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钙调磷酸酶抑制剂转换为贝利尤单抗在 HLA 致敏伴低水平供者特异性抗体的肾移植受者中的应用。

Conversion From Calcineurin Inhibitors to Belatacept in HLA-sensitized Kidney Transplant Recipients With Low-level Donor-specific Antibodies.

机构信息

Nephrology Department, Clínica Alemana de Santiago - UDD, Santiago de Chile, Chile.

Nephrology Service, Hospital Barros Luco de Santiago de Chile, Santiago de Chile, Chile.

出版信息

Transplantation. 2019 Oct;103(10):2150-2156. doi: 10.1097/TP.0000000000002592.

Abstract

BACKGROUND

Belatacept could be the treatment of choice in renal-transplant recipients with renal dysfunction attributed to calcineurin inhibitor (CNI) nephrotoxicity. Few studies have described its use in patients with donor-specific antibody (DSA).

METHODS

We retrospectively evaluated conversion from CNIs to belatacept in 29 human leukocyte antigen-immunized renal-transplant recipients. Data about acute rejection, DSA, and renal function were collected. These patients were compared with 42 nonimmunized patients treated with belatacept.

RESULTS

Patients were converted from CNIs to belatacept a median of 444 days (interquartile range, 85-1200) after transplantation and were followed up after belatacept conversion, for a median of 308 days (interquartile range, 125-511). At conversion, 16 patients had DSA. Nineteen DSA were observed in these 16 patients, of which 11/19 were <1000 mean fluorescence intensity (MFI), 7/19 were between 1000 and 3000 MFI, and one was >3000 MFI. At last follow-up, preexisting DSA had decreased or stabilized. Seven patients still had DSA with a mean MFI of 1298 ± 930 at the last follow-up. No patient developed a de novo DSA in the DSA-positive group. In the nonimmunized group, one patient developed de novo DSA (A24-MFI 970; biopsy for cause did not show biopsy-proven acute rejection or microinflammation score). After belatacept conversion, one antibody-mediated rejection was diagnosed. The mean estimated glomerular filtration rate improved from 31.7 ± 14.2 mL/min/1.73 m to 40.7 ± 12.3 mL/min/1.73 m (P < 0.0001) at 12 months after conversion. We did not find any significant difference between groups in terms of renal function, proteinuria, or biopsy-proven acute rejection.

CONCLUSIONS

We report on a safe conversion to belatacept in human leukocyte antigen-immunized patients with low DSA levels.

摘要

背景

贝他西普可能是治疗因钙调磷酸酶抑制剂(CNI)肾毒性导致肾功能障碍的肾移植受者的首选治疗方法。很少有研究描述其在具有供体特异性抗体(DSA)的患者中的应用。

方法

我们回顾性评估了 29 例人类白细胞抗原免疫的肾移植受者从 CNI 转换为贝他西普的情况。收集了急性排斥反应、DSA 和肾功能的数据。将这些患者与 42 例接受贝他西普治疗的非免疫患者进行了比较。

结果

患者在移植后中位数 444 天(四分位距,85-1200)时从 CNI 转换为贝他西普,并在贝他西普转换后中位数 308 天(四分位距,125-511)进行随访。转换时,16 例患者有 DSA。这 16 例患者中观察到 19 例 DSA,其中 11/19 例的平均荧光强度(MFI)<1000,7/19 例在 1000-3000 MFI 之间,1 例>3000 MFI。最后一次随访时,预先存在的 DSA 减少或稳定。最后一次随访时,7 例患者仍有 DSA,平均 MFI 为 1298±930。在 DSA 阳性组中,没有患者出现新的 DSA。在非免疫组中,1 例患者出现新的 DSA(A24-MFI970;因原因进行活检,未发现活检证实的急性排斥反应或微炎症评分)。贝他西普转换后,诊断为 1 例抗体介导的排斥反应。转换后 12 个月,估算肾小球滤过率从 31.7±14.2 mL/min/1.73 m 改善至 40.7±12.3 mL/min/1.73 m(P<0.0001)。我们在肾功能、蛋白尿或活检证实的急性排斥反应方面没有发现两组之间有任何显著差异。

结论

我们报告了在人类白细胞抗原免疫、低 DSA 水平的患者中安全转换为贝他西普的情况。

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