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. 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. 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. 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.

Cytomegalovirus (CMV) infection and disease are important causes of morbidity and mortality in transplant recipients. For the purpose of developing consistent reporting of CMV outcomes in clinical trials, definitions of CMV infection and disease were developed and most recently published in 2002. Since then, there have been major developments in its diagnosis and management. Therefore, the CMV Drug Development Forum consisting of scientists, clinicians, regulators, and industry representatives has produced an updated version incorporating recent knowledge with the aim to support clinical research and drug development. The main changes compared to previous definitions are the introduction of a “probable disease” category and to incorporate quantitative nucleic acid testing in some end-organ disease categories. As the field evolves, the need for updates of these definitions is clear, and collaborative efforts between scientists, regulators, and industry can provide a platform for this work.

Polyomavirus-associated nephropathy (PVAN) is an emerging cause of kidney transplant failure affecting 1–10% of patients. As uncertainty exists regarding risk factors, diagnosis, and intervention, an independent panel of experts reviewed the currently available evidence and prepared this report. Most cases of PVAN are elicited by BK virus (BKV) in the context of intense immunosuppression. No specific immunosuppressive drug is exclusively associated with PVAN, but most cases reported to date arise while the patient is on triple immunosuppressive combinations, often comprising tacrolimus and/or mycophenolate mofetil plus corticosteroids. Immunologic control of polyomavirus replication can be achieved by reducing, switching, and/or discontinuing components of the immunosuppressive regimen, but the individual’s risk of rejection should be considered. The success rate of this intervention is increased with earlier diagnosis. Therefore, it is recommended that all renal transplant recipients should be screened for BKV replication in the urine: 1) every three months during the first two years posttransplant; 2) when allograft dysfunction is noted; and 3) when allograft biopsy is performed. A positive screening result should be confirmed in <4 weeks and assessed by quantitative assays (e.g. BKV DNA or RNA load in plasma or urine). Definitive diagnosis of PVAN requires allograft biopsy. If PVAN and concurrent acute rejection is diagnosed, antirejection treatment should be considered, coupled with subsequently reducing immunosuppression. The antiviral cidofovir is not approved for PVAN, but investigational use at low doses (0.25–0.33 mg/kg intravenously biweekly) without probenicid should be considered for refractory cases. Retransplantation after renal allograft loss to PVAN remains a treatment option for patients clearing polyomavirus replication.

BackgroundThe replication of BK virus (BKV) and JC virus (JCV) is linked to polyomavirus-associated nephropathy, hemorrhagic cystitis, and multifocal

The human BK polyomavirus (BKV) is the major cause of polyomavirus‐associated nephropathy (PyVAN) putting 1–15% of kidney transplant patients at risk of premature allograft failure, but is less common in other solid organ transplants. Because effective antiviral therapies are lacking, screening kidney transplant patients for BKV replication in urine and blood has become the key recommendation to guide the reduction of immunosuppression in patients with BKV viremia. This intervention allows for expanding BKV‐specific cellular immune responses, curtailing of BKV replication in the graft, and clearance of BKV viremia in 70–90% patients. Postintervention rejection episodes occur in 8–12%, most of which are corticosteroid responsive. Late diagnosis is faced with irreversible functional decline, poor treatment response, and graft loss. Adjunct therapies such as cidofovir, leflunomide and intravenous immunoglobulins have been used, but the benefit is not documented in trials. Retransplantation after PyVAN is largely successful, but requires close monitoring for recurrent BKV viremia.