A Case of Polyomavirus-associated Nephropathy Presenting Late After Transplantation

Shweta Bansal; M Scott Lucia; Alexander Wiseman

Disclosures

Nat Clin Pract Nephrol. 2008;4(5):283-287. 

In This Article

Discussion of Diagnosis

PVAN is now recognized as an important cause of allograft failure in renal transplant recipients, requiring active surveillance and aggressive immunosuppression reduction. Two types of polyomaviruses commonly remain latent in the kidney after primary infection early in life—JC virus and BK virus. BK virus nephropathy occurs with a prevalence of 1–10% in renal transplant recipients; JC virus nephropathy is less common (prevalence <1% in renal transplant recipients) and less destructive than BK virus nephropathy.[1] Graft loss occurs within 6 months in about half of the cases of PVAN, a prognosis worse than acute rejection.[2] The usual onset of PVAN is reported to be between 1.5 months and 53 months after transplantation (median 12 months after transplantation).[2,3] All nephrologists must be aware of the diagnostic and therapeutic approaches to PVAN, as they often participate in the management of transplant patients at this stage. The present case highlights the fact that PVAN can occur late after transplantation (>80 months in this patient) and must be considered in any renal transplant recipient who experiences a change in renal function.

In the immunocompetent host, primary polyomavirus infections occur early in life and are usually asymptomatic. Approximately 50% of healthy native kidneys harbor latent BK virus.[2] In the presence of immunosuppression, BK virus replication is unmasked and progresses to interstitial nephritis without clinical signs or symptoms, except for diminished renal function over a period of weeks to months. Occasionally, patients with polyomavirus present with a ureteral stricture or hemorrhagic cystitis. Histological findings on renal biopsy are the gold standard for diagnosis, with typical findings of focal interstitial mononuclear inflammatory cell infiltrates, the presence of plasma cells, necrotic tubular epithelium, and the presence of homogeneous intranuclear inclusion bodies.[3] Immunohistochemistry staining for SV40 antigen is used to confirm the presence of polyomavirus in renal tissue. Additional methods for the detection of polyomavirus include in situ hybridization to identify polyomavirus genomes and electron microscopy to demonstrate the presence of virions of compatible morphology (i.e. nonenveloped, icosahedral particles, 40 nm in diameter).[2] In biopsies for renal dysfunction, distinct histological patterns of PVAN can be defined on the basis of the degree of viral cytopathic changes, tubulitis, tubular atrophy, and interstitial fibrosis, and these patterns can be predictive of outcome.[3] In the patient presented here, the severe tubulointerstitial inflammation and extensive tubular atrophy on index biopsy would be predicted to result in a graft loss rate of more than 75% within 2 years.

A number of noninvasive tests for predicting which patients are at risk for PVAN development following kidney transplantation have been evaluated. Urinalysis might reveal decoy cells, which are suggestive of BK virus replication in the renourinary tract; decoy cells are not, however, a specific marker of PVAN (positive predictive value 20%).[4] BK viruria detected by quantitative PCR is present in 30–40% of renal transplant recipients, with viral quantities in urine often 100-fold greater than in blood, but, like urinalysis for decoy cells, testing for urinary BK virus DNA has a high negative predictive value but a poor positive predictive value for the diagnosis of PVAN.[5] The most accurate screening test for PVAN is the assessment of polyomavirus viremia by quantitative PCR. BK virus viremia is seen in 10–40% of renal transplant recipients and in nearly 100% of PVAN cases, and has a positive predictive value for PVAN of 60%.[6]

Given the generally poor outcomes when PVAN is diagnosed in the setting of renal dysfunction, the transplant community has accepted screening for BK virus replication as a standard approach with which to identify patients at a higher risk of developing PVAN and to permit earlier interventions. Several screening strategies have been proposed to assist in the detection and treatment of PVAN, with an interdisciplinary recommendation to screen for viruria every 3 months during the first 2 years after renal transplantation, then annually until the fifth year after transplantation or until an event of renal allograft dysfunction.[7] A cost-effectiveness analysis confirms the utility of PCR-based screening in transplant populations that have a PVAN prevalence of more than 2.1%.[8] If high levels of viruria (>107 viral copies/ml)[9] or viremia (>104 viral copies/ml) persist for more than 3 weeks, a diagnosis of presumptive PVAN can be made and immunosuppression should be reduced. In a recent large prospective study, pre-emptive reduction of immunosuppression (via elimination of antimetabolites) resulted in the clearance of BK virus, with no acute rejection or PVAN after a mean of 32 ± 6 months.[6] If BK viruria and viremia is associated with renal dysfunction, a biopsy should be performed to quantify the presence and degree of injury and to rule out rejection. At least two cores should be obtained for polyomavirus-specific histological analysis, since biopsy findings of PVAN can be patchy and difficult to distinguish from acute rejection.[3]

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