他克莫司联合激素治疗Ⅴ型狼疮性肾炎的疗效

A prospective preliminary study of tacrolimus (FK506) combined with low-dose prednisone in patients with membranous lupus nephropathy

目的 :前瞻性观察他克莫司 (FK5 0 6 )治疗Ⅴ型狼疮性肾炎 (LN)的临床疗效及安全性。 方法 :利用FK5 0 6治疗 11例尿蛋白 >2 .0g/ 2 4h、肾功能正常、并经肾活检确诊的Ⅴ型LN患者。FK5 0 6起始剂量为 0 .1mg/ (kg·d) ,同时口服强的松 0 .6mg/ (kg·d)。疗效分为完全缓解 (CR ,指尿蛋白 <0 .4g/ 2 4h ,无活动性尿沉渣 ,血清白蛋白≥ 35g/L ,SCr正常 ) ,部分缓解 (PR ,指尿蛋白定量 0 .4～ 2g/ 2 4h且尿蛋白下降超过基础值的 5 0 % ,血清白蛋白≥ 30g/L ,SCr正常 )及无效 (NR ,指尿蛋白定量≥ 2g/ 2 4h ;或血清白蛋白 <30g/L ;或SCr升高超过基础值 5 0 % ;或重复肾活检病理类型转为Ⅳ型LN)。 结果 :11例患者接受FK5 0 6治疗 3～ 15个月 ,无一例退出治疗。治疗 3个月时 2例 (18.2 % )患者获得完全缓解、5例 (4 5 .5 % )获部分缓解。治疗 6个月以上的 10例患者中获得完全及部分缓解者均为 4例 (4 0 % )。达到完全或部分缓解的中位数治疗时间为 3个月 (1～ 7个月 )。FK5 0 6治疗 3个月时 ,2例尿蛋白降至正常 ,5例降至 <2 .0g/ 2 4h。治疗 6个月以上的 10例患者中尿蛋白完全、部分缓解者均为 4例。 10例低蛋白血症患者在治疗 3个月后即有 7例血清白蛋白升至正常。血清抗核抗体及抗dsDNA抗体转阴或滴度显?

Objective:Th2 cell and cytokine IL-10 play an important role in the pathogenesis of membranous lupus nephropathy. Tacrolimus (FK506), an inhibitor of calcineurin, can inhibit the synthesis of IL-10 potently. In this study, we investigated the efficacy and adverse effects of tacrolimus in patients with membranous lupus nephropathy (WHO classification, class Ⅴ lupus nephritis). Methodology:A prospective preliminary study was conducted in 11 patients with membranous lupus nephritis proven by renal biopsy. In all the patients, the daily excretion of urinary protein exceeded 2.0 g, and the serum creatinine (SCr) was less than up-lower limit of normal range (110 μmol/L). All the patients received a regimen of FK506 combined with steroids. The starting dosage of FK506 was 0.1 mg/(kg·d), combined with prednisone at 0.6 mg/(kg·d). The dosage of prednisone was tapered after 4 weeks until a maintenance dosage of 10mg/d. Complete remission (CR) referred to daily urinary protein excretion reduced to 0.4g or below,no active urinary sediment (urinary RBC<10×10 4/ml, no cast nor urinary WBC), serum albumin over 35g/L, SCr in normal range, and negativity of serum anti-dsDNA antibody. Partial remission (PR) referred to daily urinary protein excretion reduced to a range of 0.4-2.0 g and the reduction exceeded 50% or more of the baseline level, serum albumin equal or more than 30g/L, and SCr level in normal range. No-response (NR) referred to daily urinary protein excretion still exceeded 2.0g or the reduction less than 50% of the baseline value, serum albumin below 30g/L, or increment of SCr to more than 50% of the baseline value, or transformation to Class Ⅳ LN in repeat renal biopsy. Results:All the patients tolerated well to the regimen of FK506 for 3-15months, with nobody withdrew from the study. After treatment for 3 months, 2 of the 11 patients (18.2%) achieved complete remission, 5 patients (45.5%) achieved partial remission. In the 10 patients treated with FK506 for more than 6 months, 4 patients (40%) got CR and 4 patients got PR (40%) respectively. The median time to achieve CR/PR was 3 months (1-7months). In 7 of the 10 patients with hypoalbuminemia, serum albumin increased to normal range after treatment for 3 months. The titer of serum ANA and anti-dsDNA decreased,and the level of serum complement component increased significantly after treatment. Repeated renal biopsy in 8 patients (3 patients with CR, 3 with PR and 2 with NR) demonstrated that the activity index decreased from 4.8±2.38 to 2.25±1.28 (p<0.05). There was no significant exacerbation of interstitial fibrosis. The adverse effects included temporary increased SCr level in 6 patients, and diarrhea, hypertension, herpes zoster each in 1 patient respectively. Conclusion:This preliminary study demonstrated that the regime of FK506 combined with low-dose prednisone is effective for patients with membranous lupus nephropathy.