Dosing strategies for de novo once-daily extended release tacrolimus in kidney transplant recipients based on CYP3A5 genotype

Table 1 Baseline Characteristics (intent to treat population)

All patients (n = 36)
Age (yr), mean ± SD	55.5 ± 13.7
Male, n (%)	20 (55.6)
Race, n (%)
White	9 (25.0)
Black	24 (66.7)
Hispanic	2 (5.6)
Transplant type, n (%)
Deceased donor	25 (69.4)
Living donor	11 (30.6)
Hypertension, n (%)	28 (77.8)
Diabetes mellitus, n (%)	9 (25.0)
Focal segmental glomerulosclerosis, n (%)	1 (2.8)
Polycystic kidney disease, n (%)	1 (2.8)
HIV-associated nephropathy, n (%)	1 (2.8)
Lupus nephritis, n (%)	1 (2.8)
Transplant number, n (%)
One	35 (97.2)
Two	1 (2.8)
cPRA (%), median (IQR)	0 (0-10.0)
Actual body weight (kg), mean ± SD	87.4 ± 18.4
Dosing weight, n (%)
Actual	16 (44.4)
Adjusted	20 (55.6)
BMI (kg/m2), mean ± SD	30.0 ± 5.5

BMI: Body mass index; cPRA: Calculated panel reactive antibody; IQR: Interquartile range; HIV: Human immunodeficiency virus.

Table 2 Baseline characteristics (modified intent to treat population)

	Non-expresser (n = 15)	Intermediate metabolizer (n = 13)	Extensive metabolizer (n = 6)	P value
Age (yr), mean ± SD	53.8 ± 12.6	49.0 ± 14.0	58.3 ± 14.1	0.354
Male, n (%)	9 (60.0)	8 (61.5)	2 (33.3)	0.470
Race, n (%)				0.026
White	7 (46.7)	1 (7.7)	0
Black	7 (46.7)	12 (92.3)	5 (83.3)
Hispanic	1 (6.7)	0	0
Transplant type, n (%)				0.550
Deceased donor	12 (80.0)	8 (61.5)	4 (66.7)
Living donor	3 (20.0)	5 (38.5)	2 (33.3)
Hypertension, n (%)	12 (80.0)	9 (69.2)	6 (100.0)	0.304
Diabetes mellitus, n (%)	2 (13.3)	4 (30.8)	2 (33.3)	0.457
Focal segmental glomerulosclerosis, n (%)	1 (6.7)	0	0	0.521
Polycystic kidney disease, n (%)	0	1 (7.7)	0	0.435
HIV-associated nephropathy, n (%)	1 (6.7)	0	0	0.521
Lupus nephritis, n (%)	0	1 (7.7)	0	0.435
Transplant number, n (%)				0.435
One	15 (100.0)	12 (92.3)	6 (100.0)
Two	0	1 (7.7)	0
cPRA (%), median (IQR)	0 (0-20.8)	10.0 (0-10.0)	0 (0-20.8)	0.732
Actual body weight (kg), mean ± SD	85.5 ± 16.8	91.8 ± 22.2	77.4 ± 10.5	0.286
Dosing weight, n (%)				0.987
Actual	7 (53.3)	6 (53.8)	3 (50.0)
Adjusted	8 (46.7)	7 (46.2)	3 (50.0)
BMI (kg/m2), mean ± SD	29.68 ± 5.0	30.68 ± 6.9	28.88 ± 4.5	0.805

BMI: Body mass index; cPRA: Calculated panel reactive antibody; IQR: Interquartile range; HIV: Human immunodeficiency virus.

Table 3 Primary and secondary efficacy endpoints

	Non-expressers (n = 15)	Intermediate metabolizer (n = 13)	Extensive metabolizer (n = 6)	P value
Time (d) to therapeutic tacrolimus concentration, median (IQR)	4.5 (1.0-7.0)	6.0 (4.0-11.5)	13.5 (7.5-20.25)	0.025
Tacrolimus dose (mg) at therapeutic concentration, median (IQR)	12 (10-14)	16 (13-20)	16 (11-20.5)	0.010
Weight-based tacrolimus dose (mg/kg) at therapeutic concentration, median (IQR)	0.13 (0.12-0.165)	0.20 (0.125-0.25)	0.19 (0.138-0.265)	0.018
Tacrolimus dose (mg), median (IQR)	9.6 (9.2-10.1)	12.5 (10.6-14.5)	13.8 (10.4-14.4)	0.011
Weight-based tacrolimus dose (mg/kg), median (IQR)	0.128 (0.102-0.142)	0.136 (0.108-0.169)	0.176 (0.128-0.217)	0.074
Tacrolimus trough concentration (ng/mL), mean ± SD	10.78 ± 2.1	9.18 ± 1.6	7.98 ± 1.3	0.008
Weight-based tacrolimus dose at day 30 (mg/kg), mean ± SD	0.103 ± 0.429	0.154 ± 0.620	0.167 ± 0.590	0.022
Potassium (mEq/L), mean ± SD	4.29 ± 0.36	4.68 ± 0.35	4.35 ± 0.59	0.041
Serum creatinine (mg/dL) at day 30, median (IQR)	1.76 (1.29-2.62)	1.75 (1.27-2.65)	1.94 (1.2-3.0)	0.906
eGFR (mL/min/1.73 m2) at day 30, median (IQR)	40.0 (27.0-58.0)	46.0 (30.0-58.5)	31.5 (25.0-56.3)	0.701

eGFR: Estimated glomerular filtration rate; IQR: Interquartile range.