Yi-Shen-Hua-Shi regulates intestinal microbiota dysbiosis and protects against proteinuria in patients with chronic kidney disease: a randomized controlled study

Figures & data

Figure 1. Trial profile.

Table 1. Baseline characteristics and follow-up data of the cohort.

	Total (n = 103)	YSHS intervention group (n = 56)	Control group (n = 47)	p
Age	57(40-66)	61.5(43.5-66.75)	55(33-55)	0.171
Male (%)	61.2	69.6	51.1	0.079
Primary kidney disease (%)
DN	27.2	28.6	25.5	0.45
MN	28.2	19.6	38.3	0.194
IgAN	44.7	51.8	36.2	0.077
CKD stage (%)
CKD stage 1	67	60.7	74.5
CKD stage 2	12.6	14.3	10.6
CKD stage 3	20.4	25	14.9
RAASi (%)
Losartan (%)	99 (96.1)	54 (96.4)	45 (95.7)
Irbesartan (%)	4 (3.9)	2 (3.6)	2 (4.3)
SBP (mmHg)	130(125-140)	130(126-144)	130(124-140)	0.144
DBP (mmHg)	80(80-88)	80(80-83.5)	80(80-90)	0.326
Baseline weight (kg)	72 (63-82)	72 (64-82)	73 (62.25-82)	0.885
Weight after 4-months follow-up (kg)	74 (63-92)	74 (65.5-92)	73 (62-83.5)	0.428
Baseline creatinine (μmol/L)	77(57-107)	86.5(64.5-113.5)	76(52-105)	0.086
Creatinine after 4-months follow-up (μmol/L)	88 (62-113)	88.5 (64-120.75)	84.74 ± 31.14	0.286
Urea (mmol/L)	5.38(4.15-7.98)	4.84(1.04-7.98)	5.45(4.15-8.02)	0.288
Uric acid (μmol/L)	388.3 ± 104.41	410.59 ± 105.04	361.74 ± 98.28	0.05
Baseline albumin (g/L)	36.36(28.54-39.41)	36.46(29.22-39.41)	35.77(24.1-39.91)	0.361
Baseline 24-hour proteinuria excretion (g)	2.49(0.98-3.25)	2.57(1.34-3.36)	1.55(0.66-3.16)	0.128
Albumin increase during follow-up (g/L)	0.02(0-4.61)	1(0-4.77)	0.00(0.00-4.4)	0.129
24-hour proteinuria decrease during follow-up (g/L)	1.25(0.5-2.83)	1.54(0.75-2.82)	0.66(0.17-2.9)	0.022

YSHS: Yi-Shen-Hua-Shi; DN: diabetic nephropathy; MN: membranous nephropathy; CKD: chronic kidney disease; IgAN: IgA nephropathy; RAASi: renin-angiotensin-aldosterone system inhibitor; SBP: systolic blood pressure; DBP: diastolic blood pressure.

Table 2. Baseline characteristics and follow-up data of the cohort stratified by gender.

	Male			Female
	YSHS intervention group (n = 40)	Control group (n = 24)	p	YSHS intervention group (n = 16)	Control group (n = 23)	p
Age	57(36-66)	47.5(33-64.5)	0.501	62.5(56.5-67.75)	57(40-66)	0.067
Primary kidney disease (%)			0.027			0.001
DN	28.2	8.3		31.3
MN	20.5	50		18.8	69.6
IgAN	51.3	41.7		50	30.4
CKD stage (%)			0.694			0.029
CKD stage 1	64.1	66.7		56.3	82.6
CKD stage 2	15.4	8.3		6.3	13
CKD stage 3	20.5	25		37.5	4.3
RAASi (%)			0.067			0.162
Losartan (%)	100	91.7		87.5	100
Irbesartan (%)		8.3		12.5
SBP (mmHg)	130(125-144)	130(120-143)	0.275	140(132.5-148.5)	130(130-137)	0.265
DBP (mmHg)	80(80-84)	81(80-93.5)	0.462	80(80-80)	80(80-86)	0.387
Baseline creatinine (μmol/L)	87(72-114)	80(65-108)	0.515	67(48-97.5)	54(43-74)	0.277
Creatinine after 4-months follow-up (μmol/L)	97(64-134)	104.5(71.25-124.75)	0.831	77(62.5-90)	59(45-73)	0.109
Urea (mmol/L)	4.85(4.16-7.98)	5.93(5.38-8.1)	0.125	4.84(1.13-7.9)	4.53(3.24-7.5)	0.977
Uric acid (μmol/L)	404(358-488)	365.5(333-440)	0.119	338(312-452)	375(259-415)	0.493
Baseline albumin (g/L)	37.42(28.54-40.18)	37.46(24.49-40.69)	0.799	35.12(30.98-36.55)	33.27(24.1-37.61)	0.376
Baseline 24-h proteinuria excretion (g)	2.54(1.25-3.25)	1.35(0.55-3.18)	0.24	2.98(1.85-3.56)	1.8(0.9-2.99)	0.134
Albumin increase during follow-up (g/L)	1(0-5)	0.27(0.00-7.72)	0.898	1.5(0-4.77)	0(0-0)	0.034
24-h proteinuria decrease during follow-up (g/L)	1.33(0.73-2.89)	0.62(0.3-2.55)	0.034	1.97(1.3-2.82)	0.66(0.1-2.99)	0.02

YSHS: Yi-Shen-Hua-Shi; DN: diabetic nephropathy; MN: membranous nephropathy; CKD: chronic kidney disease; IgAN: IgA nephropathy; RAASi: renin-angiotensin-aldosterone system inhibitor; SBP: systolic blood pressure; DBP: diastolic blood pressure.

Figure 2. (A) The rarefaction analysis between the number of samples and the number of OTUs. (B–C) Phylogenetic diversity of the gut microbiome between patients in the control and YSHS group at baseline (C0, T0) and at 4-month follow-up (C1, T1) according to the Sobs and Shannon index. (D) Principal Coordinate Analysis (PCoA) of the gut microbiota of patients in the control group at baseline (C0) and at 4-month follow-up (C1). (E) Principal Coordinates Analysis (PCoA) of the gut microbiota of patients in the YSHS group at baseline (T0) and 4-month follow-up (T1).

Figure 3. (A) Venn diagram showing the overlaps between the patients in the control group at baseline (C0) and 4-month follow-up (C1). (B) Venn diagram showing the overlaps between the patients in the YSHS group at baseline (T0) and at 4-month follow-up (T1). (C) Relative abundance of the gut microbiota in chronic kidney disease patients in the control and YSHS group at baseline (C0, T0) and 4-month follow-up (C1, T1) at the genus level. (D) Histogram of the LDA scores computed for differentially abundant bacterial taxa between baseline (T0) and 4-month follow-up (T1) in the YSHS group.

Figure 4. (A) Relative abundance of taxa between patients in the control group at baseline (C0) and at 4-month follow-up (C1). (B) Relative abundance of taxa between patients in the YSHS group at baseline (T0) and at 4-month follow-up (T1). (C) Heatmaps showing correlations between differentially abundant microbiota genera and clinical parameters in chronic kidney disease patients treated with YSHS.

Figure 5. (A) KEGG pathway based on level 2 for the intervention group. (B) KEGG pathway based on level 3 for the intervention group. (C) Heatmaps showing correlations between microbiota genera and the KEGG pathway for the intervention group.

Data availability statement

The data described in the manuscript will be made available upon reasonable request.