Time-Limited Therapy with Belatacept in Kidney Transplant Recipients
Abstract
:1. Introduction
2. Methods
2.1. Study Population
2.2. Immunosuppression
2.3. Available Data
2.4. Statistical Analysis
2.5. Analysis of the Transcriptome Changes of PBMC, before and 3 Months after the Belatacept Discontinuation Using RNAseq
3. Results
3.1. Population
3.2. Belatacept Discontinuation
3.3. Adverse Events and Allo-Sensitization
3.4. RNA-seq Analysis of PBMCs before and after Belatacept Discontinuation
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
KT | Kidney transplantation |
CNI | Calcineurin inhibitor |
PBMC | Peripheral blood mononuclear cell |
CSA | Cyclosporin |
DSA | Donor-specific antibody |
eGFR | Estimated glomerular filtration rate |
MMF | Mycophenolate mofetil |
MPA | Mycophenolic acid |
rATG | Rabbit antithymocyte globulin |
HLA | Human leukocyte antigen |
ANOVA | Analysis of variance |
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Baseline Features | ||
---|---|---|
Sex (%) | Female | 16 (57.1) |
Male | 12 (42.9) | |
Age (mean (SD)) | 50.75 (17.19) | |
Initial nephropathy (%) | Other | 6 (21.4) |
Glomerulopathy | 7 (25.0) | |
Tubulo-interstitial or uropathy | 10 (35.7) | |
Vascular | 3 (10.7) | |
ADPKD | 2 (7.1) | |
Extrarenal epuration therapy (%) | Preemptive | 5 (17.9) |
Peritoneal dialysis | 5 (17.9) | |
Hemodialysis | 18 (64.3) | |
Diabetes (%) | No | 27 (96.4) |
Yes | 1 (3.6) | |
Donor type (%) | Brain death | 21 (75.0) |
Circulatory death | 3 (10.7) | |
Living | 4 (14.3) | |
CMV status (%) | R+ | 11 (39.3) |
D−/R− | 16 (57.1) | |
D+/R− | 1 (3.6) | |
Transplantation rank (%) | 1 | 25 (89.3) |
2 | 2 (7.1) | |
3 | 1 (3.6) | |
DSA (%) | No | 22 (78.6) |
Yes | 2 (7.1) | |
NA | 4 (14.3) | |
HLA incompatibilities (median [IQR]) | 4.00 [3, 5] | |
Induction treatment (%) | Basiliximab | 12 (42.9) |
Antithymocyte globulin | 16 (57.1) | |
Cyclosporin (%) | No | 27 (96.4) |
Yes | 1 (3.6) | |
Tacrolimus (%) | No | 1 (3.6) |
Yes | 27 (96.4) | |
Mycophenolate derivative (%) | Yes | 28 (100.0) |
Corticosteroids (%) | No | 1 (3.6) |
Yes | 27 (96.4) | |
Delayed graft function (%) | No | 18 (64.3) |
Yes | 10 (35.7) | |
Features at belatacept conversion | ||
DSA (%) | No | 22 (78.6) |
Yes | 5 (17.9) | |
NA | 1 (3.6) | |
Diabetes (%) | No | 25 (89.3) |
only dietary rules | 2 (7.1) | |
Insulin | 1 (3.6) | |
Hypertension (%) | No | 8 (28.6) |
Yes | 20 (71.4) | |
Rejection (%) | No | 27 (96.4) |
Yes | 1 (3.6) | |
Cause of switch (%) | Active ABMR | 1 (3.6) |
Poor CNI tolerance | 6 (21.4) | |
Impaired function | 21 (75.0) | |
Time since transplantation (months, mean (SD)) | 19.5 (37.6) | |
Time since transplantation (%) | Early (<3 months) | 9 (32.1) |
Intermediate (3 to 12 months) | 8 (28.6) | |
Late (>12 months) | 11 (39.3) | |
Last eGFR before switch (mL/min/1.73 m2) mean (SD) | 33 (17) | |
Immunosuppressive drug associated with belatacept | ||
Tacrolimus (%) | No | 26 (92.9) |
Yes | 2 (7.1) | |
Cyclosporin (%) | No | 27 (96.4) |
Yes | 1 (3.6) | |
Other immunosuppressants (%) | No | 1 (3.6) |
Corticotherapy | 4 (14.3) | |
MMF/MPA | 15 (53.6) | |
Corticotherapy + MMF/MPA | 8 (28.6) | |
Rejection (%) | No | 27 (96.4) |
Yes | 1 (3.6) |
Characteristics | No Belatacept Resumption n = 15 | Belatacept Resumption n = 10 | p | |
---|---|---|---|---|
Age (mean (SD)) | 51.4 (17.3) | 49.9 (15.2) | 0.826 | |
Sex (%) | Female | 8 (53.3) | 8 (80) | 0.349 |
Male | 7 (46.7) | 2 (20) | ||
Transplantation rank (%) | 1 | 13 (86.7) | 9 (90) | 0.242 |
2 | 2 (13.3) | 0 (0) | ||
3 | 0 (0) | 1 (10) | ||
Delayed graft function (%) | No | 10 (66.7) | 6 (60) | 1.000 |
Yes | 5 (33.3) | 4 (40) | ||
Belatacept duration (mean (SD)) | 578.4 (327.6) | 823.5 (341.3) | 0.085 | |
Cause of switch (%) | Active ABMR | 1 (6.7) | 0 (0) | 0.629 |
Poor CNI tolerance | 4 (26.7) | 2 (20) | ||
Poor function | 10 (66.7) | 8 (80) | ||
Cause of discontinuation (%) | Standard protocol | 13 (86.6) | 2 (20) | <0.01 |
COVID-19 pandemic | 2 (13.4) | 8 (80) | ||
Last eGFR under belatacept (mL/min/1.73 m2) (mean (SD)) | 50 (22) | 44 (13) | 0.534 | |
Corticosteroids (%) | No | 11 (73.3) | 6 (60) | 0.793 |
Yes | 4 (26.7) | 4 (40) | ||
mTOR-inhibitor (%) | No | 11 (73.3) | 9 (90) | 0.610 |
Yes | 4 (26.7) | 1 (10) | ||
CNI (%) | No | 2 (13.3) | 1 (10) | 1.000 |
Yes | 13 (86.7) | 9 (90) | ||
CNI + Mycophenolate derivative (%) | No | 5 (33.3) | 6 (60) | 0.366 |
Yes | 10 (66.7) | 4 (40) | ||
CNI + mTOR inhibitor (%) | No | 12 (80.0) | 9 (90) | 0.911 |
Yes | 3 (20.0) | 1 (10) |
At Transplantation n = 28 | Before Belatacept a n = 28 | Under Belatacept b n = 28 | After Belatacept c n = 19 d | p | ||
---|---|---|---|---|---|---|
Diabetes | 0.60 | |||||
No (%) | 27 (96.4) | 25 (89.3) | 25 (89.3) | 17 (89.4) | ||
LDI only (%) | 0 | 2 (7.1) | 2 (7.1) | 1 (5.3) | ||
Oral therapy (%) | 0 | 0 | 0 | 1 (5.3) | ||
Insulin (%) | 1 (3.6) | 1 (3.6) | 1 (3.6) | 0 | ||
Hypertension | 0.71 | |||||
No (%) | 10 (35.7) | 9 (32.1) | 10 (35.7) | 4 (21.1) | ||
Yes (%) | 18 (64.3) | 19 (67.9) | 18 (64.3) | 15 (78.9) | ||
Mean number of anti-hypertensive medication | 0.35 | |||||
1.21 | 1.18 | 1.14 | 1.21 | |||
DSA | 0.65 | |||||
No (%) | 25 (89.3) | 23 (82) | 24 (85.6) | 15 (78.9) | ||
Yes (%) | 2 (7.1) | 5 (18) | 3 (10.7) | 3 (15.9) | ||
NA (%) | 1 (3.6) | 0 | 1 (3.6) | 1 (5.3) | ||
Infections | 0.09 | |||||
Pyelonephritis (%) | 9 (32.1) | 3 (10.7) | 1 (5.3) | |||
Other bacterial (%) | 3 (10.7) | 3 (10.7) | 2 (10.6) | |||
Flu (%) | 0 | 2 (7.1) | 1 (5.3) | |||
COVID-19 (%) | 0 | 0 | 2 (10.6) | |||
Other viral (%) | 1 (3.6) | 2 (7.1) | 1 (5.3) |
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Letellier, T.; Kervella, D.; Sadek, A.; Masset, C.; Garandeau, C.; Fourgeux, C.; Gourain, V.; Poschmann, J.; Blancho, G.; Ville, S.; et al. Time-Limited Therapy with Belatacept in Kidney Transplant Recipients. J. Clin. Med. 2022, 11, 3229. https://doi.org/10.3390/jcm11113229
Letellier T, Kervella D, Sadek A, Masset C, Garandeau C, Fourgeux C, Gourain V, Poschmann J, Blancho G, Ville S, et al. Time-Limited Therapy with Belatacept in Kidney Transplant Recipients. Journal of Clinical Medicine. 2022; 11(11):3229. https://doi.org/10.3390/jcm11113229
Chicago/Turabian StyleLetellier, Thibault, Delphine Kervella, Abderrahmane Sadek, Christophe Masset, Claire Garandeau, Cynthia Fourgeux, Victor Gourain, Jeremie Poschmann, Gilles Blancho, Simon Ville, and et al. 2022. "Time-Limited Therapy with Belatacept in Kidney Transplant Recipients" Journal of Clinical Medicine 11, no. 11: 3229. https://doi.org/10.3390/jcm11113229