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肾移植后他克莫司高暴露与复发性膜性肾病的自发缓解相关。

High exposure to tacrolimus is associated with spontaneous remission of recurrent membranous nephropathy after kidney transplantation.

作者信息

Buxeda Anna, Caravaca-Fontán Fernando, Vigara Luis Alberto, Pérez-Canga José Luis, Calatayud Emma, Coloma Ana, Mazuecos Auxiliadora, Rodrigo Emilio, Sancho Asunción, Melilli Edoardo, Praga Manuel, Pérez-Sáez María José, Pascual Julio

机构信息

Department of Nephrology, Hospital del Mar, Barcelona, Spain.

Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.

出版信息

Clin Kidney J. 2023 Apr 12;16(10):1644-1655. doi: 10.1093/ckj/sfad077. eCollection 2023 Oct.

Abstract

INTRODUCTION

We aimed to characterize the incidence and clinical presentation of membranous nephropathy (MN) after kidney transplantation (KT), and to assess allograft outcomes according to proteinuria rates and immunosuppression management.

METHODS

Multicenter retrospective cohort study including patients from six Spanish centers who received a KT between 1991-2019. Demographic, clinical, and histological data were collected from recipients with biopsy-proven MN as primary kidney disease ( = 71) or MN diagnosed after KT ( = 4).

RESULTS

Up to 25.4% of patients with biopsy-proven MN as primary kidney disease recurred after a median time of 18.1 months posttransplant, without a clear impact on graft survival. Proteinuria at 3-months post-KT was a predictor for MN recurrence (rMN, HR 4.28;  = 0.008). Patients who lost their grafts had higher proteinuria during follow-up [1.0 (0.5-2.5) vs 0.3 (0.1-0.5) g/24 h], but only eGFR after recurrence treatment predicted poorer graft survival (eGFR < 30 ml/min: RR = 6.8). We did not observe an association between maintenance immunosuppression and recurrence diagnosis. Spontaneous remission after rMN was associated with a higher exposure to tacrolimus before recurrence (trough concentration/dose ratio: 2.86 vs 1.18;  = 0.028). Up to 94.4% of KT recipients received one or several treatments after recurrence onset: 22.2% rituximab, 38.9% increased corticosteroid dose, and 66.7% ACEi/ARBs. Only 21 patients had proper antiPLA2R immunological monitoring.

CONCLUSIONS

One-fourth of patients with biopsy-proven MN as primary kidney disease recurred after KT, without a clear impact on graft survival. Spontaneous remission after rMN was associated with a higher exposure to tacrolimus before recurrence.

摘要

引言

我们旨在描述肾移植(KT)后膜性肾病(MN)的发病率和临床表现,并根据蛋白尿率和免疫抑制管理评估移植肾结局。

方法

多中心回顾性队列研究,纳入了1991年至2019年间在六个西班牙中心接受KT的患者。收集了经活检证实为原发性肾病的MN患者(n = 71)或KT后诊断为MN的患者(n = 4)的人口统计学、临床和组织学数据。

结果

高达25.4%经活检证实为原发性肾病的MN患者在移植后中位时间18.1个月复发,对移植肾存活无明显影响。KT后3个月时的蛋白尿是MN复发(rMN)的预测因素(HR 4.28;P = 0.008)。移植肾失功的患者在随访期间蛋白尿水平更高[1.0(0.5 - 2.5)vs 0.3(0.1 - 0.5)g/24 h],但只有复发治疗后的估算肾小球滤过率(eGFR)可预测较差的移植肾存活(eGFR < 30 ml/min:RR = 6.8)。我们未观察到维持性免疫抑制与复发诊断之间存在关联。rMN后的自发缓解与复发前较高的他克莫司暴露量相关(谷浓度/剂量比:2.86 vs 1.18;P = 0.028)。高达94.4%的KT受者在复发后接受了一种或多种治疗:22.2%使用利妥昔单抗,38.9%增加皮质类固醇剂量,66.7%使用血管紧张素转换酶抑制剂/血管紧张素Ⅱ受体阻滞剂(ACEi/ARBs)。只有21例患者进行了适当的抗磷脂酶A2受体(antiPLA2R)免疫监测。

结论

四分之一经活检证实为原发性肾病的MN患者在KT后复发,对移植肾存活无明显影响。rMN后的自发缓解与复发前较高的他克莫司暴露量相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34f7/10539211/3b243470bd0a/sfad077fig1g.jpg

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