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Infections are a major cause of morbidity, graft failure, and mortality in solid organ transplant recipients. Preventive measures have greatly reduced the burden of posttransplant infections. However, little is known about the practice patterns of infection prevention in South Korea.A questionnaire-based cross-sectional survey was conducted. The questionnaire was developed by a multidisciplinary discussion. From the Korean Network for Organ Sharing data, a list of hospitals that performed kidney, liver, heart, and lung transplantations in 2019 was selected. We invited participants to respond to the questionnaire via email from January to March 2022.The response rates for each organ were as follows; 41% (31/76 hospitals) for kidney, 49% (25/51) for liver, 40% (8/20) for heart, and 89% (8/9) for lung transplantations. The median duration of antibacterial prophylaxis after transplant ranged from 5 to 7 days. Prophylaxis was commonly applied in cytomegalovirus (CMV) D+/R- recipients. For non-lung CMV R+ recipients, a preemptive strategy was the most common method. The duration of viral load monitoring for preemptive or hybrid strategies varied. All lung transplant programs used mold-active antifungal agents for a median of 6 months. An interferon-gamma release assay was most commonly used to screen for latent tuberculosis infections.The infection prevention protocols in most transplant programs in Korea were generally in accordance with the guidelines. However, some variability was observed regarding antibacterial prophylaxis and CMV prevention. Our results provide useful insights into practice patterns and will assist in the development of national guidelines.

Background: As the need for a nationwide organ-transplant registry emerged, a prospective registry, the Korean Organ Transplantation Registry (KOTRY), was initiated in 2014. Here, we present baseline characteristics and outcomes of the kidney-transplant cohort for 2014 through 2019. Methods: The KOTRY consists of five organ-transplant cohorts (kidney, liver, lung, heart, and pancreas). Data and samples were prospectively collected from transplant recipients and donors at baseline and follow-up visits; and epidemiological trends, allograft outcomes, and patient outcomes, such as posttransplant complications, comorbidities, and mortality, were analyzed. Results: From 2014 to 2019, there were a total of 6,129 registered kidney transplants (64.8% with living donors and 35.2% with deceased donors) with a mean recipient age of 49.4 ± 11.5 years, and 59.7% were male. ABO-incompatible transplants totaled 17.4% of all transplants, and 15.0% of transplants were preemptive. The overall 1- and 5-year patient survival rates were 98.4% and 95.8%, respectively, and the 1- and 5-year graft survival rates were 97.1% and 90.5%, respectively. During a mean follow-up of 3.8 years, biopsy- proven acute rejection episodes occurred in 17.0% of cases. The mean age of donors was 47.3 ± 12.9 years, and 52.6% were male. Among living donors, the largest category of donors was spouses, while, among deceased donors, 31.2% were expanded-criteria donors. The mean serum creatinine concentrations of living donors were 0.78 ± 0.62 mg/dL and 1.09 ± 0.24 mg/dL at baseline and 1 year after kidney transplantation, respectively. Conclusion: The KOTRY, a systematic Korean transplant cohort, can serve as a valuable epidemiological database of Korean kidney transplants.

De novo donor-specific antibody (dnDSA) is associated with a higher risk of kidney graft failure. However, it is unknown whether preemptive treatment of subclinical dnDSA is beneficial. Here, we assessed the efficacy of high-dose intravenous immunoglobulin (IVIG) and rituximab combination therapy for subclinical dnDSA. An open-label randomized controlled clinical trial was conducted at two Korean institutions. Adult (aged ≥ 19 years) kidney transplant patients with subclinical class II dnDSA (mean fluorescence intensity ≥ 1000) were enrolled. Eligible participants were randomly assigned to receive rituximab or rituximab with IVIG at a 1:1 ratio. The primary endpoint was the change in dnDSA titer at 3 and 12 months after treatment. A total of 46 patients (24 for rituximab and 22 for rituximab with IVIG) were included in the analysis. The mean baseline estimated glomerular filtration rate was 66.7 ± 16.3 mL/min/1.73 m2. The titer decline of immune-dominant dnDSA at 12 months in both the preemptive groups was significant. However, there was no difference between the two groups at 12 months. Either kidney allograft function or proteinuria did not differ between the two groups. No antibody-mediated rejection occurred in either group. Preemptive treatment with high-dose IVIG combined with rituximab did not show a better dnDSA reduction compared with rituximab alone.Trial registration: IVIG/Rituximab versus Rituximab in Kidney Transplant With de Novo Donor-specific Antibodies (ClinicalTrials.gov Identifier: NCT04033276, first trial registration (26/07/2019).

Background: Recent several reports have demonstrated that periodontitis is prevalent and adversely affects the survival in patients with chronic kidney disease (CKD) or end-stage kidney disease. However, its impact on transplant outcomes remains uncertain.Methods: This retrospective cohort study included 136 and 167 patients, respectively, who underwent living donor kidney transplantation (KT) at Seoul National University Hospital from July 2012 to August 2016 and Korea University Hospital from April 2008 to October 2018. We divided patients into three groups according to stages of periodontitis based on a new classification system. Results: Patients with severe periodontitis were older, had a higher prevalence of diabetes, a higher body mass index and C-reactive protein level, a lower cardiac output, and were more likely to be smokers, indicating its association with chronic systemic inflammation. After KT, stage IV periodontitis was independently associated with a lower incidence of acute T cell-mediated rejection, suggesting the possible effect of periodontitis on immune function. However, 1-year and 3-year estimated glomerular filtration rates were not different. Among the KT recipients followed up more than 3 years, new-onset cardiovascular disease occurred in nine patients, and coronary artery disease occurred more frequently in patients with stage IV periodontitis. However, diabetes was the independent predictor of new-onset coronary artery disease in multivariate logistic regression analysis.Conclusion: Our findings showed that periodontitis might be an important player in determining posttransplant outcomes in recipients. Further interventional trials to test whether treating periodontitis could modify transplant outcome are needed.

Iron plays an important role in hemodynamics and the immunity, independent of anemia. Since dynamic changes occur in iron storage after kidney transplantation (KT), we investigated the association between iron status and kidney outcomes in KT patients. We analyzed data from the KoreaN cohort study for Outcome in patients With KT (KNOW-KT). The iron status was classified into three groups based on ferritin or transferrin saturation (TSAT) levels one year after KT, with reference ranges of 20‒35% and 100‒300 ng/mL for TSAT and ferritin, respectively. The primary outcome was the composite outcome, which consisted of death, graft failure, and an estimated glomerular filtration rate decline ≥ 50%. In total, 895 patients were included in the final analysis. During a median follow-up of 5.8 years, the primary outcome occurred in 94 patients (19.8/1000 person-years). TSAT levels decreased one year after KT and thereafter gradually increased, whereas ferritin levels were maintained at decreased levels. The adjusted hazard ratios (95% confidence intervals) for the composite outcome were 1.67 (1.00–2.77) and 1.20 (0.60–2.40) in the TSAT > 35% and ferritin > 300 ng/mL groups, respectively. High iron status with high TSAT levels increases the risk of graft failure or kidney functional deterioration after KT.

The smoking status of kidney transplant recipients and living donors has not been explored concurrently in a prospective study, and the synergistic adverse impact on outcomes remains uncertain. The self-reported smoking status and frequency were obtained from recipients and donors at the time of kidney transplantation in a prospective multicenter longitudinal cohort study (NCT02042963). Smoking status was categorized as "ever smoker" (current and former smokers collectively) or "never smoker." Among 858 eligible kidney transplant recipients and the 858 living donors, 389 (45.3%) and 241 (28.1%) recipients were considered ever smokers at the time of transplant. During the median follow-up period of 6 years, the rate of death-censored graft failure was significantly higher in ever-smoker recipients than in never-smoker recipients (adjusted HR, 2.82; 95% CI 1.01-7.87; P = 0.048). A smoking history of >20 pack-years was associated with a significantly higher rate of death-censored graft failure than a history of ≤20 pack-years (adjusted HR, 2.83; 95% CI 1.19-6.78; P = 0.019). No donor smoking effect was found in terms of graft survival. The smoking status of the recipients and donors or both did not affect the rate of biopsy-proven acute rejection, major adverse cardiac events, all-cause mortality, or post-transplant diabetes mellitus. Taken together, the recipient's smoking status before kidney transplantation is dose-dependently associated with impaired survival.

We evaluated the temporal trend of preemptive kidney transplantation (KT) and the effect of pretransplant dialysis duration on post-transplant outcomes. This was a nationwide cohort study of the first-time 3392 living donor KT (LDKT) recipients (2014-2019). The annual changes in proportion of preemptive KT, factors associated with preemptive KT, and post-transplant outcomes were analyzed. Preemptive KT was performed in 816 (24.1%) patients. Annual trend analysis revealed gradual decrease in preemptive KT over time (P = 0.042). Among the underlying causes of preemptive KT, the proportion of diabetes increased and that of glomerulonephritis decreased during the study period. Glomerulonephritis as the primary renal disease was a predictor of preemptive KT. Patients with pretransplant dialysis >6 months showed increased graft failure risk than preemptive KT in the subdistribution of hazard model for competing risk (adjusted hazard ratio [aHR], 2.53; 95% confidence interval [CI], 1.09-5.87; P = 0.031) and in propensity score-matched analysis (aHR, 2.45; 95% CI, 1.02-5.92; P = 0.034); however, pretransplant dialysis ≤6 months showed comparable graft survival with preemptive KT in both analyses. Preemptive KT declined over successive years, associated with an increase in diabetes and a decrease in glomerulonephritis as underlying causes of KT. Short period of dialysis less than 6 months does not affect graft survival compared with preemptive KT; however, longer dialysis decreases graft survival.

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.

HLA-incompatible living donor kidney transplantation (LDKT) is one of efforts to increase kidney transplantation opportunity for sensitized patients with kidney failure. However, there are conflicting reports for outcomes of HLA-incompatible kidney transplantation compared to patients who wait for HLA-compatible deceased donor kidney transplantation (DDKT) in the United States and United Kingdom. Waiting for an HLA-compatible DDKT is relatively disadvantageous in Korea, because the average waiting time is more than five years. To study this further, we compared outcomes of HLA-incompatible LDKT with those who wait for HLA-compatible DDKT in Korea. One hundred eighty nine patients underwent HLA-incompatible LDKT after desensitization between 2006 and 2018 in two Korean hospitals (42 with a positive complement-dependent cytotoxicity cross-match, 89 with a positive flow cytometric cross-match, and 58 with a positive donor-specific antibody with negative cross-match). The distribution of matched variables was comparable between the HLA-incompatible LDKT group and the matched control groups (waiting-list-only group; and the waiting-list-or-HLA-compatible-DDKT groups; 930 patients each). The HLA-incompatible LDKT group showed a significantly better patient survival rate compared to the waiting-list-only group and the waiting-list-or-HLA-compatible-DDKT groups. Furthermore, the HLA-incompatible LDKT group showed a significant survival benefit as compared with the matched groups at all strength of donor-specific antibodies. Thus, HLA-incompatible LDKT could have a survival benefit as compared with patients who were waitlisted for HLA-compatible DDKT or received HLA-compatible DDKT in Korea. This suggests that HLA-incompatible LDKT as a good option for sensitized patients with kidney failure in countries with prolonged waiting times for DDKT.

Hypertensive living donors are potential candidates to expand the kidney donor pool. However, the impact of donor hypertension on graft survival and function remains to be clarified.We analyzed 3907 kidney transplant recipients registered in a nationwide prospective cohort from 2014 to 2018. Patients were divided by donor types and the presence of donor hypertension. The primary and secondary outcome was the occurrence of death-censored graft failure and renal allograft function, respectively.The prevalence of hypertension was 9.4% (258/2740) and 19.9% (232/1167) in living and deceased donors, respectively. During a median follow-up of 21.8 months, death-censored graft survival rate was significantly worse in recipients of hypertensive living donors than in those of normotensive living donors ( P = 0.008). In multivariable analysis, recipients of hypertensive living donors had a significantly increased risk of graft loss (adjusted hazard ratio 2.91; P = 0.009). The risk of allograft loss was not different between recipients of hypertensive living and normotensive deceased donors. Propensity score-matched analyses had consistent worse graft survival rate in recipients of hypertensive living donors compared to those of normotensive living donors ( P = 0.027), while it was not different between recipients of hypertensive living and normotensive deceased donors. Hypertension in living donors had a significant negative impact on one-year graft function (adjusted unstandardized β -3.64; P = 0.011).Hypertensive living donor recipients have significantly higher risks of renal allograft loss than normotensive living donor recipients, and showed similar outcomes compared to recipients of normotensive deceased donors.

HLA-B*58:01 is a well-known risk factor for allopurinol-induced severe cutaneous adverse reactions (SCARs). However, only a minority of HLA-B*58:01 carriers suffer SCARs after taking allopurinol. The aim of this study was to investigate subsidiary genetic markers that could identify those at further increased risk of developing allopurinol-induced drug reaction with eosinophilia and systemic symptoms (DRESS) in subjects with HLA-B*58:01.Subjects with B*58:01 were enrolled (21 allopurinol-induced DRESS and 52 allopurinol-tolerant control). HLA-A, -B, -C and -DRB1 alleles were compared. Comparison of risk between HLAs and allopurinol-induced SCAR in separate populations was performed to support the results. Kruskal-Wallis test, Pearson's chi-square test, Fisher's exact test and binary logistic regression were used to analyze the risk of SCAR development.Frequencies of A*24:02 (71.4 vs. 17.3%,The additional secondary screening with A*24:02 and DRB1*13:02 alleles may identify those at further increased risk of allopurinol-induced DRESS in B*58:01 carriers.

Communication skill is one of the critical elements to establish interactive linkage among other countries around the world in this global era. Communication strategies are defined as linguistic approaches or devices that language learners can readily employ to reach particular communicative goals and to overcome linguistic deficiencies or problems in interlanguage communication (Sukirlan, 2014). Willingness to communicate regards as “the probability of engaging communication when free to choose to do so” (MacIntyre et al., 2014), with attributes including communication apprehension, perceived communication competence, introversion-extraversion, self-esteem, and so forth. The purpose of this research was to investigate the effect of communication strategy on tertiary EFL students’ willingness to communicate (WTC) and their strategy use. The experimental group (n=51) received 7-week communication strategy-based instruction. Both quantitative and qualitative data including self-report questionnaires on communication strategy and WTC, transcription of think-aloud protocols, strategy diary, and short memos were collected. Pre-and post- oral communication tasks are given to examine their actual use of CS. The eight strategies, such as code-switching, appeal for assistance, non-verbal, word coinage, avoidance, exemplification, approximation and circumlocution were introduced through the strategy-based instruction in a college language classroom setting. The results showed that SBI of communication strategy had a positive impact on their WTC and strategy use. Specifically, there is a significant increase in the use of three coping strategies to overcome EFL speakers’ linguistic deficiency including approximation, word-coinage, and code-switching after 7 weeks of CS training. On the other hand, there is no statistical difference in the use of avoidance, exemplification, and literal translation. This session will provide pedagogical implication as well.

Late Pneumocystis jirovecii pneumonia (PJP) is not rare in the era of universal prophylaxis after kidney transplantation. We aimed to determine the nationwide status of PJP prophylaxis in Korea and compare the incidence, risk factors, and outcomes of early and late PJP using data from the Korean Organ Transplantation Registry (KOTRY), a nationwide Korean transplant cohort. We conducted a retrospective analysis using data of 4,839 kidney transplant patients from KOTRY between 2014 and 2018, excluding patients who received multi-organ transplantation or were under 18 years old. Cox regression analysis was performed to determine risk factors for early and late PJP. A total of 50 patients developed PJP. The number of patients who developed PJP was same between onset before 6 months and onsets after 6 months. There were no differences in the rate, duration, or dose of PJP prophylaxis between early and late PJP. Desensitization, higher tacrolimus dose at discharge, and acute rejection were associated with early PJP. In late PJP, old age as well as acute rejection were significant risk factors. In conclusion late PJP is as common and risky as early PJP and requires individualized risk-based prophylaxis, such as prolonged prophylaxis for old patients with a history of rejection.

The impact of pretransplant and posttransplant alcohol consumption on outcomes in kidney transplant recipients (KTRs) is uncertain. Self-reported alcohol consumption was obtained at the time of transplant and 2 years after transplant in a prospective cohort study. Among 907 KTRs, 368 (40.6%) were drinkers at the time of transplant. Compared to non-drinkers, alcohol consumption did not affect the risk of death-censored graft failure (DCGF), biopsy-proven acute rejection (BPAR), cardiovascular events, or all-cause mortality. Compared to persistent non-drinkers, the development of DCGF, BPAR, cardiovascular events, all-cause mortality, or posttransplant diabetes mellitus was not affected by the alcohol consumption pattern (persistent, de novo, or stopped drinking) over time. However, de novo drinkers had a significantly higher total cholesterol (p < 0.001) and low-density lipoprotein cholesterol levels (p = 0.005) compared to persistent non-drinkers 5 years after transplant, and had significantly higher total cholesterol levels (p = 0.002) compared to the stopped drinking group 7 years after transplant, even after adjusting for the use of lipid-lowering agents, age, sex, and body mass index. Although pretransplant and posttransplant alcohol consumption were not associated with major outcomes in KTRs during the median follow-up of 6.0 years, a new start of alcohol use after KT results in a relatively poor lipid profile.Clinical Trial Registration:clinicaltrials.gov, identifier NCT02042963.

Tacrolimus is a key drug in kidney transplantation (KT) with a narrow therapeutic index. The association between the tacrolimus metabolism rate and KT outcomes have not been investigated in large-scale multi-center studies. The Korean Organ Transplantation Registry (KOTRY) datasets were used. A total of 3456 KT recipients were analyzed. The tacrolimus metabolism rate was defined as blood trough concentration of tacrolimus (C0 ) divided by the daily dose (D). The patients were grouped into fast, intermediate, or slow metabolizers by the C0 /D measured 6 months after transplantation. The slow metabolism group was associated with a 2.7 ml/min/1.73 m2 higher adjusted estimated glomerular filtration rate (eGFR) at 6 months [95% confidence interval (C.I.) 1.2-4.3, P = 0.001], less acute rejection (AR) within 6 months [Odds ratio (OR) 0.744, 95% C.I. 0.585-0.947, P = 0.016], and less interstitial fibrosis and tubular atrophy [OR 0.606, 95% C.I. 0.390-0.940, P = 0.025]. Fast tacrolimus metabolism affected the 6-month post-KT eGFR through mediation of AR [natural indirect effect (NIE) -0.434, 95% C.I. -0.856 to -0.012, P = 0.044) and delayed graft function (DGF; NIE -0.119, 95% C.I. -0.231 to -0.007, P = 0.038). Slow tacrolimus metabolism was associated with better post-KT eGFR. AR and DGF were found to be significant mediators.

Posttransplant anemia is a common complication after kidney transplantation. Parvovi rus B19 (PVB19) infection can induce pure red cell aplasia (PRCA) in immunosuppressed transplant patients. We herein report a case of recurrent PVB19-associated PRCA in a kidney transplant patient. A 49-year-old woman presented with anemia and normal renal function 1 year after a deceased-donor kidney transplantation for immunoglobulin A ne phropathy-related end-stage renal disease. She received desensitization therapy, and 2 years later, she underwent transplantation with thymoglobulin induction. Despite repeat ed red cell transfusion and erythropoietin therapy, her anemia aggravated progressively. Bone marrow biopsy revealed normocytic normochromic PRCA. Real-time polymerase chain reaction detected a high plasma load of PVB19. Administration of intravenous im munoglobulin (IVIG) at 2 g/kg with adjuvant reduction of tacrolimus and discontinuation of myfortic acid effectively treated the anemia. However, the PVB19 load remained high, and PRCA recurred 7 months after the initial IVIG treatment. Tacrolimus was switched to cyclosporine in the second IVIG treatment, which successfully improved PRCA and reduced the PVB19 load. Our case suggested that PVB19-associated PRCA should be suspected when persistent anemia is observed in kidney transplant patients with heavy immunosuppression and that PVB19-associated PRCA can recur in the presence of per sistent PVB19 viremia.

Introduction In the Asian region, no international organ transplantation registry exists. Individual centers maintain their own database, or some countries developed a national registration system. To promote collaboration among Asian transplantation societies, the Asian Society of Transplantation (AST) has developed an international transplantation registry for the Asian countries that has been named as the Asian Society Transplant Registry (ASTREG). Methods In 2017, the AST council formed a registry committee to develop 2 kinds of databases: ASTREG-N (nationwide level), which collects yearly aggregated data of participating countries, and ASTREG-H (hospital level), which collects the data of transplant recipients and donors from individual centers. Results ASTREG-N collects each country’s aggregate data of solid-organ transplantation, such as the total number of transplantations and deceased donors. ASTREG-H collects 5 transplant domains, namely recipient baseline characteristics, immunosuppression, post-transplant event, annual post-transplant evaluation, and donor traits. For the ASTREG-H project, South Korea, Philippines, Mongolia, and Myanmar are the current participants. A web-based secure data entry platform with real-time data visualization and automated data verification systems is currently available. Any participating centers can run this platform as their own data collection system. Conclusion The ASTREG is a collaborative project that will be the representative solid-organ transplantation database in the Asian region. It can aid in the harmonization of transplantation data in the Asian region.

It is unclear whether both Kidney Donor Profile Index (KDPI) and Kidney Donor Risk Index (KDRI) scores can be applied to elderly deceased donors (DDs). This study aimed to compare the predictive values of KDRI and KDPI for the occurrence of delayed graft function (DGF) in kidney transplantation (KT) from elderly DDs.The data for 1049 DD KTs from the database of the Korean Organ Transplant Registry were reviewed retrospectively.The mean age of the 1049 DDs was 50.94 ± 10.57 years. A total of 224 DDs were ≥60 years old (21.35%). The mean KDRI and KDPI were 1.24 ± 0.40 and 63.58 ± 25.16, respectively. Ninety (8.6%) recipients had DGF postoperatively. The right-skewed distributions of KDRI in both elderly and nonelderly DDs were similar. However, the KDPI curve showed a sharp increase from a KDPI score of 60 in DDs aged ≥60 years. The areas under the curve (AUCs) of receiver operator characteristics (ROC) for KDPI and KDRI were different. In DDs aged 60 years, the estimated AUCs of ROC showed significant values for KDPI (0.577, 95% confidence interval, 0.503-0.637; P = .048) and KDRI (0.576, 0.505-0.639; P = .043). However, in DDs aged ≥60 years, KDRI score, not KDPI, was a significant value: KDRI, 0.633 (0.498-0.767; P = .034); KDPI, 0.530 (0.476-0.643; P = .138).KDRI was more reliable in predicting graft outcome than KDPI in KT from elderly DDs. A longer follow-up period is needed to assess predictors for postoperative renal functions.

Background Granulocyte colony-stimulating factor (G-CSF) can increase populations of myeloid-derived suppressor cells, innate immune suppressors that play an immunoregulatory role in antitumor immunity. However, the roles of myeloid-derived suppressor cells and G-CSF in renal ischemia-reperfusion injury remain unclear. Methods We used mouse models of ischemia-reperfusion injury to investigate whether G-CSF can attenuate renal injury by increasing infiltration of myeloid-derived suppressor cells into kidney tissue. Results G-CSF treatment before ischemia-reperfusion injury subsequently attenuated acute renal dysfunction, tissue injury, and tubular apoptosis. Additionally, G-CSF treatment suppressed renal infiltration of macrophages and T cells as well as renal levels of IL-6, MCP-1, IL-12, TNF-α, and IFN-γ, but it increased levels of IL-10, arginase-1, and reactive oxygen species. Moreover, administering G-CSF after ischemia-reperfusion injury improved the recovery of renal function and attenuated renal fibrosis on day 28. G-CSF treatment increased renal infiltration of myeloid-derived suppressor cells (F4/80-CD11b+Gr-1int), especially the granulocytic myeloid-derived suppressor cell population (CD11b+Ly6GintLy6Clow); splenic F4/80-CD11b+Gr-1+ cells sorted from G-CSF-treated mice displayed higher levels of arginase-1, IL-10, and reactive oxygen species relative to those from control mice. Furthermore, these splenic cells effectively suppressed in vitro T cell activation mainly through arginase-1 and reactive oxygen species, and their adoptive transfer attenuated renal injury. Combined treatment with anti-Gr-1 and G-CSF showed better renoprotective effects than G-CSF alone, whereas preferential depletion of myeloid-derived suppressor cells by pep-G3 or gemcitabine abrogated the beneficial effects of G-CSF against renal injury. Conclusions G-CSF induced renal myeloid-derived suppressor cells, thereby attenuating acute renal injury and chronic renal fibrosis after ischemia-reperfusion injury. These results suggest therapeutic potential of myeloid-derived suppressor cells and G-CSF in renal ischemia-reperfusion injury.

Background Anti-carbohydrate antibody responses, including those of anti-blood group ABO antibodies, are yet to be thoroughly studied in humans. Because anti-ABO antibody-mediated rejection is a key hurdle in ABO-incompatible transplantation, it is important to understand the cellular mechanism of anti-ABO responses. We aimed to identify the main human B cell subsets that produce anti-ABO antibodies by analyzing the correlation between B cell subsets and anti-ABO antibody titers. Methods Blood group A-binding B cells were analyzed in peritoneal fluid and peripheral blood samples from 43 patients undergoing peritoneal dialysis and 18 healthy volunteers with blood group B or O. The correlation between each blood group A-specific B cell subset and anti-A antibody titer was then analyzed using Pearson's correlation analysis. Results Blood group A-binding B cells were enriched in CD27+CD43+CD1c- B1, CD5+ B1, CD11b+ B1, and CD27+CD43+CD1c+ marginal zone-B1 cells in peripheral blood. Blood group A-specific B1 cells (P=0.029 and R=0.356 for IgM; P=0.049 and R=0.325 for IgG) and marginal zone-B1 cells (P=0.011 and R=0.410 for IgM) were positively correlated with anti-A antibody titer. Further analysis of peritoneal B cells confirmed B1 cell enrichment in the peritoneal cavity but showed no difference in blood group A-specific B1 cell enrichment between the peritoneal cavity and peripheral blood. Conclusions Human B1 cells are the key blood group A-specific B cells that have a moderate correlation with anti-A antibody titer and therefore constitute a potential therapeutic target for successful ABO-incompatible transplantation.

The waiting time for deceased donor kidney transplants (DDKT) is increasing. We evaluated DDKT prognosis according to the pretransplant dialysis vintage. A total of 4117 first-time kidney transplant recipients were enrolled from a prospective nationwide cohort in Korea. DDKT recipients were divided into tertiles according to pretransplant dialysis duration. Graft failure, mortality, and composite were compared between DDKT and living donor kidney transplant (LDKT) recipients. Pretransplant dialysis vintage was longer annually in DDKT recipients. In the subdistribution of the hazard model for the competing risk, the first tertile did not show an increased risk of graft failure compared with LDKT recipients; however, the second and third tertile groups had an increased risk of graft failure compared to LDKT recipients (adjusted hazard ratio [aHR] 3.59; 95% confidence interval [CI] 1.69-7.63; P 0.001; aHR 2.37; 95% CI 1.06-5.33; P = 0.037). All DDKT groups showed a significantly higher risk of patient death than LDKT, with the highest risk in the third tertile group (aHR 11.12; 95% CI 4.94-25.00; P 0.001). A longer pretransplant dialysis period was associated with a higher risk of the composite of patient death and graft failure in DDKT recipients. DDKT after a short period of dialysis had non-inferior results on graft survival compared with LDKT.

Since the waiting time for deceased donor kidney transplantation continues to increase, living donor kidney transplantation is an important treatment for end stage kidney disease patients. Barriers to living kidney donation have been rarely investigated despite a growing interest in the utilization of living donor transplantation and the satisfaction of donor safety. Here, we retrospectively analyzed 1658 potential donors and 1273 potential recipients who visited the Seoul National University Hospital for living kidney transplantation between 2010 and 2017 to study the causes of donation discontinuation. Among 1658 potential donors, 902 (54.4%) failed to donate kidneys. The average number of potential donors that received work-up was 1.30 ± 0.66 per recipient. Among living donor kidney transplant patients, 75.1% received kidneys after work-up of the first donor and 24.9% needed work-up of two or more donors. Donor-related factors (49.2%) were the most common causes of donation discontinuation, followed by immunologic or size mismatches between donors and recipients (25.4%) and recipient-related factors (16.2%). Interestingly, withdrawal of donation consent along with refusal by recipients or family were the commonest causes, suggesting the importance of non-biomedical aspects. The elucidation of the barriers to living kidney donation could ensure more efficient and safer living kidney donation.

Background: Basiliximab (BSX) and antithymocyte globulins (ATGs), are two major immunosuppressive agents commonly used as induction therapy for kidney transplant (KT) recipients. The superiority of ATG over BSX has not been well established, especially in elderly KT recipients with low immunological risk. Methods: A total of 847 elderly (≥60 years old), low-risk KT patients in the Korean Organ Transplantation Registry were propensity score-matched at a 1:2 ratio and compared according to ATG or BSX induction therapy. The primary outcome was patient and graft survival and biopsy-proven acute cellular rejection. The secondary outcome was graft function, BK virus nephropathy, infection, cancer, new-onset diabetes mellitus after transplantation (NODAT), and delayed graft function. Results: In total, 165 patients in the ATG group were matched with 298 patients in the BSX group with average ages of 64.3 and 64.2 years, respectively. During a follow-up of 28.5 ± 10.4 months, the cumulative probabilities of death-censored graft failure at 3 years posttransplantation were 1.3% and 1.4% in ATG and BSX groups, respectively, without a significant difference (p = 0.72). The cumulative probability of NODAT at 3 years posttransplantation was significantly higher in the BSX group (35.6% vs. 21.6%, p = 0.02). The median tacrolimus trough level was significantly lower at 6 months after KT in the ATG group (5.7 ng/mL vs. 6.4 ng/mL, p = 0.001). There were no differences in the other evaluated outcomes. Conclusion: Compared with BSX, in elderly, low-risk KT patients, ATG reduced tacrolimus and steroid requirements without differences in all-cause mortality, rejection, or infection, resulting in a reduced NODAT incidence.

BACKGROUND Early identification of graft loss risk and timely therapeutic intervention are crucial for preventing late renal allograft failure and improving long-term graft function. The one-year estimated glomerular filtration rate (eGFR) is the best predictor of long-term graft function in kidney transplant recipients; there is an increased risk of late graft failure in recipients with low one-year eGFR. OBJECTIVE To create a sparse model capable of predicting the one-year renal allograft dysfunction and to build a factor network suggesting risk control targets. METHODS Development data were constructed using the Korean Organ Transplant Registry (KOTRY), a national cohort data of 4317 recipients who underwent kidney transplantation between 2014 and 2019. The XGBoost algorithm was trained to predict the model outcome with 112 features, and the relevant factors were selected. The statistical significance of factors was calculated using multiple logistic regression for the development data. A factor correlation network was drawn and simplified by excluding spurious connections with LASSO (least absolute shrinkage and selection operator) regularization with EBIC (extended bayesian information criterium) model selection. The model outcome was one-year eGFR < 45 mL/min/1.73 m2, and model performance was measured using AUC, sensitivity, and specificity. A SHAP value plot was used to determine the feature importance of the model. The clinical importance of the model outcome was assessed using long-term graft survival and rejection-free survival. The factor network was built using inter-factor partial correlations and the statistical significance of each factor. RESULTS The model achieved an AUC of 0.82, a sensitivity of 0.8, and a specificity of 0.8 using seven pre- or peri-transplantation factors. Three pre-transplantation factors (donor age, recipient age, recipient-donor height difference) and four peri-transplantation factors (low eGFR at discharge, high eGFR at discharge, serum creatinine at discharge, post-transplantation stay) were chosen by the model. Model prediction was significantly associated with a five-year survival of graft and rejection-free survival (P = .02 and P = .007). Post-transplantation stay and discharge eGFR ≥ 88.0 were the most prominent risk and preventive nodes on the network, respectively. Donor age and discharge eGFR < 59.8 had a high impact on model prediction and could be effective risk control targets for their multiple connections to other risk nodes. CONCLUSIONS One-year renal allograft dysfunction could be predicted early after transplantation. The long-term outcomes of kidney transplantation might be improved by preemptive measures on donor age, kidney function at discharge, and post-transplantation stay. INTERNATIONAL REGISTERED REPORT RR2-doi: 10.1097/TXD.0000000000000678

Data for Asian kidney transplants are very limited. We investigated the relative importance of prognostic markers in Asian kidney transplants by using Korean Organ Transplantation Registry (KOTRY) cohort. Prediction models were developed by data-driven variable selection approach. The relative importance of the selected predictors was measured by dominance analysis. A total of 4854 kidney transplant donor-recipient pairs were analyzed. Overall patient survival rates were 99.8%, 98.8%, and 91.8% at 1, 3, and 5 years, respectively. Death-censored graft survival rates were 98.4%, 97.0%, and 95.8% at 1, 3, and 5 years. Biopsy-proven acute rejection free survival rates were 90.1%, 87.4%, and 87.03% at 1, 3, and 5 years. The top 3 dominant predictors for recipient mortality within 1 year were recipient cardiovascular disease history, deceased donor, and recipient age. The dominant predictors for death-censored graft loss within 1 year were acute rejection, deceased donor, and desensitization. The dominant predictors to acute rejection within 1 year were donor age, HLA mismatched numbers, and desensitization. We presented clinical characteristics of patients enrolled in KOTRY during the last 5 years and investigated dominant predictors for early post-transplant outcomes, which would be useful for clinical decision-making based on quantitative measures.

For successful human leukocyte antigen-incompatible (HLAi) or ABO-incompatible (ABOi) living-donor kidney transplantations (LDKTs), pretransplant desensitization is essential; however, early antibody-mediated rejection (ABMR) remains the most important complication after HLAi or ABOi transplantation. Here, we report a case of early acute ABMR in simultaneous HLAi and ABOi LDKT with preformed donor-specific antibody (DSA), despite desensitization. Dialysis-dependent, severe ABMR occurred with a rebound of pre-existing DSA and appearance of de novo DSA after initial normalization of renal function, 8 days postoperatively. However, a low anti-ABO antibody titer (1:8) was maintained after transplantation. Combination therapy of plasmapheresis, high-dose intravenous immunoglobulin, and bortezomib improved both ABMR and renal functions. Thus, an appropriate preventive and therapeutic management for early ABMR is important among high-risk LDKT patients. Furthermore, early AMBR can occur despite pretransplant desensitization as seen in this case, and close monitoring of the patient and prompt management are considered vital for better therapeutic outcomes.

Background Post-transplantation diabetes mellitus (PTDM) is associated with a higher risk of mortality and graft loss. The reported incidence of PTDM after kidney transplantation (KT) varies from 10% to 74% and varies by country and ethnicity. There are few reports of nationwide cohort studies on PTDM incidence and related factors in Korea. The purpose of this study was to evaluate incidence of PTDM and related factors within 1 year after KT in Korea. Methods The KoreaN cohort study for Outcome in patients With Kidney Transplantation (KNOW-KT) enrolled 1080 recipients from July 2012 to August 2016. This study included 723 recipients, excluding 273 patients with pretransplant DM and 84 patients who were lost from follow-up within 1 year after KT. Results Among 723 recipients, 85 (11.8%) recipients were diagnosed and treated with PTDM. Recipient age, HLA mismatches, hemoglobin A1c (HbA1c), waist-hip ratio (WHR), and use of prednisolone were significantly higher in PTDM group than the nondiabetic group. In the multivariable logistic regression analysis, independent risk factors for PTDM were older recipient age, higher WHR, and HbA1c before KT. Conclusion The incidence of PTDM was 11.8% in a nationwide Korean cohort study. The factors related to the development of PTDM within 1 year after KT were older recipient age and higher WHR, and HbA1c levels before KT. In recipients with high WHR, it is important to control pretransplant abdominal obesity to prevent PTDM after KT.

Background There is a high risk of fracture after kidney transplantation (KT). Recipients of KT are susceptible to persistent hyperparathyroidism and other disorders of bone and mineral metabolism. However, the risk factors for fractures after KT remain uncertain. The aim of the present study was to investigate the risk factors for fracture after KT. Methods A total of 941 recipients of KT were enrolled from a multicenter observational cohort study in Korea from 2012 to 2016. The biochemical markers were measured at the time of KT, then annually for 5 years following KT. All fracture events were recorded. A Cox proportional hazards analysis was performed to calculate hazard ratios (HR) for the association of risk factors with fractures. Results Twenty-two fractures had occurred in 20 patients during the study period. Baseline and serial changes of mineral and bone biochemical markers were similar between fracture and nonfracture patient groups. Among the total study population, 104 patients were diagnosed with osteoporosis and 422 patients were diagnosed with osteopenia in a pretransplant bone mineral density test. In a multivariate Cox analysis, pretransplant osteoporosis (HR = 11.76; 95% confidence interval [CI], 2.28-60.69; P = .003) and pretransplant osteopenia (HR = 5.21; 95% CI, 1.15-23.57; P = .032) were independent risk factors for fracture in recipients of KT. Conclusions Pretransplant osteoporosis and osteopenia were independent risk factors for fracture after KT. More careful monitoring of bone mineral density before and after KT might be beneficial to predict the risk for fracture after KT.

Numerous studies have shown that iron deficiency is common in patients with end-stage renal disease. However, change of iron deficiency after kidney transplant (KT) is not fully understood. This study was undertaken to examine sequential changes of iron level after KT.A total of 1080 KT recipients enrolled in a multicenter observational cohort study between July 2012 and August 2018. A total of 786 patients with transferrin saturation and ferritin level at pretransplant and 1 year after KT were reviewed. Iron deficiency was defined as ferritin 200 ng/mL and total saturation of transferrin (TSAT) 20%. Anemia was defined as hemoglobin (Hb) 13 g/dL (male) or 12 g/dL (female).Hemoglobin at 1 year after KT was higher than Hb at KT (13.64 [SD, 1.87] g/dL vs 10.53 [SD, 1.63] g/dL; P .001). The TSAT decreased from baseline at 1 year after KT (33.89% [SD, 18.73%] vs 29.09% [SD, 14.54%]; P .001), and ferritin level decreased from baseline at 1 year (190.63 [SD, 217.43] ng/mL vs 141.39 [194.25] ng/mL; P .001). In patients with anemia at pretransplant, the group with anemia at 1 year after KT (persistent group) and the group without anemia at 1 year after KT (improved group) were compared. The persistent group showed higher pretransplant TSAT, lower 1-year TSAT, and lower estimated glomerular filtration rate at 1 year after KT than the improved group. In multivariate analysis, low ferritin at KT, low TSAT at 1 year, and high ferritin at 1 year were the risk factors for low Hb level at 1 year after adjusting multiple variables.Anemia improved within 1 year after KT, although patients with iron deficiency increased. While ferritin reflected the inflammatory status, low TSAT at 1 year after KT was a risk factor for anemia at 1 year after KT.

Background This 24-week, multicenter, randomized, exploratory, comparative, open-label, phase-IV study assessed the safety and efficacy of prolonged-release tacrolimus (PR-T) with reduced-dose versus standard-dose corticosteroids in stable kidney transplant recipients in Korea after converting from cyclosporine-based therapy. Methods At baseline, patients were converted from cyclosporine-based to PR-T-based immunosuppression and randomized (1:1) to receive either corticosteroids maintained at prestudy dose (standard-dose group) or tapered from week 4 to 50% of the prestudy dose by week 12 (reduced-dose group). Patients were seen at baseline and weeks 1, 4, 12, and 24. The primary endpoint was change in estimated glomerular filtration rate (Modification-of-Diet-in-Renal-Disease-4) between baseline and week 24. Secondary endpoints included either acute rejection or patient-reported satisfaction with PR-T. Adverse events (AEs) were recorded. Results Overall, 150 patients were randomized into a reduced-dose group (n = 73) and a standard-dose group (n = 77). At week 24, mean ± standard deviation for corticosteroid dose was 2.5 ± 0.9 mg and 5.0 ± 1.3 mg, respectively. Mean change in estimated glomerular filtration rate from baseline to week 24 was +1.5 ± 9.1 mL/min/1.73 m2 (P = .1567) and +3.4 ± 10.6 mL/min/1.73 m2 (P = .0065), respectively, and not significantly different between groups. There were no acute rejection episodes. Most respondents (>70%) considered PR-T more convenient than cyclosporine. AE incidence was similar between groups. The most common AEs experienced by ≥3% of patients in either treatment group were gastrointestinal events (20.8% and 28.6% of patients receiving reduced- and standard-dose corticosteroids, respectively). Most AEs in both treatment groups were mild or moderate in severity. Conclusion Renal function was maintained following conversion from cyclosporine to PR-T, irrespective of corticosteroid regimen; PR-T enables reduced corticosteroid dosage.

Renal functional deterioration is associated with physical and mental burdens for kidney transplant (KT) and chronic kidney disease (CKD) patients. However, the change in health-related quality of life (HRQOL) over time in KT patients compared to that of native CKD patients has not been evaluated. We addressed this issue using KT patients registered in the KNOW-KT cohort study and patients at CKD stage 1–3 registered in the KNOW-CKD cohort study. HRQOL scores were assessed using the Kidney Disease Quality of Life Short Form at baseline, 2-, and 4-years follow-up in 842 KT patients and at baseline and 5-year follow-up in 1,355 CKD patients. SF-36 scores declined at the 4-year follow-up, whereas CKD-targeted scores showed no change in the KT group. In contrast, CKD-targeted scores as well as SF-36 scores were decreased at the 5-year follow-up in CKD patients. When prognostic factors were analyzed for longitudinal HRQOL data over time, renal functions, diabetes, cardiovascular and cerebrovascular diseases, hemoglobin level, marital status, income, employment, and health care were significant prognostic factors. Furthermore, KT was an independent prognostic factor for better HRQOL. These results highlight that KT can offer a better HRQOL than that of CKD patients, even when renal function is similar.

Background Although previous studies suggested that rituximab increases the risk of Pneumocystis jirovecii pneumonia (PJP), it is uncertain whether its primary prophylaxis for PJP is justified. Research Question Does the benefit of primary prophylaxis for PJP in patients receiving rituximab treatment outweigh the potential risk of the prophylaxis? Study Design and Methods This retrospective study included 3524 patients (hematologic diseases=2500; rheumatic diseases=559; pre/post-solid organ transplantation=465) first exposed to rituximab between 2002 and 2018 in a tertiary referral center in South Korea. Patients were classified into a control group (n=2523) and a prophylaxis group (n=1001) according to the administration of prophylactic TMP-SMX during the first 28 days after the start of rituximab (intention-to-treat analysis). In addition, exposure to TMP-SMX was examined as a time-varying variable (time-varying analysis). Primary outcome was the prophylactic effect of TMP-SMX on the 1-year incidence of PJP. Inverse probability of treatment weights was applied to minimize the baseline imbalance. Secondary outcome included the incidence of adverse drug reactions (ADRs) related to TMP-SMX. Results Over 2759.9 person-years, 92 PJP infections occurred, with a mortality rate of 27.2%. The prophylaxis group showed a significantly lower incidence of PJP (adjusted sub-distribution hazard ratio (aSHR), 0.20 [95% CI, 0.10–0.42]) than the control group. This result was consistent with the results of time-varying analysis, in which only one PJP infection occurred during TMP-SMX administration (aSHR, 0.01 [0.003–0.16]). The incidence of adverse drug reactions (ADRs) related to TMP-SMX was 18.1 (14.6–22.2)/100 person-years, and most were of mild-to-moderate severity. Based on ten severe ADRs, the number needed to harm was 101 (61.9–261.1), whereas the number needed to prevent one PJP infection was 32 (24.8–39.4). Interpretation TMP-SMX prophylaxis significantly reduces PJP incidence with a tolerable safety profile in patients receiving rituximab treatment.