切换至 "中华医学电子期刊资源库"
高级检索
中华肾病研究电子杂志

中华肾病研究电子杂志 ›› 2019, Vol. 08 ›› Issue (01) : 30 -37. doi: 10.3877/cma.j.issn.2095-3216.2019.01.007

所属专题： 文献；

论著

健脾祛湿和络方治疗难治性膜性肾病的临床观察
史彬1, 张荣融2, 王新慧2, 梁莹2, 赵宗江3, 余仁欢2,†()   
  1. 1. 100029　北京，北京中医药大学研究生院；100091　北京，中国中医科学院西苑医院肾病科
    2. 100091　北京，中国中医科学院西苑医院肾病科
    3. 100029　北京，北京中医药大学研究生院
  • 收稿日期:2018-08-01 出版日期:2019-02-28
  • 通信作者: 余仁欢

Efficacy of the traditional Chinese medicine Jianpi-Qushi-Heluo formula in treatment of patients with refractory idiopathic membranous nephropathy

Bin Shi1, Rongrong Zhang2, Xinhui Wang2, Ying Liang2, Zongjiang Zhao3, Renhuan Yu2,†()   

  1. 1. Graduate School of Beijing University of Chinese Medicine, Beijing 100029; Department of Nephrology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing 100091; China
    2. Department of Nephrology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing 100091; China
    3. Graduate School of Beijing University of Chinese Medicine, Beijing 100029
  • Received:2018-08-01 Published:2019-02-28
  • Corresponding author: Renhuan Yu
  • About author:
    Corresponding author: Yu Renhuan, Email:
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

史彬, 张荣融, 王新慧, 梁莹, 赵宗江, 余仁欢. 健脾祛湿和络方治疗难治性膜性肾病的临床观察[J]. 中华肾病研究电子杂志, 2019, 08(01): 30-37.

Bin Shi, Rongrong Zhang, Xinhui Wang, Ying Liang, Zongjiang Zhao, Renhuan Yu. Efficacy of the traditional Chinese medicine Jianpi-Qushi-Heluo formula in treatment of patients with refractory idiopathic membranous nephropathy[J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2019, 08(01): 30-37.

目的

探讨健脾祛湿和络方治疗脾虚水湿血瘀证难治性膜性肾病患者的有效性及安全性。

方法

入选病例来自2013年10月至2017年1月就诊于中国中医科学院西苑医院肾病科门诊及住院的18例经肾穿刺明确诊断为特发性膜性肾病(IMN)、经标准治疗无效、中医辨证属脾虚水湿血瘀证的难治性膜性肾病患者。健脾祛湿和络方由生黄芪、炒白术、汉防己、当归等成分组成，疗程24周，随访24周。随访期间，完全缓解患者停用健脾祛湿和络方，其余患者继续本方治疗。主要观察指标为24 h尿蛋白定量，次要疗效指标为中医证积分变化、血清白蛋白、血肌酐、估算的肾小球滤过率(eGFR)。同时观察不良事件的发生。采用SPSS 21. 0软件包进行统计学分析。

结果

健脾祛湿和络方治疗至24周时较基线水平，尿蛋白下降(t＝4.493，P＝0.041)、中医证候积分降低( t＝－13.872，P＝0.033)，血白蛋白升高(t＝2.434, P＝0.018)，并随着治疗周期延长，其疗效更显著：随访至48周时与24周的24 h尿蛋白定量、中医证候积分下降差值、血白蛋白升高差值比较差异有统计学意义(F＝29.45，P＝0.043; F＝64.32，P＝0.010；F＝54.24，P＝0.028)。随访48周的西医指标总缓解率高于24周的总缓解率(83.3%与66.7%，χ2 ＝15.635，P<0.05)。48周的总有效率高于24周的总有效率(94.4%与88.9%，χ2＝1.843，P>0.05)。

结论

健脾祛湿和络方治疗难治性膜性肾病在降低尿蛋白及减轻临床症状方面疗效显著，且有更好的安全性。

关键词: 难治性膜性肾病, 健脾祛湿和络方, 中医药治疗
Objective

To evaluate the efficacy and safety of the traditional Chinese medicine (TCM) Jianpi-Qushi-Heluo formula (JPQSHLF) in the treatment of patients with refractory membranous nephropathy of the TCM spleen-deficiency dampness blood-stasis syndrome.

Methods

The selected 18 cases, admitted to the Department of Nephrology, Xiyuan Hospital of China Academy of Chinese Medical Sciences from October 2013 to January 2017, were diagnosed as idiopathic membranous nephropathy (IMN) by renal biopsy. As standard treatment proved to be invalid, the disease in these patients was also called refractory membranous nephropathy, belonging to the TCM spleen-deficiency dampness blood-stasis syndrome. The JPQSHLF was composed of astragalus root, fried atractylodes, Stephania tetrandra, and angelica, etc. The JPQSHLF was administered orally twice a day for 24 weeks, and the patients were followed up for 24 weeks. The main observation was 24h urine protein quantitation, while the secondary observations were TCM syndrome score changes, serum albumin, serum creatinine, and estimated glomerular filtration rate (eGFR), and the occurrences of adverse events were also observed. The SPSS 21.0 software was used for statistical analysis.

Results

The JPQSHLF reduced urinary protein significantly (-2.96±2.24, P<0.05), decreased TCM syndrome scores (-16.88±5.61, P<0.05), increased serum albumin level (10.35±5.83, P<0.05). And with the extension of the treatment cycle, its efficacy was more significant. After 48 weeks of the treatment, the differences in 24 h urine protein quantitation decline, TCM syndrome scores decline (-3.99±2.64, F=29.45; 18.14±6.37, F=64.32) and serum albumin elevation (15.08±7.81, F=54.24) were all greater than those after 24 weeks of the treatment (P< 0.05), but the differences in serum creatinine and eGFR levels were not statistically significant (P> 0.05). The total remission rate of indices in western medicine after 48 weeks of treatment was higher than that after 24 weeks of treatment (83.3% vs 66.7%, χ2=15.635, P< 0.05). The total effective rate after 48 weeks of treatment was higher than that after 24 weeks of treatment (94.4% vs 88.9%, χ2=1.843, P> 0.05).

Conclusion

During the treatment of refractory membranous nephropathy, the JPQSHLF had significant efficacy in reducing urinary protein and alleviating clinical symptoms, and had better safety as well.

Key words: Refractory membranous nephropathy, Jianpi-Qushi-Heluo formula, Treatment of traditional Chinese medicine
表1 难治性膜性肾病患者临床特征、基线尿蛋白量及血清白蛋白水平
患者序号 年龄(年) 性别(女/男) 病程(月) 病理分期(Ⅰ-Ⅳ) 初始治疗 疗程(月) 疗效 ACEI/ARB 24 h尿蛋白量(g/d) 血白蛋白(g/L)
1 47 男 10 Ⅰ cCTX/GC 9 抵抗 厄贝沙坦 4.40 27.90
2 62 女 12 Ⅱ CsA/GC 10 不耐受 贝那普利 5.60 22.50
3 44 男 14 Ⅱ CsA/GC 12 复发 厄贝沙坦 4.47 24.20
4 49 女 8 Ⅰ-Ⅱ cCTX/GC 7 抵抗 雷米普利 4.00 25.30
5 45 女 16 Ⅱ cCTX/GC 10 抵抗 氯沙坦 7.28 22.10
6 26 男 15 Ⅱ TAC 7 不耐受 缬沙坦 4.80 23.70
7 40 男 28 Ⅰ TAC 12 不耐受 厄贝沙坦 5.72 25.92
8 51 男 32 Ⅱ CsA/GC 12 复发 厄贝沙坦 10.00 19.00
9 17 男 29 Ⅰ-Ⅱ cCTX/GC 15 抵抗 贝那普利 6.17 24.00
10 36 男 18 Ⅰ CsA/GC 10 复发 氯沙坦 3.10 27.10
11 28 女 30 Ⅱ CsA/GC 8 复发 厄贝沙坦 5.10 24.50
12 43 女 27 Ⅱ cCTX/GC 10 抵抗 缬沙坦 6.08 26.30
13 54 男 17 Ⅰ-Ⅱ CsA/GC 11 抵抗 缬沙坦 5.08 24.20
14 57 男 19 Ⅰ cCTX/GC 8 复发 雷米普利 4.20 23.70
15 61 男 8 Ⅰ CsA/GC 6 抵抗 厄贝沙坦 13.00 15.80
16 32 女 10 Ⅰ cCTX/GC 10 抵抗 氯沙坦 4.48 27.10
17 54 女 16 Ⅱ TAC 8 不耐受 厄贝沙坦 5.72 25.92
18 35 女 15 Ⅱ CsA/GC 12 不耐受 贝那普利 13.0 15.80
表2 难治性膜性肾病患者治疗期间各随访时间点中医证候积分及检验指标变化情况(±s)
随访时间(周) 例数 中医证候积分(分) 24 h尿蛋白量(g ) Scr(μmol/L) eGFR(ml/(min·1.73 m2) ALB(g/L)
0 18 24.42±3.96 6.23±2.87 80.33±26.43 96.48±28.91 23.61±3.53
4 18 17.16±5.21 4.13±1.42 79.32±23.13 95.38±27.73 26.51±7.64
12 18 11.81±4.65 3.93±1.68 77.21±19.24 94.62±25.33 29.96±9.39
24 18 7.54±3.02 3.10±1.96 71.07±20.31 103.53±29.06 33.67±11.36
48 18 6.28±2.63 1.96±1.25a 78.56±21.96 101.17±28.09 38.72±8.60
24周与基线比较 ? ? ? ? ? ?
t值 ? －13.872 4.493 0.778 －1.765 2.434
P值 ? 0.033 0.041 0.731 0.639 0.018
48周与基线比较 ? ? ? ? ? ?
t值 ? －15.481 5.261 0.504 －1.972 －5.098
P值 ? 0.018 0.024 0.843 0.871 0.010
图1 激素和(或)免疫抑制剂治疗后及健脾祛湿活络方治疗后24 h尿蛋白定量水平变化曲线
图2 激素和(或)免疫抑制剂治疗后及健脾祛湿活络方治疗后血清白蛋白水平变化曲线
图3 激素和(或)免疫抑制剂治疗后及健脾祛湿活络方治疗后血肌酐水平变化曲线
表4 难治性膜性肾病患者治疗24周、48周时中医证候积分及检验指标与基线水平的差值比较(±s)
随访时间(周) 中医证候积分(分) 24 h尿蛋白量(g ) Scr(μmol/L) eGFR(ml/(min·1.73 m2) ALB(g/L)
24 －16.88±5.61 －2.96±2.24 －7.24±3.72 7.05±3.62 10.35±5.83
48 －18.14±6.37 －3.99±2.64 －5.39±3.13 4.69±2.98 15.08±7.81
F值 64.32 29.45 132.86 96.32 54.24
P值 0.010 0.043 0.872 0.673 0.028
表5 难治性膜性肾病患者治疗24周、48周时临床总缓解率比较
随访时间(周) 例数 疗效判定 总缓解率
完全缓解[例(%)] 部分缓解[例(%)] 例数 百分率(%)
24 18 2(11.1) 10(55.6) 12 66.7
48 18 4(22.2) 11(61.1) 15 83.3
χ2值 ? ? ? ? 15.635
P值 ? ? ? ? 0.038
表6 难治性膜性肾病患者治疗24周、48周时中医证候总有效率比较
时间(周) 例数 疗效判定 总缓解率
显效[例(%)] 有效[例(%)] 无效[例(%)] 例数 百分率(%)
24 18 12(66.7) 4(22.2) 2(11.1) 16 88.9
48 18 15(83.3) 2(11.1) 1(5.6) 17 94.4
χ2值 ? ? ? ? ? 1.843
P值 ? ? ? ? ? 0.774
表3 难治性膜性肾病患者治疗12周、24周及随访24周后主要实验室指标
患者序号 治疗12周 治疗24周 随访24周
24 h尿蛋白量(g ) ALB(g/L) Scr(μmol/L) 24 h尿蛋白量(g ) ALB(g/L) Scr(μmol/L) 24 h尿蛋白量(g ) ALB(g/L) Scr(μmol/L)
1 6.13 20.20 74.10 6.18 20.40 74.1 3.59 35.2 97.00
2 2.80 26.70 89.31 5.70 18.00 126.0 3.75 18.80 142.02
3 2.82 37.90 96.00 1.60 40.00 80.0 1.13 41.00 93.00
4 2.65 37.50 70.00 0.19 46.10 70.0 0.28 47.00 72.00
5 5.07 24.66 74.00 2.87 32.89 60.0 1.33 45.00 57.00
6 3.08 29.30 72.00 1.16 44.60 70.0 1.60 44.32 77.00
7 3.18 34.54 53.00 3.78 34.97 60.0 2.78 40.00 60.00
8 6.92 25.40 92.00 3.34 28.10 89.0 2.11 38.60 87.00
9 4.58 30.40 67.00 1.63 46.60 74.00 0.17 47.36 79.00
10 1.45 43.00 52.70 0.23 49.00 44.5 0.21 49.00 52.00
11 2.00 44.50 69.00 1.80 41.40 52.0 1.13 45.00 76.00
12 3.44 30.60 74.00 3.25 39.40 44.0 1.78 42.00 63.00
13 2.47 41.80 63.70 1.58 39.70 56.3 2.45 39.70 60.00
14 6.80 14.80 67.00 6.20 14.50 70.0 3.30 21.80 66.00
15 5.53 15.40 68.00 5.20 18.00 52.0 3.32 29.63 57.00
16 3.14 32.70 82.00 2.17 39.5 75.4 0.27 43.00 80.20
17 3.179 34.54 89.00 3.78 34.97 83.0 2.78 40.00 95.00
18 5.53 15.4 137.00 5.2 18 99.0 3.316 29.63 101.00
[1]
Zhou FD,Zhao MH,Zou WZ, et al. The changing spectrum of primary glomerular diseases within 15years: a survey of 3331 patients in a single Chinese centre [J]. Nephrol Dial Transplant, 2009, 24 (3): 870-876.
[2]
Zhu P,Zhou FD,Wang SX et al., Increasing frequency of idiopathic membranous nephropathy in primary glomerular disease: a 10-year renal biopsy study from a single Chinese nephrology centre [J]. Nephrology (Carlton), 2015, 20(8): 560-566.
[3]
Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO clinical practice guideline for glomerulonephritis [J]. Kidney Int Suppl, 2012, 2(2): 139-274.
[4]
Bufvereijken PW,Branten AJ,Wetzels JF, et al. Cytotoxic therapy for membranous nephropathy and renal insufficiency: improved renal survival but high relapse rate [J]. Nephrol Dial Transplant, 2004, 11(23): 1142-1148.
[5]
Jha V,Ganguli A,Saha TK, et al. A randomized, controlled trial of steroids and cyclophosphamide in adults with nephrotic syndrome caused by idiopathic membranous nephropathy [J]. J Am Soc Nephrol, 2007, 8(6): 1899-1904.
[6]
Shiki H,Saito T,Nishitani Y, et al. Prognosis and risk factors for idiopathic membranous nephropathy with nephrotic syndrome in Japan [J]. Kidney Int, 2004, 65(4): 1400-1407.
[7]
郑晓萸. 中药新药临床研究指导原则[M]. 北京：中国医药科技出版社，2002: 156-168.
[8]
Couser WG. Primary membranous nephropathy [J]. Clin J Am Soc Nephrol，2017, 12(6): 983-997.
[9]
Dahan K. Membranous nephropathy: diagnosis，new insights in pathophysiology，and therapeutic approach [J]. Rev Med Interne, 2016, 37(10): 674-679.
[10]
Zhang Q,Huang B,Liu X, et al. Ultrasensitive quantitation of anti-phospholipase A2 receptor antibody as a diagnostic and prognostic indicator of idiopathic membranous nephropathy [J]. Sci Rep, 2017, 7(1): 12049.
[11]
Ramachandran R,Kumar V,Kumar A, et al. PLA2R antibodies, glomerular PLA2R deposits and variations in PLA2R1 and HLA-DQA1 genes in primary membranous nephropathy in South Asians [J]. Nephrol Dial Transplant, 2016, 31(9): 1486-1493.
[12]
Ren S,Wang Y,Xian L, et al. Comparative effectiveness and tolerance of immunosuppressive treatments for idiopathic membranous nephropathy: a network meta-analysis [J]. PLoS One, 2017, 12(9): e0184398.
[13]
Pourcine F，Dahan K，Mihout F，et al. Prognostic value of PLA2R autoimmunity detected by measurement of anti-PLA2R antibodies combined with detection of PLA2R antigen in membranous nephropathy: a single centre study over 14 years [J]. PLoS One, 2017, 12 (3): e0173201.
[14]
Xu NX,Xie QH,Sjn ZX, et al. Renal phospholipase A2 receptor and the clinical features of idiopathic membranous nephropathy [J]. Chin Med J (Engl), 2017, 130(8) : 892-898.
[15]
Katsuno T,Ozaki T,Kim H, et al. Single-dose rituximab therapy for refractory idiopathic membranous nephropathy: a single-center experience [J]. Intern Med, 2017, 56(13): 1679-1686.
[16]
Van de Logt AE，Beerenhout CH，Brink HS，et al. Synthetic ACTH in high risk patients with idiopathic membranous nephropathy: a prospective，open label cohort study [J]. PLoS One, 2015, 10(11): e0142033.
[17]
Hartono C,Chung M,Kuo SF, et al. Bortezomib therapy for nephrotic syndrome due to idiopathic membranous nephropathy [J]. J Nephrol, 2014, 27(1): 103-106.
[18]
Hamilton P,Kanigicherla D,Hanumapura P, et al. Peptide GAM immunoadsorption therapy in primary membranous nephropathy (PRISM): phase II trial investigating the safety and feasibility of peptide GAM immunoadsorption in anti-PLA2R positive primary membranous nephropathy [J]. J Clin Apher, 2018, 33(3): 283-290.
[19]
Liu S，Li X，Li H，et al. Comparison of tripterygium wilfordii multiglycosides and tacrolimus in the treatment of idiopathic membranous nephropathy: A prospective cohort study [J]. BMC Nephrol, 2015, 16(4): 200.
[20]
陈婷，李海坚，麦伟民. 昆仙胶囊联合强的松治疗难治性肾病综合征的临床观察[J]. 中药药理与临床，2011，27(6): 97-99.
[21]
耿建国. 肾性水肿辨证论治探讨[J]. 陕西中医学院学报，2004，27(1): 10- 11.
[22]
余仁欢．聂莉芳教授运用调理脾胃法治疗慢性肾脏病的经验[J]．中华中医药杂志，2010，25(8)：1241-1243.
[23]
李飞静，陈宁．补脾胃泻阴火升阳汤加减治疗慢性肾病蛋白尿30例[J]．浙江中医杂志，2010，45(1)：43.
[24]
胡克杰．张琪研究员从脾胃治疗肾病的经验[J]．黑龙江中医药，1992，(6)：1-3.
[25]
屈欢欢，余仁欢．阴火学说内涵及其对慢性肾病湿热证辨治的启迪[J]．中医杂志，2013，54(3)：255.
[26]
屈欢欢，余仁欢. 东垣阴火学说的内涵及其对慢性肾脏病湿热证治的启迪[J]. 中医杂志，2013, 54(3): 255-257.
[27]
余凌，李惊子，王海燕. 黄芪、当归在肾脏疾病中的应用及其机制研究进展[J]. 中国中西医结合杂志，2001, 21(5)：396-399.
[28]
杨娥，钟艳梅，冯毅凡. 白术化学成分和药理作用的研究进展[J]. 广东药科大学学报，2012, 28(2)：218-221.
[29]
孟立强，屈磊，李晓玫. 黄芪当归合剂对肾间质纤维化的多靶点抑制作用[J]. 中国药理学通报，2006, 22(3)：296-302.
[30]
窦红霞，高玉兰. 防风的化学成分和药理作用研究进展[J]. 中医药信息，2009, 26(2)：15-17.
[31]
马艳春，周波，孙许涛，等. 中药干预肾小球系膜细胞增殖的机制[J]. 中国临床保健杂志，2010, 13(4)：446-448.
[1] 樊均明, 马欣, 沈宏春. 特发性膜性肾病的非免疫抑制治疗及中医药治疗[J]. 中华肾病研究电子杂志, 2015, 04(06): 286-289.
[2] 周相男, 刘殿刚, 刘春涛. 胃食管反流病的中医药应用进展[J]. 中华胃食管反流病电子杂志, 2022, 09(02): 103-108.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号