期刊
AMERICAN JOURNAL OF TRANSPLANTATION
卷 21, 期 8, 页码 2833-2845出版社
WILEY
DOI: 10.1111/ajt.16563
关键词
biomarker; clinical decision-making; clinical research/practice; clinical trial; immunobiology; immunosuppression/immune modulation; immunosuppressive regimens - minimization/withdrawal; kidney transplantation/nephrology; rejection: acute
资金
- European Union [305147]
- Instituto de Salud Carlos III (ISCIII) [ICI14/00242, PI16/01321]
- Department of Health of the Generalitat de Catalunya [SLT002/16/00183]
- European Society of Transplantation (ESOT)
Personalizing immunosuppression in kidney transplant recipients with low immunological risk through biomarker-guided trials of tacrolimus monotherapy was found to be non-inferior to standard of care in terms of 6-month biopsy-proven acute rejection rates. However, recruitment challenges led to the early termination of the trial.
Personalizing immunosuppression is a major objective in transplantation. Transplant recipients are heterogeneous regarding their immunological memory and primary alloimmune susceptibility. This biomarker-guided trial investigated whether in low immunological-risk kidney transplants without pretransplant DSA and donor-specific T cells assessed by a standardized IFN-gamma ELISPOT, low immunosuppression (LI) with tacrolimus monotherapy would be non-inferior regarding 6-month BPAR than tacrolimus-based standard of care (SOC). Due to low recruitment rates, the trial was terminated when 167 patients were enrolled. ELISPOT negatives (E-) were randomized to LI (n = 48) or SOC (n = 53), E+ received the same SOC. Six- and 12-month BPAR rates were higher among LI than SOC/E- (4/35 [13%] vs. 1/43 [2%], p = .15 and 12/48 [25%] vs. 6/53 [11.3%], p = .073, respectively). E+ patients showed similarly high BPAR rates than LI at 6 and 12 months (12/55 [22%] and 13/66 [20%], respectively). These differences were stronger in per-protocol analyses. Post-hoc analysis revealed that poor class-II eplet matching, especially DQ, discriminated E- patients, notably E-/LI, developing BPAR (4/28 [14%] low risk vs. 8/20 [40%] high risk, p = .043). Eplet mismatch also predicted anti-class-I (p = .05) and anti-DQ (p < .001) de novo DSA. Adverse events were similar, but E-/LI developed fewer viral infections, particularly polyoma-virus-associated nephropathy (p = .021). Preformed T cell alloreactivity and HLA eplet mismatch assessment may refine current baseline immune-risk stratification and guide immunosuppression decision-making in kidney transplantation.
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