Background. Tacrolimus (TAC) is an immunosuppressant widely prescribed following an allogenic organ transplant. Due to wide interindividual pharmacokinetic (PK) variability, optimizing TAC dosing based on genetic factors is required to minimize nephrotoxicity and acute rejections. Methods. We enrolled 1133 participants receiving TAC from 4 cohorts, consisting of 3 with kidney transplant recipients and 1 with healthy males from clinical trials. The effects of clinical factors were estimated to appropriately control confounding variables. A genome-wide association study, haplotype analysis, and a gene-based association test were conducted using the Korea Biobank Array or targeted sequencing for 114 pharmacogenes. Results. Genome-wide association study verified that CYP3A5*3 is the only common variant associated with TAC PK variability in Koreans. We detected several CYP3A5 and CYP3A4 rare variants that could potentially affect TAC metabolism. The haplotype structure of CYP3A5 stratified by CYP3A5*3 was a significant factor for CYP3A5 rare variant interpretation. CYP3A4 rare variant carriers among CYP3A5 intermediate metabolizers displayed higher TAC trough levels. Gene-based association tests in the 61 absorption, distribution, metabolism, and excretion genes revealed that CYP1A1 are associated with additional TAC PK variability: CYP1A1 rare variant carriers among CYP3A5 poor metabolizers showed lower TAC trough levels than the noncarrier controls. Conclusions. Our study demonstrates that rare variant profiling of CYP3A5 and CYP3A4, combined with the haplotype structures of CYP3A locus, provide additive value for personalized TAC dosing. We also identified a novel association between CYP1A1 rare variants and TAC PK variability in the CYP3A5 nonexpressers that needs to be further investigated.

This study analyzed the association between medication adherence and the intrapatient variability (IPV) of tacrolimus concentrations among kidney transplant recipients through a post hoc analysis of the dataset from a recently conducted randomized controlled trial. Among 138 patients enrolled in the original trial, 92 patients with ≥ 5 months of medication event monitoring system (MEMS) use and ≥ 4 tacrolimus trough values were included in this post hoc analysis. The variability of tacrolimus trough levels was calculated using coefficient variation (CV) and mean absolute deviation. Adherence was assessed using MEMS and self-report via the Basal Assessment of Adherence to Immunosuppressive Medication Scale. There were no statistically significant differences in the CV [median 16.5% [interquartile range 11.6–25.5%] and 16.0% [11.5–23.5%], respectively, P = .602] between the nonadherent (n = 59) and adherent groups (n = 33). There was also no significant correlation between the CV and adherence detected by MEMS (taking adherence, ρ = − 0.067, P = .527; dosing adherence, ρ = − 0.098, P = .352; timing adherence, ρ = − 0.113, P = .284). Similarly, adherence measured by self-report did not significantly affect the IPV (P = .452). In this post hoc analysis, nonadherent behavior, measured through electronic monitoring or self-report, did not affect the IPV.

Extrahepatic portal vein obstruction (EHPVO) is the most common cause of pediatric portal hypertension and can cause life-threatening variceal bleeding. Meso-Rex shunt (MRS) is a surgical procedure that restores physiological portal venous blood flow to the liver by using a graft to connect the superior mesenteric vein and the left portal vein within the Rex recess, and can relieve variceal bleeding and other complications associated with EHPVO. Although the MRS is regarded as an optimal and potentially curative treatment with good long-term patency, graft thrombosis or failure due to unknown causes is not rare, prompting the need for further research on the risk factors of graft failure or poor patency. Herein, we report two cases of EHPVO in patients with recurrent or uncontrolled variceal bleeding, one treated with the classic Rex shunt and the other with the modified Rex shunt, which resulted in a failure and success, respectively.

Intravascular fasciitis (IVF) is a very rare disease that is difficult to diagnose preoperatively. Frequently, it can be misdiagnosed as a malignancy or deep vein thrombosis. A 26-year-old man presented with a 6-month history of intermittent cramping pain in the right calf. Duplex ultrasonography, computed tomography, magnetic resonance imaging, and positron emission tomography were performed in various hospitals. The work-up revealed a hypermetabolic mass in the femoral vein, suggestive of a malignancy, such as leiomyosarcoma. The tumor was located inside the femoral vein with no invasion, and the mass was resected en bloc with the vein wall. Intraoperative frozen section biopsy revealed no malignancy, and the final pathological diagnosis was IVF. Herein, we report a case of IVF and discuss the role of imaging studies in its preoperative diagnosis, with an extensive literature review.

Background The intrapatient variability (IPV) of tacrolimus (Tac) is associated with the long‐term outcome of kidney transplantation. The CYP3A single‐nucleotide polymorphism (SNP) may affect the IPV of Tac. We investigated the impact of IPV and genetic polymorphism in pediatric patients who received kidney transplantation. Methods A total of 202 pediatric renal transplant recipients from 2000 to 2016 were analyzed retrospectively. The IPV was calculated between 6 and 12 months after surgery. Among these patients, CYP3A5 polymorphism was analyzed in 67 patients. Results The group with high IPV had a significantly higher rate of de novo donor‐specific human leukocyte antigen antibodies (dnDSA) development (35.7% vs. 16.7%, p = .003). The high IPV group also had a higher incidence of T‐cell‐mediated rejection (TCMR; p < .001). The high IPV had no significant influence on Epstein–Barr virus, cytomegalovirus, and BK virus viremia but was associated with the incidence of posttransplant lymphoproliferative disorders (p = .003). Overall, the graft survival rate was inferior in the high IPV group (p < .001). The CYP3A5 SNPs did not significantly affect the IPV of Tac. In the CYP3A5 expressor group, however, the IPV was significantly associated with the TCMR‐free survival rate (p < .001). Conclusion The IPV of Tac had a significant impact on dnDSA development, occurrence of acute TCMR, and graft failure in pediatric patients who received renal transplantation. CYP3A5 expressors with high IPV of Tac showed worse outcomes, while the CYP3A5 polymorphism had no impact on IPV of Tac.