泼尼松治疗成人局灶节段性肾小球硬化的临床疗效

Efficacy of oral prednisone alone for adult patients with focal segmantal glomerulosclerosis

目的:前瞻性观察口服足量泼尼松8周疗法治疗成人局灶节段性肾小球硬化(FSGS)的疗效及不良反应。方法:(1)泼尼松治疗方案:足量泼尼松[剂量为1mg/(kg.d)]治疗8周,如患者完全缓解,则自第9周开始逐渐撤减;如第8周达到部分缓解,则足量泼尼松延长至第10周,自第11周再开始减量。(2)病例入选标准:年龄18～60岁,肾活检证实FSGS,SCr<265.2μmol/L,肾小球滤过率>30ml/min.1.73m2,尿蛋白定量>3.5g/24h,血清白蛋白≤30g/L,排除继发FSGS。(3)疗效判断:完全缓解(尿蛋白定量<0.4g/24h,血清白蛋白≥35g/L,SCr≤109.6μmol/L);部分缓解(尿蛋白定量<3.5g/24h,且下降超过基础值50%以上,肾功能稳定);无效指尿蛋白下降程度<基础值50%,并>3.5g/24h,或SCr倍增。结果:(1)入选病例31例,男性22例,女性9例,年龄18～47岁。(2)经足量泼尼松治疗8周后,26例有效,总有效率为83.9%,其中8例(25.8%)完全缓解(2周缓解2例、4周4例、8周2例);18例(58.1%)部分缓解(2周部分缓解12例,4周2例,8周4例),5例(16.1%)无效。18例部分缓解患者延长疗程至第10周,仅1例达到完全缓解,完全缓解率为29.0%。(3)疗效影响因素:初治患者总有效率明显高于非初治患者(94.8%vs66.7%,P<0.05);完全缓解患者尿RBP阳性率明显低于部分缓解(25.0%vs83.3%,P<0.01)和无效患者(25.0%vs100%,P<0.01);伴急性肾功能损害者完全缓解率显著低于无急性肾功能损害者(0%vs36.4%,P<0.05)。(4)不良反应:9例(29.0%)出现ALT和(或)AST升高;5例(16.1%)表现库兴综合征;5例(9.7%)出现感染,其中1例军团菌肺炎、2例上呼吸道感染、2例皮肤带状疱疹;1例(3.2%)类固醇性糖尿病;1例(3.2%)于治疗过程中出现SCr升高超过基础值50%(97.2～172.3μmol/L)。结论:口服泼尼松8周疗法治疗成人FSGS是有效的,总有效率达83.9%,其中完全缓解率25.8%、部分缓解率58.1%;延长疗程至第10周完全缓解率上升至29.0%。初治病例、肾小管间质病变轻、无肾功能损害者疗效较好。治疗不良反应依次为转氨酶升高、感染和库兴综合征。该疗法完全缓解率不高(25.8%)、不良反应较明显,停药后复发问题也有待进一步阐明。进一步观察小剂量激素加二线免疫抑制剂联合治疗的疗效,有助于为FSGS患者的临床治疗提供新的途径。

Objective：Focal segmental glomerulosclerosis （FSGS） is a common type of adult glomerular disease which manifest nephrotic proteinuria and progress to chronic renal failure. Although several therapeutic regimens have been used on FSGS, the results were unsatisfied. It has been reported that high-dose prednisone and long-range therapy （6- month or longer） may be effective. But the total remission rates were only about 50%. However, the side-effects of this therapy should be paid attention. In this study, we conducted a single-center prospective non-randomized trial to investigate the therapeutic effecy of oral prednisone therapy for adult patients with FSGS. Methodology： （ 1 ） Patient criteria： age 18 - 60 years ; biopsy proven FSGS ; SCr 〈 265.2 μmol/L; eGFR 〉 30 ml/min per 1.73 m^2, urine protein 〉 3.5 g/24h, and serum albumins〈30 g/L. The secondary FSGS was excluded. （2）Therapeutic regimens： In the initial 8 weeks, the prednisone was full-dose of lmg/kg BW/day （Max 60 mg/day）. If the patients were complete remission at the 8^th week, the prednisone should be tapered gradually ; if the patients were partial remission, the prednisone extended to 10^th week, and then tapered. （3）Evaluation： CR （proteinuria 〈 0. 4 g/24h, serum albumin 1〉35 g/L and normal value of SCr）, and PR （ proteinuria 〈 3.5 g/24h and declined 〉 50% of baseline with stable kidney function）. Results： （ 1 ） Thirty-one patients, twenty-two males and nine females, with age 18 - 47 years old, were enrolled this study. （2） At the prednisone ta- pering time which was the 8^th week, 26 patients （83.9%） had the total remission. Among them, 8 patients （25. 8% ） had CR, 18 patients （58.1%） PR, and 5 patients （ 16. 1% ） had NR. At the 10^th week, the total remission rate was also 83.9%, just 1 case transformed from PR to CR, 5 cases （16. 1% ） had still NR. （3）The total remission rate in initial treatment was higher than that in non-initial patients＇ （94. 8% vs 66.7% , P 〈0. 05）. The urine RBP positive rate in CR patients＇was lower than that in PR patients＇ （25.0% vs 83.3%, P 〈 0. 01 ） and NR patients＇ （25.0% vs 100%, P 〈 0. 01 ）. The CR rate in ARF was lower than that in non-ARF patients＇（0% vs 36.4%, P 〈 0. 05）. （4）Complications and adverse effects： 9 cases （29. 0% ） had an increase level of serum glutamic-pyruvic transaminase （ over twice normal val- ue）, 5 （16. 1% ） Cushingg syndrome, 5 （16. 1% ） infection, one （3.2%） steroid-induced diabetes, and one （3. 2% ） had an increase level of SCr （97. 2 to 172. 3 μmol/L）. Conclusion：Oral full-dose prednisone alone （8-weeks therapy） is effective for the treatment of adult patients with FSGS. However, the CR rate was not high （25.8%） and adverse effects were serious. And the relapse after the stop of the therapy should be further observed and discussed in the following studies.