The First Case of Jc Virus Allograft Nephropathy

Abstract

New-onset diabetes is considered one of the most serious complications of transplantation, impacting heavily on graft function and survival and patient morbidity and mortality, as well as on quality of life and healthcare costs. Furthermore, development of diabetes after transplantation is a major determinant of the increased cardiovascular morbidity and mortality observed in transplant recipients, imposing a greater relative risk than hyperlipidemia and hypertension in this patient population (1). The additional risk for serious macrovascular and microvascular complications comparable to type 1 and type 2 diabetes mellitus compound the already complex management of the transplant recipient, adding to the posttransplantation care requirements and imposing further significant economic burden on healthcare systems (2).Despite consistent improvements in transplant graft survival with the advent of new immunosuppressive drugs, the incidence of new-onset diabetes after transplantation remains high yet underreported, with recorded incidences varying between 2% and 53% in the first year after transplantation (3). These variable data reflect the need for a standard definition for new-onset diabetes after transplantation and highlight the lack of awareness of this serious complication among the transplant community. Because the immunosuppressive regimen plays a major role in the development of diabetes after transplantation, the approach to management before and after transplantation is equally important. Indeed, a higher rate of new-onset diabetes after transplantation has been observed with the calcineurin inhibitor tacrolimus compared with cyclosporine (4), despite a trend to use less steroids. Consequently, guidelines have been warranted for many years to provide recommendations (i) for a standard definition and diagnostic criteria for newonset diabetes after transplantation; (ii) to minimize the risk of developing diabetes; (iii) for monitoring patients after transplantation; and (iv) for the management of patients who develop new-onset diabetes after transplantation.With this in mind, I commend the recent international consensus guidelines for new-onset diabetes after transplan-tation recently reported by Davidson et al. (5), which build on and compliment recommendations developed by the Canadian working group (6). These guidelines examine the impact of new-onset diabetes after transplantation and provide practical recommendations for the diagnosis and management of this condition as a priority in transplant recipients. The guidelines highlight the need for risk assessment and counseling for each patient before transplantation and appropriate tailoring and adjustment of immunosuppressive therapy. Strategies to minimize the risk for development of diabetes after transplantation include avoidance or minimization of steroids and tacrolimus and conversion to less diabetogenic regimens (eg, cyclosporine). Although further research into new-onset diabetes after transplantation is warranted, these guidelines will help to r...

Viral Infection in the Renal Transplant Recipient

“…Infection by JC polyomavirus (JCV) has been observed in renal allograft recipients as both nephropathy (in association with BK virus or alone) (148) and/or progressive multifocal encephalopathy (149 -153). JCV establishes renal latency but receptors are present in multiple tissues including in the brain.…”

Polyomaviruses BK- And JC-DNA quantitation in kidney allograft biopsies

“…Asymptomatic viruria may occur in both immunocompetent subjects and immunocompromised patients, while in transplanted kidney viral replication may determine polyomavirus-associated nephropathy (PVAN) in 1-10% of the patients, leading to graft failure in 30 up to 80% of the cases (Hirsch et al, 2005;Hirsch et al, 2006). Today, PVAN is one of the most common viral disease affecting renal allografts, with BKV being the most frequent causal agent and JCV being responsible in less than 3% of the cases (Kazory et al, 2003;Wen et al, 2004;Cavallo et al, 2007). However, in a recent study (Drachenberg et al, 2007) a biopsy-proven PVAN was diagnosed in six renal transplant recipients with exclusive JCV viruria out of 75 patients (8%) with BKV and/or JCV viruria, with an overall incidence during the study period of 0.9%.…”

Rearranged JC Virus Noncoding Control Regions Found in Progressive Multifocal Leukoencephalopathy Patient Samples Increase Virus Early Gene Expression and Replication Rate

“…Although JCV-associated nephropathy may occur in kidney transplant (14,33) and HIV/AIDS patients (6,27), the most prominent JCV disease is progressive multifocal leukoencephalopathy (PML) (44,60). The pathology of PML was first described in 1958 as a rare complication of patients with chronic lymphocytic leukemia or Hodgkin's lymphoma (3).…”