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 < .0001). Among clinical factors (sex, disease, transplant type, alemtuzumab use, cytomegalovirus [CMV] viremia, graft-versus-host disease [GVHD], donor HLA C7 allele), only CMV viremia was more common in patients with BKV infection (P < or = .04). There was a direct relationship between blood and urine BKV levels and the occurrence, and degree, of hematuria (P < or = .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=.000002) and alternative-donor transplantation (P=.002) were independent predictors of development of post-HSCT renal impairment, with BK viremia associated with a median 1.62mg/dL rise in creatinine from the pretransplant baseline. Among 8 patients in the surveillance cohort with BK viremia, 2 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.

Figure 1

Cumulative incidence and timing of development of BK viruria and viremia for the prospectively-monitored cohort (n = 57).

Figure 2. Relationship between both median (LEFT PANEL) and maximum (RIGHT PANEL) levels of urinary BKV and degree of microscopic hematuria post-HSCT

A direct relationship was seen between higher median and maximum levels of urinary BKV with greater amounts of microscopic hematuria. RBC = red blood cells.

Figure 3. Impact of BK viremia on change in creatinine post-HSCT

Change in creatinine represents the difference between the maximum post-HSCT creatinine level and the pre-transplant baseline creatinine. BK viremia was the factor having the greatest absolute effect on creatinine elevation in this study: the creatinine rise was 1.62 mg/dL in patients with BK viremia, but only 0.64 mg/dL in those without BKV in the blood (P = 0.001).

Figure 4. Photomicrographs of the pathologic findings in two patients with biopsy-proven BK virus-induced nephropathy

A (TOP PANEL) = high-powered view of enlarged tubular epithelial cells showing viral cytopathic effect and intranuclear inclusions in one of the two affected patients in our study. Glomeruli and vascular structures are normal; B (MIDDLE PANEL) = SV40 immunohistochemical stain further demonstrating the intranuclear viral inclusions in the same patient (SV40 and BKV share a significant region of homology); C = (BOTTOM PANEL) = similar pathologic findings in the kidney of the second patient in our study with BKV nephropathy.