Clinical Relevance of Absolute BK Polyoma Viral Load Kinetics in Patients With Biopsy Proven BK Polyomavirus Associated Nephropathy

Abstract

Introduction: The absolute BK viral load is an important diagnostic surrogate for BK polyomavirus associated nephropathy (PyVAN) after renal transplant (KTX) and serial assessment of BK viremia is recommended. However, there is no data indicating which particular viral load change, i.e., absolute vs. relative viral load changes (copies/ml; percentage of the preceding viremia) is associated with worse renal graft outcomes. Materials and Methods: In this retrospective study of 91 biopsy proven PyVAN, we analyzed the interplay of exposure time, absolute and relative viral load kinetics, baseline risk, and treatment strategies as risk factors for graft loss after 2 years using a multivariable Poisson-model. Results: We compared two major treatment strategies: standardized immunosuppression (IS) reduction (n = 53) and leflunomide (n = 30). The median viral load at the index biopsy was 2.15E+04 copies/ml (interquartile range [IQR] 1.70E+03-1.77E+05) and median peak viremia was 3.6E+04 copies/ml (IQR 2.7E+03-3.3E+05). Treatment strategies and IS-levels were not related to graft loss. After correction for baseline viral load and estimated glomerular filtration rate (eGFR), absolute viral load decrease/unit remained an independent risk factor for graft loss [incidence rate ratios [IRR] = 0.77, (95% CI 0.61-0.96), p = 0.02]. Conclusion: This study provides evidence for the prognostic importance of absolute BK viremia kinetics as a dynamic parameter indicating short-term graft survival independently of other established risk factors.

Keywords: graft survival; polyomavirus nephropathy; renal transplantation; viral kinetic; viral load.

Figure 1

Flowchart. Displays the flow-chart of the study; PyVAN, BK polyomavirus nephropathy; eGFR-CKD-EPI, estimated glomerular filtration rate measured by the CKD-EPI equation; BKV, BK-Virus.

Figure 2

Graft function in the 24 months after biopsy; shows the eGFR in ml/min/1.73 m² measured by the CKD-EPI equation between two major therapy groups. IS: immunosuppression reduction vs. Leflunomide. Dotted line between months 12 and 24 was used for visualization purposes.

Figure 3

Multivariable Poisson regression model; shows the incidence rate ratios (IRRs) for death censored graft loss after 2 years for absolute viral load changes corrected for the baseline eGFR and baseline viral load at biopsy. Absolute delta viral load over 24 months was assessed between months 0–1, 1–3, 3–6, 6–12, and 12–24. Poisson models for estimation of IRR with 95% CIs; eGFR-CKD-EPI: estimated glomerular filtration rate measured by the CKD-EPI equation, base viral load: BK-Virus viral load in plasma at the time of diagnosis.

Figure 4

Heat map of BANFF single lesions in the index biopsy in relation to absolute viral load; shows the mean value of BANFF scores (color scaled) at the index biopsy according to the viral load at the time of the diagnosis, (copies/ml), h, arteriolar hyalinosis; g, glomerulitis; i, interstitial inflammation; v, intimal arteritis; t, tubulitis; cg, transplant glomerulopathy; ci, interstitial fibrosis; ct, tubular atrophy; cv, arterial fibrous intimal thickening, color scale describes the mean score of each group.