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监测接受治疗性血浆置换和利妥昔单抗治疗的肾移植后局灶节段性肾小球硬化症患者的 suPAR 水平。

Monitoring suPAR levels in post-kidney transplant focal segmental glomerulosclerosis treated with therapeutic plasma exchange and rituximab.

机构信息

Department of Medicine, Division of Nephrology, The Johns Hopkins University School of Medicine, Baltimore, USA.

Division of Nephrology, Johns Hopkins Hospital, 600 Wolfe St. Carnegie 344B, Baltimore, MD, 21287, USA.

出版信息

BMC Nephrol. 2018 Dec 17;19(1):361. doi: 10.1186/s12882-018-1177-x.

DOI:10.1186/s12882-018-1177-x
PMID:30558559
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6296111/
Abstract

BACKGROUND

Therapeutic plasma exchange (TPE) is an important therapy for recurrent focal segmental glomerulosclerosis (rFSGS) post kidney transplant. suPAR has been causally implicated in rFSGS, and shown to be a unique biomarker for the occurrence and progression of chronic kidney disease. This study was targeted to evaluate the application of monitoring suPAR in TPE treated rFSGS.

METHODS

A retrospective (n = 19) and a prospective (n = 15) cohort of post transplant FSGS patients treated with TPE and rituximab were enrolled. We measured serum suPAR levels before and after the combined therapies, and assessed the role of suPAR changes on proteinuria reduction and podocyte β3- integrin activity.

RESULTS

Treatment with TPE and rituximab resulted in significant decrease in proteinuria and suPAR levels. Among the variables including baseline suPAR, serum creatinine, proteinuria, eGFR, age at diagnosis, age at transplantation, transplantation numbers, time to recurrence, and TPE course numbers, only the reduction in suPAR levels and baseline proteinuria significantly correlated with the changes in proteinuria after treatment, with the former performed better in predicting proteinuria alteration. Additionally, the mean podocyte β3 integrin activity significantly decreased after TPE and rituximab treatment (1.10 ± 0.08) as compared to before treatment (1.34 ± 0.08), p < 0.05. Only the reduction in suPAR predicted the response to therapies with an odds ratio of 1.43, 95% CI (1.02, 2.00), p < 0.05.

CONCLUSIONS

Serum suPAR levels reduced significantly after TPE and rituximab treatment in post transplant FSGS patients. The reduction in suPAR levels may be utilized to assess the changes in proteinuria and monitor the response to the therapies. Larger, multi-centered prospective studies monitoring serum suPAR levels in TPE managed post transplant FSGS are warranted.

摘要

背景

治疗性血浆置换(TPE)是肾移植后复发性局灶节段性肾小球硬化(rFSGS)的重要治疗方法。suPAR 已被确定与 rFSGS 有关,并被证明是慢性肾脏病发生和进展的独特生物标志物。本研究旨在评估监测 TPE 治疗 rFSGS 中 suPAR 的应用。

方法

回顾性(n=19)和前瞻性(n=15)队列研究纳入了接受 TPE 和利妥昔单抗治疗的移植后 FSGS 患者。我们在联合治疗前后测量了血清 suPAR 水平,并评估了 suPAR 变化对蛋白尿减少和足细胞β3-整合素活性的作用。

结果

TPE 和利妥昔单抗治疗导致蛋白尿和 suPAR 水平显著下降。在包括基线 suPAR、血清肌酐、蛋白尿、eGFR、诊断时年龄、移植时年龄、移植次数、复发时间和 TPE 疗程数在内的变量中,只有 suPAR 水平的降低和基线蛋白尿与治疗后蛋白尿的变化显著相关,前者在预测蛋白尿改变方面表现更好。此外,与治疗前(1.34±0.08)相比,TPE 和利妥昔单抗治疗后足细胞β3 整合素活性明显降低(1.10±0.08),p<0.05。只有 suPAR 的降低预测了治疗反应,优势比为 1.43,95%CI(1.02,2.00),p<0.05。

结论

移植后 FSGS 患者接受 TPE 和利妥昔单抗治疗后血清 suPAR 水平显著降低。suPAR 水平的降低可用于评估蛋白尿的变化并监测治疗反应。需要更大规模、多中心的前瞻性研究来监测 TPE 治疗后移植 FSGS 患者的血清 suPAR 水平。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c637/6296111/aab8086f8b95/12882_2018_1177_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c637/6296111/3b30bf07aba8/12882_2018_1177_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c637/6296111/015268aace42/12882_2018_1177_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c637/6296111/a336d37ffb20/12882_2018_1177_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c637/6296111/aab8086f8b95/12882_2018_1177_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c637/6296111/3b30bf07aba8/12882_2018_1177_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c637/6296111/015268aace42/12882_2018_1177_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c637/6296111/a336d37ffb20/12882_2018_1177_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c637/6296111/aab8086f8b95/12882_2018_1177_Fig4_HTML.jpg

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