Bone marrow aplasia and graft loss in a pediatric renal transplant patient with polyomavirus nephropathy

Abstract

Sirs, BK-virus nephropathy (BKN) is an important cause of graft dysfunction in kidney transplant recipients. Severe allograft dysfunction and graft loss are well-known complications [1–3]. However, pancytopenia caused by an infection of the bone marrow is thus far an unknown complication of BK virus (BKV) infection. We report a 17-year-old boy with end-stage renal disease due to peripartal asphyxia who was transplanted with a cadaveric kidney. Posttransplantation immunosuppressive therapy (IS) consisted of tacrolimus, mycophenolate mofetil (MMF), prednisolone, and basiliximab (Simulect ®) as induction therapy. Eighteen months after transplantation, IS was diminished because of detection of BK viruria and viremia. As this could not improve the number of BKV copies and serum creatinine increased, cidofovir (Vistide ® 1 mg/kg) was administered IV weekly (four times). A graft biopsy 4 months later showed a BKN Drachenberg B1 [3] without signs of acute humoral or cellular rejection. MMF was discontinued, and tacrolimus was diminished until trough levels of 4–5 μg/l were achieved. Despite these interventions, our patient was hospitalized 2 months later because of high and recurrent fever, pancytopenia, and deterioration of renal function. BKV polymerase chain reaction (PCR) in plasma at that time was strongly elevated: >5,000,000 copies/ml (7.7 log copies/ml), and hemoglobin, white blood cell, and thrombocyte count were unacceptably low. Adjunctive therapy was started: six extra doses of cidofovir and five of immunoglobulin (Multigam ® 2 g/kg) were administrated IV over a period of 4 weeks. A bone marrow biopsy showed global aplasia, and PCR was positive for BKV (>5,000,000 copies/ml). All other causes of pancytopenia, such as Epstein-Barr virus (EBV), cytomegalovirus (CMV), Parvovirus B19, human herpes virus-6 (HHV-6), malignancy, or hemophagocytic syndrome were excluded; tacrolimus and prednisolone were discontinued, and treatment with granulocyte colony stimulating factor (GCS) and erythropoietin was started. As the boy’s condition was life threatening due to persistent pancytopenia, deterioration of renal function, and systemic aspergillosis, and as severe BKN with BKV infection of the bone marrow seemed to be the cause of this, it was decided to remove the graft 2.5 months after the initial biopsy. The nephrectomy specimen showed BKN Drachenberg grade B3 [3], without signs of acute rejection. After removal of the graft, the patient’s general condition improved quickly: fever disappeared, and plasma BKV PCR copies decreased rapidly. BKV was no longer detectable in plasma after 11 days and in urine 3 months after transplantectomy. The bone marrow recovered very slowly over several months. Figure 1 shows the evolution of hemoglobin (Hb), white blood cell count (WBC), creatinine, and polyomavirus (BK) copy numbers after discovery of BK shedding in urine. S. H. M. Gardeniers :D. Mekahli : E. Levtchenko : R. Van Damme-Lombaerts Department of Pediatric Nephrology, UZ Leuven, Leuven, Belgium