Association of treatment with 15-deoxyspergualin and BK virus nephropathy in kidney allograft recipients.
OBJECTIVE
BK virus nephropathy (BKVN) has been proposed as an important cause of allograft dysfunction and loss in kidney allograft recipient over the last decade. Intense immunosuppression and tubular injury have been shown to promote the replication of polyomavirus. 15-deoxyspergualin (DSG), an effective immunosuppressive agent, is used as a rescue drug for acute rejection in clinical renal transplantation in Japan. To determine whether DSG is a risk factor for BKVN and outline the relationship among BKVN, DSG, and other risk factors, we analyzed 88 patients who received living-related renal transplantation between January 1999 and April 2003.


METHODS
A total of 114 biopsy specimens from 88 living-related kidney transplantation recipients (performed between January 1999 to April 2003) were retrospectively analyzed. Patients received immunosuppression therapy based on calcineurin inhibitors and corticosteroid [tacrolimus (TAC) 33 and cyclosporin (CyA) 55]. Additionally, mycophenolate mofeteil (MMF) was used in 21 patients; DSG was used in seven patients; and anti-CD3 monoclonal antibody was used in 16 patients. We analyzed the degree of donor/recipient human leucocyte antigen (HLA) compatibility assessed by the number of HLA-A, -B, and -DR-mismatched antigens in 88 patients. The diagnosis of BKVN was made by the light microscopic examination and a positive immunohistochemical staining of anti-40 antibody in biopsy specimens. Patients were divided into two groups of group A (mild histological change) and group B (moderate or severe histological change) to determine the risk factors in different histological staging. The clinical course of two typical patients in different histological stage is described briefly to outline the risk factors of BKVN.


RESULTS
We identified seven cases of BKVN (8.0%) from 88 transplanted patients. Significantly higher incidence of combination regimen consisting of TAC and MMF in BKVN group was noticed compared with non-BKVN group (57.1% vs. 9.9%; p = 0.003). BKVN was associated with a significantly higher incidence of DSG administration compared with non-BKVN group (57.1% vs. 3.7%; p </= 0.001). No difference was found in HLA mismatch between BKVN and non-BKVN group. Additionally, a significantly higher incidence of acute rejection episode prior to BKVN diagnosis was found in group B compared with group A (100% vs. 0%; p = 0.002), and the same statistical difference was shown in the number of anti-rejection therapy between group B and group A (100% vs. 0%; p = 0.002). We recognized a significant difference between group B and group A in terms of the combine regimen therapy of TAC with MMF (p = 0.002) and no difference in graft loss rate (p = 0.092), even though it was 50% in group B and was 0% in group A.


CONCLUSIONS
In this study, our data indicated excessive intense immunosuppression with TAC-MMF is related to the development of BKVN. In addition, we found that anti-rejection therapy, especially with DSG, may accelerate the development of BKVN.
Shi
Yi
Y
Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan.
Moriyama
Toshiki
T
Namba
Yukiomi
Y
Yamanaka
Masaki
M
Hanafuse
Takanori
T
Imamura
Ryoichi
R
Ichimaru
Naotsugu
N
Oka
Kazumasa
K
Kyo
Masahiro
M
Tian
Ye
Y
Takahara
Shiro
S
Ichikawa
Seiji
S
Okuyama
Akihiko
A
D000328:Adult; D001739:BK Virus; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy; D006146:Guanidines / Q000627:therapeutic use*; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000453:epidemiology* / Q000821:virology; D016030:Kidney Transplantation; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D027601:Polyomavirus Infections / Q000453:epidemiology* / Q000821:virology; D015995:Prevalence; D012189:Retrospective Studies; D012307:Risk Factors; D016559:Tacrolimus / Q000627:therapeutic use; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014412:Tumor Virus Infections / Q000453:epidemiology* / Q000821:virology
D006146:Guanidines; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; C037258:gusperimus; D016559:Tacrolimus