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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 (GWAS), haplotype analysis, and a gene-based association test were conducted using the Korea Biobank Array or targeted sequencing for 114 pharmacogenes. Results GWAS verified that CYP3A5*3 is the only common variant associated with TAC PK variability in Koreans. We detected several CYP3A5 and CYP3A4 rare variants which 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 (ADME) 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 which needs to be further investigated.Supplemental Visual Abstract; http://links.lww.com/TP/C134.

Objective Vascular surgeons can be useful in non-vascular surgery cases, especially in oncology where complete resection is important. Such activity has been quantified at least locally, but maybe not adequately reported in a systematic manner, or studied prospectively. This study aimed to describe the roles of vascular surgeons in oncovascular surgery (OVS) and non-vascular surgery (NVS), and to analyse the yearly trends of consult surgery, early mortality and morbidity and risk factors for poor outcomes. Methods This study was a five year retrospective review of the role of vascular surgeons in various settings at a tertiary hospital. Electronic medical records and images were reviewed retrospectively. Between January 2014 and December 2018, the vascular surgery registry data of Seoul National University Hospital were reviewed for OVS or NVS assisted by vascular surgeons and operations primarily done by vascular surgeons. Demographic data, clinical characteristics, operative data, vascular related data and operative outcomes were collected. The operations were classified into primary surgery or consult surgery. Consult procedures were divided into planned or unplanned surgery. Results Of 564 cases, vascular surgeons performed 74 OVS as primary surgery, and retroperitoneal tumour was the most frequent diagnosis (n = 34). There were 490 intra-operative requests for a vascular surgeon's assistance, of which 109 were emergency calls. Total intra-operative consultations increased by 115.9% over five years, and the proportion of unplanned operations also increased. Unplanned assistance was most commonly requested for bleeding, whereas node dissection was the most common reason for planned surgery. The mortality rate was not different between the planned and unplanned surgery groups, but the latter showed worse outcomes in total operating time, length of hospital stay, post-operative consultations, and post-operative vascular related complications. Conclusion Vascular surgeons have an essential role to play in the modern practice of cancer surgery. Oncovascular surgery enables gross resection of a tumour even in the presence of major vessel invasion. Emergency unplanned surgery had worse outcomes; therefore, pre-operative vascular consultation and multidisciplinary management are highly recommended for better patient outcomes.

With the recent update to the Oxford classification for allograft IgA nephropathy (IgAN), additional investigations on the clinical significance of the updated components are warranted. We performed a retrospective cohort study at two tertiary hospitals. Kidney transplant recipients diagnosed with allograft IgAN were included in the study after additional review by specialized pathologists. We applied the updated Oxford classification and determined the MEST-C scores of the patients. The main study outcome was death-censored graft failure within 10 years after the establishment of allograft IgAN diagnosis and was assessed using the Cox regression analysis. Three hundred thirty-three allograft IgAN patients were reviewed: 100 patients with confirmed native IgAN and 233 patients with other, clinical, or unknown primary causes for end-stage renal disease (ESRD). The updated Oxford classification for allograft IgAN demonstrated prognostic value for graft failure, and patients with multiple MEST-C components had worse outcomes. M, E, S, and C were significantly associated with the prognosis of recurred IgAN and T was the only independent prognostic parameter for allograft IgAN without confirmed native IgAN. Therefore, we suggest reporting MEST-C scores in allograft biopsies and careful interpretation of the results according to the primary cause of ESRD.

Background Dyslipidemia is common in kidney transplant (KT) recipients. We analyzed the ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) in KT recipients to identify risk factors for major cardiovascular events (MACE). Methods We retrospectively included KT recipients with a lipid profile performed 1 year after transplantation. We classified patients according to the TG/HDL-C divided into quintiles. Subsequently, we analyzed the association between TG/HDL-C and MACE, defined as heart failure, coronary artery disease, and cerebrovascular disease confirmed by imaging studies. Results A total of 1301 KT recipients were enrolled. The median follow-up duration was 7.4 years (interquartile range 4.4–11.1 years). During the follow-up period, 80 (6.2%) patients developed MACE, which included 38 of unstable anginas, 9 of MIs, 19 of heart failures, 18 of cerebral infarcts, and 4 of cerebral hemorrhages. The fourth and fifth quintiles of TG/HDL-C showed a significantly increased risk of MACE [fourth quintile: adjusted hazard ratio (aHR), 3.38; 95% confidence interval (CI) 1.44–7.95; p = 0.005, fifth quintile: aHR, 2.67; 95% CI 1.13–6.30; p = 0.02]) compared to the second quintile of TG/HDL-C. This association is particularly evident in subgroups of non-DM, HTN, no history of CVD, and statin users. Conclusions Higher TG/HDL-C levels may be associated with MACE risk in KT recipients.

Introduction: Current guidelines recommend the placement of vascular access 6 months before the anticipated start of hemodialysis therapy; however, many patients start hemodialysis using a central venous catheter. We investigated the timing of referral for vascular access, the vascular access type at hemodialysis initiation, and the barriers to a timely referral. Methods: The study involved a retrospective review of 237 patients for whom the first vascular access for hemodialysis was created between January and November 2017. Results: Among the 237 patients, 58.2% were referred before hemodialysis initiation, while 41.8% were referred after hemodialysis initiation. Among the 138 patients, 55, 59, and 24 patients were referred more than 6 months, between 2 and 6 months, and within 2 months before hemodialysis initiation, respectively. Within these subgroups, 3.6%, 10.2%, and 75.0% patients underwent hemodialysis initiation with a central venous catheter, respectively. Among the 99 patients referred after hemodialysis initiation, the reasons for late referral were as follows: unexpected rapid progression of kidney disease (n = 23), noncompliance (n = 21), late visit to the nephrologist (initial visit within 2 months of hemodialysis initiation; n = 14), change of treatment strategy from peritoneal dialysis or transplants (n = 9), and unknown reasons (n = 32). Conclusion: Only 23% of patients were referred for vascular access 6 months before the anticipated hemodialysis therapy. In addition, 53% of patients initiated hemodialysis with a central venous catheter. Avoidance of catheter insertion was mostly successful in patients referred 2 months before hemodialysis initiation. The most common modifiable barrier to the timely referral was noncompliance.

Background: Preoperative mapping with duplex ultrasonography is crucial for successful vascular access creation for hemodialysis. The aims of this study are to assess the baseline characteristics of arm vessels by preoperative duplex ultrasonography in Korean patients, to find out a preoperative duplex ultrasonography parameter precluding distal arteriovenous fistula creation, to assess the maturation failure rate of arteriovenous fistulas, and to identify associated risk factors. Methods: Preoperative duplex ultrasonography mapping for vascular access creation was done in all patients with end-stage renal diseases during the year 2015. The baseline data of duplex ultrasonography were retrospectively analyzed with follow-up clinical data. Results: A total of 299 end-stage renal disease patients (mean age = 62 years, 62% male) were included. On preoperative duplex ultrasonography, mean diameters of radial artery and cephalic vein at wrist were 2.03 and 2.40 mm in the non-dominant arm and 2.10 and 2.26 mm in the dominant arm, respectively. The most common reason for precluding radial-cephalic arteriovenous fistula at wrist was small-sized cephalic vein. Multivariate logistic regression analysis revealed that the risk factors for inadequate vessels were warfarin treatment, old age (⩾75 years), and peripheral arterial occlusive disease. The rate of arteriovenous fistula maturation failure was 21% and vein diameter Conclusion: Preoperative duplex ultrasonography evaluation is important to find out inadequate vessels for native arteriovenous fistula and to determine the location of vascular access.

Few reports detail the actual outcome of Hepatitis B Surface Antigen-positive patients after kidney transplant. HBsAg-positive patients who underwent kidney transplant between January, 1999, and December, 2018, were reviewed retrospectively. Outcomes including hepatitis B reactivation rate, risk factors for reactivation, and patient and graft survival rates were analyzed. Seventy-seven patients were enrolled (47.1 ± 11.5 years old). Patients received ABO-incompatible (n = 5), crossmatch positive transplant (n = 2), and re-transplant (n = 4). Forty-six patients received prophylactic; 19, medication at least 3 months before the transplant; and 12, did not receive medication. Seventeen out of 76 patients developed reactivation post-transplant. 52.9% of HBV reactivation was accompanied by hepatitis. Inappropriate, other than lifelong prophylactic, antiviral agents (HR = 7.34, 95% CI 1.51–35.69, P = 0.01) and high hepatitis DNA (≥ 1000 IU/ml) pre-transplant (HR = 4.39, 95% CI 1.08–17.81, P = 0.04) increased reactivation risk. There was no significant difference in patient and graft survival between antigen positive patients who received antiviral agent and propensity score matched negative patients. HBsAg positivity in kidney transplant recipients is associated with substantial HBV reactivation rate. Lifelong antiviral therapy is mandatory, and patients with high preop HBV titer should be monitored closely for HBV reactivation.

Objective A systematic review and meta-analysis of randomised controlled trials (RCTs) was performed to determine the effectiveness and safety of drug coated balloon (DCB) angioplasty compared with uncoated plain balloon (PB) angioplasty in treating arteriovenous access stenosis. Methods MEDLINE, Embase, Scopus, and the Cochrane Central Register of Controlled Trials were searched for RCTs comparing paclitaxel coated DCB and PB angioplasty for arteriovenous access stenosis. The last date of the literature search was 31 December 2020. Risk of bias of the retrieved studies was assessed with the Cochrane Collaboration tool for assessing risk of bias (RoB 2.0). The random effects model was used to estimate the risk of loss of target lesion patency (six and 12 months) and circuit patency (six and 12 months). Procedure related adverse events and mortality rate were also compared. Patency results were pooled using the time to event meta-analytical method and the quality of evidence was assessed according to the GRADE approach. Results Sixteen eligible trials, including 1 682 lesions, were included in the quantitative analysis for the efficacy and safety of paclitaxel coated DCBs. DCBs were associated with a lower risk of loss of target lesion patency at six months (HR 0.53, 95% CI 0.42 – 0.66) and 12 months (HR 0.60, 95% CI 0.47 – 0.76), and were also associated with improved six and 12 month circuit patency. Overall quality of evidence was moderate to low. Procedural complications were rare, and the risk of death up to 12 months was similar between the two groups (OR 1.03, 95% CI 0.68 – 1.56). Conclusion Paclitaxel coated DCBs reduced the risk of loss of target lesion patency and circuit patency in arteriovenous access stenosis compared with PBs. Considering the heterogeneity of the included trials, there is a need to investigate optimal treatment regimens regarding drug dose and agent of the DCB and the treatment procedure.

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.

Background Synchronous cancer in patients with abdominal aortic aneurysm (AAA) increases morbidity and mortality after AAA repair. However, little is known about the impact of the history of cancer on mortality after AAA repair. Methods Patients with intact AAA who were treated with endovascular aneurysm repair or open surgical repair were selected from the Health Insurance and Review Assessment data in South Korea between 2007 and 2016. Primary endpoints included the 30- and 90-day mortality and long-term mortality after AAA repair. The Cox proportional hazards models were constructed to evaluate independent predictors of mortality. Results A total of 1999 patients (17.0%, 1999/11785) were diagnosed with cancer prior to the AAA repair. History of cancer generally had no effect in short-term mortality at 30 and 90 days. However, short-term mortality rate of patients with a history of lung cancer was more than twice that of patients without it (3.07% vs. 1.06%, P = 0.0038, 6.14% vs. 2.69%, P = 0.0016). Furthermore, the mortality rate at the end of the study period was significantly higher in AAA patients with a history of cancer than in those without a history of cancer (21.21% vs. 17.08%, P Conclusions The history of cancer in AAA patients increases long-term mortality but does not affect short-term mortality after AAA repair. However, AAA repair could increase both short- and long-term mortality in patients with lung cancer history, and those cases should be more carefully selected.

An immunosuppressant weaning protocol in failing allografts has not yet been established. Maintaining immunosuppressants would preserve residual renal function (RRF) and prevent graft intolerance syndrome and sensitization but would increase the risks of infection and malignancy. In this study, graft failure cases after kidney transplantation in a single center were reviewed retrospectively. The outcome differences in all-cause mortality, infection-related hospitalization, cancer, graft intolerance syndrome, re-transplantation, and RRF duration between the immunosuppressant maintaining and weaning groups 6 months after graft failure were compared. Among the weaning group, the outcome differences according to low-dose steroid use were also compared at 6 and 12 months. In a total of 131 graft failure cases, 18 mortalities, 42 infection-related hospitalizations, 22 cancer cases, 11 graft intolerance syndrome cases, and 28 re-transplantations occurred during the 94-month follow-up. Immunosuppressant maintenance significantly decreased the patient survival rate 6 months after graft failure compared with weaning (log-rank P = 0.008) and was an independent risk factor for mortality, even after adjustments (hazard ratio, 3.01; P = 0.025). Infection-related hospitalization, graft intolerance syndrome development, and re-transplantation were not affected by the immunosuppressant weaning protocol. Among the immunosuppressant weaning group, low-dose steroid maintenance at 6 and 12 months helped preserved RRF (P = 0.008 and P = 0.003, respectively).

Background Thin basement membrane nephropathy (TBMN) is the most common cause of persistent glomerular hematuria. Most individuals with TBMN show a benign course, although it can be difficult to distinguish it from early stages of progressive renal diseases. However, only limited studies address the prognosis of donors with TBMN and their recipients. Methods From 2007 to 2016, 11 recipients received kidney grafts from donors with TBMN, and their clinical data were analyzed retrospectively. Follow-up protocol kidney biopsies were given to the recipients at 10 days and 1 year after transplantation. The donors were also received a follow-up evaluation of their renal function and were interviewed via telephone survey. Results All donors were living, and their kidney grafts showed TBMN on pretransplantation biopsy. The recipients were followed for 57.4 ± 28.6 months posttransplantation. Seven recipients showed acute rejection by a median of 9.7 months, and all recipients recovered their renal function after treatment. Although 1 kidney failed due to graft arterial occlusion, the functions of the others were preserved during the follow-up period. The donors were followed for 41.0 ± 39.1 months and additionally contacted via telephone survey (in total, 56.8 ± 32.0 months). All the donors maintained their renal function upon clinical follow-up without significant complications and denied any discomfort at the time of the telephone interview. Conclusions Kidney transplant donors with TBMN and their recipients maintained their renal function through midterm follow-up without significant complications. Therefore, kidney transplantation from donors with TBMN could be a safe option.

Desensitization therapy may enable the patient to get allograft in sensitized recipient or solve the organ shortage in ABO-incompatible relationship in kidney transplantation (KT). However, the graft outcome and morbidity remains unclear. We retrospectively analyzed 845 KT patients from January 2010 to February 2016 at Seoul National University Hospital. The patients were divided into three groups as follows: HLA-incompatible (HLAi) group, ABO-incompatible (ABOi) group, and control group. The HLAi group comprised patients who received desensitization therapy due to the presence of donor-specific antibodies (DSAs) or high panel reactive antibodies (PRAs). The ABOi group is defined as those undergoing preoperative desensitization therapy for anti-ABO antibodies. Of the total of 845 recipients, 48 (5.6%) were HLAi KTs and 71 (13.9%) were ABOi KTs, respectively. Pre-emptive KT is done more frequently in ABOi group, therefore, they had shorter dialysis duration than the others. HLAi recipients had a higher proportion of women than the ABOi group and a higher proportion of re-transplantation. During the 38.4 (0.4–76.9) months of follow-up, there were more acute antibody-mediated rejections (AAMRs) in the HLAi (6.7%) and ABOi (8.5%) groups than in the control group (1.9%) (P = 0.001). However, there was no difference in graft survival, patient survival, and annual allograft among three groups. Despite the higher incidence of AAMRs, HLAi and ABOi KTs showed a favorable graft and patient outcome after desensitization therapy.

Objective Ipsilateral arteriovenous fistula (AVF) may cause symptoms of coronary steal in patients who had undergone coronary artery bypass graft (CABG) using internal thoracic artery. The purpose of this study was to evaluate the adverse effects of ipsilateral AVF to CABG, including the incidence of coronary steal, and to analyze the risk factors for coronary steal. Methods Between 2000 and 2013, a total of 25 patients undergoing hemodialysis via upper extremity AVF, ipsilateral to the preexisting CABG, were reviewed retrospectively. Clinical assessment related to coronary steal, echocardiography before AVF, and coronary angiography after symptoms were assessed. The definition of coronary steal was the new development of one or more of the following symptoms within 12 weeks after AVF creation: chest pain, chest discomfort, and dyspnea. Results Three patients were clinically diagnosed as coronary steal. Left ventricular ejection fraction (LVEF) was statistically lower in coronary steal group compared to no-steal group (41.7% vs. 50.9%; p = 0.036). Patients with coronary steal were older at the age of CABG surgery and showed a higher incidence of regional wall motion abnormality. Conclusions Coronary steal after ipsilateral AVF creation in patients with CABG using in situ internal thoracic artery (ITA) developed in 12%, which can be related to low LVEF. In patients with CABG requiring AVF for hemodialysis, the ipsilateral fistula to the grafted ITA should be carefully selected and performed.

Background Post-transplant cancer (PTC) is a critical complication after kidney transplantation. However, whether successfully cured PTC affects the long-term graft outcome remains unclear. Methods We retrospectively reviewed 1,629 kidney transplant recipients from 1995 to 2017 after excluding patients with post-transplant hematologic or advanced non-curable cancers and who underwent allograft nephrectomy because of cancer. Cured PTCs were defined as cancers treated with curative methods and/or adjuvant therapy without recurrence during ≥ 2 years. Propensity score matching was performed to match cured PTC patients with cancer-naïve patients (i.e., non-PTC group). Results During the median period of 7 years (maximum, 23 years), 70 patients (4.3%) had cured PTCs. The PTC group showed significantly higher risks of death-censored graft failure (adjusted hazard ratio [HR], 2.56 [1.05–6.23]), class II donor-specific antibodies (adjusted HRs, 3.37 [1.30–8.71]), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (adjusted HR, 2.68 [1.43–5.02]) and random urine protein/creatinine ratio > 1 g (adjusted HR, 3.61 [1.92–6.79]) compared to non-PTC group. However, the risk of mortality was not different between the PTC and non-PTC groups. According to the cancer type, only urogenital cancer had a significant association with graft failure (adjusted HR, 4.26 [1.19–15.22]) and the gastrointestinal cancer showed elevated risk of T cell mediated rejection compared to non-PTC (adjusted HR, 20.44 [6.02–69.39]). Conclusion Appropriate monitoring of graft function is necessary in patients with cured PTCs., Graphical Abstract

With small kidneys, EBKTs could provide sufficient renal mass but could lead to inefficient use of resources, while SKTs could result in insufficient function due to small renal mass. We aimed to compare the outcomes of EBKT and SKT from small donors weighing ≤15 kg to pediatric recipients. We retrospectively reviewed all pediatric patients who met the inclusion criteria between January 1, 1984, and April 30, 2019, at a single institution. Of a total of 23 patients, 12 received EBKT and 11 received SKT. The median age of donors, weight of donors, and weight of recipients were comparable between the two groups. The median age of recipients and median weight of allografts were greater in the EBKT group than in the SKT group. The median follow-up was 53.9 months. There was no significant difference in eGFR, protein creatinine ratios at 1-year follow-up, and overall graft survival. The size of the kidney increased by approximately 13%-43% in the EBKT group and 40%-60% in the SKT group. This study demonstrated that kidneys from small donors weighing 5-15 kg could be split in pediatric recipients without compromising the outcome.

Background Although immunoglobulin A nephropathy (IgAN) is associated with an increased risk of renal allograft failure, evidences for its treatment, including renin-angiotensin-aldosterone system blockade (RAASB) usage, remain limited. Methods In this bi-center retrospective cohort study, we included patients who were recently diagnosed with IgAN through allograft biopsies. We identified their 6-month antihypertensive medication prescriptions and investigated the association between the medication types, albuminuria changes, and risk of 5-year death-censored-graft-failure (DCGF). The mixed effect model and cox regression analysis were used. Results A total of 464 allograft IgAN patients were included: 272, 38, 33, and 121 patients in the no antihypertensive medication, single agent RAASB, single agent beta blocker (BB)/calcium channel blocker (CCB), and combination therapy groups, respectively. High-degree albuminuria after 6 months of allograft IgAN diagnosis was an important prognostic parameter and a partial mediator for the association between the subgroups and 5-year DCGF. The usage of single RAASB was associated with decrement of albuminuria from allograft IgAN diagnosis (P for interaction = 0.03). The single BB/CCB group demonstrated significantly worse prognosis than the single RAASB group (adjusted hazard ratio, 2.76 [1.09–6.98]; P = 0.03). Conclusions In conclusion, RAASB may be beneficial for graft prognosis in early allograft IgAN patients who require single antihypertensive medication therapy, by means of reducing albuminuria. Further investigation of treatment strategy in allograft IgAN is warranted.

Background Post-transplant lymphoproliferative disease (PTLD) is one of the major complications of organ transplantation, especially in children with Epstein-Barr virus (EBV) viremia (EV). We performed a retrospective study to evaluate risk factors for PTLD in children with EV. Methods Among 199 pediatric kidney transplantation (KT) recipients at our center from January 2001 to October 2015, records of those with EBV viral loads of > 1,000 copies/mL and/or PTLD were reviewed. Results Diagnosis of PTLD was made in seven patients (PTLD group), and 39 patients had EV only (EV only group). The median time from KT to EV and PTLD diagnosis was 6.7 (range 0.4–47.8) months and 8.2 (range, 2.8–98.9) months, respectively. There were no significant differences between the groups in terms of sex, age at transplantation, donor type, EBV viral load, or EV-free duration after KT. Higher tacrolimus level before EV (hazard ratio, 44.5; P = 0.003) was an independent risk factor for PTLD in multivariate Cox regression analysis. Six patients with a high EBV load (median 171,639 copies/mL) were treated with preemptive rituximab (RTX) therapy, resulting in transient reduction of EBV load. None of these patients developed PTLD (median follow-up 51.5 months); however, two had neutropenia and two developed infection requiring hospital admission. Conclusion In pediatric KT recipients, higher tacrolimus levels were associated with a higher incidence of PTLD. Conversely, those who received preemptive RTX for EV did not develop PTLD., Graphical Abstract

The purpose of this study was to identify genotypes associated with dose-adjusted tacrolimus trough concentrations (C0/D) in kidney transplant recipients using whole-exome sequencing (WES). This study included 147 patients administered tacrolimus, including seventy-five patients in the discovery set and seventy-two patients in the replication set. The patient genomes in the discovery set were sequenced using WES. Also, known tacrolimus pharmacokinetics-related intron variants were genotyped. Tacrolimus C0/D was log-transformed. Sixteen variants were identified including novel CYP3A7 rs12360 and rs10211 by ANOVA. CYP3A7 rs2257401 was found to be the most significant variant among the periods by ANOVA. Seven variants including CYP3A7 rs2257401, rs12360, and rs10211 were analyzed by SNaPshot in the replication set and the effects on tacrolimus C0/D were verified. A linear mixed model (LMM) was further performed to account for the effects of the variants and clinical factors. The combined set LMM showed that only CYP3A7 rs2257401 was associated with tacrolimus C0/D after adjusting for patient age, albumin, and creatinine. The CYP3A7 rs2257401 genotype variant showed a significant difference on the tacrolimus C0/D in those expressing CYP3A5, showing its own effect. The results suggest that CYP3A7 rs2257401 may serve as a significant genetic marker for tacrolimus pharmacokinetics in kidney transplantation.

Background The number of elderly patients with end-stage renal disease is increasing rapidly. The higher prevalence of comorbidities and shorter life expectancy in these patients make it difficult to decide on the type of vascular access (VA). We explored the optimal choice for VA in elderly hemodialysis patients. Methods We included elderly patients (> 65 years) visiting our VA clinic and divided them into three groups as follows: radiocephalic arteriovenous fistula (AVF), brachiocephalic AVF, and prosthetic arteriovenous graft (AVG). The primary outcomes were VA abandonment and all-cause mortality. The secondary outcome was maturation failure (MF). Results Of 529 patients, 61.2% were men. The mean age was 73.6 ± 6.0 years. The VA types were as follows: 49.9% radiocephalic AVF, 31.8% brachiocephalic AVF, and 18.3% AVG. Patients with an AVG tended to be older, female, and have a lower body mass index. More than half of patients (n = 302, 57.1%) started dialysis with central catheters, but the proportion of predialysis central catheter placement was not different among the VA types. Radiocephalic AVF was significantly superior to AVG in terms of VA abandonment (P = 0.005) and all-cause mortality (P

Deceased donor kidneys (DDKs) with acute kidney injury (AKI) are difficult to allocate for fear of the expected graft outcome. We aimed to evaluate the impact of donors' AKI severity and trend on graft outcomes in DDK transplantation. This was a retrospective study of DDK transplantation performed from 2005 to 2014. Based on maximum and terminal serum creatinine values before transplantation, the AKI trends were categorized as improving or worsening. Of 413 DDKs, 275 developed AKI: 177 stage 1, 52 stage 2, and 46 stage 3. DDKs with AKI had 212 improving AKI and 63 worsening AKI. Graft outcomes were similar based on AKI stage. Worsening AKI did not affect delayed graft function development; however, it significantly elevated graft failure risk even after adjusting for AKI stage and Kidney Donor Risk Index. Graft survival of the improving group was similar to DDKs with no AKI. This study showed that AKI severity of DDKs did not affect overall graft outcomes. Notably, DDKs with improving AKI showed a similar graft survival rate to DDKs without AKI, although worsening AKI had a worse prognosis. Consideration of the AKI trend, rather than its severity, is needed when DDKs with AKI are allocated.

Postoperative portomesenteric venous thrombosis (PMVT) is a rare but potentially serious complication of gastric surgery. This study analyzed the incidence, characteristics, risk factors, and outcomes of PMVT following gastric surgery. Medical records of patients who underwent gastric surgery between January 2007 and December 2012 were reviewed retrospectively. The risk factors of PMVT were analyzed by a logistic regression analysis with control group matched 1:4 by age, sex, and cancer stage and by a Poisson regression analysis with unmatched control group. The resolution rate of PMVT in 12 months was compared between the treatment group and the nontreatment group. The total incidence of PMVT after gastric surgery was 0.67 % (31/4611). Most (54.84 %) PMVT cases were detected within 1 month postoperatively. No accompanying deep vein thrombosis (DVT) was noted. Multivariate comparison with 1:4 matched control showed that combined splenectomy, synchronous malignancy, and intra-abdominal complication were independent risk factors. Advanced stage, combined splenectomy, and synchronous malignancy were independent risk factors in Poisson regression analysis using unmatched controls. The resolution rate of PMVT was not different from patients treated with anticoagulation (n = 6) or antiplatelet therapy (n = 1) and were not significantly different with those of the untreated group [85.7 % (6/7) vs. 82.3 % (14/17), p = 0.935] during 1-year follow up. PMVT after gastric surgery was associated with advanced cancer stage, combined splenectomy, and synchronous malignancy, but it was not related to laparoscopy or DVT. Significant differences in the natural course of PMVT were not found between the treatment group and observation group.

Objective Middle aortic syndrome (MAS) is a rare condition characterized by severe stenosis of the distal thoracic or abdominal aorta. The aims of this study are to define the anatomic characteristics of MAS and to review the various surgical methods and their outcomes in terms of long-term durability Materials and methods Ten adult patients were diagnosed with MAS caused by Takayasu arteritis (TA) or midaortic dysplastic syndrome and underwent surgical treatment between July 1992 and January 2013. Result The aortic lesions were mostly suprarenal ( n = 7) and stenoses were commonly found in the celiac axis ( n = 6), SMA ( n = 7), and renal artery ( n = 6). Indications for operation were uncontrolled hypertension in six patients and lower extremity claudication in four. Eight aortic bypasses, one supraceliac aortic interposition graft, and one bilateral aorto-renal bypass were performed. Adjunctive renal bypass with saphenous vein graft ( n = 4) and IMA reimplantation ( n = 2) were performed simultaneously. There was no post-operative mortality, and one complication of iliac dissection at the distal anastomosis site was detected and treated by stenting. Hypertension was cured or improved in five of the six patients, and lower extremity claudication improved in all of them. With a median follow up of 60 months (range, 12–263), all the aortic bypasses were patent and one adjunctive renal artery bypass graft with aortic bypass was occluded 29 months post-operatively. Conclusions Aortic bypass for MAS is safe and shows excellent long-term durability. Considering the patients are relatively young with a long life expectancy, aggressive surgical treatment could be beneficial. Lifelong follow up to monitor complications and disease progression is necessary.

The prognosis of patients with allograft IgA nephropathy (IgAN) requires further investigation. We performed a bicenter retrospective cohort study on kidney transplant recipients diagnosed with IgAN in allograft biopsy. Recipients without allograft IgAN but with known IgAN before transplantation were included as the control group. We investigated the associations between clinicopathological characteristics, including allograft crescents, and the risk of death-censored graft failure. In total, 1256 IgAN patients in both pre- and posttransplant stages were included. Among them, 559 were diagnosed with allograft IgAN, which was a time-dependent risk factor for worse prognosis (adjusted hazard ratio = 5.009 [3.610-6.951]; P .001) during a median of 8.1 years of follow-up. Of the patients with allograft IgAN, 88 (15.9%) had glomerular crescents, including 40 patients (7.2%) with10% crescent formation in the total biopsied glomeruli. The presence of glomerular crescents in IgAN was associated with a worse graft prognosis, and the association was still valid with the C scores of the current Oxford classification. In conclusion, allograft IgAN is a time-dependent event and is associated with worse graft outcomes. The pathological characteristics of allograft, particularly the degree of glomerular crescent formation, may represent important risk factors for a poor prognosis.

Introduction: Arteriovenous graft (AVG) infection can result in life-threatening sepsis and loss of vascular access. A retrospective study was performed to establish an appropriate treatment strategy for AVG infection. Methods: A total of 50 cases of AVG infection were treated between January 2005 and June 2016. The surgical methods used were total graft excision (TGE) (n = 34), or partial graft excision (PGE) with interposition graft (n = 16). Results: Infection was noted at a puncture site (n = 22), a prior incision for surgery or endovascular therapy (n = 20), and abandoned (currently unused) grafts (n = 5). Infection occurred within 1 month after AVG creation (n = 1), or any intervention (n = 14), and more than 1 month after creation or intervention (n = 35). Simultaneous remote infection was identified in 7 patients, 2 of whom underwent an operation for infective endocarditis and spondylitis. After PGE, 5 patients (5/16, 31.2%) having recurrent infection were treated with further graft excision; however, no patient showed life-threatening complications. After TGE, a central venous catheter (CVC) was inserted and used for a median period of 90 days. Among 34 patients who underwent TGE, new vascular access was created in 18 patients at a median period of 2 months later, and 12 patients continued to use a CVC until last follow-up or death. Conclusions: PGE could be a treatment option for AVG infection to achieve both infection eradication and vascular access preservation in selected patients. Because of a higher risk of recurrent infection, sufficient surgical removal and careful postoperative management are warranted.

Background Atypical hemolytic uremic syndrome (aHUS) is a rare disease that is often associated with genetic defects. Mutations of complement factor H (CFH) are the most common genetic defects that cause aHUS and often result in end-stage renal disease. Since CFH is mainly produced in the liver, liver transplantation (LT) has been performed in patients with defective CFH. Methods The clinical courses of four kidney allograft recipients who lost their native kidney functions due to aHUS associated with a CFH mutation were reviewed. Results Subject A underwent kidney transplantation (KT) twice, aHUS recurred and the allograft kidney failed within a few years. Subject B received a KT and soon experienced a recurrence of aHUS coinciding with infection. Her allograft kidney function has worsened, and she remains on plasma infusion therapy. Subject C underwent LT followed by KT. She is doing well without plasma infusion therapy after combined LT-KT for 3 years. Subject D received KT following LT and is now recurrence-free from aHUS. Conclusion In patients with aHUS associated with a CFH mutation, KT without LT was complicated with a recurrence of aHUS, which might lead to allograft loss. Conversely, LT was successful in preventing the recurrence of aHUS and thus might be another option for a recurrence-free life for aHUS patients associated with CFH mutation., Graphical Abstract

To evaluate the prognostic value of CT venography for catheter-directed thrombolysis (CDT) in iliac vein compression syndrome (IVCS) patients with deep venous thrombosis (DVT). The institutional review board approved this retrospective study and waived informed consent. Among the 201 consecutive patients treated in our interventional suite for DVT from January 2001 to June 2013, 48 IVCS patients (12 men, 36 women) who underwent pre-procedural CT venography, CDT with stenting, and follow-up imaging were analyzed. To identify possible determinants of 6-month patency, CT venography was evaluated with Fisher’s exact test and logistic regression analyses. Based on the analyses, image-based criteria were established and compared to the current symptom duration-based approach by receiver-operating-characteristic curve analyses and the McNemar test. Recoiling of external iliac vein (EIV) diameter (

Introduction Although a latent tuberculosis (TB) infection is a risk factor for active TB, the diagnosis of latent TB infection is difficult in end-stage renal disease patients. Patients and Methods We retrospectively compared the results of the QuantiFERON-TB (QFT) test and the tuberculin skin test in patients on the waiting list for kidney transplantation (KT), and investigated whether the QFT test can predict TB development in KT recipients in an intermediate-TB-burden country. Results The incidence of post-KT TB was 283 cases/100,000 patient-years among 1274 KT recipients at the Seoul National University Hospital. The overall standardized incidence ratio of TB was 4.358 compared with the general population. A past history of TB infection, smoking history, myocardial infarction after KT, and pneumocystis infection were significant predictors of subsequent TB development (adjusted odds ratios were 3.618, 2.959, 9.993, and 5.708, respectively). Among the 129 recipients who had the QFT test, 42 patients (32.5%) had positive a QFT. At a median follow-up of 8.4 ± 6.8 months, 1 patient with positive QFT results developed TB after KT, and 1 of the 87 patients with negative QFT results developed TB after KT. In both of these 2 cases, active TB developed despite isoniazid prophylaxis. Among 272 patients on the waiting list for KT, the tuberculin skin test and QFT were positive in 22.8% and 35.3%, respectively. The degree of agreement between the 2 tests was poor (κ = 0.352). Conclusions The QFT test did not predict subsequent short-term TB development. Furthermore, a long-term and larger-scale study is needed to confirm our results.

Background Nonadherence to immunosuppressive therapy after renal transplantation is associated with poor graft outcomes. We aimed to evaluate whether the use of the Adhere4U mobile medication manager application could improve adherence among renal transplant recipients ≥1 year posttransplantation. Adhere4U can provide medication reminders, monitor medication use, and provide information on immunosuppressants. Methods We conducted a prospective randomized controlled study to compare the rate of nonadherence to index immunosuppressant (tacrolimus or cyclosporine) in a group using the Adhere4U app (mobile group) and in another group receiving conventional care (control group). The primary outcome was the nonadherence rate, which was evaluated using an electronic medication event monitoring system during the 6-month intervention period. Our secondary outcome included self-reported adherence using the Basel Assessment of Adherence to Immunosuppressive Medication Scale (BAASIS) and the visual analog scale (VAS) based on a 4-week recall on days 28, 90, and 180. Longitudinal data of repeated measures of self-rated adherence were analyzed using generalized estimating equations (GEE) to compare the between-group difference in adherence change over time. Results Between November 2013 and May 2015, 138 renal transplant recipients were randomly allocated to the control (n = 67) or the mobile group (n = 71). The overall nonadherence rate over the 6-month study period by electronic monitoring was 63.6%, with no between-group difference [mobile group, 65.0% (n = 39/60); control group, 62.1% (n = 36/58); odds ratio 1.14; 95% confidence interval 0.53–2.40; p = 0.89]. Self-rated nonadherence assessed using the BAASIS and VAS at baseline was 53.7% and 51.5%, respectively. Although the self-rated nonadherence by BAASIS of the mobile group was lower than the control group throughout the study period, there was no between-group difference in the change of nonadherence over time (χ2 = 2.82, df = 3, p = 0.42 by logistic GEE). There also was no significant between-group difference in the nonadherence by VAS (χ2 = 1.71, df = 3, p = 0.63 by logistic GEE) over time. The main limitation of this study was the low rate of patient engagement with the app among the mobile group. The rate of app use was 47.6% (31/65) at 28 days, 33.9% (19/56) at 90 days, and 11.5% (6/52) at 180 days. Conclusions The Adhere4U application did not improve adherence to immunosuppressive therapy. Our evidence is limited by the high rate of attrition. Further studies on strategies to facilitate patient engagement with mobile interventions are warranted.

Background Conservative treatment is feasible in most patients with spontaneous isolated dissection of the superior mesenteric artery (SID-SMA). However, the role of antiplatelet agents and anticoagulants is not well defined in either symptomatic or asymptomatic SID-SMA. This study aimed to conduct a meta-analysis, including a single-arm study, comparing the resolution rate of conservative management with versus without antithrombotics for symptomatic and asymptomatic SID-SMA. Methods A systematic search of electronic databases, including PubMed, EMBASE, and Cochrane Library, on August 22nd, 2018, was performed to identify studies concerning SID-SMA. Meta-analyses were conducted to determine the primary resolution rate, long-term aneurysmal change for symptomatic SID-SMA, and any event for asymptomatic SID-SMA. We calculated pooled risk ratios and 95% confidence intervals (CIs) using random-effects model in studies with two arms and in studies with two arms or a single arm. Results We included data from 35 articles involving 727 patients with SID-SMA (symptomatic 693, asymptomatic 134). No significant differences were observed in the successful resolution rate between conservative management with and without antithrombotics (random-effects model, risk ratio [RR] 0.96; 95% CI, 0.87–1.05]). The pooled resolution rate from combining single-arm studies was 91% (95% CI, 85–95) and 95% (95% CI, 88–100) in conservative management with and without antithrombotic, respectively, which was not statistically significant (RR, 0.97; 95% CI, 0.91–1.02). The pooled morphologic progression rate from combining single-arm studies was 3% (95% CI, 0–8) and 11% (95% CI, 2–26) in conservative management with and without antithrombotics, respectively, which was not statistically significant (RR, 0.44; 95% CI, 0.12–1.64). The adverse event was 0% for both groups for asymptomatic SID-SMA. Conclusions Additional antithrombotic therapy for both symptomatic and asymptomatic SID-SMA did not benefit the outcomes. We do not recommend the use of antithrombotics for SID-SMA, unless further evidence shows any beneficial effect.

Peritoneal dialysis catheters (PDCs) can be inserted by a percutaneous, open surgical, or laparoscopic approach. Considerable controversy surrounds the mode of catheter placement and its impact on technical success. We compared the complications and survival characteristics of PDCs that were inserted by the open approach versus those inserted percutaneously. We reviewed the outcomes of 167 patients who received PDCs between September 2009 and February 2012. Of these, 89 were placed percutaneously and 78 were placed by open surgical techniques. The mechanical complication rates, including catheter bleeding, wrapping, migration, leakage, and technical failure of intraperitoneal placement were compared between the two groups. Additionally, peritonitis episodes, exit site infection rates, and tunnel infection rates were compared between groups. The incidence of one or more previous intra-abdominal surgeries was significantly higher in the open group (4.5 percutaneous vs 21.7 % open; P = 0.001). Although the overall number of complications did not differ between the two groups, the incidence of early mechanical complications (11.2 vs 0 %; P = 0.002) and the number of catheter removals due to mechanical complications (7.9 vs 1.3 %; P = 0.047) were higher in the percutaneous group. Of the 15 mechanical complications in the percutaneous group, one third were due to technical failures compared to none in the open group (5.6 vs 0 %; P = 0.034). The 1 year survival rate of the PDCs for the percutaneous and open groups was 89.9 and 93.3 %, respectively (P = 0.249). The placement modality did not affect catheter survival. However, early mechanical complications, including technical failures, were more frequent in the percutaneous group, despite the proportion of patients with a history of one or more previous intra-abdominal surgeries being significantly lower in that group. The direct visualized open method of catheter insertion may provide the most reliable and secure access for a PDC.

BACKGROUND There is a growing concern about the therapeutic equivalence of the generic tacrolimus formulation (GEN Tacrolimus) to the reference tacrolimus (REF Tacrolimus) in solid organ transplantation. METHODS A prospective, randomized study of 126 de novo renal transplant patients was conducted to compare the efficacy, safety and pharmacokinetic (PK) profiles between GEN tacrolimus (n = 63) and REF tacrolimus (n = 63). The PK of tacrolimus was evaluated on Day 10 and 6 months under steady-state condition. Crossover study was carried out in 66 patients at 6 months. RESULTS On Day 10, 117 patients completed PK profiles (54 GEN tacrolimus and 63 REF tacrolimus) and GEN tacrolimus showed comparable C(0) (9.8 ± 2.5 versus 9.7 ± 3.0 ng/mL, P = 0.80) but significantly higher dose-normalized C(max) (309.1 ± 191.9 versus 192.5 ± 95.2 ng/mL/mg/kg, P < 0.001). The dose-normalized AUC(0-12) tended to be higher in the GEN tacrolimus than in the REF tacrolimus group (1513.4 ± 935.4 versus 1262.5 ± 593.5 ng.h/mL/mg/kg, P = 0.084). Because of this early and high C(max) with a rapid decline in GEN tacrolimus concentration, the trough concentration was maintained lower than that of REF tacrolimus. At 6 months, GEN tacrolimus showed equivalent dose-normalized AUC(0-12) (1882.2 ± 935.6 versus 1718.1 ± 946.3 ng.h/mL/mg/kg, P = 0.429) but still higher dose-normalized C(max) (346.3 ± 184.4 versus 273.2 ± 148.9 ng/mL/mg/kg, P = 0.056), despite a reduced trough concentration (5.7 ± 1.6 versus 6.9 ± 2.2 ng/mL, P = 0.004). PK profiles evaluated at 9 months showed that generic substitution also resulted in an 'early and high C(max)'. Efficacy and safety data were comparable over the 9-month study period. CONCLUSIONS Therapeutic equivalence and the PK of GEN tacrolimus should be evaluated in patients undergoing de novo renal transplantation.

Background Tuberculosis (TB) is a common opportunistic infection after kidney transplantation (KT). The QuantiFERON-TB-Gold In-Tube test (QFT) is widely used for assessing latent TB; however, it is currently unclear whether the pre-KT QFT of the recipient and donor can predict post-KT TB. Methods We retrospectively reviewed patients who received KT between January 2009 and December 2015 at Seoul National University Hospital. The QFT was performed in 458 KT recipients and 239 paired living donors, and 138 KT recipients underwent both the QFT and tuberculin skin test (TST). After excluding 12 patients diagnosed as having clinically latent TB, we evaluated whether the QFT of the recipient and donor was predictive for new-onset active TB after KT. Results The QFT was positive in 101 (22.1%) recipients and associated with clinically latent TB before KT (P

Purpose The aim of this study was to determine whether stratification of deceased donors by the United Network for Organ Sharing (UNOS) criteria negatively impacts graft survival. Materials and Methods We retrospectively reviewed deceased donor and recipient pretransplant variables of kidney transplantations that occurred between February 1995 and December 2009. We compared clinical outcomes between standard criteria donors (SCDs) and expanded criteria donors (ECDs). Results The deceased donors consisted of 369 patients. A total of 494 transplant recipients were enrolled in this study. Mean age was 41.7±11.4 year (range 18–69) and 273 patients (55.4%) were male. Mean duration of follow-up was 8.8±4.9 years. The recipients from ECD kidneys were 63 patients (12.8%). The overall mean cold ischemia time was 5.7±3.2 hours. Estimated glomerular filtration rate at 1, 2, and 3 years after transplantation were significantly lower in ECD transplants (1 year, 62.2±17.6 vs. 51.0±16.4, p0.05), although patient survival was lower in ECDs than SCDs (Log rank test, p=0.011). Conclusion Our data demonstrate that stratification by the UNOS criteria does not predict graft survival. In order to expand the donor pool, new criteria for standard/expanded donors need to be modified by regional differences.

Background: Vascular access (VA) is essential for hemodialysis (HD) patients, and its dysfunction is a major complication. However, little is known about outcomes in patients with recurrent VA dysfunction. We explored the influence of recurrent VA dysfunction on cardiovascular (CV) events, death and VA abandonment. Methods: This is a single-center, retrospective study conducted in patients who underwent VA surgery between 2009 and 2014. VA dysfunction was defined as VA stenosis or thrombosis requiring intervention after the first successful cannulation. Patients with ≥2 interventions within 180 days were categorized as having recurrent VA dysfunction. Outcomes were analyzed using Cox proportional hazards model before and after propensity score matching. Results: Of 766 patients (ages 59.6 ± 14.3 years, 59.7% male), 10.1% were in the recurrent VA dysfunction group. Most baseline parameters after matching were similar between the recurrent and non-recurrent groups. A total of 213 propensity score-matched patients were followed for 28.7 ± 15.8 months, during which 46 (21.6%), 30 (14.1%) and 14 (6.6%) patients had de novo CV outcomes, died and abandoned VA, respectively. Recurrent VA dysfunction after adjustment remained an independent risk factor for CV events (adjusted hazards ratio (aHR), 2.71; 95% CI 1.48-4.98; p = 0.001). Moreover, recurrent VA dysfunction predicted composite all-cause mortality (ACM)/CV events (aHR 1.99; 95% CI 1.21-3.28; p = 0.007). Conclusions: Recurrent VA dysfunction was a novel independent risk factor for CV and composite ACM/CV events in HD patients, but not for VA abandonment. Patients with recurrent vascular dysfunction should be carefully monitored not only for VA patency but also for CV events.

BACKGROUND Wide variation in tacrolimus concentrations and low tacrolimus exposure have been reported to be associated with poor renal graft outcomes in non-Asians. The CYP3A5 polymorphism is a representative genetic factor that might affect this association, together with environmental factors. We investigated whether tacrolimus variability or the mean tacrolimus trough concentration can influence kidney allograft outcomes in Asians and whether the CYP3A5 polymorphism (rs776746) can affect this relationship. METHODS Data from renal transplant patients between 2000 and 2010 were analyzed retrospectively. The tacrolimus intraindividual variability (IIV) and the mean tacrolimus trough concentration were calculated from the tacrolimus concentrations between 6 and 12 months after transplantation. RESULTS A total of 249 renal transplant patients were enrolled. The patients with higher tacrolimus IIV had shorter rejection-free survival (P = 0.002). However, there was no difference in rejection-free survival between CYP3A5 expressers and nonexpressers. The tacrolimus IIV was not associated with the CYP3A5 polymorphism. High IIV of tacrolimus was an independent risk factor of biopsy-proven acute rejection after adjusting for mean tacrolimus concentration, HLA mismatch, induction therapy, donor type, and CYP3A5 polymorphism (hazard ratio 2.655, 95% confidence interval 1.394-5.056). Interestingly, the impact of tacrolimus IIV on acute rejection was significant in CYP3A5 expressers, whereas it was not in CYP3A5 nonexpressers. CONCLUSIONS The IIV of tacrolimus trough concentrations had a significant impact on rejection-free survival. The effect was influenced by CYP3A5 polymorphism, although the tacrolimus variability itself was not determined by the CYP3A5 polymorphism.

This study was designed to compare the hospital-related costs of elective abdominal aortic aneurysm (AAA) treatment and cost structure between endovascular aneurysm repair (EVAR) and open surgical repair (OSR) in Korean health care system. One hundred five primary elective AAA repairs (79 OSRs and 26 EVARs) performed in the Seoul National University Hospital from 2005 to 2009 were included. Patient characteristics were similar between two groups except for older age (P = 0.004) and more frequent history of malignancy (P = 0.031) in EVAR group. Thirty-day mortality rate was similar between two groups and there was no AAA-related mortality in both groups for 5 yr after repair. The total in-hospital costs for the index admission were significantly higher in EVAR patients (mean, KRW19,857,119) than OSR patients (mean KRW12,395,507) (P < 0.001). The reimbursement was also significantly higher in EVAR patients than OSR patients (mean, KRW14,071,081 vs KRW6,238,895, P < 0.001) while patients payments was comparable between two groups. EVAR patients showed higher follow-up cost up to 2 yr due to more frequent imaging studies and reinterventions for type II endoleaks (15.4%). In the perspective of cost-effectiveness, this study suggests that the determination of which method to be used in AAA treatment be more finely trimmed and be individualized.

Objective Spontaneous isolated dissection of the superior mesenteric artery (SIDSMA) is extremely rare. Various treatment options are currently available, including conservative management, anticoagulation, endovascular stenting, and surgical repair. Herein, we present our experience in the treatment of symptomatic SIDSMA. Methods A retrospective study was conducted on 14 consecutive patients with symptomatic SIDSMA between January 2000 and January 2010. All patients had acute onset abdominal pain. The decision to intervene was based on patient symptoms and signs, as well as the morphologic characteristics of superior mesenteric artery (SMA) dissection on computed tomography (CT) angiography. Endovascular stenting (ES) was indicated in patients with severe compression of the true lumen or dissecting aneurysm likely to rupture. Self-expandable stents were placed via a right common femoral approach. None of the patients underwent anticoagulation, and patients who underwent ES were maintained on antiplatelet therapy for 3 months postoperatively. Results The median age of the study subjects was 59 years (range, 50-75 years). The median follow-up time was 27.5 months (range, 2-64 months). Treatment included conservative management without the use of anticoagulation in seven patients, ES in six, and necrotic bowel resection in one. Four patients with severe compression of the true lumen or large dissecting aneurysm underwent ES as a primary treatment. ES was additionally performed in two patients in whom initial conservative treatment failed (increasing dissecting aneurysm at 7-day follow-up CT scan in one and a reappearance of abdominal pain after resuming diet in the other). The median fasting time was significantly shorter in patients with primary ES (2.5 days) than in those managed conservatively (8.0 days). No complications associated with the SIDSMA or ES were developed. The patency of stents was demonstrated on follow-up CT scans up to 60 months (range, 1-60 months). Conclusions Conservative management without anticoagulation can be applied successfully to the patients with symptomatic SIDSMA. Primary endovascular stenting is indicated if patients have suspected bowel ischemia, compression of the true lumen of the SMA >80%, or SMA aneurysm of >2.0 cm in diameter on initial CT scan. Endovascular stenting can also be provided to the patients in whom initial conservative treatment failed, as a rescue therapy.

Continuous efforts have been made by the organ donation and transplantation community in Korea to increase organ donation by the deceased. The authors detailed trends of organ donation and utilization over the past 10 yr using data provided by the KONOS. The yearly number of deceased donors has grown gradually since 2003. The number and percentage of old donors (or = 50 yr) and donors dying from intracranial hemorrhage has increased continuously. Therefore, the percentage of standard criteria donors (SCD) has been declining significantly, from 94% in 2000 to 79.2% in 2009. The number of organs transplanted per donor (OTPD) has also declined slightly since 2007, from 3.28 in 2007 to 2.95 in 2009. This decline may be attributable to increases in the number and percentage of extended criteria donors (ECD) and donors after cardiac death (DCD), since the OTPD was 2.25 for DCD, 2.5 for ECD, and 3.09 for SCD in 2009. In summary, the makeup of donors has changed significantly. There is an urgent need for establishment of an institutional framework including an independent organ procurement organization and for improvement for the National Transplant Act to increase deceased donor pool and to optimize management of ECD and DCD.

Background We aimed to assess whether patients colonized with certain organisms in the genitourinary tract would have greater urinary tract infection (UTI) risk during the post-transplantation period, and whether information on the perioperatively colonized organisms may help identify the causal organisms during early UTI. Methods We retrospectively reviewed the culture results of preoperative urine, preoperative urethral swab, and postoperative urinary catheter tip specimens of 420 renal transplant recipients. The colonization status was compared to the culture results during the first UTI episode within 6 months after transplantation. Results Twenty six (6.2%) patients developed early UTI, and the presence of common uropathogens in the perioperative genitourinary specimen was positively associated with a higher early UTI risk odds ratio [OR], 3.23; 95% confidence interval [CI], 1.44 to 7.24; P = 0.003). However, the actual causal organism during UTI was observed perioperatively only in 15 patients (40.5%). Neither perioperative colonization nor early UTI was associated with subsequent acute cellular rejection or graft failure. Conclusions Renal transplantation patients who were colonized with common uropathogens were more likely to develop early UTI. However, the usefulness of the culture results of perioperative colonizers in predicting the causal organism during early UTI seems limited due to the low concordance rate.

Background Segmental arterial mediolysis (SAM) is a rare non-atherosclerotic, non-inflammatory vascular disorder varying widely in clinical course. The purpose of this study is to analyze detailing clinical and imaging manifestations over time in patients with SAM through a literature review and to suggest an optimal management strategy. Methods A retrospective review of eight consecutive patients diagnosed with SAM between January, 2000 and January, 2012 was conducted. All presented with acute-onset abdominal or flank pain. Clinical features, imaging studies, and laboratory findings served as grounds for diagnosis, having excluded more common conditions (ie, fibromuscular dysplasia, collagen vascular disorders, or arteritis). CT angiography was done initially and repeated periodically (Week 1, Month 3, then yearly). Treatment was conservative, utilizing endovascular intervention as warranted by CT diagnostics. In a related systematic review, all English literature from 1976 to 2015 was screened via the PubMed database, assessing patient demographics, affected arteries, clinical presentations, and treatment methods. Findings Ultimately, 25 arterial lesions identified in eight patients (median age, 62.8 years; range, 40–84 years) were monitored for a median period of 26 months (range, 15–57 months). At baseline, celiac axis (3/8, 37.5%), superior mesenteric (4/8, 50%), and common hepatic (2/8, 25%) arteries were involved, in addition to isolated lesions of right renal, splenic, right colic, middle colic, gastroduodenal, left gastric, right gastroepiploic, proper hepatic, right hepatic, and left hepatic arteries. Compared with prior publications, celiac axis and superior mesenteric artery were more commonly affected in cohort. Arterial dissections (n = 8), aneurysms (n = 5), stenoses or occlusions (n = 4), and a single pseudoaneurysm were documented. Despite careful conservative management, new splanchnic arterial lesions (n = 4) arose during follow-up. Considering the few available reports of new arterial lesions in the literature, newly developing pathology is a distinctive feature of our patients, four of whom eventually required endovascular interventions. Conclusions Careful clinical observation via periodic CT angiography is required in patients with SAM, checking for newly developing lesions. The natural history of SAM should be clarified in a larger patient population.

Background Persistent sciatic artery (PSA) is a relatively rare congenital variant of the lower limb vasculature and can have highly variable clinical presentations. The purpose of this study was to analyze the relationship between PSA anatomy and clinical presentation, and to suggest an optimal management strategy. Methods Between 2001 and 2014, 24 PSAs in 19 patients were diagnosed by computed tomography and referred to the vascular surgery department. Patient demographics, types of PSA and femoral artery, aneurysmal changes, symptoms, and treatment methods were assessed. Additionally, all English literature from 1964 to 2014 was reviewed and compared using the PubMed database (224 PSAs in 171 patients). Results PSA was diagnosed in 10 men (52.6%) and nine women (47.4%). PSAs were bilateral in five patients (26.3%) and symptomatic in 12 patients, while in seven patients PSA was found incidentally. According to the Pillet-Gauffre classification, Type 2a was the most common variant ( n = 15/24, 62.5%), with unclassifiable types in two limbs. Compared with cases in the literature, the PSA occlusion rate in this study was higher ( n = 10/24, 41.7% vs. n = 54/224, 27.5%), but aneurysm incidence was higher in the literature cases ( n = 5/24, 20.8% vs. n = 112/224; 50.7%). In this study, 16 limbs (66.6%) were treated conservatively, and six limbs were treated by open surgery, including four bypasses, one amputation, and one thrombo-embolectomy. Endovascular coil embolization was performed in one limb, and a hybrid procedure with stent graft was performed in one limb with PSA aneurysm. Based on the present series and the literature review, a new classification system and treatment option is proposed according to the anatomic status and the presence of aneurysm. According to the new classification, class III was the most common in both the present study (18/24; 75%) and the literature review, and the presence of aneurysm was the most important determinant of surgical treatment. Conclusions The new classification system is simple and provides guidance for management. Limb anatomy of the femoral artery system and the presence of PSA aneurysm should be considered when selecting the optimal treatment. The risk of embolism from the presence of aneurysm is an important factor for treatment, and bypass surgery is mostly required in classes III and IV.

The purpose of this study was to investigate immunoglobulin A nephropathy recurrence rate after transplant in children and adults and to identify recurrence rates by clinical progression before transplant.There were 56 patients with immunoglobulin A nephropathy who had renal transplant between 1989 and 2005. We categorized recipient age intoor ≥ 20 years at transplant. Each age category was divided into 2 levels based on recurrence.The recurrence rate was higher in patients aged20 years(53.8%) than ≥ 20 years. Proteinuria was more frequently diagnosed in patients aged20 years (57.1% vs 25.0%; P = .047). In patients aged ≥ 20 years, the duration of dialysis was 4.55 months in the recurrence group and 17.78 months in the no recurrence group (P = .032). Time from progressive symptoms to renal replacement therapy was significantly shorter in patients aged ≥ 20 years with recurrence than patients aged ≥ 20 years with no recurrence. The univariate relative risk of recurrent immunoglobulin A nephropathy after transplant was 9.8 for recipients aged ≥ 20 years who had progressive symptoms to renal replacement therapy24 months (P = .046).Patients aged20 years had more rapid disease progression to end-stage renal disease and a higher recurrence rate after transplant than patients aged ≥ 20 years. If patients aged ≥ 20 years progress rapidly from progressive symptoms to renal replacement therapy, renal transplant may be considered after 24 months because of high recurrence risk.

FSGS is the second most common cause of idiopathic NS in children. It often progresses to ESRD and commonly recurs after KT. To investigate the risk factors and the prognosis of recurrence in pediatric idiopathic FSGS in Korea, retrospective review of 43 KT in 38 children with idiopathic FSGS of last two decades was conducted. The patients presented at the median age of 5.1 yr (range 1.1-13.8 yr) and received KT 5.7 yr later (range 1.3-17.6 yr). FSGS recurred in 20 allografts immediately after transplantation, only in those who presented with NS but not in those who presented with AUA. The risk factors for recurrence were age of onset >5 yr and progression to ESRD within six yr but not sooner than 18 months. CR was achieved in 13 patients with FSGS recurrence and sustained in nine without subsequent relapse over a median of six and a half yr (0.6-20.7 yr). Pediatric idiopathic FSGS presenting with NS recurred in more than half of patients after transplantation. Interestingly, more rapid progression within less than 18 months did not predict recurrence. To identify high-risk patients of recurrence, an international cooperative study would be necessary.

As tacrolimus has a rather narrow therapeutic range and high individual variability in its pharmacokinetics, it is important to determine the cause of the variation in tacrolimus pharmacokinetics. The purpose of this study was to establish a population pharmacokinetic–pharmacogenetic model of tacrolimus and identify covariates that affect pharmacokinetic parameters to prevent fluctuations in the tacrolimus trough concentration during the early period after transplantation. Data from 1501 trough concentrations and 417 densely collected concentrations were compiled from 122 patients who were on post-operative days 10–20 and analysed with a nonlinear mixed-effect model. The first-order conditional estimation (FOCE) with interaction method was used to fit the model using the NONMEM program. Clinical/laboratory data were also collected for the same period, and CYP3A5 and ABCB1 genotypes were analysed for use in modelling from all included patients. An empirical Bayesian approach was used to estimate individual pharmacokinetic profiles. A one-compartment model with first absorption and elimination and lag time best described the data. The estimated population mean of clearance (CL/F), volume of distribution (V/F) and absorption rate (Ka) were 21.9 L/hr, 205 L, and 3.43/hr, respectively, and the lag time was fixed at 0.25 hr. Clearance increased with days after transplantation and decreased with CYP3A5*3/*3 about 18.4% compared with CYP3A5*1 carriers (p

The pharmacokinetics, efficacy and safety of once-daily tacrolimus formulation (Tac-OD) were assessed in 34 stable pediatric kidney transplant recipients. Enrolled patients received their dose of twice-daily tacrolimus formulation (Tac-BID) on study Days 0 through 7. On the morning of study Day 8, the total daily doses for patients were converted to Tac-OD on a 1:1 basis and maintained on a once-daily morning dosing regimen. Tacrolimus pharmacokinetic profiles were obtained on study Days 7, 14 and 28 (after dose adjustment). Although the mean C0 concentrations (4.10 ± 1.16-3.53 ± 1.10 ng/mL, p = 0.004), and AUC0-24 (151.8 ± 41.6-129.8 ± 39.3 ng h/mL, p < 0.001) were decreased significantly after a 1:1 based conversion, there was high interindividual variability. The dose of Tac-OD was decreased in 26.5% and increased in 44.1% of patients. The resultant tacrolimus dose and pharmacokinetic profiles on study Day 28 were comparable to those on Day 7. There were no serious adverse events. In conclusion, Tac-BID can be safely converted to Tac-OD in stable pediatric kidney transplant patients with the heightened therapeutic drug monitoring. Effects of drug conversion on the cardiovascular risk factors, neurological side effects and adherence should be further evaluated.

Acute arterial thromboembolism (ATE) is rare in childhood, but this medical emergency requires immediate treatment. Described herein are separate instances of lower extremity ATE in 2 children, both of whom were successfully managed through image-guided thromboembolectomy (IGT). One patient, a 34-month-old female child with nephrotic syndrome, developed bilateral iliac and popliteal thromboembolic arterial occlusions after high-dose steroid therapy. Another 9-year-old girl suffered an embolism of left popliteal artery due to infectious endocarditis. Both patients underwent IGT using over-the-wire Fogarty catheters. During follow-up, presenting symptoms resolved without significant complications.

Although monitoring the intracellular concentration of immunosuppressive agents may be a promising approach to individualizing the therapy after organ transplantation, additional studies on this issue are needed prior to its clinical approval. We investigated the relationship between intracellular and whole blood concentrations of tacrolimus (IC-TAC and WB-TAC, respectively), the factors affecting this relationship, and the risk of rejection based upon IC-TAC in stable kidney recipients. Both IC-TAC and WB-TAC were measured simultaneously in 213 kidney recipients with stable graft function using LC-MS/MS. The tacrolimus ratio was defined as IC-TAC per WB-TAC. The genetic polymorphism of ABCB1 gene and flow cytometric analyses were conducted to probe the correlation between tacrolimus concentrations and the immunoreactivity status as a potential risk of rejection, respectively. The correlation between IC-TAC and WB-TAC was relatively linear (r = 0.67; P

The present work describes the preliminary results of a new method of minimally invasive thrombectomy in the treatment of thrombosed arteriovenous fistula (AVF) with dilated aneurysm. Data from 25 patients who were treated with this minimal venotomy technique were retrospectively reviewed. The minimal venotomy was made on the dilated fistula, and thrombectomy was performed with forceps and Fogarty catheters through the venotomy site. Technical and clinical success was achieved in all 25 patients. There were two major and two minor complications (8% each). The two major complications consisted of bleeding at the venotomy site after early suture removal.

Background. Idiopathic focal segmental glomerulosclerosis (FSGS) occurring at young age is known to predispose to poor graft outcome, but the outcome of adulthood-onset FSGS (A-FSGS) has not been thoroughly investigated. Here, we compared the graft outcomes between kidney recipients with A-FSGS and childhood-onset FSGS (C-FSGS). Methods. We enrolled 47 A-FSGS recipients and 60 CFSGS recipients with an onset age of � 15, from four of the largest transplant centers in Korea. Results. The baseline characteristics were similar between two groups. The 1- and 3-year cumulative recurrence rates were 20.0 and 22.1%, respectively. FSGS was recurrent in 19 C-FSGS patients [median duration, 2 months (interquartile range, IQR, 1–35)], and 11 patients had recurrent disease in A-FSGS [5 months (IQR, 3–37)]. The recurrence rate was similar between two groups (P ¼ 0.126). The 5- and 10-year graft survival rates were 90.0 and 78.5%, respectively. The overall graft survival rates were not different between two groups. After adjusting baseline characteristics, the development of major outcomes was similar between two groups except acute rejection that was more frequent in A-FSGS. The age of disease onset did not affect recurrence in both groups. While grafts with recurrence had poorer graft survival in the A-FSGS group (P ¼ 0.005), the recurrence was not associated with graft loss in the C-FSGS group (P ¼ 0.558). Conclusions. The onset age did not affect the graft outcome in patients with FSGS, and the recurrence significantly affected graft survival in A-FSGS. Therefore, the main focus should aim for the management of recurrence.