Introduction: BK virus DNAemia (BKV-D) continues to be a burden for kidney transplant recipients (KTRs) with the lack of approved direct antiviral therapies, and the mainstay of treatment being reduction of immunosuppression, which is associated with a risk of acute rejection(AR). Herein, we describe our experience of treatment of BKV-D with high-dose IVIG (HDIVIG) in a multi-ethnic cohort of KTRs.
Methods: In this single-centre, retrospective cohort study we analysed 146 KTRs transplanted between 1-Apr-2019 and 31-Dec-2023. BK DNA levels were screened at monthly intervals post-transplant from months 1-9, then 3-monthly until 24-months post-transplant. Management of BKV-D consisted of halving of anti-metabolite dose followed by cessation, and institution of HDIVIG at 2g/kg every 4-6 weeks for BKV-D > 3log, followed by conversion to mTOR-inhibitors(mTORi), cessation of calcineurin inhibitor(CNI) or other adjunctive therapy. Allograft biopsy was performed in cases of allograft dysfunction. Outcomes of KTRs with BKV-D were manually abstracted from case records.
Results: Baseline characteristics are as per the table below.

There were no significant differences in demographics, induction or maintenance immunosuppression in KTRs who developed BKV-D vs those who did not. Mean time to detection of BKV-D was 93 days post-transplant (range 26 – 644 days), with time to peak BKV-D noted at 125 days post-transplant. Antimetabolite was stopped in 19(43%), mTORi was commenced in 9(20%), 4 cases received leflunomide and 2 cases had cessation of CNI. 25 KTRs (56%) received HDIVIG.  KTRs who received HDIVIG had higher peak BKV-D (4.54log vs 2.98log, p<0.05). KTRs with higher peak BKV-D were more likely to have cessation of anti-metabolite and develop AR. HDIVIG did not significantly affect risk of AR(Fig.1)

7 KTRs developed AR within 6 months of BKV-D, with 4 preceded by de-novo donor specific antibody development. AR was associated with reduced eGFR at last check (44 vs 59ml/min/1.73m2, p=0.024).
93% of cases resolved, at a median of 68 days (range 16 – 636). Median peak DNAemia was 4.70 log in cases without resolution of BKV-D vs 3.78 log in cases with resolution (p=0.049). There were no cases of biopsy-proven BK nephropathy at median 3.27 years post-transplant, and 1 case of graft loss due to immunosuppression non-compliance.
Conclusions: The high-risk cohort of KTRs with BKV-D >4log requiring aggressive immunosuppression reduction remain at risk of AR and suboptimal allograft function. Further studies are warranted to refine strategies to manage this complex patient cohort.