Monitoring the progress of BK virus associated nephropathy in renal transplant recipients

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Abstract
Background. Nephropathy associated with BK virus (BKVAN) has recently emerged as an important cause of allograft failure following renal transplantation. The aim of this study was to evaluate the effectiveness of laboratory markers in the follow-up of patients with BKVAN. Methods. Serial samples from seven renal transplant recipients with biopsy proven BKVAN were studied. The median follow-up time from diagnosis was 76 weeks. Intervention after the diagnosis of BKVAN included immunosuppression dose reduction, alternative immunosuppressive agents and/or antiviral therapy with cidofovir. Serial urine samples (n = 127) were collected for electron microscopy (EM), decoy cell detection and quantitative urine BK viral load using real-time polymerase chain reaction. Serum BK viral load was also measured serially (n = 72). Results. All patients showed a reduction in serum and urine viral load during the period of follow-up co-incident with the loss of decoy cells and negative urine EM. Urine samples that were negative for decoy cells or polyomavirus by EM had a urine viral load 6 copies/ml and a corresponding serum viral load 3 copies/ml. In paired serum/urine samples, there was a proportional relationship between serum and urine viral load with each urine viral load ∼1000-fold higher than the corresponding serum level. Serum and urine viral loads that decreased to 6 copies/ml, respectively, correlated with histological improvement. Conclusion. Negative EM and absence of decoy cells could be used as broad indicators of a response to intervention. However, measurement of BK virus DNA level provided a wider dynamic range and could be a better choice for determining the extent of viral control.