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Gwibi-tang for Renal Anemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Article information

J Korean Med. 2023;44(3):201-224
Publication date (electronic) : 2023 September 1
doi : https://doi.org/10.13048/jkm.23042
Mikyung Kim1orcid_icon, Chang-ho Han2orcid_icon
1Department of Internal Medicine, Dongguk University Ilsan Oriental Medicine Hospital
2Department of Internal Medicine, College of Korean Medicine, Dongguk University
Correspondence to: Chang-ho Han, Dongguk University WISE Campus, 123, Dongdae-ro, Gyeonju-si, Gyeongsangbuk-do, 38066, Tel: +82-54-770-1260, E-mail: hani@dongguk.ac.kr
Received 2023 July 22; Revised 2023 August 14; Accepted 2023 August 17.

Abstract

Objectives

The purpose of this study was to evaluate the effect of Gwibi-tang (GBT) on renal anemia.

Methods

A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to investigate changes in anemia levels before and after oral administration of GBT in patients with renal anemia. Relevant literature published up to May 25, 2023, was searched in 10 academic electronic databases.

Results

Data from 489 patients from 7 RCTs were obtained and analyzed. All participants were receiving erythropoietin-stimulating agent treatment, and most of them were under hemodialysis. Additional administration of GBT to the participants significantly increased the hemoglobin concentration (10.55 g/L, 95% CI 6.99 to 14.11) compared to the control group. Hematocrit, red blood cell count, serum ferritin concentration, transferrin saturation, and the total effective rate for anemia was also significantly higher in the GBT-treated group than in the control group.

Conclusions

This study suggests that GBT may be considered to be a promising option for the effective management of patients with renal anemia under conventional treatment. However, the limitations of this study, including the quantitative and qualitative weakness of the RCTs, the lack of safety-related evidence, and the absence of long-term follow-up data, should be taken into account when interpreting the results of this study.

Keywords: chronic kidney disease; Guipi decoction; Gwibi-tang; Kihi-to; renal anemia
Fig. 1

Flowchart of study search and selection

Fig. 2

Summary of risk of bias of included studies

Fig. 3

Effect of oral administration of Gwibi-tang for renal anemia (Gwibi-tang plus conventional treatment versus conventional treatment)

(A) Red blood cell count (x 1012/L)

(B) Hemoglobin concentration (g/L)

(C) Hematocrit (%)

(D) Serum ferritin concentration (ng/mL)

(E) Transferrin saturation (%)

Fig. 4

Effect of oral administration of Gwibi-tang on total effective rate for renal anemia (Gwibi-tang plus conventional treatment versus conventional treatment)

Characteristics of Included Studies

Prescription Composition of Gwibi-tang Used in Included Studies

Certainty of Evidence Assessed with the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) Methodology

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Article information Continued

Fig. 1

Fig. 1

Flowchart of study search and selection

Fig. 2

Fig. 2

Summary of risk of bias of included studies

Fig. 3

Fig. 3

Effect of oral administration of Gwibi-tang for renal anemia (Gwibi-tang plus conventional treatment versus conventional treatment)

(A) Red blood cell count (x 1012/L)

(B) Hemoglobin concentration (g/L)

(C) Hematocrit (%)

(D) Serum ferritin concentration (ng/mL)

(E) Transferrin saturation (%)

Fig. 4

Fig. 4

Effect of oral administration of Gwibi-tang on total effective rate for renal anemia (Gwibi-tang plus conventional treatment versus conventional treatment)

Table 1

Characteristics of Included Studies

Study ID Participants Intervention Outcomes
Gender (M/F) Age Baseline Hb (g/L) PI Formulation Dosea Frequency Duration RBC Hb Hct SF TS TEF Etc.
Cheng 05 TG: 23/10 TG: 44.65±11.53 TG: 63.22±15.14 ND Pill 18 g 3 12 wk O O O O O O
CG: 22/10 CG: 44.36±9.28 CG: 65.42±14.27
Cheng 14 Total: 51/23 Total: 53±4.5 TG: 63.24±15.21 ND Decoction 1 packb 2 16 wk O O O O O
CG: 65.51±14.29
Fang 11 TG: 16/13 TG: 46.8±10.4 TG: 63.22±15.25 ND Pill 18 g 3 12 wk O O O O O
CG: 18/12 CG: 50.2±13.5 CG: 65.48±14.37
Huang 22 TG: 33/27 TG: 62.2±1.4 TG: 70.8±2.6 Yc Decoction 1 pack 2 16 wk O O O O EPO, BUN, Cr
CG: 31/29 CG: 61.8±2.2 CG: 71.1±2.2
Jia 21 Total: 33/27 Total: 46.57±2.62 TG: 64.78±15.52 ND Capsule 3.6 to 2.7 ge 3 12 wk O O O O O
CG: 64.46±15.56
Ma 14 TG: 16/14 TG: 52.17±7.32 TG: 62.24±8.36 Yd Pill 30 g 5 8 wk O O O O EPO, hs-CRP, IL-6, TNF-α
CG: 15/15 CG: 55.96±6.97 CG: 63.98±8.46
Qu 19 TG: 15/10 TG: 57.65±2.48 TG: 65.36±15.90 ND Decoction 1 pack 2 24 wk O O O O O Albumin, WHOQOL-BREF
CG: 14/11 CG: 57.89±2.51 CG: 65.29±15.84
*

Abbreviations

M: male, F: female, Hb: hemoglobin concentration, PI: pattern identification, RBC: red blood cell count, Hct: hematocrit, SF: serum ferritin, TF: transferrin saturation, TEF: total effective rate, TG: treatment group, CG: control group, ND: not done, wk: week, Y: yes, w: week, EPO: erythropoietin, BUN: blood urea nitrogen, Cr: creatinine, hs-CRP: high sensitive C reactive protein, IL: interleukin, TNF: tumor necrosis factor, WHOQOL-BREF: The World Health Organization Quality of Life brief questionnaire

*

Superscripts

a

dose for 1 day,

b

pack = 貼,

c

qi deficiency and blood stasis (氣血兩虛),

d

spleen deficiency (脾虛) and blood deficiency (血虛),

e

start with 3.6 g/day and reduce to 2.7 g/day when

Table 2

Prescription Composition of Gwibi-tang Used in Included Studies

Study ID/ingredients Astragali Radix Ginseng Radix Atractylodis Rhizoma Alba Poria Cocos Wolf Angelicae Gigantis Radix Longanae Arillus Zyzyphi Spinosae Semen Polygalae radix Aucklandiae Radix Glycyrrhizae Radix Zingiberis Rhizoma Crudus Jujubae Fructurs Other ingredients.
(黃芪) (人蔘) (白朮) (茯 ) (當歸) ( 眼肉) (酸棗仁) (遠志) (木香) (甘草) (生薑) (大棗)
Cheng05a DNR DNR* DNR DNR DNR DNR DNR DNR DNR DNR DNR
Cheng14b 4 4 3 4 4 4 2 .2
Fang11a DNR DNR* DNR DNR DNR DNR DNR DNR DNR DNR DNR
Huang22b 20 15* 15 15 10 20 15 10 10 10 6 6 grains Rehmanniae Radix Preparata (熟地 ) 12, Paeoniae Radix Alba (白芍藥) 10,Polygonati Rhizoma (精) 15
Jia21c DNR DNR* DNR DNR DNR DNR DNR DNR DNR DNR DNR
Ma14a DNR DNR* DNR DNR DNR DNR DNR DNR DNR DNR DNR
Qu19b 30 20* 12 15 12 20 20 10 10 6 Psoraleae Fructus 10 (補骨脂), White Aconi Radix (白附片)10,Citri Pericarpium (陳皮) 10

The number in the table represents the daily dose (gram) of each ingredient.

*

Codonopsis Pilosulae Radix (黨參) was used instead of Panax Ginseng C.A. Meyer.

Abbreviation: DNR, dosage not reported

Superscripts:

a

pill (九芝堂归脾丸(浓缩丸)(湖南九芝堂股份有限公司)),

b

decoction,

c

capsule (归脾胶囊(安徽省先锋制药有限公司))

Table 3

Certainty of Evidence Assessed with the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) Methodology

Outcomes Participants (studies) Risk of bias Inconsistency Indirectness Imprecision Effect size, absolute (95% CI) Certainty
RBC 175 (3 RCTs) seriousa not serious not serious seriousb MD 0.7 higher (0.57
higher to 0.83 higher)		 ⨁⨁○○
Low
Hb 489 (7 RCTs) seriousa seriousc not serious not serious MD 10.55 higher
(6.99 higher to 14.11 higher)		 ⨁⨁○○
Low
Hct 489 (7 RCTs) seriousa seriousc not serious not serious MD 5.16 higher
(2.94 higher to 7.38 higher)		 ⨁⨁○○
Low
SF 429 (6 RCTs) seriousa not serious not serious not serious MD 12.08 higher
(10.25 higher to 13.92 higher)		 ⨁ ⨁ ⨁○
Moderate
TS 259 (4 RCTs) seriousa not serious not serious seriousb MD 1.91 higher
(0.06 higher to 3.77 higher)		 ⨁⨁○○
Low
TEF 489 (7 RCTs) seriousa not serious seriousd not serious 215 more per 1,000
(from 159 more to 254 more)		 ⨁⨁○○
Low
*

Abbreviations

CI: confidence interval, RBC: red blood cell count (x 1012/L), RCT, randomized controlled trial, Hb: hemoglobin concentration (g/L), Hct: hematocrite (%), SF: serum ferritin (ng/mL), TS: transferrin saturation (%), TEF: total effective rate, MD: mean difference

*

Explanations

a

Some concerns were raised about the risk of bias in all included studies.

b

The number of participants included in the meta-analysis is lower than 400.

c

The I2 value was 75% or more.

d

The outcome is not internationally used as an official tool to evaluate the treatment response of renal anemia.