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他克莫司治疗狼疮性肾炎的长期数据。

Long-term data on tacrolimus treatment in lupus nephritis.

作者信息

Yap Desmond Y H, Ma Maggie K M, Mok Maggie M Y, Kwan Lorraine P Y, Chan Gary C W, Chan Tak Mao

机构信息

Division of Nephrology, Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, SAR, China.

出版信息

Rheumatology (Oxford). 2014 Dec;53(12):2232-7. doi: 10.1093/rheumatology/keu265. Epub 2014 Jul 4.

Abstract

OBJECTIVE

Calcineurin inhibitors are effective immunosuppressants. They also reduce proteinuria in glomerular diseases but are potentially nephrotoxic. Short-term data suggest that tacrolimus (TAC) combined with corticosteroids is effective in LN, but long-term data are lacking. This study examined the long-term outcomes and tolerability of TAC for the treatment of LN.

METHODS

We retrospectively reviewed 29 LN patients who received TAC treatment for 46.9 months (s.d. 37.9).

RESULTS

In 17 patients with class III/IV or V LN and persistent proteinuria >2 g/day despite induction immunosuppression, response rates after 12 and 24 months of add-on TAC treatment were 66.7% and 80.0%, respectively. In 10 patients with nephrotic syndrome due to class V LN who were given prednisolone and TAC as initial treatment, the response rate was 60.0% and 90.0% after 12 and 24 months, respectively. TAC facilitated steroid minimization in two patients with lupus podocytopathy. As a group, proteinuria decreased from 3.6 g/day (s.d. 2.6) to 1.0 (s.d. 1.1) (P < 0.05). Four patients developed end-stage renal failure, with 3-, 5- and 8-year renal survival rates of 93%, 83% and 83%, respectively. In the remaining patients, serum creatinine and estimated GFR remained stable after 36 months. One patient with pre-existing chronic renal failure developed TAC nephrotoxicity. Four renal flares occurred, all associated with low TAC blood levels. Six patients (20.1%) had deterioration of hypertension and one patient (3.4%) had new-onset diabetes mellitus. Six patients (20.1%) had infections that required hospitalization. Two deaths occurred: one due to pneumonia and one to breast cancer.

CONCLUSION

The results suggest efficacy of TAC in LN, especially in reducing proteinuria, and its role as a long-term maintenance agent warrants further investigation.

摘要

目的

钙调神经磷酸酶抑制剂是有效的免疫抑制剂。它们还可减少肾小球疾病中的蛋白尿,但具有潜在肾毒性。短期数据表明,他克莫司(TAC)联合皮质类固醇对狼疮性肾炎(LN)有效,但缺乏长期数据。本研究考察了TAC治疗LN的长期疗效和耐受性。

方法

我们回顾性分析了29例接受TAC治疗46.9个月(标准差37.9)的LN患者。

结果

17例III/IV或V级LN且尽管进行了诱导免疫抑制但持续性蛋白尿>2 g/天的患者,在加用TAC治疗12个月和24个月后的缓解率分别为66.7%和80.0%。10例因V级LN导致肾病综合征且初始接受泼尼松龙和TAC治疗的患者,在12个月和24个月后的缓解率分别为60.0%和90.0%。TAC有助于两名狼疮性足细胞病患者减少类固醇用量。总体而言,蛋白尿从3.6 g/天(标准差2.6)降至1.0(标准差1.1)(P<0.05)。4例患者发展为终末期肾衰竭,3年、5年和8年肾脏生存率分别为93%、83%和83%。其余患者在36个月后血清肌酐和估算肾小球滤过率保持稳定。1例既往有慢性肾衰竭的患者发生了TAC肾毒性。发生了4次肾脏活动,均与TAC血药浓度低有关。6例患者(20.1%)高血压病情恶化,1例患者(3.4%)新发糖尿病。6例患者(20.1%)发生需要住院治疗的感染。发生了2例死亡:1例死于肺炎,1例死于乳腺癌。

结论

结果表明TAC对LN有效,尤其是在减少蛋白尿方面,其作为长期维持药物的作用值得进一步研究。

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