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Volume 40 Issue 5
Sep.  2022
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ZHAO Linna, LIU Li, LI Hongyan, SUN Wencai, WU Wen, DONG Xuebin. Observation on the effect of Kunxian capsule combined with candesartan cilexetil in the treatment of chronic nephritis with hypertension[J]. Journal of Pharmaceutical Practice and Service, 2022, 40(5): 481-484. doi: 10.12206/j.issn.2097-2024.202105112
Citation: ZHAO Linna, LIU Li, LI Hongyan, SUN Wencai, WU Wen, DONG Xuebin. Observation on the effect of Kunxian capsule combined with candesartan cilexetil in the treatment of chronic nephritis with hypertension[J]. Journal of Pharmaceutical Practice and Service, 2022, 40(5): 481-484. doi: 10.12206/j.issn.2097-2024.202105112

Observation on the effect of Kunxian capsule combined with candesartan cilexetil in the treatment of chronic nephritis with hypertension

doi: 10.12206/j.issn.2097-2024.202105112
  • Received Date: 2021-05-24
  • Rev Recd Date: 2022-01-05
  • Available Online: 2022-09-29
  • Publish Date: 2022-09-25
  •   Objective  To investigate the effect of Kunxian capsule combined with candesartan axetil on blood pressure, renal function, blood lipids and inflammatory factors in patients with chronic glomerulonephritis complicated with hypertension.   Methods  101 patients with chronic glomerulonephritis who were admitted to our hospital from November 2017 to December 2019 were selected and randomly divided into observation group (51 cases) and control group (50 cases). The control group was treated with candesartan cilexetil on the basis of conventional treatment, and the observation group was treated with Kunxian capsule on the basis of the control group. The clinical efficacy and adverse reactions of the two groups were compared.   Results  The total effective rate of the observation group was significantly higher than that of the control group (P<0.05). After treatment, the blood pressure, renal function indexes (24 h Upro, BUN, Scr), blood lipid indexes (TG, TC, LDL-C), and inflammatory factors of the two groups (IL-6, hs-CRP) significantly decreased, and the observation group was significantly lower than the control group (P<0.05). After treatment, the blood lipid index HDL-C of the two groups increased significantly, and the blood lipid index HDL-C of the observation group was significantly higher than that of the control group (P<0.05).   Conclusion  Kunxian capsule combined with candesartan axetil can enhance the clinical efficacy, improve renal function, regulate blood lipids and reduce inflammation in patients with chronic glomerulonephritis complicated with hypertension.
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    [5] 吴炜飞, 程志群, 施向东. 雷公藤多苷联合缬沙坦治疗慢性肾小球肾炎合并高血压患者的临床疗效及对炎症因子的影响[J]. 中国生化药物杂志, 2016, 36(8):101-104.
    [6] 华斐. 雷公藤多甙片对慢性肾小球肾炎患者血清IL-6 、IL-8及T细胞亚群的影响[J]. 国际泌尿系统杂志, 2019, 39(6):1077-1080. doi:  10.3760/cma.j.issn.1673-4416.2019.06.032
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    [8] SETHI S, FERVENZA FC. Standardized classification and reporting of glomerulonephritis[J]. Nephrol Dial Transplant,2019,34(2):193-199. doi:  10.1093/ndt/gfy220
    [9] 巩昭勇, 黄芳, 薛丕良, 等. 活血益肾汤联合氯沙坦钾治疗慢性肾小球肾炎疗效及对血脂和炎症反应的影响[J]. 现代中西医结合杂志, 2019, 28(23):2587-2589. doi:  10.3969/j.issn.1008-8849.2019.23.021
    [10] 毛娅妮, 田少江. 补肾清利活血汤联合奥美沙坦酯治疗慢性肾小球肾炎疗效观察[J]. 现代中西医结合杂志, 2017, 26(10):1111-1113. doi:  10.3969/j.issn.1008-8849.2017.10.031
    [11] ZHOU A, YU L, LI J, et al. Renal protective effects of blocking the intrarenal renin-angiotensin system: angiotensin II type I receptor antagonist compared with angiotensin-converting enzyme inhibitor[J]. Hypertens Res,2000,23(4):391-397. doi:  10.1291/hypres.23.391
    [12] URATA H, KINOSHITA A, PEREZ D M, et al. Cloning of the gene and cDNA for human heart chymase[J]. J Biol Chem,1991,266(26):17173-17179. doi:  10.1016/S0021-9258(19)47355-9
    [13] 涂晓, 杨梦蝶, 李亚妤, 等. 昆仙胶囊与雷公藤多苷片治疗慢性肾脏病的疗效及安全性比较[J]. 浙江中医药大学学报, 2021, 45(6):582-587,602.
    [14] REMUZZI A, PERICO N, SANGALLI F, et al. ACE inhibition and ANG II receptor blockade improve glomerular size-selectivity in IgA nephropathy[J]. Am J Physiol,1999,276(3):F457-F466.
    [15] MACKINNON M, SHURRAW S, AKBARI A, et al. Combination therapy with an angiotensin receptor blocker and an ACE inhibitor in proteinuric renal disease: a systematic review of the efficacy and safety data[J]. Am J Kidney Dis,2006,48(1):8-20. doi:  10.1053/j.ajkd.2006.04.077
    [16] ITO K, IMANISHI M, KITO G. Comparison of the hypotensive effects of TCV-116 and losartan in chronic renal hypertensive dogs[EB/OL]. 1996
    [17] NODA M, MATSUO T, FUKUDA R, et al. Effect of candesartan cilexetil (TCV-116) in rats with chronic renal failure[J]. Kidney Int,1999,56(3):898-909. doi:  10.1046/j.1523-1755.1999.00614.x
    [18] KUROKAWA K, ABE K, SARUTA T, et al. Antiproteinuric effect of candesartan cilexetil in patients with chronic glomerulonephritis[J]. J Renin Angiotensin Aldosterone Syst,2002,3(3):167-175. doi:  10.3317/jraas.2002.037
    [19] 邓晓蔚, 熊有明, 张维, 等. 昆仙胶囊联合百令胶囊治疗慢性肾小球肾炎临床研究[J]. 中国药业, 2019, 28(9):53-55. doi:  10.3969/j.issn.1006-4931.2019.09.015
    [20] TANG Y, ZHANG Y, LI L, et al. Kunxian capsule for rheumatoid arthritis: inhibition of inflammatory network and reducing adverse reactions through drug matching[J]. Front Pharmacol,2020,11:485. doi:  10.3389/fphar.2020.00485
    [21] 张宁, 易无庸. 昆仙胶囊临床应用进展[J]. 中医临床研究, 2014, 6(7):147-148. doi:  10.3969/j.issn.1674-7860.2014.07.083
    [22] 张楠, 郭晓琴, 田云凤, 等. 昆仙胶囊对慢性肾小球肾炎的临床疗效观察[J]. 中国中西医结合肾病杂志, 2020, 21(12):1096-1097. doi:  10.3969/j.issn.1009-587X.2020.12.020
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Observation on the effect of Kunxian capsule combined with candesartan cilexetil in the treatment of chronic nephritis with hypertension

doi: 10.12206/j.issn.2097-2024.202105112

Abstract:   Objective  To investigate the effect of Kunxian capsule combined with candesartan axetil on blood pressure, renal function, blood lipids and inflammatory factors in patients with chronic glomerulonephritis complicated with hypertension.   Methods  101 patients with chronic glomerulonephritis who were admitted to our hospital from November 2017 to December 2019 were selected and randomly divided into observation group (51 cases) and control group (50 cases). The control group was treated with candesartan cilexetil on the basis of conventional treatment, and the observation group was treated with Kunxian capsule on the basis of the control group. The clinical efficacy and adverse reactions of the two groups were compared.   Results  The total effective rate of the observation group was significantly higher than that of the control group (P<0.05). After treatment, the blood pressure, renal function indexes (24 h Upro, BUN, Scr), blood lipid indexes (TG, TC, LDL-C), and inflammatory factors of the two groups (IL-6, hs-CRP) significantly decreased, and the observation group was significantly lower than the control group (P<0.05). After treatment, the blood lipid index HDL-C of the two groups increased significantly, and the blood lipid index HDL-C of the observation group was significantly higher than that of the control group (P<0.05).   Conclusion  Kunxian capsule combined with candesartan axetil can enhance the clinical efficacy, improve renal function, regulate blood lipids and reduce inflammation in patients with chronic glomerulonephritis complicated with hypertension.

ZHAO Linna, LIU Li, LI Hongyan, SUN Wencai, WU Wen, DONG Xuebin. Observation on the effect of Kunxian capsule combined with candesartan cilexetil in the treatment of chronic nephritis with hypertension[J]. Journal of Pharmaceutical Practice and Service, 2022, 40(5): 481-484. doi: 10.12206/j.issn.2097-2024.202105112
Citation: ZHAO Linna, LIU Li, LI Hongyan, SUN Wencai, WU Wen, DONG Xuebin. Observation on the effect of Kunxian capsule combined with candesartan cilexetil in the treatment of chronic nephritis with hypertension[J]. Journal of Pharmaceutical Practice and Service, 2022, 40(5): 481-484. doi: 10.12206/j.issn.2097-2024.202105112
  • 慢性肾小球肾炎又称慢性肾炎,是终末期肾病最主要的病因之一[1]。它以蛋白尿、血尿、高血压等为主要临床表现。治疗方法多以对症支持治疗或免疫抑制剂、激素为主 [2]。坎地沙坦酯是一种非肽类血管紧张素受体阻滞剂(ARB),目前在世界各地被广泛用作口服降压药,可有效的改善肾功能,减少24 h尿蛋白(24 h Upro)[3]。昆仙胶囊是一种中成药,因其具有类激素、免疫制剂等作用被广泛应用于临床,多用于风湿性关节炎、肾炎等疾病。据Meta分析报道,昆仙胶囊的不良反应包括生殖毒性、肝损害、肾功能障碍等,但不良反应率明显低于雷公藤片[4]。目前还未确定是否可以联合使用昆仙胶囊和ARB来改善原发性肾小球肾炎的治疗。本研究采用随机对照设计,观察昆仙胶囊联合坎地沙坦酯治疗慢性肾小球肾炎合并高血压患者的疗效及对血脂水平和炎症反应的影响。

    • 2017年11月至2019年12月,我们招募了101名参与者,随机分配到观察组或对照组,对照组50例,观察者51例。患者的基线特征如表1所示,对照组和观察组的年龄、病程等特征均无统计学差异(P>0.05)。

      特征对照组观察组
      n=50n=51
      年龄45.74±9.7544.92±9.68
      男性,n(%)29(58.00%)31(60.78%)
      病程(年)4.64±2.074.12±1.63
      SBP(mmHg)154.24±8.45151.98±7.98
      DBP(mmHg)95.40±4.4696.69±5.27
      24 h尿蛋白(g)1.73±0.631.68±0.56
      Scr(μmol/L)148.01±20.49149.76±21.05
      BUN(mmol/L)11.62±1.6611.90±1.80
      TG(mmol/L)2.10±0.232.02±0.21
      TC(mmol/L)6.25±1.096.31±0.83
      LDL-C(mmol/L)4.21±1.084.26±0.89
      HDL-C(mmol/L)1.10±0.131.12±0.15
      IL-6(pg/ml)171.22±19.47175.28±23.71
      hs-CRP(mg/L)3.58±0.783.57±0.74

      纳入标准[5-6] :符合2010年第十一届全国中西医结合肾病学术会议制订的有关慢性肾小球肾炎的相关诊断标准;有蛋白尿等临床表现。收缩压(SBP)为140~180 mmHg,舒张压(DBP)为90~109 mmHg。

      排除标准:糖尿病;过敏性紫癜性肾炎;系统性红斑狼疮肾炎;透析;肾移植;血压<90/60 mmHg;一直或最近(<1年)使用糖皮质激素、免疫抑制剂治疗;最近2周内有服用保护肾功能,降低胆固醇、三酰甘油、低密度脂蛋白胆固醇,升高高密度脂蛋白胆固醇,缓解炎症的其他中成药或汤剂的;在过去4周内,曾接受RAS阻滞剂治疗的患者;妊娠或哺乳期;大脑、肝脏、心血管或造血系统严重功能障碍,或其它可能影响患者生活的严重疾病;易过敏或已知对药物过敏;以及同期参加另一项临床研究的。

      本院伦理委员会批准了该协议。所有参与者及其家属在接受任何与研究相关的程序之前都将签署书面知情同意书。参与者及其家属将有足够的时间阅读知情同意书,并在提供书面同意之前询问试验的细节。

    • 常规治疗:2组均进行低盐低蛋白饮食、纠正水电解质失调和酸碱平衡紊乱、抗凝等常规治疗。对照组在常规治疗的基础上服用坎地沙坦酯(浙江永宁药业股份有限公司,国药准字H20050323,规格:0.8 mg /片),每次 8 mg, 每日服用1次。治疗组服用昆仙胶囊((广州白云山陈李济药厂有限公司生产,商品名:陈李济,批准文号:国药准字Z20060267,批号:K31010,规格:0.3 g/粒)和坎地沙坦酯。连服12周。如果患者出现过度低血压、慢性肾小球肾炎加重或临床重大不良事件,则停止治疗。治疗前后测量血压(BP)和心率,并进行实验室检查(血液和尿液分析)。饮食习惯不允许发生重大改变。

    • 疗效评定标准[5-6]:显效:临床症状基本消失,血脂、肾功能等指标恢复正常,24 h尿蛋白定量<0.2 g,患者的收缩压/舒张压≤130/85 mmHg;有效:临床症状明显改善,肾功能、血脂等指标改善,24 h尿蛋白定量减少大于40%,收缩压/舒张压仍大于130/85 mmHg,收缩压下降15~30 mmHg;无效:临床症状、血脂、肾功能等指标及24 h尿蛋白定量无明显好转。总有效率=(显效+有效)/总例数×100%。

    • 所有患者治疗前后的血压变化;取清洁中段尿,采用尿液干化学分析仪测24 h尿蛋白;采集空腹静脉血,离心后取血清检测血脂四项水平,及肾功能指标Scr和尿素氮(BUN)、炎症因子(IL-6、hs-CRP)水平。

    • 安全指标将包括白细胞计数的减少、肝功能异常、高钾血症和其他不良事件。不良事件被记录下来,它们与研究药物的可能关联被归类为以下类别之一:相关的、可能不相关的和与研究药物无关的。与研究药物相关的、可能相关的和可能相关的事件被认为是药物不良反应。

    • 所有分析均使用SAS 9.2软件进行。统计学显著性水平设为0.05。计量资料采用($\bar x $±s)表示,描述,组间或组内比较行t检验;计数资料行卡方检验。

    • 治疗后,观察组和对照组的SBP、DBP均显著下降(P<0.05),且观察组显著低于对照组(P<0.05),见表2

      组别SBP(mmHg)DBS(mmHg)
      治疗前治疗后治疗前治疗后
      对照组154.24±8.45138.24±10.38*95.40±4.4684.02±4.71*
      观察组151.98±7.98127.14±12.09*#96.69±5.2778.22±6.72*#
      *P<0.05,与同组治疗前比较;#P<0.05,与对照组治疗后比较。
    • 治疗后,观察组和对照组肾功能指标(24 hUpro、BUN、Scr)均显著下降(P<0.05),且观察组显著低于对照组(P<0.05),见表3

      组别24 Upro(g)Scr(μmol/L)BUN(mmol/L)
      治疗前治疗后治疗前治疗后治疗前治疗后
      对照组1.73±0.630.93±0.58*148.01±20.49105.01±18.32*11.62±1.667.11±1.06*
      观察组1.68±0.560.71±0.13*#149.76±21.0592.76±15.37*#11.90±1.806.29±0.96*#
      *P<0.05,与同组治疗前比较;#P<0.05,与对照组治疗后比较。
    • 治疗12周后,观察组和对照组血脂指标TG、TC、LDL-C均显著下降(P<0.05),且观察组显著低于对照组(P<0.05),;两组血脂指数HDL-C显著升高,且观察组显著高于对照组(P<0.05),见表4

      组别TG(mmol/L)TC(mmol/L)LDL-C(mmol/L)HDL-C(mmol/L)
      治疗前治疗后治疗前治疗后治疗前治疗后治疗前治疗后
      对照组2.10±0.231.65±0.31*6.25±0.785.47±0.59*4.21±1.083.45±0.53*1.10±0.131.31±0.16*
      观察组2.02±0.211.47±0.23*#6.31±0.834.50±0.64*#4.26±0.892.40±0.78*#1.12±0.151.43±0.18*#
      *P<0.05,与同组治疗前比较;#P<0.05,与对照组治疗后比较。
    • 治疗12周后,观察组和对照组炎症因子(IL-6、hs-CRP)均显著下降(P<0.05),且观察组显著低于对照组(P<0.05),见表5

      组别IL-6(pg/ml)Hs-CRP(mg/L)
      治疗前治疗后治疗前治疗后
      对照组171.22±19.47115.22±15.31*3.58±0.782.68±0.64*
      观察组175.28±23.7193.28±15.48*3.57±0.741.75±0.52*
      *P<0.05,与同组治疗前比较;#P<0.05,与对照组治疗后比较。
    • 观察组的总有效率为96.1%(49/51),高于对照组82.0%(41/50),具有统计学意义(χ2=4.27,P=0.039)。且两组均无不良反应的发生,见表6

      组别例数显效有效无效总有效(率)
      对照组5016(32.0%)25(50.0%)9(18.0%)41(82.0%)
      观察组5129(56.9%)20(39.2%)2(3.9%)49(96.1%)*
      *P<0.05,与对照组比较。
    • 慢性肾小球肾炎与免疫介导的炎症性疾病相关,在终末期肾病中频繁发生,严重影响患者的生存。生物学和临床观察的结果表明,它以血尿、蛋白尿、动脉高血压为主要表现 [7-8]。多项研究发现慢性肾炎患者体内尿蛋白、Scr、BUN等肾功能指标升高的同时,伴随血脂异常,炎症因子hs-CRP和IL-6偏高[9-10], 与本临床观察的结果一致。

      治疗慢性肾小球肾炎最为主要的目的是抑制或延缓肾功能的恶化。用于减缓疾病进展的方法是饮食控制和药物控制,常见的治疗药物有肾素-血管紧张素系统阻滞剂,包括血管紧张素转化酶抑制剂(ACEI)和ARBs[11]。与ACEI相比,ARB还可以作为由非ACE途径形成的Ang II的拮抗剂[12]。另一个优点是,与ACEI不同,ARB不影响缓激肽新陈代谢,这意味着这些药物作为不良反应与干咳的发生相关的频率要低得多[13-14]。在各种非糖尿病肾病中,ARBs可以减少24 h Upro,稳定了全身和肾脏的血压,防止肾脏疾病的发展 [15]

      而坎地沙坦酯是ARBs药物中的一种,作为一种降压药已在国际上获得了专家们的广泛认可。该药在多种高血压动物模型的实验结果中发现,其均有降压作用[16],同时也能有效的减少慢性肾小球肾炎患者的尿蛋白,除此之外,也能延缓肾小球硬化的进展,抑制肾小管间质纤维化改变[17]。Kurokawa等发现使用2、4、8 mg剂量的坎地沙坦酯治疗慢性肾小球肾炎12周时,8 mg的疗效最好。坎地沙坦酯可以显著地降低24 h Upro,改善肾功能(Scr和BUN在治疗后显著降低)[18]。用坎地沙坦酯治疗12周时收缩压和舒张压显著下降,这提示,血压的降低程度可能是坎地沙坦酯导致的尿蛋白排泄减少的原因之一[19]。由本临床观察发现坎地沙坦酯可以降血压、显著降低了24 hUpro、BUN、Scr、TG、TC、LDL-C及炎症因子IL-6和hs-CRP,并能显著上调HDL-C水平。但是昆仙胶囊联合坎地沙坦酯治疗的效果比单用坎地沙坦酯的效果更佳。

      昆仙胶囊由昆明山海棠、淫羊藿、菟丝子、枸杞4种中药组成。其中昆明山海棠是最重要的成分,因为它的提取物含有雷公藤内酯醇,具有抗炎、免疫抑制等重要作用;淫羊藿苷是淫羊藿的主要提取物,有抗炎等作用;甜菜碱是枸杞子的重要提取物之一,有造血、保护肝脏等作用;黄酮类为菟丝子最重要的提取物,有护肝等作用[19]。以往的研究表明,昆仙胶囊可以下调慢性肾小球肾炎患者中的炎症因子,抑制炎症反应[20]。张宁等也发现昆仙胶囊能显著抑制炎症因子IL-6、hs-CRP的表达[21]。张楠[22]等发现昆仙胶囊用于治疗慢性肾小球炎症的总有效率高达90%,并且能显著降低Scr、ALT、ALB。

      本研究在昆仙胶囊联合坎地沙坦酯治疗12周后,血压、蛋白尿、肾功能指标、炎症因子、血脂TG、TC、LDL-C显著降低,并且临床疗效总有效率为96.1%,而且这些指标明显优于单独使用坎地沙坦酯。除此之外,本研究并无明显不良反应,表明两者联合治疗慢性肾小球肾炎效果确切,安全可靠。

      综上所述,慢性肾小球肾炎患者在常规治疗的同时加用昆仙胶囊联合坎地沙坦酯治疗可提高临床疗效,改善肾功能,调节血脂,减轻炎症反应。

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