Influence of uridine diphosphate-glucuronosyltransferases (1A9) polymorphisms on mycophenolic acid pharmacokinetics in patients with renal transplant

Figures & data

Table 1. Demographics and clinical of renal transplant patients and healthy control.

Demographic characteristics	(Mean ± SD)
Baseline demographics
Healthy control (n)	100
Age of healthy control (n)	41.98 ± 22.08
Gender of healthy control (n) (female/male)	42/58
Number of patients (n)	125
Gender (female/male)	54/71
Age (years)	43.34 ± 12.13
Body weight (kg)	61.69 ± 11.72
Pre creatinine (mg/dL)	7.33 ± 1.82
Pre HLA antibodies: positive/negative	18 (14.4%)/107 (85.6%)
Primary kidney disease n (%)
Chronic glomerulonephritis	54 (43.2%)
Tubulointerstitial nephritis	9 (7.2%)
Unknown	31 (24.8%)
Primary nephrosclerosis	10 (8.0%)
Amyloidosis	6 (4.8%)
Diabetic nephropathy	15 (12.0%)
Transplant characteristics
Post-transplant follow-up (months)	26.32 ± 10.26
Hospitalization duration (months)	16.82 ± 9.74
Dialysis duration (months)	22.57 ± 12.13
Retransplantation (%)	7 (5.6%)
HLA mismatch
0	15 (12.0%)
1–5	89 (71.2%)
>6	21 (16.8%)
Post creatinine (mg/dL)	1.22 ± 0.22
Post HLA antibodies: positive/negative	27 (21.6%)/98 (78.4%)
eGFR	83.17 ± 16.94
Acute rejection (%)	25 (20.0%)
Biopsy-proven acute rejection (%)	19 (76.0%)
Clinical rejection (%)	6 (24.0%)
Anti-rejection therapy (%)
Steroid n (%)	6 (24.0%)
Antithymocyte globulin (ATG) (%)	16 (64%)
Steroid intravenous immunoglobulin (IVIG) (%)	3 (12%)
Induction therapy	7 (5.6%)

Table 2. Frequency of UGT1A9 1399 C > T SNPs in renal transplant patients.

Genotype	n	Renal transplant patients (n:125) (%)	n	Healthy controls subjects (n:100) %	p value
CC	85	68.0	63	63.0	.480^a
CT	29	23.2	23	23.0	.999^b
TT	11	8.8	14	14.0	.286^c
Total	100	100.0	100	100.0

^a CC versus TT/CT.

^b CT versus CC/TT.

^c TT versus CC/CT.

Table 3. Comparison of MPA biochemical, baseline and transplantation-related parameters between mutant type of UGT1A9 1399 C > T SNP and wild-type.

	Wild-type	Mutant-type	p value
Number of patients	85 (68.0%)	40 (32.0%)
Baseline characteristics
Recipient gender (female/male)	35/50	19/21	.285
Body weight (kg)	60.12 ± 10.46	59.41 ± 12.75	.843
Age (yr)	44.18 ± 11.48	43.24 ± 10.49	.982
Transplantation-related characteristics
Post-transplant follow-up (months)	27.18 ± 11.14	25.08 ± 12.22	.108
Hospitalization duration (months)	15.79 ± 10.12	16.91 ± 11.48	.649
Post HLA antibodies: positive/negative	16/69	11/29	.068
Acute rejection	16 (12.8%)	9 (7.2%)	.064
Toxicity	5 (4.0%)	8 (6.4%)	.128
Biochemical parameters
Post creatinine (mg/dL)	1.28 ± 0.12	1.35 ± 0.35	.105
eGFR	81.12 ± 13.22	78.19 ± 15.32	.084
Steroid dose (mg/day)	5.5 ± 1.1	5.2 ± 1.6	.412
Tacrolimus daily dose (mg/kg/d) (Month 1)	0.12 ± 0.08	0.11 ± 0.06	.123
	15.44 ± 7.29	16.92 ± 7.33	.095
Tacrolimus daily dose (mg/kg/d) (Month 3)	0.11 ± 0.10	0.09 ± 0.15	.076
	6.21 ± 2.36	7.15 ± 2.48	.239

Data are presented as mean ± SD.

Table 4. Comparison of MPA pharmacokinetics parameters between mutant type of UGT1A9 1399 C > T SNP and wild-type.

Parameters	Wild-type	Mutant-type	p value
Month 1
MPA daily dose (mg/kg/d)	0.11 ± 0.08	0.09 ± 0.05	.128
MPA blood concentration (µg/mL)	4.9 ± 1.98	5.5 ± 1.47	.046*
Blood concentration/dose (µg/mL per mg/kg)	44.5 ± 24.7	61.1 ± 29.4	.021*
Month 3
MPA daily dose (mg/kg/d)	0.09 ± 0.05	0.09 ± 0.03	.745
MPA blood concentration (µg/mL)	4.8 ± 1.25	5.1 ± 0.59	.118
Blood concentration/dose (µg/mL per mg/kg)	53.3 ± 25.0	56.6 ± 19.7	.225
		OR 95%CI
Genotypes	(N) blood concentrations (mean ± SD)	p value
Month 1
Wild-type	85	1.35 (0.81–1.58)
Mutant-type	40	0.046^a
Month 3
Wild-type	85	2.01 (0.95–2.64)
Mutant-type	40	0.118^a

Data are presented as mean ± SD.

^a Compared with Mutant-type genotype.

* p < .05.