Polyomavirus-Associated Nephropathy in Renal Transplantation: Interdisciplinary Analyses and Recommendations

Abstract

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.

Effects of Rituximab on the Development of Viral and Fungal Infections in Renal Transplant Recipients

“…Previously, Kamar et al noted that BK virus was the most common virus detected in RTX-treated patients [8], and Habicht et al found a nonsignificantly higher rate of BK in ABO-incompatible recipients administered RTX [11]. The rates of BK viremia and nephropathy in our cohort are congruent with rates previously reported in the renal transplant population [18][19][20][21]. However, viremia and nephropathy occurred 2-3x more often in the RTX cohort.…”

Host-Specific Replication of BK Virus DNA in Mouse Cell Extracts Is Independently Controlled by DNA Polymerase α-Primase and Inhibitory Activities

“…BKV is the etiological agent of PVAN in about 10% of renal transplant patients (18). It has been shown that BKV DNA replication is restricted in murine cells and extracts (28).…”

“…In recent years, BKV has been associated with nephropathy (polyomavirus-associated nephropathy, or PVAN) in up to 10% of renal transplant patients. Once established, the disease results in allograft loss in 45 to 70% of the patients (18). Importantly, BKV preferentially replicates in human cells and less well in cells of other primates, and the virus is highly tumorigenic in rodents (21,41,44).…”

Pretransplantation Donor–Recipient Pair Seroreactivity Against BK Polyomavirus Predicts Viremia and Nephropathy After Kidney Transplantation

“…Sustained viremia and BKPyV loads >10 4 genome copies per milliliter (c/mL) are associated with BKPyVAN development (1,2,10). To identify this subgroup of recipients at risk who require tapering of immunosuppression (14,17), most kidney transplantation centers regularly evaluate recipients currently for detectable BKPyV DNA in blood (10)(11)(12)16). …”