Proteomics Profiling of Bilirubin Nanoparticle Treatment against Myocardial Ischemia-Reperfusion Injury.

In myocardial infarction, ischemia-reperfusion injury (IRI) poses a significant challenge due to a lack of effective treatments. Bilirubin, a natural compound known for its anti-inflammatory and antioxidant properties, has been identified as a potential therapeutic agent for IRI. Currently, there are no reports about proteomic studies related to IRI and bilirubin treatment. In this study, we explored the effects of bilirubin nanoparticles in a rat model of myocardial IRI. A total of 3616 protein groups comprising 76,681 distinct peptides were identified using LC-MS/MS, where we distinguished two kinds of protein groups: those showing increased expression in IRI and decreased expression in IRI with bilirubin treatment, and vice versa, accounting for 202 and 35 proteins, respectively. Our proteomic analysis identified significant upregulation in the Wnt and insulin signaling pathways and increased Golgi markers, indicating their role in mediating bilirubin nanoparticle's protective effects. This research contributes to the proteomic understanding of myocardial IRI and suggests bilirubin nanoparticles as a promising strategy for cardiac protection, warranting further investigation in human models.

Donor fat-to-muscle ratio and kidney transplant outcomes: A proposition of metabolic memory.

AIMS: The impact of donor abdominal fat-to-muscle ratio (FMR) on kidney transplant (KT) outcomes was assessed. Given the transient nature of the donor's metabolic environment in transplant recipients, this study investigated the capacity of body composition to induce metabolic memory effects. MATERIALS AND METHODS: KT patients (n = 895) who received allografts from living donors (2003-2013) were included. Donor fat and muscle were quantified using pre-KT abdominal computed tomography scans. Patients were categorised into donor FMR tertiles and followed up for graft outcomes. Additionally, genome-wide DNA methylation analysis was performed on 28 kidney graft samples from KT patients in the low- and high-FMR groups. RESULTS: Mean recipient age was 42.9 ± 11.4 years and 60.9% were males. Donor FMR averaged 1.67 ± 0.79. Over a median of 120.9 ± 42.5 months, graft failure (n = 127) and death-censored graft failure (n = 109) were more frequent in the higher FMR tertiles. Adjusted hazard ratios for the highest versus lowest FMR tertile were 1.71 (95% CI, 1.06-2.75) for overall graft failure and 1.90 (95% CI, 1.13-3.20) for death-censored graft failure. Genome-wide DNA methylation analysis identified 58 differentially methylated regions (p < 0.05, |Δß| > 0.2) and 35 genes showed differential methylation between the high- (FMR >1.91) and low-FMR (FMR <1.27) groups. CONCLUSIONS: Donors with increased fat and reduced muscle composition may negatively impact kidney allograft survival in recipients, possibly through the transmission of epigenetic changes, implying a body-composition-related metabolic memory effect.

Outcomes of ABO-Incompatible Living Donor Kidney Transplantation Compared to Waiting or Deceased Donor Kidney Transplantation.

INTRODUCTION: ABO-incompatible (ABOi) living donor kidney transplantation (LDKT) is considered only for patients who do not have an ABO-compatible (ABOc) LD. Therefore, a clinically practical question is whether to proceed with ABOi LDKT or remain on dialysis while waiting for ABOc deceased donor kidney transplantation (DDKT). However, this issue has not been addressed in Asian countries, where ABOi LDKT programs are more active than DDKT programs. METHODS: A total of 426 patients underwent ABOi-LDKT between 2010 and 2020 at Seoul National University Hospital and Severance Hospital, Korea. We compared outcomes between the ABOi-LDKT and the propensity-matched control groups (waiting-list-only group, n = 1,278; waiting-list-or-ABOc-DDKT group, n = 1,278). RESULTS: The ABOi-LDKT group showed a significantly better patient survival rate than the waiting-list-only group (p = 0.001) and the waiting-list-or-ABOc-DDKT group (p = 0.048). When the ABOi-LDKT group was categorized into a high-titer group (peak anti-ABO titer ≥1:128) and a low-titer group (peak anti-ABO titer ≤1:64), the low-titer group showed better patient survival rates than those of the waiting-list-or-ABOc-DDKT group (p = 0.046) or the waiting-list-only group (p = 0.004). In contrast, the high-titer ABOi-LDKT group showed no significant benefit in patient survival compared to the waiting-list-or-ABOc-DDKT group. Death-censored graft survival in the ABOi-LDKT group was not significantly different from that in the ABOc-DDKT group (p = 0.563). CONCLUSION: The ABOi-LDKT group has better outcomes than the waiting-list-or-ABOc-DDKT group in a country with a long waiting time.

Association of Serum Activin Levels with Allograft Outcomes in Patients with Kidney Transplant: Results from the KNOW-KT.

INTRODUCTION: Serum activin A has been reported to contribute to vascular calcification and kidney fibrosis in chronic kidney disease. We aimed to investigate whether higher serum activin levels were associated with poor allograft outcomes in patients with kidney transplantation (KT). METHODS: A total of 860 KT patients from KNOW-KT (Korean Cohort Study for Outcome in Patients with Kidney Transplantation) were analyzed. We measured serum activin levels pre-KT and 1 year after KT. The primary outcome was the composite of a ≥50% decline in estimated glomerular filtration rate and graft failure. Multivariable cause-specific hazard model was used to analyze association of 1-year activin levels with the primary outcome. The secondary outcome was coronary artery calcification score (CACS) at 5 years after KT. RESULTS: During the median follow-up of 6.7 years, the primary outcome occurred in 109 (12.7%) patients. The serum activin levels at 1 year were significantly lower than those at pre-KT (488.2 ± 247.3 vs. 704.0 ± 349.6). When patients were grouped based on the median activin level at 1 year, the high-activin group had a 1.91-fold higher risk (95% CI, 1.25-2.91) for the primary outcome compared to the low-activin group. A one-standard deviation increase in activin levels as a continuous variable was associated with a 1.36-fold higher risk (95% CI, 1.16-1.60) for the primary outcome. Moreover, high activin levels were significantly associated with 1.56-fold higher CACS (95% CI, 1.12-2.18). CONCLUSION: Post-transplant activin levels were independently associated with allograft functions as well as coronary artery calcification in KT patients.

Clinical relevance of the living kidney donor profile index in Korean kidney transplant recipients.

BACKGROUND: The Living Kidney Donor Profile Index (LKDPI) was developed in the United States to predict graft outcomes based on donor characteristics. However, there are significant differences in donor demographics, access to transplantation, proportion of ABO incompatibility, and posttransplant mortality in Asian countries compared with the United States. METHODS: We evaluated the clinical relevance of the LKDPI score in a Korean kidney transplant cohort by analyzing 1860 patients who underwent kidney transplantation between 2000 and 2019. Patients were divided into three groups according to LKDPI score: <0, 1-19.9, and ≥20. RESULTS: During a median follow-up of 119 months, 232 recipients (12.5%) experienced death-censored graft loss, and 98 recipients (5.3%) died. High LKDPI scores were significantly associated with increased risk of death-censored graft loss independent of recipient characteristics (LKDPI 1-19.9: HR 1.389, 95% CI 1.036-1.863; LKDPI ≥20: HR 2.121, 95% CI 1.50-2.998). High LKDPI score was also significantly associated with increased risk of biopsy-proven acute rejection and impaired graft renal function. By contrast, overall patient survival rates were comparable among the LKDPI groups. CONCLUSION: High LKDPI scores were associated with an increased risk of death-censored graft loss, biopsy-proven acute rejection, and impaired graft renal function among a Korean kidney transplant cohort.

Impact of Blood Pressure on Allograft Function and Survival in Kidney Transplant Recipients.

The optimal target blood pressure for kidney transplant (KT) patients remains unclear. We included 808 KT patients from the KNOW-KT as a discovery set, and 1,294 KT patients from the KOTRY as a validation set. The main exposures were baseline systolic blood pressure (SBP) at 1 year after KT and time-varying SBP. Patients were classified into five groups: SBP <110; 110-119; 120-129; 130-139; and ≥140 mmHg. SBP trajectories were classified into decreasing, stable, and increasing groups. Primary outcome was composite kidney outcome of ≥50% decrease in eGFR or death-censored graft loss. Compared with the 110-119 mmHg group, both the lowest (adjusted hazard ratio [aHR], 2.43) and the highest SBP (aHR, 2.25) were associated with a higher risk of composite kidney outcome. In time-varying model, also the lowest (aHR, 3.02) and the highest SBP (aHR, 3.60) were associated with a higher risk. In the trajectory model, an increasing SBP trajectory was associated with a higher risk than a stable SBP trajectory (aHR, 2.26). This associations were consistent in the validation set. In conclusion, SBP ≥140 mmHg and an increasing SBP trajectory were associated with a higher risk of allograft dysfunction and failure in KT patients.

Low skeletal muscle mass is associated with mortality in kidney transplant recipients.

Muscle wasting in chronic kidney disease is associated with increased cardiovascular events, morbidity, and mortality. However, whether pretransplantation skeletal muscle mass affects kidney transplantation (KT) outcomes has not been established. We analyzed 623 patients who underwent KT between 2004 and 2019. We measured the cross-sectional area of total skeletal muscle at the third lumbar vertebra level on pretransplantation computed tomography scan. The patients were grouped into low and normal skeletal muscle mass groups based on the sex-specific skeletal muscle mass index lowest quartile. During the entire follow-up period, 45 patients (7.2%) died and 56 patients (9.0%) experienced death-censored graft loss. Pretransplantation low skeletal muscle mass was independently associated with all-cause mortality (adjusted hazard ratio, 2.269; 95% confidence interval, 1.232-4.182). Low muscle mass was also associated with an increased risk of hospital readmission within 1 year after transplantation. Death-censored graft survival rates were comparable between the 2 groups. The low muscle group showed higher creatinine-based estimated glomerular filtration rates (eGFRs) than the normal muscle group. Although cystatin C-based eGFRs were measured in only one-third of patients, cystatin C-based eGFRs were comparable between the 2 groups. Pretransplantation low skeletal muscle mass index is associated with an increased risk of mortality and hospital readmission after KT.

Survival Benefit of Kidney Transplantation in Patients With End-Stage Kidney Disease and Prior Acute Myocardial Infarction.

Patients with end stage kidney disease (ESKD) and a previous acute myocardial infarction (AMI) have less access to KT. Data on ESKD patients with an AMI history who underwent first KT or dialysis between January 2007 and December 2018 were extracted from the Korean National Health Insurance Service. Patients who underwent KT (n = 423) were chronologically matched in a 1:3 ratio with those maintained on dialysis (n = 1,269) at the corresponding dates, based on time-conditional propensity scores. The 1, 5, and 10 years cumulative incidences for all-cause mortality were 12.6%, 39.1%, and 60.1% in the dialysis group and 3.1%, 7.2%, and 14.5% in the KT group. Adjusted hazard ratios (HRs) of KT versus dialysis were 0.17 (95% confidence interval [CI], 0.12-0.24; p < 0.001) for mortality and 0.38 (95% CI, 0.23-0.51; p < 0.001) for major adverse cardiovascular events (MACE). Of the MACE components, KT was most protective against cardiovascular death (HR, 0.23; 95% CI, 0.12-0.42; p < 0.001). Protective effects of KT for all-cause mortality and MACE were consistent across various subgroups, including patients at higher risk (e.g., age >65 years, recent AMI [<6 months], congestive heart failure). KT is associated with lower all-cause mortality and MACE than maintenance dialysis patients with a prior AMI.

Pretransplant and Posttransplant Alcohol Consumption and Outcomes in Kidney Transplantation: A Prospective Multicenter Cohort Study.

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.

Presence of a survival benefit of HLA-incompatible living donor kidney transplantation compared to waiting or HLA-compatible deceased donor kidney transplantation with a long waiting time.

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.

Effects of bisphosphonates on long-term kidney transplantation outcomes.

BACKGROUND: Bisphosphonates are administered to post-transplantation patients with mineral and bone disorders; however, the association between bisphosphonate therapy and long-term renal graft survival remains unclear. METHODS: This nested case-control study investigated the effects of bisphosphonates on long-term graft outcomes after kidney transplantation. We enrolled 3836 kidney transplant recipients treated from April 1979 to June 2016 and matched patients with graft failure to those without (controls). Annual post-transplant bone mineral density assessments were performed and recipients with osteopenia or osteoporosis received bisphosphonate therapy. The associations between bisphosphonate use and long-term graft outcomes and graft survival were analyzed using conditional logistic regression and landmark analyses, respectively. RESULTS: A landmark analysis demonstrated that death-censored graft survival was significantly higher in bisphosphonate users than in non-users in the entire cohort (log-rank test, P < 0.001). In the nested case-control matched cohort, bisphosphonate users had a significantly reduced risk of graft failure than did non-users (odds ratio = 0.38; 95% confidence interval 0.30-0.48). Bisphosphonate use, increased cumulative duration of bisphosphonate use >1 year and increased cumulative bisphosphonate dose above the first quartile were associated with a reduced risk of graft failure, after adjustments. CONCLUSIONS: Bisphosphonates may improve long-term graft survival in kidney transplant recipients.

Outcomes of ABO-incompatible kidney transplantation in older patients: a national cohort study.

BACKGROUND: Outcomes of ABO-incompatible living donor kidney transplantation (ABOi LDKT) in older individuals have not been established. METHODS: This multicentric observational study, using data from the Korean Organ Transplantation Registry database, included 634 older patients (≥60 years) undergoing kidney transplantation. We compared clinical outcomes of ABOi LDKT (n = 80) with those of ABO-compatible LDKT (ABOc LDKT, n = 222) and deceased donor kidney transplantation (DDKT, n = 332) in older patients. RESULTS: Death-censored graft survival was similar between the three groups (P = 0.141). Patient survival after ABOi LDKT was similar to that after ABOc LDKT (P = 0.489) but higher than that after DDKT (P = 0.038). In multivariable analysis, ABOi LDKT was not risk factor (hazard ratio [HR] 1.73, 95% confidence interval [CI] 0.29-10.38, P = 0.548), while DDKT was significant risk factor (HR 3.49, 95% CI 1.01-12.23, P = 0.049) for patient survival. Although ABOi LDKT showed higher biopsy-proven acute rejection than ABOc LDKT, the difference was not significant after adjustment with covariates. However, ABOi LDKT was significant risk factor for infection (HR 1.66, 95% CI 1.12-2.45, P = 0.012). CONCLUSIONS: In older patients, ABOi LDKT was not inferior to ABOc LDKT and was superior to DDKT for patient survival. ABOi LDKT can be recommended for older patients, rather than waiting for DDKT.

Impact of recipient and donor smoking in living-donor kidney transplantation: a prospective multicenter cohort study.

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.

Glomerular subepithelial microparticles - a footprint for podocyte injury.

The aim of this study was to clarify the nature and clinical significance of glomerular subepithelial microparticles (SMPs), located between the basal surface of the podocytes and the glomerular basement membrane. Ultrastructural morphology of 79 renal biopsy samples (obtained from 25 native and 54 transplanted kidneys), showing SMPs in the last 3 years, was reevaluated with regard to the podocyte changes and clinical condition of the patients. One hundred and nine SMPs were identified, with 32.9% of the samples having two or more per glomerulus. Overall, they were most frequently located in the open capillary loops (55%). However, in the native kidney samples with mesangial deposits, 64.3% of SMPs were present in the mesangium-bound areas. Each vesicle ranged from 46.9 to 87.1 nm, and vesicles were admixed with curved strands in larger SMPs. Diffuse effacement of the foot processes and condensation of the actin filaments were present in 56.0% and 62.4% of the samples, respectively. SMPs were associated with hematuria, proteinuria of ≥ 1 gm, and immune complex deposition in the patients with native kidneys, whereas they were related to hyperglycemia and elevated serum creatinine levels in the patients with renal allografts. Patients with native and transplanted kidneys most commonly presented with IgA nephropathy and allograft rejection, respectively. Finding SMPs in the renal biopsy samples is not rare and they may act as a footprint of podocyte injury caused by diverse etiologies. Considering their size, podocyte exosomes could be a possible source of SMPs.

Transplant outcomes in positive complement-dependent cytotoxicity- versus flow cytometry-crossmatch kidney transplant recipients after successful desensitization: a retrospective study.

BACKGROUND: Despite the obvious survival benefit compared to that among waitlist patients, outcomes of positive crossmatch kidney transplantation (KT) are generally inferior to those of human leukocyte antigen (HLA)-compatible KT. This study aimed to compare the outcomes of positive complement-dependent cytotoxicity (CDC) crossmatch (CDC + FC+) and positive flow cytometric crossmatch (CDC-FC+) with those of HLA-compatible KT (CDC-FC-) after successful desensitization. METHODS: We retrospectively analyzed 330 eligible patients who underwent KTs between June 2011 and August 2017: CDC-FC- (n = 274), CDC-FC+ (n = 39), and CDC + FC+ (n = 17). Desensitization protocol targeting donor-specific antibody (DSA) involved plasmapheresis, intravenous immunoglobulin (IVIG), and rituximab with/without bortezomib for positive-crossmatch KT. RESULTS: Death-censored graft survival and patient survival were not different among the three groups. The median estimated glomerular filtration rate was significantly lower in the CDC + FC+ group than in the compatible group at 6 months (P < 0.001) and 2 years (P = 0.020). Biopsy-proven rejection within 1 year of CDC-FC-, CDC-FC+, and CDC + FC+ were 15.3, 28.2, and 47.0%, respectively. Urinary tract infections (P < 0.001), Pneumocystis jirovecii pneumonia (P < 0.001), and cytomegalovirus viremia (P < 0.001) were more frequent in CDC-FC+ and CDC + FC+ than in CDC-FC-. CONCLUSIONS: This study showed that similar graft and patient survival was achieved in CDC-FC+ and CDC + FC+ KT compared with CDC-FC- through DSA-targeted desensitization despite the higher incidence of rejection and infection than that in compatible KT.

Enhanced immune-modulatory effects of thalidomide and dexamethasone co-treatment on T cell subsets.

Thalidomide (TM) has been reported to have anti-cancer and anti-inflammatory properties, and dexamethasone (DX) is known to reduce inflammation and inhibit production of inflammatory cytokines. Many studies have reported that combinatorial therapy with TM and DX is clinically used to treat multiple myeloma and lupus nephritis, but the mechanism responsible for its effects has not been elucidated. In this study, we determined that TM and DX co-treatment had an enhanced immune-modulatory effect on T cells through regulating the expression of co-stimulatory molecules. Splenic naive T cells from C57BL/6 mice were sort-purified and cultured for CD4+ T cell proliferation and regulatory T (Treg) cell conversion in the presence of TM and/or DX. Following incubation with the drugs, cells were collected and OX40, 4-1BB, and glucocorticoid-induced tumour necrosis factor receptor-related protein (GITR) expression was quantified by flow cytometry. TM (1 or 10 µm) decreased CD4+ T cell proliferation in a dose-dependent manner, whereas TM/DX (0·1 or 1 nm) co-treatment further decreased proliferation. Treg cell populations were preserved following drug treatment. Furthermore, expression of co-stimulatory molecules decreased upon TM/DX co-treatment in effector T (Teff) cells and was preserved in Treg cells. Splenic CD4+ T cells isolated from TM- and DX-treated mice exhibited the same patterns of Teff and Treg cell populations as observed in vitro. Considering the selective effect of TM on different T cell subsets, we suggest that TM may play an immunomodulatory role and that TM/DX combinatorial treatment could further enhance these immunomodulatory effects by regulating GITR, OX40, and 4-1BB expression in CD4+ T cells.

Rituximab and hepatitis B reactivation in HBsAg-negative/ anti-HBc-positive kidney transplant recipients.

Background: Hepatitis B virus (HBV) reactivation is a well-known complication of immunosuppressive therapy. Although rituximab is increasingly used for desensitization of ABO-incompatible or positive crossmatch kidney transplantation, the risk of HBV reactivation in hepatitis B surface antigen (HBsAg)-negative/hepatitis B core antibody (anti-HBc)-positive kidney transplant patients receiving rituximab desensitization remains undetermined. Methods: We analysed 172 resolved HBV patients who underwent living donor kidney transplantation between 2008 and 2014. Patients were divided into rituximab ( n = 49) or control ( n = 123) groups. All patients were observed for HBV reactivation, which was defined as the reappearance of hepatitis B surface antigen or HBV DNA. Results: During the follow-up period (median, 58 months; range, 4-95 months), five patients (10.2%) in the rituximab group and two patients (1.6%) in the control group experienced HBV reactivation (P = 0.003). In the rituximab group, two patients experienced HBV-related severe hepatitis, and one patient died due to hepatic failure. The median time from rituximab desensitization to HBV reactivation was 11 months (range, 5-22 months). By contrast, no patients in the control group experienced severe hepatitis. The status of hepatitis B surface antibody was similar between groups. Rituximab desensitization [hazard ratio (HR), 9.18; 95% confidence interval (CI), 1.74-48.86; P = 0.009] and hepatitis B surface antibody status (HR, 4.74; 95% CI, 1.05-21.23, P = 0.04) were significant risk factors for HBV reactivation. Conclusions: Rituximab desensitization for incompatible kidney transplantation significantly increased the risk of HBV reactivation in HBsAg-negative/anti-HBc-positive patients. Therefore, close monitoring of HBV DNA is required in these patients.

De novo low-dose sirolimus versus mycophenolate mofetil in combination with extended-release tacrolimus in kidney transplant recipients: a multicentre, open-label, randomized, controlled, non-inferiority trial.

BACKGROUND: Most of the previous studies reported that tacrolimus (TAC) with sirolimus (SRL) was associated with worse post-transplant outcomes in kidney transplantation, compared with TAC with mycophenolate mofetil (MMF). These might be attributable to high-dose SRL. However, outcomes using low-dose SRL with TAC for kidney transplantation are uncertain. The aim of this study was to assess the efficacy and safety of low-dose SRL with extended-release tacrolimus (ER-TAC) versus MMF with ER-TAC. METHODS: We randomly assigned 158 renal transplant patients to receive low-dose SRL or MMF in combination with ER-TAC and corticosteroid. The primary endpoint was the composite efficacy failure rate, including biopsy-proven acute rejection (BPAR), graft loss, death or loss to follow-up, within 12 months post-transplantation. This trial is registered with ClinicalTrial.gov (number NCT01680952). RESULTS: The efficacy failure rate was 6.6% in the low-dose SRL group and 13.3% in the MMF group in the intention-to-treat population (absolute difference, 6.8%; 95% confidence interval, -2.8% to 16.3%). The incidence of BPAR within 12 months post-transplantation was 5.3% in the low-dose SRL group and 13.3% in the MMF group (P = 0.09). The mean estimated glomerular filtration rate at 12 months post-transplantation was 53.2 mL/min/1.73 m2 in the low-dose SRL group and 52.4 mL/min/1.73 m2 in the MMF group (P = 0.76). The incidences of adverse events and serious adverse events were similar between groups. CONCLUSION: Low-dose SRL with ER-TAC was not inferior to MMF with ER-TAC with respect to efficacy and safety. When used for immunosuppression in kidney transplantation, low-dose SRL with ER-TAC can effectively prevent acute rejection and preserve renal function.

The clinicopathological relevance of pretransplant anti-angiotensin II type 1 receptor antibodies in renal transplantation.

BACKGROUND: Anti-angiotensin II type 1 receptor antibodies (AT1R-Abs) have been suggested as a risk factor for graft failure and acute rejection (AR). However, the prevalence and clinical significance of pretransplant AT1R-Abs have seldom been evaluated in Asia. METHODS: In this multicenter, observational cohort study, we tested the AT1R-Abs in pretransplant serum samples obtained from 166 kidney transplant recipients. Statistical analysis was used to set a threshold AT1R-Abs level at 9.05 U/mL. RESULTS: Pretransplant AT1R-Abs were detected in 98/166 (59.0%) of the analyzed recipients. No graft loss or patient death was reported during the study period. AT1R-Abs (+) patients had a significantly higher incidence of biopsy-proven AR than AT1R-Abs (-) patients (27.6 versus 10.3%, P = 0.007). Recipients with pretransplant AT1R-Abs had a 3.2-fold higher risk of AR within a year of transplantation (P = 0.006). Five study subjects developed microcirculation inflammation (score ≥2). Four of them were presensitized to AT1R-Abs. In particular, three patients had a high titer of anti-AT1R-Abs (>22.7 U/mL). CONCLUSIONS: Pretransplant AT1R-Abs is an independent risk factor for AR, especially acute cellular rejection, and is possibly associated with the risk of antibody-mediated injury. Pretransplant assessment of AT1R-Abs may be useful for stratifying immunologic risks.

Successful launch of an ABO-incompatible kidney transplantation program to overcome the shortage of compatible living donors: experience at a single center
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AIMS: ABO-incompatible (ABOi) kidney transplantation (KT) is being increasingly performed to overcome donor shortages. However, debate persists regarding the post-transplant outcomes of ABOi KT vs. that of ABO-compatible (ABOc) KT. METHODS: A total 454 recipients who underwent living-donor KT (LDKT) between June 2010 and July 2014 at Severance Hospital (Seoul) were retrospectively reviewed. 100 ABOi and 354 ABOc KTs were compared. Recipients with a pretransplant positive crossmatch to their donors, pretransplant donor-specific anti-HLA antibody (DSA), or high panel reactive antibody (PRA ≥ 50%) were excluded from both the ABOi and ABOc KT groups. Finally, the authors compared the transplant outcomes of 95 of these ABOi KTs and 121 ABOc KTs performed over the same period. RESULTS: No significant difference in incidence of biopsy-proven acute rejection was observed between the ABOi and ABOc KT groups (p = 0.230), and group glomerular filtration rate of ABOi KT was comparable to that of ABOc KT (p > 0.05 at all time points). 3-year death-censored graft survival rates were similar (96.8 vs. 96.6%, respectively; p = 0.801). However, the incidences of postoperative bleeding, cytomegalovirus infection, fungal infection, and serious infection rates were significantly higher after ABOi KT. CONCLUSIONS: In this study, graft renal function and survival after ABOi KT were excellent, and the incidence of acute rejection was similar to that of ABOc KT. However, efforts are needed to reduce hemorrhagic and infectious complications after ABOi KT. ABOi KT can be a good strategy to overcome ABO antibody barriers and relieve donor shortage.
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