Efficacy of iguratimod on mineral and bone disorders after kidney transplantation: a preliminary study

Figures & data

Figure 1. Study cohort. (A) Study cohort of the clinical trial. (B) Study cohort of this study.

Table 1. Baseline characteristics of the study cohort.

Factors	IGU group	Control group	P value
N	20	23
Age (years)	40.5$\pm$7.3	41.8$\pm$10.2	0.642
Male%(N)	75.0(15)	65.2(15)	0.555
Female%(N)	25.0(5)	30.4(7)
Menopausal%(N)	40.0(2)	14.3(1)	0.745
BMI (kg/m^2)	20.5$\pm$2.7	21.4$\pm$2.4	0.287
Primary diseases%(N)
CGN	100.0(20)	95.7(22)	1.000
Others	0.0(0)	4.3(1)
Renal replacement therapy%(N)
HD	90.0(18)	82.6(19)	1.000
PD	10.0(2)	13.0(3)
Pre-emptive	0.0(0)	4.3(1)
Duration of dialysis (months)	40.2$\pm$38.4	36.0$\pm$35.0	0.716
Pre-operative hypertension, %(N)	89.5(17)	90.9(20)	1.000
Pre-operative diabetes, %(N)	5.0(1)	0.0(0)	0.465
Smoking%(N)	10.0(2)	17.4(4)	0.669
Alcohol taking%(N)	5.0(1)	4.3(1)	1.000
Calcineurin inhibitors%(N)
Tacrolimus	95.0(19)	91.3(21)	1.000
Cyclosporine	5.0(1)	8.7(2)
Sirolimus%(N)	10.0(2)	17.4(4)	0.669
Glucocorticoid accumulation(g)	4926.0$\pm$869.7	4596.1$\pm$435.5	0.123
Postoperative calcium use, %(N)	5.0(1)	4.3(1)	1.000
Postoperative calcitriol use, %(N)	15.0(3)	13.0(3)	1.000
Postoperative cinacalcet use, %(N)	0.0(0)	0.0(0)	1.000
Postoperative parathyroid hyperplasia/nodule, %(N)	25.0(5)	26.0(6)	1.000
TPTX + AT, %(N)	0.0(0)	9.1(2)	0.492
Pre-transplant
iPTH (pg/mL)	270.95$\pm$172.44	302.61$\pm$150.22	0.718
Ca(mmol/L)	2.38$\pm$0.27	2.34$\pm$0.33	0.571
Pi(mmol/L)	1.45$\pm$0.52	1.38$\pm$0.65	0.812
25(OH)vitD(nmol/L)	36.09$\pm$23.81	37.27$\pm$22.06	0.910
OC(ng/mL)	169.11$\pm$133.32	174.18$\pm$123.73	0.822
BALP(U/L)	27.34$\pm$15.65	30.58$\pm$22.58	0.628
NTx(ng/ml)	310.29$\pm$239.21	342.45$\pm$240.53	0.544
CTx(ng/ml)	1.73$\pm$0.77	1.82$\pm$0.73	0.724
eGFR (mL/min *1.73 m^2)
at the beginning of study	80.5$\pm$23.2	81.4$\pm$19.2	0.722
at the end of study	78.83$\pm$15.4	80.1$\pm$19.3	0.619

IGU: iguratimod; BMI: body mass index; CGN: chronic glomerular nephritis; HD: hemodialysis; PD: peritoneal dialysis; iPTH: intact parathyroid hormone; Ca: calcium; Pi: phosphorus; OC: osteocalcin; BALP: bone alkaline phosphatase; NTx: Type I collagen amino-terminal peptide; CTx: Type I collagen carboxy-terminal peptide; eGFR: estimated glomerular filtration rate, by MDRD equation.

Annotation: Independent sample t test was used for comparing normally distributed continuous variables, Wilcoxon nonparametric test was used for comparing non-normally distributed continuous variables, and chi-square test or Fisher’s exact probability method was used for comparing between two groups.

32 patients (15 in the iguratimod group and 17 in the control group) had pretransplant data of iPTH, 25(OH)vitD, OC, BALP, NTx and CTx.

Table 2. Serum iPTH,25(OH)vitD, Ca, Pi, BTMs, BMD, and vascular calcification score at 52 weeks.

Factors	IGU group	Control group	P value
N	20	23
iPTH (pg/mL)	107.95$\pm$77.44	115.61$\pm$66.58	0.732
Ca(mmol/L)	2.35$\pm$0.13	2.44$\pm$0.16	0.119
Pi(mmol/L)	0.87$\pm$0.16	0.86$\pm$0.20	0.843
25(OH)vitD(nmol/L)	43.51$\pm$13.38	39.91$\pm$16.94	0.442
OC(ng/mL)	22.95$\pm$15.23	39.32$\pm$23.22	0.010
BALP(U/L)	17.27$\pm$15.41	27.03$\pm$15.41	0.015
NTx(ng/ml)	64.17$\pm$34.73	127.66$\pm$79.97	0.007
CTx(ng/ml)	0.55$\pm$0.36	0.89$\pm$0.39	0.012
FN BMD (g/cm^2)	0.69$\pm$0.10	0.71$\pm$0.10	0.476
V BMD (g/cm^2)	0.93$\pm$0.15	0.91$\pm$0.12	0.618
TAC score	200.14$\pm$358.66	2349.26$\pm$3279.52	0.036
CAC score	11.68$\pm$23.00	198.90$\pm$352.19	0.080

iPTH: intact parathyroid hormone; Ca: calcium; Pi: phosphorus; OC: osteocalcin; BALP: bone alkaline phosphatase; NTx: Type I collagen amino-terminal peptide; CTx: Type I collagen carboxy-terminal peptide; FN BMD: femoral neck bone mineral density; V BMD: vertebral bone mineral density; CAC: coronary arterial calcification; TAC: thoracic aortic calcification.

Annotation: Independent sample t test was used for comparing normally distributed continuous variables and Wilcoxon nonparametric test was used for comparing non-normally distributed continuous variables between two groups.

27 patients (14 in the iguratimod group and 13 in the control group) had the data of TAC and CAC at 52 weeks after enrollment.

Table 3. Mineral and bone metabolism indexes among iPTH low and high clusters.

Factors	iPTH low(n = 18)			iPTH high(n = 25)
	IGU group	Control	P value	IGU group	Control	P value
iPTH(pg/mL)	50.73$\pm$18.19	51.47$\pm$20.96	0.938	154.77$\pm$75.98	156.85$\pm$50.52	0.935
Ca(mmol/L)	2.41$\pm$0.15	2.38$\pm$0.13	0.582	2.36$\pm$0.15	2.39$\pm$0.11	0.608
Pi(mmol/L)	0.91$\pm$0.15	1.02$\pm$0.16	0.151	0.83$\pm$0.18	0.75$\pm$0.15	0.221
25(OH)vitD(nmol/L)	44.04$\pm$16.73	37.64$\pm$15.53	0.413	43.07$\pm$10.76	41.38$\pm$18.20	0.787
OC(ng/mL)	15.70$\pm$6.38	24.39$\pm$6.10	0.012	28.89$\pm$17.95	47.84$\pm$25.22	0.046
BALP(U/L)	13.48$\pm$6.08	16.56$\pm$4.66	0.264	20.38$\pm$9.49	33.02$\pm$16.30	0.024
NTx(ng/ml)	52.92$\pm$24.84	100.91$\pm$36.16	0.012	74.17$\pm$40.41	142.25$\pm$94.42	0.048
CTx(ng/ml)	0.38$\pm$0.25	0.70$\pm$0.25	0.032	0.70$\pm$0.38	0.99$\pm$0.43	0.132
FN BMD (g/cm^2)	0.75$\pm$0.10	0.71$\pm$0.08	0.376	0.72$\pm$0.11	0.70$\pm$0.08	0.535
V BMD (g/cm^2)	0.87$\pm$0.10	1.00$\pm$0.11	0.019	0.92$\pm$0.13	0.92$\pm$0.11	0.927

iPTH: intact parathyroid hormone; Ca: calcium; Pi: phosphorus; OC: osteocalcin; BALP: bone alkaline phosphatase; NTx: Type I collagen amino-terminal peptide; CTx: Type I collagen carboxy-terminal peptide; FN BMD: femoral neck bone mineral density; V BMD: vertebral bone mineral density.

Annotation: In both the high and low iPTH groups, independent sample t test was used for comparing normally distributed continuous variables and Wilcoxon nonparametric test was used for comparing non-normally distributed continuous variables between two groups.

Table 4. Patient reported adverse events during the clinical trial.

Adverse effect	IGU group(n = 27)	Control group(n = 27)	P value
Lung Infection	7	5	0.40
Neutropenia	3	2	1.00
Headache	1	1	1.00
Somnolence	1	1	1.00
Insomnia	1	0	1.00
Elevated ALT	1	1	1.00
Abdominal Distension	0	1	1.00
Bloating	0	3	0.24
Nausea	0	3	0.24
Vomiting	0	1	1.00
Total	14	18	0.40

IGU: Iguratimod, ALT: alanine aminotransferase.

Annotation: The adverse events were compared between the two groups using the chi-square test or Fisher’s exact probability method.

Data availability

Reasonable requests for data will be accommodated by contacting the corresponding author.