Urgent Standardization of Plasma BK Viral Load Assays (BKVL) Is Necessary to Reduce Graft Loss from BK Virus-Associated Nephropathy (BKVAN)

Abstract

Background: BK virus-associated nephropathy (BKVAN) is a major cause of renal dysfunction and graft loss in renal transplant recipients (RT). Monitoring plasma BK viral load (BKVL) is the recommended screening strategy to predict BKVAN. American Society of Transplantation (AST) guidelines define a BKVL of ≥4 log10/mL (10,000 copies) as “presumptive BKVAN and recommend reduction in immunosuppression. We evaluated the clinical sensitivity of the quantitative BKV DNA assay in predicting risk for BKVAN using the AST recommended BKVL cut off. Methods: In a retrospective, single-center study all patients (pts) who underwent RT at Henry Ford Hospital from 2008-2011 were analyzed (n=460). Pts were included if they had atleast 1 yr of follow-up post-RT and a minimum of 4 visits/yr. Plasma BKVL assay (commercial send-out assay) was done in all pts as per protocol (at least every 3 months during the first 2 yr post-RT). Renal biopsy was done in all pts if there was a rise in serum creatinine >0.5mg from baseline. BKVAN was confirmed by biopsy. Results: 413 pts met inclusion criteria and were included.in the analysis. Of these 222 pts had BK viremia; 23/222 (10%) had BKVL of ≥4 log10/mL and 20/23 (87%) had BKVAN confirmed on biopsy. Among the 248 pts who had a renal biopsy done for rising sr creatinine 31(12.5%) were found to have BKVAN. Eleven of The 31(35%) pts had BKVL consistently < 4 log10/mL and hence, were not diagnosed as presumptive BKVAN using the ATS recommended BKVL cutoff of ≥4 log10/mL. A total of 8 patients lost their graft due to BKVAN including 3 patients with BKVL < 4 log10/m. Using a cut point of plasma BKVL of ≥4 log10/mL the sensitivity, specificity, positive predictive value and negative predicative value of the PCR assay for the diagnosis of BKVAN is 64.5%, 98.4%, 87.0%, and 94.5% respectively. Conclusion: Utilizing the current AST guideline cut off of ≥4 log10/mL the PCR assay used at our center underestimated the diagnosis of presumptive BKVAN. Urgent standardization of the various BKVL assays and establishment of universal cut-points is imperative to avoid BKVAN related graft loss.