The effects of Tripterygium wilfordii Hook F on renal outcomes in type 2 diabetic kidney disease patients with severe proteinuria: a single-center cohort study

Figures & data

Figure 1. The flowchart of patient screening.

T2DKD: type 2 diabetic kidney disease; EMR: electronic medical records; GN: glomerulonephritis; 24hUP: 24-h proteinuria; eGFR: estimated glomerular filtration rate; TwHF: Tripterygium wilfordii Hook F.

Table 1. The baseline characteristics of the TwHF and non-TwHF groups.

	Non-TwHF (n = 57)	TwHF (n = 67)	p
Age, years	55 (42, 63)	59 (50, 62)	0.118
Male, n (%)	43 (75)	54 (81)	0.635
BMI, kg/m^2	25.39 (22.64, 27.7)	24.69 (22.77, 27.56)	0.898
Follow-up time, years	1.63 (1.12, 2.57)	2.33 (1.47, 3.24)	0.017
Follow-up over 2 years, n (%)	34 (60)	28 (42)	0.072
SBP, mmHg	140 (129, 149)	135 (130, 145)	0.574
DBP, mmHg	80 (75, 90)	80 (75, 95)	0.789
Smoking, n (%)	26 (46)	21 (31)	0.148
Cardiovascular disease, n (%)	14 (25)	22 (33)	0.416
cerebral stroke, n (%)	3 (5)	4 (6)
coronary artery disease, n (%)	6 (11)	12 (18)
heart failure, n (%)	5 (9)	10 (15)
Large vascular disease, n (%)	2 (4)	1 (2)	0.553
Peripheral neuropathy, n (%)	19 (33)	29 (43)	0.343
DR, n (%)	44 (78)	57 (89)	0.105
Hypertension, n (%)	43 (75)	60 (90)	0.065
Hemoglobin, g/L	121.14 ± 21.38	124.66 ± 19.00	0.339
HbA1c, %	6.8 (6.18, 8.45)	7.3 (6.4, 7.95)	0.788
FBG, mmol/L	6.5 (5.5, 8.1)	7.2 (5.82, 8.95)	0.312
UA, mmol/L	398 (334, 456)	385 (330, 448)	0.521
Cholesterol, mmol/L	5.12 (4.53, 6.19)	5.35 (4.24, 6.5)	1
Triglycerides, mmol/L	1.64 (1.29, 2.46)	1.59 (1.13, 2.59)	0.559
LDL-C, mmol/L	2.88 (2.72, 3.8)	2.86 (2.14, 3.91)	0.318
Serum albumin, g/L	37 (32, 42)	37 (32.5, 39)	0.288
Serum creatinine, μmol/L	111 (90, 149)	124 (92, 191.5)	0.185
eGFR, mL/min/1.73m^2	63.09 (44.52, 81.63)	57.18 (34.75, 79.66)	0.187
CKD category			0.375
CKD 1–2, n (%)	30	31
CKD 3, n (%)	27	36
24hUP, g/24 h	3.5 (2.4, 6.93)	5.06 (3.42, 7.9)	0.008
24hUP > 5 g, n (%)	19 (33)	35 (52)	0.053
Oral hypoglycemic drugs, n (%)	39 (68)	54 (81)	0.176
SGLT2i, n (%)	15 (26)	25 (37)	0.266
Insulin, n (%)	40 (70)	47 (70)	1
GLP 1-RA, n (%)	5 (9)	7 (10)	0.992
RASi, n (%)	52 (91)	60 (90)	0.990

BMI: body mass index; SBP: systolic blood pressure; DBP: diastolic blood pressure; FBG: fasting blood glucose; UA: uric acid; LDL-C: low-density lipoprotein-cholesterol; eGFR: estimated glomerular filtration rate; CKD: chronic kidney disease; 24hUP: 24-h proteinuria; DR: diabetic retinopathy; SGLT2i: Sodium/glucose cotransporter-2 inhibitor; GLP1-RA: Glucagon-like peptide 1 receptor agonist; RASi: renin-angiotensin system inhibitor; TwHF: Tripterygium wilfordii Hook F.

Table 2. The characteristics of the TwHF and non-TwHF groups at the end of the follow-up period.

	Non-TwHF (n = 57)	TwHF (n = 67)	p
Serum creatinine, μmol/L	173 (123, 393)	158 (113, 261)	0.152
eGFR, mL/min/1.73 m^2	35.5 (13.12, 54.47)	39.9 (24.38, 60.13)	0.251
24hUP, g/24h	3.16 (1.4, 5.4)	1.76 (0.9, 3.6)	0.005
Serum albumin, g/L	37.48 ± 6.41	35.85 ± 5.32	0.132
FBG, mmol/L	6.1 (4.9, 7.6)	6.9 (5.9, 8.4)	0.121
UA, mmol/L	400.74 ± 80.94	397.9 ± 84.68	0.849
Cholesterol, mmol/L	4.83 (4.16, 5.68)	5.03 (4.24, 6.03)	0.326
Triglycerides, mmol/L	1.33 (1.04, 1.82)	1.64 (1.21, 1.98)	0.179
LDL-C, mmol/L	2.75 (2.07, 3.34)	2.59 (2.23, 3.24)	0.808
The decline value of eGFR, mL/min/1.73 m^2	18.64 (7.64, 42.51)	15.88 (4.89, 22.4)	0.016
The reduction of 24hUP, g/24h	1.0 (-0.87, 2.42)	3.26 (1.94, 5.11)	< 0.001
Renal outcomes, n (%)	23 (40)	11 (16)	0.006
ESKD, n (%)	16 (28)	8 (12)	0.042
Double serum creatinine, n (%)	21 (37)	9 (13)	0.005

eGFR, estimated glomerular filtration rate; 24hUP, 24-h proteinuria; FBG, fasting blood glucose; UA, uric acid; LDL-C, low-density lipoprotein-cholesterol; ESKD, end-stage kidney disease; TwHF, Tripterygium wilfordii Hook F.

Table 3. The univariate and multivariate Cox regression analysis for renal outcomes.

	The univariate analysis			The multivariate analysis
	HR	95%CI	p	HR	95%CI	p
Age, years	0.968	0.939–0.996	0.028	0.972	0.945–0.998	0.048
Gender (Male/Female)	1.007	0.436–2.323	0.988
Duration of diabetes, years	0.964	0.921–1.009	0.117
BMI, kg/m^2	0.911	0.827–1.004	0.061	0.914	0.828–1.008	0.073
Smoking (Yes/No)	1.268	0.635–2.531	0.5
SBP, mmHg	0.998	0.993–1.004	0.608
DBP, mmHg	1.031	0.996–1.067	0.081
Hypertension(Yes/No)	0.687	0.296–1.592	0.381
Cardiovascular disease(Yes/No)	1.075	0.510–2.262	0.85
DR(Yes/No)	1.085	0.671–1.755	0.739
Peripheral neuropathy(Yes/No)	1.216	0.612–2.415	0.577
hemoglobin, g/L	0.963	0.945–0.982	<0.001	0.980	0.960–1.005	0.055
FBG, mmol/L	1.001	0.878–1.142	0.984
HbA1c, %	1.047	0.812–1.351	0.723
UA, mmol/L	1.003	0.999–1.006	0.126
Cholesterol, mmol/L	1.059	0.892–1.258	0.51
Triglycerides, mmol/L	0.968	0.892–1.05	0.428
LDL-C, mmol/L	1.004	0.929–1.084	0.921
Serum albumin, g/L	0.898	0.854–0.945	<0.001	0.915	0.858–0.976	0.007
eGFR, mL/min/1.73 m^2	0.979	0.965–0.993	0.003	0.982	0.969–0.996	0.012
Serum creatinine, μmol/L	1.009	1.005–1.014	<0.001
24hUP, g/24h	1.123	1.050–1.202	<0.001	1.168	1.066–1.279	0.001
RASi	0.882	0.764–1.142	0.354
SGLT2i(Yes/No)	0.266	0.093–0.758	0.013	0.312	0.103–0.944	0.039
GLP1RA(Yes/No)	0.876	0.266–2.887	0.828
TwHF(Yes/No)	0.330	0.159–0.684	0.003	0.271	0.120–0.613	0.002

BMI: body mass index; CI: confidence interval; HR: hazard ratio; SBP: systolic blood pressure; DBP: diastolic blood pressure; DR: diabetic retinopathy; FBG: fasting blood glucose; UA: uric acid; LDL-C: low-density lipoprotein-cholesterol; eGFR: estimated glomerular filtration rate; 24hUP: 24-h proteinuria; SGLT2i: Sodium/glucose cotransporter-2 inhibitor; GLPI-RA: Glucagon-like peptide 1 receptor agonist; TwHF: Tripterygium wilfordii Hook F.

Figure 2. Kaplan-Meier curves for the renal outcomes in the overall cohort.

The renal outcomes were defined as doubling serum creatinine level or ESKD (dialysis or renal transplant), whichever occurred first. The non-TwHF group has a significantly lower proportion of patients without renal outcomes than the TwHF group (p = 0.0018). TwHF, Tripterygium wilfordii Hook F.

Figure 3. Comparison of the proportion of patients without renal outcomes between the two groups at three years using the restricted mean survival time method.

The pink part indicates RMST, and the orange part indicates RMTL. The y-axis denotes the proportion of patients without an outcome, and the x-axis shows the number of months. Abbreviations: RMST, restricted mean survival time; RMTL, restricted mean time lost.

Table 4. Multivariate Cox regression analysis of renal outcomes in two subgroups according to TwHF use.

	CKD1-2 stage			CKD3 stage
	HR	95%CI	p	HR	95%CI	p
Model 1^a	0.097	0.012–0.767	0.027	0.439	0.192–0.953	0.037
Model 2^b	0.131	0.016–1.103	0.061	0.412	0.174–0.976	0.044
Model 3^c	0.166	0.015–1.859	0.145	0.274	0.081–0.932	0.039

^aUnadjusted. ^bAdjusted for age and body mass index ^cAdjusted for age, BMI, eGFR, hemoglobin, serum albumin, 24-hUP, and SGLT2i use.

BMI: body mass index; CI: confidence interval; eGFR: estimated glomerular filtration rate; HR: hazard ratio; 24hUP: 24-h proteinuria; SGLT2i: Sodium/glucose cotransporter-2 inhibitor; TwHF: Tripterygium wilfordii Hook F.

Table 5. Adverse events of TwHF during the follow-up period.

	TwHF group (n = 67)	Discontinuation, n (%)
All adverse events, n (%)	12 (17.91%)	2 (2.98%)
Gastrointestinal, n (%)	5 (7.46%)	0 (0.00%)
Liver dysfunction, n (%)	2 (2.98%)	1 (1.49%)
Decrease in WBC count, n (%)	1 (1.49%)	0 (0.00%)
Itchy rash, n (%)	1 (1.49%)	1 (1.49%)
Irregular menstruation, n (%)	3 (4.48%)	0 (0.00%)

WBC: white blood cell; TwHF: Tripterygium wilfordii Hook F.

Data availability statement

Research data are not shared due to privacy restrictions.