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Master Thesis

Conversion to mTOR-inhibitors with adjunction of IV immunoglobulins in kidney-transplant recipients with BKV infection: a retrospective study

Abstract : Introduction: BK virus-associated nephropathy (PvAN) is linked to a high risk of graft failure and, thus, justifies active therapy. Studies suggest that conversion to mammalian target of rapamycin inhibitors (mTORi) and lowering immunosuppression could prevent the risk of PvAN. Human polyclonal immunoglobulins (IVIg) increase anti-BKV antibody titers in kidney-transplant (KT) recipients. Our monocentric retrospective study assessed the efficacy of mTORi/IVIg therapy versus reduced immunosuppression on BKV DNAemia clearance at 1-year post-KT. Methods: Forty KT patients were included between March 2013 and October 2020. They formed an intervention group: mTORi/IVIg (everolimus conversion and 1200 mg/kg of IVIg over 6 months) after the first incidence of DNAemia; and a control group where immunosuppression was reduced. The primary outcome was BKV DNAemia clearance at one year. Renal function, rejection rate, evolution to PvAN, and complications were assessed. Results: BKV DNAemia clearance at 1-year post-treatment was greater in the control group compared to the mTORi/IVIg group (88.9% vs. 45.5%, p=0.004). Death-censored graft survival did not differ between the mTORi/IVIg and control groups after 20.6 [19.4--21.8] and 59.2 [43.9--68.9] months, respectively (p=0.18), after medical interventions. Rate of T-cell and antibody-mediated rejections and kidney-graft function at 12-months were similar between the two groups. Multivariate analyses showed that reducing immunosuppression compared to mTORi/IVIg conversion and an absence of sustained viremia were significantly associated with BKV DNAemia clearance (OR = 0.04 [0.01--0.39], p=0.015 and 0.07 [0.01–0.65], p= 0.03, respectively). Conclusions: Our study demonstrates a benefit to standard-of-care treatment for BKV infections (i.e., reduced immunosuppression) over a treatment based on mTORi conversion plus IVIg perfusion. Larger randomized studies need to evaluate the responses of mTORi and/or IVIg to treat active BKV infections.
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Master Thesis
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https://dumas.ccsd.cnrs.fr/dumas-03352461
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Submitted on : Thursday, September 23, 2021 - 11:22:11 AM
Last modification on : Sunday, September 26, 2021 - 3:17:58 AM

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Carla Vela. Conversion to mTOR-inhibitors with adjunction of IV immunoglobulins in kidney-transplant recipients with BKV infection: a retrospective study. Human health and pathology. 2021. ⟨dumas-03352461⟩

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