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Original Article • Food Sci. Technol (Campinas) 41 (4) • Oct-Dec 2021 • https://doi.org/10.1590/fst.23620 copy

The benefits and harms of Chinese medicinal herbs for the treatment of rapidly progressive glomerulonephritis in adult patients

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objective

The aim of this review was to assess the benefits and harms of Chinese medicinal herbs for the treatment of rapidly progressive glomerulonephritis (RPGN) in adult patients.

Methods

Our study included only randomized controlled trials (RCTs). We designed a strategy for searching the EMBASE, CENTRAL, PubMed, CBM, CNKI, and VIP. All studies were analyzed using the criteria of the Cochrane Handbook. All studies included were assessed the risk of bias. Review Manager ver. 5.3.5 was used for the data analysis. GRADE profiler was used to evaluate quality.

Results

Two studies were studied (74 Chinese participants were included). We found that compared with supportive therapies combined with specific therapies, Chinese medicinal formulae plus supportive therapies combined with specific therapies significantly reduced the serum creatinine levels (SCr; two studies, 62 participants: mean difference (MD), -145.93 μmol/L; 95% confidence interval (CI), -236.75 to –55.11; I²=0%) and utilization number of methylprednisolone and prednisone (two studies, 74 participants: MD, -1.64 g; 95% CI, -1.87 to -1.40; I²=0%).

Conclusion

Our study suggested that there were insufficient evidences to confirm that the use of Chinese medicinal formulae for adults with RPGN was beneficial and safe.

Keywords:
chinese medicinal herbs; rapidly progressive glomerulonephritis; supportive therapy; specific therapy

Study ID	Herbs (Composition) in three language	Methods of administration
Deng et al. (2004)Deng, Y. Y., Chen, Y. P., Wang, L., Hu, Z.Y., Jin, Y.M., Shen, L.M., Zhu, R., & Zhong, Y.W. (2004). Heat-clearing and Blood-activating prescription for middle-advanced crescent nephritis clinical study. Chinese Journal of Integrated Traditional and Western Medicine, 24(12), 1084-1086.	Self-Developed clear hear and activate blood prescription: Baihuasheshecao (Herba Hedyotidis Diffusae / Spreading Hedyotis Herb), Rendongteng (Caulis Lonicerae / Japanese Honeysuckle Stem), Zihuadiding (Herba Violae / Philippine Violet Herb), Chishao (Radix Paeoniae Rubra / Red Paeony Root), Shengdi (Radix Rehmanniae / Rehmannia Root), Huangjing (Rhizoma Polygonati / Manyflower Solomonseal Rhizome / Siberian Solomonseal Rhizome / King Solomonseal Rhizome), Dangshen (Radix Codonopsis / Pilose Asiabell Root / Moderate Asiabell Root / Szechwon Tangshen Root), Danshen (Radix Salviae Miltiorrhizae / Danshen Root), Zhidahuang (Radix Rumicis / Dock Root), Huoxiang (Herba Agastaches / Wrinkled Gianthyssop Herb).	Oral administration
Wang et al. (2008)Wang, H., Zhang, W. P., & Liao, H. (2008). Integration of traditional Chinese and Western medicine for 21 cases middle-advanced crescent nephritis clinical study. Journal of Sichuan of Traditional Chinese Medicine, 26(4), 57-58.	1.Pattern of accumulation of dampness-heat and blood stasis in the kidney collateral: Baihuasheshecao (Herba Hedyotidis Diffusae / Spreading Hedyotis Herb), Pugongying (Herba Taraxacig / Mongolian Dandelion Herb), Banzhilian (Herba Scutellariae Barbatae / Barbed Skullcap Herb), Rendongteng (Caulis Lonicerae / Japanese Honeysuckle Stem), Zihuadiding (Herba Violae / Philippine Violet Herb), Danshen (Radix Salviae Miltiorrhizae / Danshen Root), Chishao (Radix Paeoniae Rubra / Red Paeony Root), Taoren (Semen Persicae / Peach Seed), Shengdi (Radix Rehmanniae / Rehmannia Root), Mugua (Fructus Chaenomelis / Common Floweringquince Fruit), Zhidahuang (Radix Rumicis / Dock Root), Gancao (Radix Glycyrrhizae / Liquoric Root); 2. Pattern of kidney yin deficiency and blood stasis in the kidney collateral: Shengdi (Radix Rehmanniae / Rehmannia Root), Maidong (Radix Ophiopogonis / Dwarf Lilyturf Tuber), Shanzhuyu (Fructus Corni / Common Macrocarpium Fruit), Huangjing (Rhizoma Polygonati / Manyflower Solomonseal Rhizome / Siberian Solomonseal Rhizome / King Solomonseal Rhizome), Shihu (Herba Dendrobii / Dendrobium), Guiban (Carapax et Plastrum Testudinis / Tortoise Shell), Zhimu (Rhizoma Anemarrhenae / Common Anemarrhena Rhizome), Duzhong (Cortex Eucommiae / Eucommia Bark), Huangbai (Cortex Phellodendri / Amur Corktree Bark), Danshen (Radix Salviae Miltiorrhizae / Danshen Root), Chishao (Radix Paeoniae Rubra / Red Paeony Root), Zhidahuang (Radix Rumicis / Dock Root); 3.Pattern of dual deficiency of the spleen-kidney and blood stasis in the kidney collateral: Huangqi (Radix Astragali / Root), Huaishanyao (Rhizoma Diosscoreae / Common Yam Rhizome / Wingde Yan Rhizome), Chuanxiong (Rhizoma Chuanxiong / Szechuan Lovage Rhizome), Gegen (Radix Puerariae / Kudzuvine Root), Huangjing (Rhizoma Polygonati / Manyflower Solomonseal Rhizome / Siberian Solomonseal Rhizome/King Solomonseal Rhizome), Shanzhuyu (Fructus Corni / Common Macrocarpium Fruit), Xianlingpi (Herba Epimedii / Epimedium Herb), Bajitian (Radix Morindae Officinalis / Medicinal Indianmulberry Root), Taoren (Semen Persicae / Peach Seed), Honghua (Flos Carthami / Safflower), Baizhu (Rhizoma Atractylodis Macrocephalae / Largehead Atractylodes Rhizome), Zhidahuang (Radix Rumicis / Dock Root).	Oral administration

Study	Parts	Contents
Deng et al. (2004)Deng, Y. Y., Chen, Y. P., Wang, L., Hu, Z.Y., Jin, Y.M., Shen, L.M., Zhu, R., & Zhong, Y.W. (2004). Heat-clearing and Blood-activating prescription for middle-advanced crescent nephritis clinical study. Chinese Journal of Integrated Traditional and Western Medicine, 24(12), 1084-1086. [18]	Methods	Randomized controlled trial (RCT): randomization mentioned, described in detail. Allocation concealment: not mentioned. Follow-up: not mentioned. Study duration: 3 months. Parallel/crossover/factorial RCT: parallel RCT. Randomization method: random number table. Blinding: no detailed information on blinding was offered. ITT: Not mentioned.
	Participants	Setting: outpatients. Country: China. Number (randomized/analyzed): treatment group (16/16); control group (16/16). Treatment group: 16 (6 males; 37.5%; 10 females; 62.5%), age 28 - 57 (average 36.1 ± 18.3) years old; disease duration: 2 – 13 (average 0.87 ± 0.62) months. Control group: 16 (7 males; 43.8%; 9 females; 56.2%), age 31 – 76 (average 37.4 ± 17.5) years old; disease duration: 2 – 13 (average 0.87 ± 0.62) months. Biopsy-proven membranous nephropathy (types I, II and III).
	Interventions	Treatment group: Self-Developed clear hear and activate blood prescription plus supportive therapies combined with specific therapies. Self-Developed clear hear and activate blood prescription: Baihuasheshecao 30 g, Rendongteng 30 g, Zihuadiding 30 g, Chishao 15 g, Shengdi 15 g, Huangjing 15 g, Dangshen 30 g, Danshen 30 g, Zhidahuang 12 g, and Huoxiang 12 g boiled in 3 L of water and decocted to 300 mL. Orally twice daily (bid)/ one dose daily for 3 months. Supportive therapies: Consistent with the control group. Specific therapies: 15 cases were given methylprednisolone shock treatment (dose of 160–480mg/d) for 3 days, with the dose gradually reduced afterward; they were then switched to oral prednisone 0.8–1.0mg/kg/d after 7–14 days. The prednisone dose was then reduced according to the conventional reduction method. While on the reduced prednisone dose, four cases also underwent cyclophosphamide shock treatment 1.5g/d oral, and eight also underwent cyclophosphamide shock treatment 0.8g/month. In the treatment process, only one case did not use immunosuppressant therapy. Control group: supportive therapies combined with specific therapies. Supportive therapies including blood pressure control using amlodipine besylate tablets 5–10 mg/d, subcutaneous erythropoietin 4000–6000 U/week when Hb ≤ 90 g/L, and hemodialysis when SCr > 707 μm. Specific therapies: 16 cases were given methylprednisolone shock treatment (dose of 320–1000 mg/d) for 3 days, with the dose gradually reduced afterward; they were then switched to oral prednisone 0.8–1.0 mg/kg/d after 7–14 days. The prednisone dose was then reduced according to the conventional reduction method. While on the reduced prednisone dose, three patients were also given mycophenolate mofetil 1.5–2.0 g/d oral, and 11 cases also underwent cyclophosphamide shock treatment 0.8 g/ month. In the treatment process, 16 patients used immunosuppressant therapy.
	Outcomes	1. ESKD; 2. SCr, BUN; 3. Hb, HCT; 4. Utilization number of immunosuppressive agents (including Methylprednisolone and prednisone, Mycophenolate Mofetil, and Cyclophosphamide); 5. Oliguria or anuria remission.
	Notes	1. Mortality: not mentioned; 2. ALT, AST: not mentioned; 3. 24 hour urine volume return to normal time: not mentioned; 4. Quality of life: not mentioned; 5. Tongue coat and pulse condition: not mentioned; 6. Economic index: not mentioned; 7. Adverse events: not mentioned; 8. Withdrawal: not mentioned; 9. Project support: not mentioned; 10. Overall, participant demographic data were similar between groups; 11. The protocol: not mentioned; 12. Informed consent: not mentioned, but we confirmed by telephone that an informed consent form was obtained from each participant; 13. Ethics committee approval: not mentioned.
Wang et al., 2008Wang, H., Zhang, W. P., & Liao, H. (2008). Integration of traditional Chinese and Western medicine for 21 cases middle-advanced crescent nephritis clinical study. Journal of Sichuan of Traditional Chinese Medicine, 26(4), 57-58. [19]	Methods	RCT: randomization mentioned, described in detail. Allocation concealment: not mentioned, but a telephone interview with the author revealed that randomization method described could not allow investigators/participants to know or influence intervention group before eligible participant entered in the study. Follow-up: not mentioned. Study duration: 3 months. Parallel/crossover/factorial RCT: parallel RCT. Randomization method: random number table. Blinding: no detailed information on blinding was offered. A telephone interview with the author revealed that participants did not know drugs used status and blinding of outcome assessment was not used. ITT: Not mentioned
	Participants	Setting: outpatients. Country: China. Number (randomized/analyzed): treatment group (21/21); control group (21/21). Treatment group: 21 (12 males; 57.1%; 9 females; 42.9%), age 25 - 57 (average 34.6 ± 17.3) years old; disease duration: 3 – 15 (average 0.88 ± 0.65) months. Control group: 21 (11 males; 52.4%; 10 females; 47.6%), age 27-56 (average 35.4 ± 18.2) years old; disease duration: 2-14 (average 0.84 ± 0.62) months. Biopsy proven membranous nephropathy (types I, II and III).
	Interventions	Treatment group: Chinese medicinal herbs formulae plus supportive therapies combined with specific therapies. 1.Pattern of accumulation of dampness-heat and blood stasis in the kidney collateral: Baihuasheshecao 20 g, Pugongying 12 g, Rendongteng 12 g, Zihuadiding 15 g, Danshen 15 g, Chishao 12 g, Taoren 12 g, Shengdi 18 g, Mugua 12 g, Zhidahuang 6 g, Gancao 6 g; 2. Pattern of kidney yin deficiency and blood stasis in the kidney collateral: Shengdi 18 g, Maidong 12 g, Shanzhuyu 10 g, Huangjing 15 g, Shihu 15 g, Guiban 20 g, Zhimu 12 g, Duzhong 15 g, Huangbai 12 g, Danshen 15 g, Chishao 12 g, Zhidahuang 6 g; 3. Pattern of dual deficiency of the spleen-kidney and blood stasis in the kidney collateral: Huangqi 20 g, Huaishanyao 18 g, Chuanxiong 10 g, Gegen 15 g, Huangjing 15 g, Shanzhuyu 12 g, Xianlingpi 12 g, Bajitian 12 g, Taoren 12 g, Honghua 6 g, Baizhu 15 g, Zhidahuang 6 g. Supportive therapies: Consistent with the control group. Specific therapies: 19 cases were given methylprednisolone shock treatment (dose of 160–480mg/d) for 3 days, with the dose gradually reduced afterward; they were then switched to oral prednisone 0.8–1.0mg/kg/d after 7–14 days. The prednisone dose was then reduced according to the conventional reduction method. While on the reduced prednisone dose, five cases were also given mycophenolate mofetil 1.5g/d oral, and nine cases also underwent cyclophosphamide shock treatment 0.8g/ month. In the treatment process, 2 causes did not use immunosuppressant therapy. Control group: supportive therapies combined with specific therapies. Supportive therapies including blood pressure control by using amlodipine besylate tablet 5–10 mg/d, subcutaneous erythropoietin 4000–6000U/week when Hb ≤ 90 g/L, and hemodialysis when SCr > 707μm. Specific therapies: 21 cases were given methylprednisolone shock treatment (dose of 320–1000mg/d) for 3 days, with the dose gradually reduced afterward; they were then switched to oral prednisone 0.8–1.0mg/kg/d after 7–14 days. The prednisone dose was then reduced according to the conventional reduction method. While on the reduced prednisone dose, three cases were also given mycophenolate mofetil 1.5-2.0g/d oral, 11 cases also underwent cyclophosphamide shock treatment 0.8g/ month. In the treatment process, 21 cases used immunosuppressant therapy.
	Outcomes	1. ESKD; 2. SCr, BUN; 3. Hb, HCT; 4. Utilization number of immunosuppressive agents (including Methylprednisolone and prednisone, Mycophenolate Mofetil, and Cyclophosphamide); 5. Oliguria or anuria remission.
	Notes	1. Mortality: not mentioned; 2. ALT, AST: not mentioned; 3. 24 hour urine volume return to normal time: not mentioned; 4. Quality of life: not mentioned; 5. Tongue coat and pulse condition: not mentioned; 6. Economic index: not mentioned; 7. Adverse events: not mentioned; 8. Withdrawal: not mentioned; 9. Project support: not mentioned; 10. Overall, participant demographic data were similar between groups; 11. The protocol: not mentioned; 12. Informed consent: not mentioned, but an informed consent form was obtained from each participant by telephone confirmed; 13. Ethics committee approval: not mentioned.

Chinese medicinal herbs plus supportive therapies combined with specific therapies versus supportive therapies combined with specific therapies for rapidly progressive glomerulonephritis in adults
Patient or population: patients with rapidly progressive glomerulonephritis in adults Settings: inpatients and outpatients Intervention: Chinese medicinal herbs plus supportive therapies combined with specific therapies versus supportive therapies combined with specific therapies
Outcomes	Illustrative comparative risks^* * The basis for the assumed risk (e.g. the median control group risk across studies) was provided in footnotes. The corresponding risk (and its 95% CI) was based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval. RR: Risk ratio. GRADE Working Group grades of evidence: high quality, further research was very unlikely to change our confidence in the estimate of effect; moderate quality, further research was likely to have an important impact on our confidence in the estimate of effect and may change the estimate; low quality, further research was very likely to have an important impact on our confidence in the estimate of effect and was likely to change the estimate; very low quality, we were very uncertain about the estimate. 1 High risk of detection bias; 2 Few studies included; 3 Two studies included. (95% CI)		Relative effect (95% CI)	Number of Participants (studies)	Quality of the evidence (GRADE)	Comments
Outcomes	Assumed risk	Corresponding risk	Relative effect (95% CI)	Number of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Control Supportive combined with specific therapies	Chinese medicinal herbs plus supportive therapies combined with specific therapies versus supportive therapies combined with specific therapies
ESKD	Study population		RR 0.5 (0.17 to 1.51)	74 (2 studies)	⊕⊕⊝⊝ low^1,2	Important
	216 per 1000	108 per 1000 (37 to 326)
	Moderate
	228 per 1000	114 per 1000 (39 to 344)
SCr		The mean SCr in the intervention groups was 145.93 lower (236.75 to 55.11 lower)		62 (2 studies)	⊕⊕⊝⊝ low^1,2	Important
BUN		The mean BUN in the intervention groups was 4.45 lower (9 lower to 0.11 higher)		62 (2 studies)	⊕⊕⊝⊝ low^1,3	Important
Hb		The mean Hb in the intervention groups was 0.19 higher (20.87 lower to 21.25 higher)		74 (2 studies)	⊕⊕⊝⊝ low^1,3	Important
HCT		The mean HCT in the intervention groups was 0.39 lower (5.91 lower to 5.13 higher)		74 (2 studies)	⊕⊕⊝⊝ low^1,3	Important
methylprednisolone and prednisone		The mean methylprednisolone and prednisone in the intervention groups was 1.64 lower (1.87 to 1.4 lower)		74 (2 studies)	⊕⊕⊝⊝ low^1,3	Important
cyclophosphamide		The mean cyclophosphamide in the intervention groups was 0.87 lower (1.95 lower to 0.21 higher)		74 (2 studies)	⊕⊕⊝⊝ low^1,3	Important
mycophenolate		The mean mycophenolate in the intervention groups was 5.63 higher (19.86 lower to 31.12 higher)		74 (2 studies)	⊕⊕⊝⊝ low^1,3	Important

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