Prospective study of polyomavirus type BK replication and nephropathy in renal-transplant recipients.
BACKGROUND
Nephropathy associated with the polyomavirus type BK (BKV) nephropathy has emerged as a cause of allograft failure linked to immunosuppressive regimens containing tacrolimus or mycophenolate mofetil. The presence of viral inclusions, known as "decoy cells," in urine and the presence of BKV DNA in plasma have been proposed as markers for the replication of BKV and associated nephropathy, but data from prospective studies have been lacking.


METHODS
In a prospective, single-center study, we followed 78 renal-transplant recipients who were receiving immunosuppressive therapy that included tacrolimus (37 patients) or mycophenolate mofetil (41 patients). Urine was tested for the presence of decoy cells at routine visits. BKV DNA was measured 3, 6, and 12 months after transplantation and whenever decoy cells were detected. The viral load in plasma was quantified with the use of a real-time polymerase-chain-reaction method. Renal biopsy was performed if allograft function deteriorated.


RESULTS
Twenty-three patients had decoy-cell shedding a median of 16 weeks after transplantation (range, 2 to 69), 10 patients had BKV viremia at a median of 23 weeks (range, 4 to 73), and 5 had BKV nephropathy at a median of 28 weeks (range, 8 to 86). Kaplan-Meier estimates of the probability of decoy-cell shedding, viremia, and nephropathy were 30 percent (95 percent confidence interval, 20 to 40 percent), 13 percent (95 percent confidence interval, 5 to 21 percent), and 8 percent (95 percent confidence interval, 1 to 15 percent), respectively. Antirejection treatment, particularly with corticosteroids, was associated with BKV replication and nephropathy. The viral load in plasma was higher in patients with BKV nephropathy than in those without nephropathy (P<0.001 by the Mann-Whitney test). BKV antibodies were detected in 77 percent of the 78 patients before transplantation, including 4 of 5 with BKV nephropathy.


CONCLUSIONS
BKV nephropathy in renal-transplant recipients represents a secondary infection associated with rejection and its treatment in most cases and could be monitored by measuring the viral load in plasma.
Hirsch
Hans H
HH
Division of Infectious Diseases, University of Basel, Basel, Switzerland. hans.hirsch@unibas.ch
Knowles
Wendy
W
Dickenmann
Michael
M
Passweg
Jakob
J
Klimkait
Thomas
T
Mihatsch
Michael J
MJ
Steiger
Jürg
J
D000328:Adult; D000368:Aged; D001739:BK Virus / Q000502:physiology*; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy / Q000821:virology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007674:Kidney Diseases / Q000821:virology*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D027601:Polyomavirus Infections / Q000150:complications*; D011446:Prospective Studies; D014412:Tumor Virus Infections / Q000150:complications*; D019562:Viral Load; D014779:Virus Replication
D007166:Immunosuppressive Agents