mTOR 抑制剂和静脉注射免疫球蛋白治疗肾移植受者多瘤 BK 肾病的疗效：一项经活检证实的研究。

Efficacy of mTOR Inhibitors and Intravenous Immunoglobulin for Treatment of Polyoma BK Nephropathy in Kidney Transplant Recipients: A Biopsy-Proven Study.

机构信息

From the Department of General Surgery and Transplantation, University of Health Sciences, Izmir Bozyaka Education and Research Hospital, Izmir, Turkey.

出版信息

Exp Clin Transplant. 2024 Jan;22(Suppl 1):118-127. doi: 10.6002/ect.MESOT2023.O29.

DOI:10.6002/ect.MESOT2023.O29

PMID:38385385

Abstract

OBJECTIVES

We investigated the efficacy of a predetermined protocol that consisted of immunosuppressive drug reduction/withdrawal and intravenous immunoglobulin administration for the treatment of polyoma BK virus nephropathy.

MATERIALS AND METHODS

Patients with biopsy-proven polyoma BK virus nephropathy received a treatment regimen based on discontinuation of both calcineurin inhibitors and antiproliferative agents and switching to mTOR inhibitors accompanied by intravenous immunoglobulin administration.

RESULTS

Our study included 508 patients, with polyoma BK viremia detected in 80 patients. The mean age was 45.3 ± 9.5 years (range, 18-71 y), 64% were male, and mean follow-up was 37 ± 21 months (6-94 mo). All 16 patients who developed polyoma BK virus nephropathy and 9 patients who had highgrade polyoma BK viremia without nephropathy received intravenous immunoglobulin treatment. Compared with patients with viremia, patients with polyoma BK virus nephropathy had significantly higher rates of graft loss due to rejection (18.8% vs 1.6%; P = .024) and all-cause graft loss (31.2% vs 6.3%; P = .014). Histopathologically, viral inclusion bodies disappeared and SV40 became negative after treatment in all 13 patients who underwent protocol biopsies. Unfortunately, histopathologically complete recovery without chronic tubular and interstitial tissue damage was achieved in only 4 patients after treatment. In addition, 3 patients lost their grafts due to acute antibody-mediated or mixed-type rejection (18.8%).

CONCLUSIONS

In patients with polyoma BK virus nephropathy, clearance of viremia and SV40 should not be the sole outcomes to obtain. Aggressive reductions in maintenance immunosuppression and switching to double-drug therapy combined with high-dose intravenous immunoglobulin leads to high rates of graft loss/rejection and sequalae of chronic histological changes.

摘要

目的

我们研究了一种预先设定的方案的疗效，该方案包括免疫抑制药物的减少/停用和静脉注射免疫球蛋白的给予，用于治疗多瘤 BK 病毒肾病。

材料和方法

经活检证实患有多瘤 BK 病毒肾病的患者接受了一种治疗方案，包括停用钙调磷酸酶抑制剂和抗增殖剂，并改用 mTOR 抑制剂，同时给予静脉免疫球蛋白。

结果

我们的研究包括 508 例患者，其中 80 例患者检测到多瘤 BK 病毒血症。患者的平均年龄为 45.3 ± 9.5 岁（范围 18-71 岁），64%为男性，平均随访时间为 37 ± 21 个月（6-94 个月）。所有 16 例发生多瘤 BK 病毒肾病和 9 例高等级多瘤 BK 病毒血症但无肾病的患者均接受了静脉免疫球蛋白治疗。与病毒血症患者相比，多瘤 BK 病毒肾病患者因排斥反应导致移植物丢失的发生率显著更高（18.8%比 1.6%；P =.024），且因所有原因导致移植物丢失的发生率也更高（31.2%比 6.3%；P =.014）。在所有接受方案活检的 13 例患者中，治疗后病毒包涵体消失，SV40 变为阴性。不幸的是，治疗后只有 4 例患者在组织病理学上完全恢复，且无慢性肾小管和间质组织损伤。此外，由于急性抗体介导或混合性排斥反应，3 例患者失去了移植物（18.8%）。