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Clinical Trial
. 2024 Dec 23:15:1491514.
doi: 10.3389/fimmu.2024.1491514. eCollection 2024.

Tacrolimus to belatacept conversion in proteinuric kidney transplant recipients

Orhan Efe  1 , Ayman Al Jurdi  1 , Morgan Mabey Eiting  2 , Christine Rogers Marks  2 , Mariesa Ann Cote  2 , David Wojciechowski  3 , Kassem Safa  1 , Hannah Gilligan  1 , Jamil Azzi  4 , Nitender Goyal  5 , Marc Raynaud  6 , Alexandre Loupy  6 , Astrid Weins  7 , Leonardo V Riella  1   8
Affiliations
Clinical Trial

Tacrolimus to belatacept conversion in proteinuric kidney transplant recipients

Orhan Efe et al. Front Immunol. .

Abstract

Background: Proteinuria is associated with worse allograft outcomes in kidney transplant recipients (KTRs) and treatment strategies are limited. We examined the outcomes of calcineurin inhibitor (CNI) to belatacept conversion in proteinuric KTRs.

Methods: In a pilot phase II single-arm multicenter prospective trial, we recruited adult KTRs >6 months post-kidney transplantation with an estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73m2 and proteinuria >1 g/day. Patients were converted from CNI to belatacept. The primary outcome was a 25% reduction in proteinuria at 12 months.

Results: A total of 15 KTRs were recruited who had pre-conversion median (interquartile range) proteinuria of 1.8 (IQR 1.4 - 3.5) g/g and estimated glomerular filtration rate (eGFR) of 48 (IQR 32 - 52.5) ml/min/1.73m2. At 12 months post-conversion, median proteinuria was 1.4 (IQR 0.4 - 2.2) g/g (P = 0.068) and eGFR was maintained at 43 (34 - 54.5) ml/min/1.73m2. The primary outcome of at least a 25% reduction in proteinuria occurred in 53% (8/15) at 12 months. Abbreviated IBOX scores predicting 7-year graft survival were also stable at 1-year post-conversion compared to baseline. At extended follow-up at 5 years, both proteinuria and eGFR remained stable at 0.69 (0.24 - 2.15) g/g and 39 (31 - 57) ml/min/1.73m2, respectively.

Conclusions: CNI to belatacept conversion was associated with preserved allograft function in KTRs with significant proteinuria. These findings need to be confirmed in a larger randomized clinical trial.

Clinical trial registration: https://clinicaltrials.gov/, identifier NCT0232740.

Keywords: belatacept conversion; graft function; kidney transplantation; proteinuria; proteinuria reduction.

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Conflict of interest statement

LR reports receiving research funding from Bristol-Meyers Squibb, Caredx, Natera, and Visterra; reports serving as a scientific advisor of Veloxis; and is in part supported by the Harold and Ellen Danser Endowed/Distinguished Chair in Transplantation at Massachusetts General Hospital Boston, MA. OE receives research support from ASN Ben J. Lipps Research Fellowship Program. CM is currently an employee at Novo Nordisk Inc. DW receives research support from Natera, CareDx, AlloVIr, Horizon Therapeutics, Transplant Genomics; and serves as a scientific advisor for Natera, eGenesis, and Memo Therapeutics. HG receives funding support from CareDX, Transplant Genomics and CSL. NG is employed by Alnylam pharmaceuticals. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Primary outcome and allograft function. (A) Probability of achieving the primary outcome of ≥25% reduction in proteinuria over time; (B) Change in proteinuria from baseline to 12 months post-conversion for individual patients; (C) Changes in serum creatinine values and (D) estimated glomerular filtration rate (eGFR) from baseline to post-conversion 12 months for each patient. a Wilcoxon test. b Paired t test.
Figure 2
Figure 2
Long-term outcomes of allograft function and proteinuria. Line graph showing the maintenance of (A) estimated glomerular filtration rate (eGFR) and (B) proteinuria throughout the years.
See this image and copyright information in PMC

References

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