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南非狼疮肾炎患者尿 MCP-1 和 TWEAK 作为疾病活动和治疗反应的非侵入性标志物。

Urinary MCP-1 and TWEAK as non-invasive markers of disease activity and treatment response in patients with lupus nephritis in South Africa.

机构信息

Division of Nephrology and Hypertension, University of Cape Town, Cape Town, South Africa.

Kidney and Hypertension Research Unit, University of Cape Town Cape Town, Cape Town, South Africa.

出版信息

Int Urol Nephrol. 2021 Sep;53(9):1865-1873. doi: 10.1007/s11255-020-02780-9. Epub 2021 Jan 18.

DOI:10.1007/s11255-020-02780-9
PMID:33459955
Abstract

BACKGROUND

Treatment of patients with lupus nephritis (LN) requires judicious use of immunosuppression. Novel biomarkers may be useful for monitoring disease activity and treatment response. We assessed the utility of urinary monocyte chemoattractant protein-1 (uMCP-1) and urinary tumour necrosis factor-like weak inducer of apoptosis (uTWEAK) for disease activity and treatment response monitoring in South Africans with LN.

METHODS

We recruited consenting patients with active LN confirmed on kidney biopsy. Urinary levels of MCP-1 and TWEAK were assayed at baseline and after completion of induction therapy using ELISA methods. We also collected relevant demographic, clinical and biochemical data for patients included in this study.

RESULTS

The mean age of patients in this study was 29.8 ± 10.7 years, 60% were patients of mixed ancestry, 70% had proliferative LN and mean spot urine proteinuria at baseline was 0.37 (0.18-0.59) g/mmolCr. At completion of induction therapy, the level of uMCP-1 had reduced to 314.5 (IQR: 197.0-622) pg/mgCr from a baseline of 1092.7 (IQR 578.6-1848) pg/mgCr (P = 0.06) while uTWEAK had reduced to 36.0 (IQR 17.0-88.0) pg/mgCr from 159.0 (IQR: 88.5-295.5) pg/mgCr (P = 0.03). For patients reaching early complete or partial remission (n = 17), both biomarkers had significantly declined in their urine: uMCP-1 (P = 0.018) and uTWEAK (P = 0.015). There was no reduction of both biomarkers in patients not achieving remission and no association between uMCP-1 or uTWEAK with renal histological features.

CONCLUSION

Our study shows that uMCP-1 and uTWEAK are elevated in patients with active LN, correlated with the remission status (response to treatment) at the end of induction therapy and can, therefore, be useful for monitoring disease activity and treatment response.

摘要

背景

治疗狼疮肾炎(LN)患者需要合理使用免疫抑制剂。新型生物标志物可能有助于监测疾病活动度和治疗反应。我们评估了尿单核细胞趋化蛋白-1(uMCP-1)和尿肿瘤坏死因子样弱凋亡诱导剂(uTWEAK)在南非 LN 患者中监测疾病活动度和治疗反应的效用。

方法

我们招募了经肾活检证实为活动性 LN 的同意患者。使用 ELISA 方法在基线和诱导治疗完成后测定尿 MCP-1 和 TWEAK 水平。我们还为纳入本研究的患者收集了相关的人口统计学、临床和生化数据。

结果

本研究中患者的平均年龄为 29.8±10.7 岁,60%为混合血统患者,70%为增生性 LN,基线时尿蛋白/肌酐比的平均点尿蛋白为 0.37(0.18-0.59)g/mmolCr。在诱导治疗完成时,uMCP-1 水平从基线时的 1092.7(IQR:578.6-1848)pg/mgCr 降至 314.5(IQR:197.0-622)pg/mgCr(P=0.06),uTWEAK 水平从 159.0(IQR:88.5-295.5)pg/mgCr 降至 36.0(IQR:17.0-88.0)pg/mgCr(P=0.03)。对于达到早期完全或部分缓解的患者(n=17),两种生物标志物在尿液中的含量均显著下降:uMCP-1(P=0.018)和 uTWEAK(P=0.015)。未达到缓解的患者的两种生物标志物均未减少,uMCP-1 或 uTWEAK 与肾脏组织学特征之间也没有关联。

结论

我们的研究表明,uMCP-1 和 uTWEAK 在活动性 LN 患者中升高,与诱导治疗结束时的缓解状态(治疗反应)相关,因此可用于监测疾病活动度和治疗反应。

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