Risk factors for progression from low level BK dnaemia to unfavorable outcomes after BK management via immunosuppressive reduction
Abish Kharel, Arjang Djamali, Margaret R. Jorgenson, Beyann Alzoubi, Kurtis J. Swanson, Neetika Garg, Fahad Aziz, Maha Mohamed, Didier A. Mandelbrot, Sandesh Parajuli
Abstract
Abstract Backgrounds Effective management of BK viremia (BKPyV‐DNAemia) in kidney transplant recipients (KTRs) involves regular monitoring and adjustment of immunosuppression. With this strategy, the majority of patients will clear BK or have ongoing, but non‐significant, low‐level BKPyV‐DNAemia. However, despite adjustments, some will develop more severe sequelae of BK including BKPyV‐DNAemia >5 log 10 copies/mL and BK nephropathy, and others may develop de novo DSA (dnDSA) or acute rejection (AR). Methods This was a single‐center study of KTRs transplanted at the University of Wisconsin‐Madison between 01/01/2015 and 12/31/2017. In this study, we sought to elucidate characteristics associated with the progression of BKPyV‐DNAemia to unfavorable outcomes after decreasing immunosuppressive medications for the management of BK viremia as described in consensus guidelines. Results A total of 224 KTRs fulfilled our selection criteria; 118 (53%) resolved or had persistent low DNAemia, 64 (28%) had severe BK/nephropathy, and 42 (19%) developed dnDSA or AR. In multivariable analysis, female gender (HR: 2.05; 95% CI: 1.08‐3.90; P = .02); previous rejection (HR: 2.90; 95% CI: 1.04‐8.12; P = .04), and early infection (HR: 0.81; 95% CI: 0.72‐0.90; P < .001) were associated with the development of severe BK/nephropathy. Conversely, non‐depleting induction at transplant (HR: 2.06; 95% CI: 1.03‐4.11; P = .03), HLA mismatches >3 (HR: 2.27; HR: 1.01‐5.06; P = .04), and delayed graft function (HR: 4.14; 95% CI: 1.12‐15.28; P = .03) were associated with development of dnDSA and/or rejection. Conclusion Our study suggests that almost half of KTRs with BKPyV‐DNAemia managed by our immunosuppressant adjustment protocol progress unfavorably. Identification of these risk factors could assist the frontline clinician in creating an individualized immunosuppressive modification plan potentially mitigating negative outcomes.