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

Mikyung Kim; Chang-ho Han; Kim, Mikyung; Han, Chang-ho

doi:10.13048/jkm.23042

JKM > Volume 44(3); 2023 > Article

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

Review Article

The Journal of Korean Medicine 2023; 44(3): 201-224.

Published online: September 1, 2023

DOI: https://doi.org/10.13048/jkm.23042

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

Mikyung Kim¹

, Chang-ho Han²

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 July 22, 2023 Revised August 14, 2023 Accepted August 17, 2023

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)

(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)

Table 1

Characteristics of Included Studies

Study ID	Participants					Intervention							Outcomes

	Gender (M/F)	Age	Baseline Hb (g/L)	PI	Formulation	Dose^a	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
Cheng 05	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 pack^b	2	16 wk		O	O	O	O	O
Cheng 14			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
Fang 11	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	Y^c	Decoction	1 pack	2	16 wk		O	O	O		O	EPO, BUN, Cr
Huang 22	CG: 31/29	CG: 61.8±2.2	CG: 71.1±2.2												EPO, BUN, Cr

Jia 21	Total: 33/27	Total: 46.57±2.62	TG: 64.78±15.52	ND	Capsule	3.6 to 2.7 g^e	3	12 wk		O	O	O	O	O
Jia 21			CG: 64.46±15.56

Ma 14	TG: 16/14	TG: 52.17±7.32	TG: 62.24±8.36	Y^d	Pill	30 g	5	8 wk	O	O	O			O	EPO, hs-CRP, IL-6, TNF-α
Ma 14	CG: 15/15	CG: 55.96±6.97	CG: 63.98±8.46												EPO, hs-CRP, IL-6, TNF-α

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
Qu 19	CG: 14/11	CG: 57.89±2.51	CG: 65.29±15.84												Albumin, WHOQOL-BREF

* 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.
Study ID/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)
Cheng05^a	DNR	DNR^*	DNR	DNR	DNR	DNR	DNR	DNR	DNR	DNR		DNR

Cheng14^b	4	4	3		4	4		4	2	.2

Fang11^a	DNR	DNR^*	DNR	DNR	DNR	DNR	DNR	DNR	DNR	DNR		DNR

Huang22^b	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

Jia21^c	DNR	DNR^*	DNR	DNR	DNR	DNR	DNR	DNR	DNR	DNR		DNR

Ma14^a	DNR	DNR^*	DNR	DNR	DNR	DNR	DNR	DNR	DNR	DNR		DNR

Qu19^b	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)	serious^a	not serious	not serious	serious^b	MD 0.7 higher (0.57 higher to 0.83 higher)	⨁⨁○○ Low
Hb	489 (7 RCTs)	serious^a	serious^c	not serious	not serious	MD 10.55 higher (6.99 higher to 14.11 higher)	⨁⨁○○ Low
Hct	489 (7 RCTs)	serious^a	serious^c	not serious	not serious	MD 5.16 higher (2.94 higher to 7.38 higher)	⨁⨁○○ Low
SF	429 (6 RCTs)	serious^a	not serious	not serious	not serious	MD 12.08 higher (10.25 higher to 13.92 higher)	⨁ ⨁ ⨁○ Moderate
TS	259 (4 RCTs)	serious^a	not serious	not serious	serious^b	MD 1.91 higher (0.06 higher to 3.77 higher)	⨁⨁○○ Low
TEF	489 (7 RCTs)	serious^a	not serious	serious^d	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.

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