D147 - Associations Between Adjunctive Therapy and BKPyV Infection Outcomes in Kidney Transplant Recipients

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Author Block: D. Wojciechowski¹, B. Marafino², D. B. Adey³, L. Chen⁴, M. Horton⁵, E. Ku², ¹University of Texas Southwestern, Dallas, TX, ²UCSF, San Francisco, CA, ³Medicine, Transplant Nephrology, UCSF, San Francisco, CA, ⁴UC Davis Transplant Center, Sacramento, CA, ⁵University of Texas Southwestern Medical Center, Dallas, TX
*Purpose: The treatment for BKPyV is the reduction of maintenance immunosuppression (IS). There are no approved anti-viral agents and studies assessing adjunctive treatments are mixed. Consensus guidelines have suggested a possible role for IVIG due to the presence of anti-BKPyV neutralizing antibodies in commercially available IVIG products.
*Methods: Retrospective analysis of kidney transplant recipients from 2012-2024 with at least two plasma BKPyV DNAemia measurements >1,000 copies/mL at 3 academic centers. The index date for each patient was the first BKPyV DNAemia >1,000 copies/mL. Relative to this index date, we identified treatments delivered within 180 days based on EHR and claims data and classified them into six adjunctive treatment categories: IVIG only, fluoroquinolone (FQ) only, cidofovir only, leflunomide only, IVIG with cidofovir, and IVIG with leflunomide. We examined associations between these adjunctive therapies and three primary outcomes: graft failure, rejection, and eGFR rate with IVIG as the reference group.
*Results: 860 patients with BKPyV DNAemia were identified; 394 patients received adjunctive treatment and were included for study (Table 1). The type of adjunctive treatments included: IVIG 229 (48.3%), FQ 201 (42.4%), cidofovir 128 (27%), and leflunomide 158 (33.3%). Adjunctive treatment was not associated with graft failure; cidofovir and FQ were associated with a lower risk of rejection (Table 2; models adjusted for age at BKPyV index, donor type, induction therapy, and eGFR at or before BKPyV index). The impact of adjunctive treatments on eGFR trajectory varied, with significantly greater declines in eGFR observed for leflunomide, fluoroquinolones, and IVIG combination regimens compared with IVIG alone, but not for cidofovir.
*Conclusions: Of the adjunctive treatments examined only cidofovir demonstrated an association of lower rejection risk AND no association with eGFR decline. Further studies are warranted to further assess the efficacy of cidofovir for BKPyV treatment.

Table 1

Age at BK index, mean (IQR)	51.9 (42-64)
Male (%)	246 (62.4)
White (%)	132 (33.5)
Black (%)	62 (15.7)
Living donor (%)	65 (16.5)
rATG induction (%)	282 (71.6)
Rejection post-index (%)	143 (36.3)
Biopsy proven BKPyVAN post-index (%)	101 (25.6)

Table 2

	Graft failure (HR [95% CI])	Rejection (HR [95% CI])	eGFR slope (mL/min/1.73 m2 per year [95% CI])
IVIG	ref	ref	ref
Cidofovir	0.66 (0.22-1.95)	0.43 (0.24-0.78)	-0.22 (-1.10 to 0.66)
Leflunomide	0.53 (0.14-2.02)	0.91 (0.51-1.63)	-1.30 (-1.85 to -0.74)
FQ	0.80 (0.30-2.13)	0.24 (0.12-0.46)	-1.81 (-2.37 to -1.25)
IVIG + Cidofovir	0.73 (0.09-5.99)	0.98 (0.46-2.06)	-2.50 (-3.68 to -1.32)
IVIG + Leflunomide	1.48 (0.54-4.10)	0.81 (0.44-1.48)	-3.26 (-3.92 to -2.59)