidities, especially kidney injury, warrants prospective evaluation.