Kreetachon Veerakikosol, Pajaree Chariyavilaskul, Natavudh Townamchai and Supeecha Wittayalertpanya
Cytochrome P450 (CYP) 3A5 is a major isoform metabolizing tacrolimus. Individual variation in the metabolism may result from CYP3A5 single nucleotide polymorphisms (SNPs). CYP3A5*3 polymorphism is strongly associated with tacrolimus pharmacokinetic variations in 65%–85% of Asian populations. A minor polymorphism related to requirement for tacrolimus is the POR*28 mutation, which increases in vivo CYP3A activity for tacrolimus. These two SNPs might affect individual maintenance dosages of tacrolimus.
To determine the association of CYP3A5*3 and POR*28 SNPs with maintenance dosage requirements for tacrolimus in Thai recipients of kidney transplants.
We enrolled 150 Thai recipients of kidney transplants. Clinical laboratory data were recorded 3 months after first administration of tacrolimus. Two SNPs; rs776746 A > G (CYP3A5*3 allele) and rs1057868 C > T (POR*28 allele) were assessed. All 300 genotypes were analyzed by real-time polymerase chain reactions.
Recipients were classified into 9 groups according to possible matching genotypes. The mean dosage required for the maintenance phase was significantly higher in the CYP3A5*1 allele or CYP3A5 expressers (groups 1-6, 0.163, 0.167, 0.141, 0.128, 0.131, and 0.174 mg/kg/day, respectively) than those not expressing CYP3A5*3/*3 or CYP3A5 (groups 7-9, 0.081, 0.073, and 0.069 mg/kg/day, respectively, P < 0.05). When the mean dosage was compared under POR*28 one or two alleles in CYP3A5 expressers, P was significantly smaller than in CYP3A5 expressers with POR*1/*1.
CYP3A5 polymorphism is key to determining tacrolimus dosage requirements during the maintenance phase in kidney transplant recipients and POR*28 may contribute to the interindividual variability
Piyawan Kittiskulnam, Paweena Susantitaphonga, Natavudh Townamchai, Khajohn Tiranathanagul, Talerngsak Kanjanabuch, Yingyos Avihingsanon, Kearkiat Praditpornsilpa and Somchai Eiam-Ong
Vitamin D status of Thai patients receiving renal replacement therapy (RRT) is incompletely known.
To determine the prevalence of vitamin D deficiency or insufficiency in adult Thai patients receiving various RRT modalities, and factors associated with low vitamin D levels.
In this retrospective, observational, single-center, cross-sectional study, we evaluated dialysis-related laboratory test variables from 111 patients receiving RRT. Serum 25-hydroxyvitaminD concentration [25(OH)D] < 15 ng/mL was defined as deficiency, and 15–30 ng/mL as insufficiency.
Low vitamin D levels were identified in 100% patients receiving peritoneal dialysis (PD; 81% deficient, 19% insufficient), 94% patients receiving online-hemodiafiltration (OL-HDF; 50% deficient, 44% insufficient), and 100% patients with kidney transplants (KT; 55% deficient, 45% insufficient). PD patients showed significantly lower serum [25(OH)D] than OL-HDF or KT patients (10.5 ± 5.9 vs 17.7 ± 8.5 vs 15.4 ± 6.1 ng/mL respectively, P < 0.001). OL-HDF patients with vitamin D deficiency had significantly lower vascular access flow than those without deficiency (833 ± 365 vs 1239 ± 385 mL/min, P = 0.008). KT recipients from deceased donors had lower serum [25(OH)D] than KT recipients from living, related donors (13.7 ± 6.0 vs 17.5 ± 5.7 ng/mL, P = 0.045). Multiple logistic regression found treatment by renin-angiotensin system blockade, serum triglyceride, and intact parathyroid hormone levels significantly associated with vitamin D deficiency after adjusting for sex, and serum calcium, phosphate, and albumin levels.
Nearly 100% patients receiving RRT had vitamin D deficiency or insufficiency, and RRT modalities might be related.