Search

BACKGROUND Patients receiving ABO-incompatible (ABOi) or human leukocyte antigen (HLA)-incompatible (HLAi) kidney transplantation (KT) require potent immunosuppression and are thus at a higher risk of infectious complications. We evaluated the clinical outcomes of KT stratified by ABO and HLA incompatibilities and identified the factors associated with the clinical outcomes. MATERIAL AND METHODS Recipients who underwent living-related KT between 2012 and 2017 were included and classified into 4 groups: ABO-compatible and HLA-compatible (ABOc/HLAc), HLA-incompatible (ABOc/HLAi), ABO-incompatible (ABOi/HLAc), and ABO-incompatible and HLA-incompatible (ABOi/HLAi). Cox proportional hazards regression analyses were carried out to evaluate the risk factors of acute rejection. Out of the 1732 patients who underwent KT, 1190, 131, 358, and 53 were in the ABOc/HLAc, ABOi/HLAc, ABOc/HLAi, and ABOi/HLAi groups, respectively. RESULTS The ABO/HLAi group showed the lowest 5-year graft survival rate (91.7%). Death-censored graft survival was not significantly different among the groups. The mortality rate from infections was significantly higher in the ABOi/HLAi group (7.5%) than the other groups. Antibody-mediated rejection-free graft survival was the lowest in the ABOi/HLAi group, with significant differences compared with the ABOi/HLAc group (P=0.02) and the ABOc/HLAi group (P=0.03). ABOi/HLAi (hazard ratio [HR], 2.63; 95% confidence interval [CI], 1.04-6.65; P<0.01) and combined infection (HR, 1.91; 95% CI, 1.45-2.51; P<0.01) were significant risk factors for acute rejection. CONCLUSIONS Patients with both ABO and HLA incompatibilities showed inferior rates of overall patient and graft survival due to infectious complications. Infection was a prominent risk factor of acute rejection following KT after adjusting for possible confounders including ABO and HLA incompatibility.

Little is known about the characteristics and clinical implications of specific subsets of intragraft natural killer (NK) cells in kidney transplant recipients. We analyzed 39 for-cause renal transplant biopsies performed at our center from May 2015 to July 2017. According to histopathologic reports, 8 patients (20.5%) had no rejection (NR), 11 (28.2%) had T cell-mediated rejections (TCMR) only, and 20 (51.3%) had antibody-mediated rejection (ABMR). NK cells were defined as CD3 - CD56 + lymphocytes that are positive for CD57, CD49b, NKG2A, or KIR. The density of NK cells was significantly higher in the ABMR group (2.57 ± 2.58/mm 2 ) than in the NR (0.12 ± 0.22/mm 2 ) or the TCMR (0.25 ± 0.34/mm 2 ) group (P = 0.002). Notably, CD56 + CD57 + infiltrates (2.16 ± 1.89) were the most frequently observed compared with CD56 + CD49b + (0.05 ± 0.13), CD56 + NKG2A + (0.21 ± 0.69), and CD56 + KIR + (0.15 ± 0.42) cells in the ABMR group (P < 0.001). Death-censored graft failure was significantly higher in patients with NK cell infiltration than those without (Log-rank test, P = 0.025). In conclusion, CD56 + CD57 + infiltrates are a major subset of NK cells in kidney transplant recipients with ABMR and NK cell infiltration is significantly associated with graft failure post-transplant.

Background: Crossmatching (XM) between organ donors and recipients is correlated with clinical outcomes. This study evaluates the results of HLA-incompatible kidney transplant (HLA-i KT) according to pre-transplant XM modalities., Methods: This study included 731 consecutive patients. HLA-i KT was defined as a transplant under conditions of complement-dependent cytotoxicity (CDC) XM positivity, flow-cytometric XM (FCXM) positivity, and/or maximal donor-specific antibody (DSA) mean fluorescence intensity (MFI) ≥5000., Results: The incidence of antibody-mediated rejection (AMR) within 1 year after transplant was significantly higher in the HLA-i group than in the HLA compatible (HLA-c) group (15 vs 9 patients, 14.2% vs 1.4%; P < 0.01). Multivariate analysis indicated that a DSA MFI ≥5000 (odds ratio [OR] = 2.63; 95% confidence interval [CI], 1.00-6.98; P = 0.05) was significantly associated with acute rejection (AR), whereas CDC (OR = 2.09; 95% CI, 0.55-7.99; P = 0.28) and FCXM positivity (OR = 2.07; 95% CI, 0.73-5.87; P = 0.17) were not. Similarly, DSA MFI ≥ 5000 (OR = 4.14; P = 0.02) was the only significant factor affecting the risk of AMR., Conclusions: Of the various XM tests, DSA MFI ≥5000 was the most prominent predictor of AR in patients undergoing HLA-i KT., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: The aim of the present study was to investigate the clinical outcomes of kidney transplantation (KT) in elderly recipients compared with those in young recipients., Methods: We compared the incidence of biopsy-proven acute rejection, death-censored allograft survival and all-cause mortality, and also compared the impact of high sensitization or desensitization on the clinical outcomes of elderly and young recipients., Results: A total of 4966 KT recipients from the Korean Organ Transplantation Registry were included. The definition of elderly recipients was based on age >60 years (n = 356), and recipients aged <60 years were defined as young recipients (n = 4610). The incidence of biopsy-proven acute rejection did not differ between the two groups irrespective of the donor type; however, the impact of high sensitization was significant only in young recipients. Being an elderly recipient was an independent risk factor for death-censored allograft failure in terms of overall and living donor KT, but not with deceased donor KT. In regard to patient death, being an elderly recipient was a significant predictor in general and in the two subgroups, and desensitization showed a significant interaction with death in the elderly recipients in the living donor KT group., Conclusions: In conclusion, KT in elderly recipients might be associated with poor allograft or patient survival in general, and especially, desensitization therapy carried out in these patients might increase the risk of patient mortality. Geriatr Gerontol Int 2019; 19: 392-398., (© 2019 Japan Geriatrics Society.)

BACKGROUND BK nephropathy (BKN) affects graft function and increases the risk of graft failure. The reduction of immunosuppression is the main treatment for BKN. However, acute rejection may develop following immunosuppression reduction, and data regarding the risk factors of acute rejection during the post-reduction period are insufficient. MATERIAL AND METHODS Of 758 patients who received a kidney transplantation (KT) between 2008 and 2011, 79 who underwent immunosuppression reduction as BKN treatment were enrolled. The risk factors of acute rejection after immunosuppression reduction were identified using multivariate logistic regression analysis. RESULTS During the median follow-up period (75 months), acute rejection developed in 21.5% of study group patients and in 22.5% of KT recipients without BKN. The rejection group showed a trend of higher body mass index (24.13±3.92 vs. 22.40±3.31 kg/m², P=0.070) and lower tacrolimus levels than the no rejection group, although mycophenolate mofetil (MMF) doses were not lower in the rejection group. The rejection group showed worse graft survival than the no rejection group (P=0.001 by the log rank test). A greater number of patients in the rejection group exhibited reduced calcineurin inhibitor (CNI) level by >20% at 1 month after initial BKV detection (34.2% vs. 7.9%, P=0.008). Multivariate analysis indicated that the peak BKV PCR level (odds ratio [OR], 0.136; 95% confidence interval [CI], 0.025-0.732; P=0.020), MMF discontinuation (vs. MMF reduction; OR, 0.112; 95% CI, 0.020-0.618; P=0.012) and CNI level reduction >20% (OR, 33.752; 95% CI, 4.263-267.251; P=0.001) were significantly associated with acute rejection. CONCLUSIONS Acute rejection after immunosuppression reduction for BKN showed worse allograft survival than the patients without acute rejection. In addition, a CNI dose reduction >20% at 1 month after the initial BKV detection can increase the risk of acute rejection.

The Luminex test can detect low levels of donor-specific antibody (DSA) that cannot be detected by flow-cytometric cross-matching (FCXM) in kidney transplantation (KT). This study evaluated the impact of DSA on clinical outcomes in KT recipients negative on FCXM. Of 575 consecutive patients who underwent living donor KT between January 2013 and July 2016, 494 (85.9%) were DSA-negative and 81 (14.1%) were DSA-positive. Although rates of acute cellular rejection (ACR) at 1 year were similar in the 2 groups (P = .54), the incidence of antibody-mediated rejection (ABMR) was significantly higher in the DSA-positive group (P < .01). There was no statistically significant association between rejection-free graft survival (RFGS) rates and pretransplant class I DSA. However, evaluation of pretransplant class II DSA showed that RFGS rates were significantly lower in patients with mean fluorescence intensity (MFI) >3000 than in patients with DSA-negative (P < .01). On multivariate analyses, class II DSA MFI ≥5000 was a significant risk factor for acute rejection (hazard ratio, 7.48; P < .01). These findings suggested that pretransplant DSA alone did not affect graft survival in KT recipients without desensitization. However, class II DSA MFI >5000 was an independent predictor of acute rejection in DSA-positive patients., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The role of elevated post-transplant red cell distribution width (RDW) as a predictive factor for graft loss remains unclear, although RDW was reported to be significantly associated with poor prognosis in various clinical fields. We performed a retrospective cohort study with 2,939 kidney transplant patients from two tertiary teaching hospitals in Korea. RDW level at transplantation and 3-months post-transplantation were collected. Those with RDW in the upper quartile range were considered to have increased RDW (>14.9%). Death-with-graft-function (DWGF), death-censored graft failure (DCGF), and composite graft loss were assessed as the study outcomes, using multivariable cox proportional hazard model. At the median follow-up duration of 6.6 (3.6-11.4) years, 336 patients experienced graft loss. There were 679 patients with elevated RDW at 3-months post-transplant. Elevated RDW was associated with composite graft loss (adjusted hazard ratio, 1.60, 95% confidence interval, 1.23-2.07, P < 0.001), even after adjusted for hemoglobin and various clinical factors. The 1% increment of post-transplant RDW was also significantly associated with the outcome, regardless of the presence of anemia. The worst prognosis was seen in patients with elevated RDW after transplantation, but not at baseline. Therefore, post-transplant RDW level may be significantly associated with patient prognosis, independent of hemoglobin values.

It remains inconclusive whether hyperuricemia is a true risk factor for kidney graft failure. In the current study, we investigated the association of hyperuricemia and graft outcome. We performed a multi-center cohort study that included 2620 kidney transplant recipients. The patients were classified as either normouricemic or hyperuricemic at 3 months after transplantation. Hyperuricemia was defined as a serum uric acid level ≥ 7.0 mg/dL in males or ≥ 6.0 mg/dL in females or based on the use of urate-lowering medications. The two groups were compared before and after propensity score matching. A total of 657 (25.1%) patients were classified as hyperuricemic. The proportion of hyperuricemic patients increased over time, reaching 44.2% of the total cohort at 5 years after transplantation. Estimated glomerular filtration rate and donor type were independently associated with hyperuricemia. Hyperuricemia was associated with graft loss according to multiple Cox regression analysis before propensity score matching (hazard ratio [HR] = 1.56, 95% confidence interval [CI] = 1.14-2.13, P = 0.005) as well as after matching (HR = 1.65, 95% CI = 1.13-2.42, p = 0.010). Cox regression models using time-varying hyperuricemia or marginal structural models adjusted with time-varying eGFR also demonstrated significant hazards of hyperuricemia for graft loss. Cardiovascular events and recipient survival were not associated with hyperuricemia. Overall, hyperuricemia, especially early onset after transplantation, showed an increased risk for graft failure. Further studies are warranted to determine whether lowering serum uric acid levels would be beneficial to graft survival.

Chronic active/acute antibody-mediated rejection (cABMR) is the main cause of late renal allograft loss. Severe peritubular capillary basement membrane multilayering (PTCML) assessed on electron microscopy is one diagnostic feature of cABMR according to the Banff 2013 classification. We aimed to refine the PTCML criteria for an earlier diagnosis of cABMR. We retrospectively investigated ultrastructural features of 159 consecutive renal allografts and 44 nonallografts. The presence of serum donor-specific antibodies at the time of biopsy of allografts was also examined. Forty-three patients (27.0%) fulfilled the criteria of cABMR, regardless of PTCML, and comprised the cABMR group. Forty-one patients (25.8%) did not exhibit cABMR features and comprised the non-cABMR allograft control group. In addition, 15 zero-day wedge resections and 29 native kidney biopsies comprised the nonallograft control group. When the diagnostic accuracies of various PTCML features were assessed using the cABMR and non-cABMR allograft control groups, ≥4 PTCML, either circumferential or partial, in ≥2 peritubular capillaries of the three most affected capillaries exhibited the highest AUC value (0.885), greater than the Banff 2013 classification (0.640). None of the nonallograft control groups exhibited PTCML features. We suggest that ≥4 PTCML in ≥2 peritubular capillaries of the three most affected cortical capillaries represents the proper cutoff for cABMR., (© 2017 Steunstichting ESOT.)

Background: Although high-dose steroid therapy has been attempted for the management of clinically suspected allograft rejection, before testing for BK viral activity or acute cellular rejection accompanied by BK polyomavirus nephropathy, its long-term outcome remains unknown. We investigated the impact of high-dose steroids on BK viral activity and long-term graft outcomes in patients with BK viremia., Methods: The study population comprised 144 kidney transplant recipients with BK viremia. They were divided into 2 groups based on the amount of steroids administered: low-dose group (<2 g, n=123) or high-dose group (≥2 g, n=21)., Results: The baseline serum BK viral loads were 5.4±1.1 log cp/mL in the low-dose group and 6.0±1.3 in the high-dose group (P=.054). These changed to 5.2±1.3 and 6.1±1.4, 1 month after steroid treatment (P=.03) and 4.9±1.3 and 5.9±1.4 at 2 months (P=.033), respectively. From 3 months to 1 year, the serum BK viral titers were not different between groups. Kaplan-Meier analyses demonstrated that the rates of the decline of graft function and graft failure were higher in the high-dose group (P=.02 and P=.04, respectively). High-dose steroids (P=.012, hazard ratio [HR] 5.04, 95% confidence interval [CI] 1.42-17.85) and log serum BK viral load at 2 months after steroid treatment (P=.042, HR 1.52, 95% CI 1.02-2.28) were independent risk factors for the decline of graft function., Conclusion: High-dose steroids induced BK viral activation and subsequently resulted in poor long-term graft function and early graft failure in patients with BK viremia., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Antiphospholipid syndrome (APS), autoantibodies directed against phospholipid-binding proteins are associated with cause vascular thrombosis. Patients with APS requiring renal transplantation are at risk of early graft loss due to arterial or venous thrombosis, or thrombotic microangiopathy (TMA). Here, we report 3 cases of successful renal transplantation in patients with APS., Clinical Findings: A 53-year-old man with end-stage renal disease (ESRD) had experienced bilateral deep venous thrombosis (DVT) in the lower extremities 16 years ago and was administered warfarin. However, he frequently experienced recurrent DVT despite of anticoagulation therapy. Before the surgery, APS was confirmed based on positive results lupus anticoagulant in serological tests. A 40-year-old man with polycystic kidney disease and a history recurrent DVT tested positive for lupus anticoagulant and anticardiolipin antibodies. Lastly, a 42-year-old woman with ESRD was diagnosed with APS 7 years ago. She also developed DVT and tested positive for lupus anticoagulant and anti-B2-glycoprotein 1., The Anticoagulation Protocol Was as Follows in All Cases: Warfarin was stopped 5 days before living donor renal transplantation and intravenous heparin therapy was started. During surgery, bolus heparin injections (3000 U) were administered to prevent arterial or venous thrombosis. Heparin was substituted with warfarin on postoperative day 4. The third patient (42/F) developed clinical rejection indicated by increased serum creatinine levels and donor-specific antibodies (DSA) and received steroid pulse therapy, plasmapheresis, and rituximab. This treatment restored graft function to within the normal range. The latest graft function in all patients was maintained at normal levels in the outpatient clinic., Conclusions: Living donor renal transplantation may be successful in patients with APS following perioperative anticoagulation therapy. However, because of the high risk of TMA or vascular thrombosis in the early postoperative period, close monitoring for hypercoagulability and continuous anticoagulation is essential for maintaining graft function., Competing Interests: The authors have no funding and conflicts of interest to disclose.

Background: Recurrent IgA nephropathy (IgAN) after kidney transplantation (KT) has been reported to range between 12 and 65%. However, few data are available on second transplantation in recurrent IgAN. Therefore, this study aimed to build bottom-line data for the possibility of second transplantation in patients who lost first transplanted kidney due to recurrent IgAN., Methods: Patients who received KT twice due to recurrent IgAN at four large academic hospitals in Korea between March 1985 and December 2013 were reviewed. They were followed up until October 2014. All patients were identified as having recurrent IgAN in the first graft biopsies. The clinical outcomes of the second KT in these patients were compared with the first KT and with all cases of second KT (n = 169) performed at one center in the same period., Results: 28 patients were enrolled in this study. First grafts failed after 106.64 ± 48.72 months (mean ± SD). Following the second transplantation, recurrent IgAN was identified in only 2 patients during the follow-up of 61.61 ± 47.23 months. In 1 patient, the second graft was lost due to chronic rejection without mesangial IgA deposit. The second KT showed comparable graft survival compared with the first KT and the overall second KT (p = 0.308 by log-rank test). At the final follow-up, the serum creatinine level was 1.16 ± 0.33 mg/dL in the second graft except in 1 patient., Conclusions: Second KT in recurrent IgAN showed reasonably good long-term results. Therefore, clinicians might be able to suggest second transplantation as an option for patients who lost the first graft due to recurrent IgAN.

Objectives: Basiliximab is used alongside tacrolimus-based immunosuppression for routine induction therapy, even for well-matched living-donor renal transplant recipients. Because tacrolimus is a different drug from cyclosporine, this study examined the utility of tacrolimus-based immunosuppression without basiliximab for well-matched living-donor renal transplant recipients., Materials and Methods: This prospective study evaluated 36 patients who underwent 1 to 3 human leukocyte antigens mismatched living-donor renal transplants without basiliximab induction therapy between April 2012 and March 2015 (group 1). All transplants were ABO compatible and T-flow negative and were followed until April 2015. Tacrolimus-based triple therapy was used for maintenance immunosuppression. The control group comprised 72 age- and sex-matched patients who underwent 1 to 3 human leukocyte antigens mismatched living-donor renal transplants with basiliximab induction therapy during the same period (group 2)., Results: Two patients in group 1 and 12 patients in group 2 had infection,with cytomegalovirus infection and Pneumocystis pneumonia infection occurring only in group 2 and BK virus and urinary tract infection reported in both groups, with a similar incidence. One patient from group 2 had sepsis. Although the incidence of infection tended to be lower in group 1 than in group 2 (5.6% vs 16.7%), the overall incidence of infection was not significantly different (P=.135). In addition, there were no significant differences in incidence of acute rejection between groups 1 and 2 (2.8% vs 4.2%; P=.699). All patients showed stable renal function after treatment., Conclusions: Tacrolimus-based triple drug maintenance immunosuppression without basiliximab might be an optimal treatment choice for individuals undergoing well-matched living-donor renal transplant.

Living donor pancreas transplantation (LDPT) has several advantages over deceased donor pancreas transplantation (DDPT), including better HLA matching, shorter ischemic time, and shorter waiting time. It remains an attractive option for diabetes mellitus (DM) patients with end stage renal disease. We reviewed 20 cases of LDPT performed in Asan Medical Center between October 1992 and March 2015. Six cases (30%) were pancreas transplantation alone (PTA), and the rest (70%) were simultaneous pancreas and kidney transplantation (SPK). Relations of donor and recipient were parents in 7 (35%), siblings in 6 (30%), spouse in 6 (30%), and cousin in 1 (5%). Graft survival in SPK at 1, 3, 5, and 10 years was 91.7%, 83.3%, 83.3%, and 83.3%, respectively, and that in PTA recipients was 50%, 33.3%, 16.7%, and 16.7%, respectively (p = 0.005). Causes of graft failure in SPK were thrombosis (one case), and rejection (one case), whereas those in PTA were noncompliance (two cases), thrombosis (one case), reflux pancreatitis (one case), and chronic rejection (one case). In terms of pancreas exocrine drainage, two grafts (25%) maintained their function in bladder drainage, while all grafts maintained in enteric drainage p < 0.05). Seven (35%) donors experienced minor pancreatic juice leakage and one underwent reoperation due to postoperative hematoma. Most donors maintained normoglycemia and normal renal function. However, two donors developed DM (at 1 and 90 months postdonation), and were treated with oral hypoglycemic agents. Graft survival in PTA recipients was poorer than in SPK due to poor compliance and bladder drainage-related problems. The surgical and metabolic complication rates of donors can be minimized by applying strict donor criteria. Therefore, LDPT with enteric drainage is an acceptable treatment for SPK., (© Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objective: Although E/e´ is prognostic of mortality in patients with end-stage renal disease (ESED), little is known about the prognostic implications of E/e´ following kidney transplant (KT). The objective of this study was to evaluate whether an elevated E/e´ is associated with graft function, postoperative hemodialysis, and overall mortality in end-stage renal disease patients following KT., Design: A retrospective observational study., Setting: Tertiary teaching hospital., Participants: In total, 1,045 patients underwent KT at the authors' hospital between January 2006 and December 2013., Intervention: None., Measurements and Main Results: Patients were divided into groups with an E/e´<15 or≥15, as assessed by preoperative echocardiography (median time from preoperative assessment of echocardiography to surgery: 37 days [IQR: 16-68 days]). Of 1,045 patients, 821 patients (78.6%) had an E/e´<15, and 224 patients (21.4%) had an E/e´≥15. Multivariate analysis indicated that age (odds ratio [OR]: 1.03; 95% confidence interval [CI]: 1.01-1.04, p = 0.001), diabetes mellitus (OR: 2.7; CI: 1.94-3.83, p<0.001), β-blocker (OR: 1.4; CI: 1.03-1.95, p = 0.034), left atrial dimension (OR: 1.07; CI: 1.04-1.11, p<0.001), and left ventricular mass index (OR: 1.02; CI: 1.01-1.03, p<0.001) are predictive of E/e´≥15. After adjustment using inverse probability of treatment weighting, E/e´≥15 also was associated independently with postoperative hemodialysis (OR: 2.0; 95% CI: 1.5-2.6, p<0.001), graft failure (OR: 1.7; 95% CI: 1.4-2.2; p<0.001), and overall mortality (hazard ratio [HR]: 3.2; 95% CI: 2.1-4.8, p<0.001)., Conclusions: Preoperative E/e´ is a prognostic indicator of overall mortality in ESRD patients undergoing KT., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The goal of this study was to identify immunological markers for use in antigen-specific assays that predict long-term survival after renal allograft and distinguish stable-functioning (SP) patients from poorly functioning (PP) patients. For this prospective study, 20 patients were enrolled. Eight SP and six PP patients were enrolled in this study. Serum cytokine/chemokine levels were analyzed by the Luminex multiplex assay. To detect indirect alloreactive T cells, we performed indirect mixed lymphocyte reaction using donor-antigen-pulsed autologous dendritic cells as stimulators. Serum induced protein-10 levels were significantly higher in the serum of PP patients, whereas sCD40L levels were higher in SP patients. The PP patients had significantly higher numbers of donor-specific CD4(+)CD43(high)CD45RO(+) T cells after indirect allostimulation, whereas this cell population was unchanged in SP patients. The donor-specific CD4(+)CD43(high)CD45RO(+) T cells had the effector memory T cell phenotype. Prospectively, we studied whether these cells influence graft outcome and found that their strong proliferation in pre-transplant patients is related to a poorly functioning graft. Indirectly allostimulated CD4(+)CD43(high)CD45RO(+) T cells may not only contribute to chronic allograft nephropathy development but may also have a role in the progression of acute rejection. Thus, these cells may have potential use as immune-monitoring markers in a noninvasive in vitro assay that predicts graft outcome., (© 2015 by the Society for Experimental Biology and Medicine.)

Although hyponatremia is related to poorer outcomes in several clinical settings, its significance remains unresolved in kidney transplantation. Data on 1,786 patients who received kidney transplantations between January 2000 and December 2011 were analyzed. The patients were divided into two groups according to the corrected sodium values for serum glucose 3 months after their transplantations (<135 mmol/L vs. ≥135 mmol/L). Subsequently, the hazard ratios (HRs) for biopsy-proven acute rejection, graft failure, and all-cause mortality were calculated after adjustments for several immunological and non-immunological covariates. 4.0% of patients had hyponatremia. Patients with hyponatremia had higher risks for graft failure and all-cause mortality than did the counterpart normonatremia group; the adjusted HRs for graft failure and mortality were 3.21 (1.47-6.99) and 3.03 (1.21-7.54), respectively. These relationships remained consistent irrespective of heart function. However, hyponatremia was not associated with the risk of acute rejection. The present study addressed the association between hyponatremia and graft and patient outcomes in kidney transplant recipients. Based on the study results, our recommendation is to monitor serum sodium levels after kidney transplantations.

Background: Rituximab is widely used in kidney transplantation. However, it is not clear whether the conventional doses of maintenance immunosuppressant in rituximab-treated kidney transplantation (KT) are appropriate. In our previous study, decreasing mycophenolate mofetil (MMF) dose due to infection did not increase the incidence of rejection or graft failure. Based on these experiences, we developed a new protocol with a lower dose of MMF and studied its clinical outcomes in rituximab-treated KT., Methods: We enrolled all patients who underwent ABO-incompatible or human leukocyte antigen (HLA)-sensitized living donor KT with the new immunosuppressant protocol after preconditioning with rituximab, but without splenectomy from November 2011 to May 2013. Seventy-two patients (group 1) were consecutively enrolled in this study and followed until November 2013. Patients from our previous study served as control groups. Sixty-seven patients received KT using rituximab with a conventional dose of MMF (group 2), and 87 patients received ABO compatible KT without need for rituximab (group 3). Clinical outcomes, including rejection, infection, and graft survival, were compared between the groups. The χ (2) test and Fisher's exact test were used for categorical variables, the Student's t-test and Mann-Whitney U test were used for continuous variables, and a log-rank test was used for mortality analysis., Results: Doses of postoperative MMF (g/day) were lower in group 1 than in the other groups (1.03 ± 0.19, 1.48 ± 0.34 and 1.48 ± 0.32 g/day at 1 week, p < 0.001). Infectious complications occurred more often in groups with conventional MMF doses (group 2 and 3) than in group 1 (16.7 vs. 37.3 %, p = 0.007 and 16.7 vs. 34.5 %, p = 0.012, respectively). Notably, group 1 showed a lower incidence of cytomegalovirus infection than group 2. However, reduction in MMF dose did not increase the incidence of acute rejection (4.2, 4.5 and 10.3 %). Only one graft failure occurred in group 2 due to vessel kinking after operation. There were no significant differences in the incidence of malignancy and mortality between groups., Conclusions: A low MMF dose reduces infection without increasing rejection or graft loss and it may be appropriate to reduce the dose of MMF for rituximab-treated KT patients.

Objective: This study aimed to investigate the incidence and related clinical factors of LV hypertrophy (LVH) regression after kidney transplantation and its effect on graft outcome., Methods: Among the 3373 kidney transplant recipients who were enrolled in a multicentre cohort from 1997 to 2012, a total of 767 patients who underwent echocardiography before and after transplantation were included in this study followed for a median of 7.5 years., Results: LVH regression steadily increased from 7.4% at 1 year to 35.4% at 5 year over the 5-year post-transplantation period. The probability of LVH regression decreased in the patients who received a kidney transplant due to end-stage renal disease of unknown aetiology (p=0.041) or who underwent pretransplant haemodialysis (p=0.020). The probability of LVH regression also decreased as the pretransplant LV mass index (p<0.001) and post-transplant systolic blood pressure increased (p=0.005). Conversely, LVH regression was significantly associated with the highest tertile of the pretransplant haemoglobin level (p=0.029). Furthermore, in the 5th year after transplantation, persistent LVH was independently associated with allograft failure (HR 1.95; 95% CI 1.14 to 3.33; p=0.015) and the LV mass index reliably predicted graft outcome., Conclusions: LVH consistently regressed after kidney transplantation in most patients. Persistent LVH, low haemoglobin levels and elevated blood pressure were associated with an increased risk of allograft failure in kidney transplant recipients., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

We investigated the effects of pregnancy and delivery on renal function in transplant recipients and the relationship between doses of immunosuppressants and blood drug levels during pregnancy in 75 women with 88 deliveries. Significant serum creatinine elevation (> 0.5 mg/dL) was found in eight deliveries. In the remaining 80 cases, serum creatinine was reduced by an average of 0.14 mg/dL and returned to pre-pregnant levels after delivery. Tacrolimus was used in 28 deliveries and cyclosporine in others. Tacrolimus blood trough level declined from 5.8 ± 2.8 ng/mL 12 months before delivery to 4.2 ± 1.8 ng/mL at second trimester; therefore, drug dose was increased from 4.1 ± 1.9 mg/d at first trimester to 5.5 ± 2.5 mg/d at delivery. Similarly, cyclosporine levels were 125.1 ± 65.1 ng/mL 12 months before delivery and 75.4 ± 35.0 ng/mL at second trimester resulting in dose elevation from 183.0 ± 71.8 mg/d at first trimester to 225.4 ± 85.1 mg/d at delivery. Renal function in female kidney transplant recipients improved slightly during pregnancy and returned to pre-pregnant level after delivery. The dose elevation of calcineurin inhibitor by approximately 20-25% should be considered during gestational period to maintain optimal blood drug level., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The long-term impact of human leukocyte antigen (HLA) mismatches combined with expanded criteria donors (ECD) on clinical outcomes has not been fully evaluated in recipients of deceased donor (DD) kidney transplantations. Of 595 DD renal transplant recipients in our center between 1991 and 2011, 210 recipients (36%) had 0-3 HLA mismatches/standard criteria donor (SCD), 353 (59%) had 4-6 HLA mismatches/SCD or 0-3 HLA mismatches/ECD, and 32 (5%) had 4-6 HLA mismatches/ECD. The mortality rate was significantly highest in the patients with 4-6 HLA mismatches/ECD (p = 0.040). The most common cause of death in this group was infection (50%). There were no significant differences in overall graft survival and death-censored graft survival. The biopsy-proven acute rejection rate was significantly higher in the 4-6 HLA mismatches/ECD group (p = 0.011). Cox-regression multivariate analyses showed that 4-6 HLA mismatches plus ECD (adjusted hazard ratio [AHR], 3.2; 95% confidence interval [CI], 1.17-10.56) and diabetes (AHR, 4.3; 95% CI, 1.50-12.28) were significant predictors of recipient mortality. In conclusion, ≥4 HLA mismatches plus ECD were associated with significantly higher rates of biopsy-proven acute rejection and mortality compared with other groups undergoing DD kidney transplantation., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: CD56+ and CD163+ cell infiltration in human kidney transplant biopsies have not been fully evaluated., Methods: We investigated the association of CD56+ and CD163+ cell infiltration with human kidney transplant biopsies with antibody- or T-cell-mediated rejection (TCMR) and other histologic lesions. One hundred and seventy four clinically indicated transplant biopsies were included in this analysis. Immunohistochemical staining for C4d, CD56 and CD163 was performed., Results: One hundred and seventy four indication biopsies were divided into early (≤1 year posttransplant; n = 49) and late (>1 year posttransplant; n = 125) biopsies. High numbers of CD56+ cells were uncommon in early biopsies except for those with antibody-mediated rejection (AMR) only. On the other hand, high numbers of CD56+ cells were observed in late biopsies diagnosed as TCMR only, AMR only, and TCMR combined with AMR. In early biopsies, both CD56+ and CD163+ infiltrates correlated strongly with interstitial inflammation, tubulitis, and peritubular capillaritis (ptc) scores. The ci and ct scores, however, were correlated only with the number of CD56+ cells. In late biopsies, on the other hand, the number of CD56+ infiltrates was correlated only with ptc, while the number of CD163+ infiltrates was weakly correlated with any histologic lesion. Multivariable analyses showed that chronic active AMR and the number of CD56+ cells/10 HPF were independently associated with death-censored graft failure post-biopsy. The number of CD163+ cells was not correlated with any pathologic lesion and post-biopsy graft failure. CD56+ infiltrates were also associated with interstitial fibrosis and tubular atrophy., Conclusions: Intragraft CD56+ cell infiltrates were significantly associated with AMR and subsequent poor clinical outcomes., (© 2015 S. Karger AG, Basel.)

Background: Acute rejection (AR) after solid organ transplantation has been known to be a risk factor for cytomegalovirus (CMV) infection. However, data regarding the risk for CMV infection during and after anti-rejection therapy are limited. This study investigated whether the risk of CMV infection and disease within 6 months of kidney transplantation (KT) increases in CMV-seropositive KT recipients who develop AR., Methods: A total of 992 seropositive KT recipients, including 75 patients (8%) who developed AR within 6 months after KT and 917 patients (92%) who did not, were recruited between May 2007 and April 2012., Results: No significant difference was found in the incidence of CMV infection between the groups (AR group, 13% [10/75] vs. non-AR group, 10% [92/917], P = 0.37). The number of KT recipients in each group receiving preemptive therapy for CMV was similar (5% [4/75] vs. 6% [53/917], P > 0.99). While the incidence of CMV syndrome was comparable (0% [0/75] vs. 1% [12/917], P > 0.99), the incidence of tissue-invasive CMV disease (8% [6/75] vs. 3% [27/917], P = 0.04), particularly gastrointestinal CMV disease, was significantly greater in patients who experienced AR. No CMV-related mortality occurred in either group. AR (odds ratio, 2.81; 95% confidence interval, 1.08-7.29; P = 0.03) was an independent risk factor for tissue-invasive CMV disease within 6 months of KT., Conclusions: A high index of suspicion and active evaluation for tissue-invasive CMV disease in KT recipients suffering AR may be necessary to ensure appropriate treatment., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Asian patients undergoing kidney transplantation (KT) generally have better renal allograft survival and a lower burden of cardiovascular disease than those of other racial groups. The KNOW-KT aims to explore allograft survival rate, cardiovascular events, and metabolic profiles and to elucidate the risk factors in Korean KT patients., Methods: KNOW-KT is a multicenter, observational cohort study encompassing 8 transplant centers in the Republic of Korea. KNOW-KT will enroll 1,000 KT recipients between 2012 and 2015 and follow them up to 9 years. At the time of KT and at pre-specified intervals, clinical information, laboratory test results, and functional and imaging studies on cardiovascular disease and metabolic complications will be recorded. Comorbid status will be assessed by the age-adjusted Charlson co-morbidity index. Medication adherence and information on quality of life (QoL) will be monitored periodically. The QoL will be assessed by the Kidney Disease Quality of Life Short Form. Donors will include both living donors and deceased donors whose status will be assessed by the Kidney Donor Risk Index. Primary endpoints include graft loss and patient mortality. Secondary endpoints include renal functional deterioration (a decrease in eGFR to <30 mL/min/1.73 m2), acute rejection, cardiovascular event, albuminuria, new-onset diabetes after transplant, and QoL. Data on other adverse outcomes including episodes of infection, malignancy, recurrence of original renal disease, fracture, and hospitalization will also be collected. A bio-bank has been established for the acquisition of DNA, RNA, and protein from serum and urine samples of recipients at regular intervals. Bio-samples from donors will also be collected at the time of KT. KNOW-KT was registered in an international clinical trial registry (NCT02042963 at http://www.clinicaltrials.gov) on January 20th, 2014., Conclusion: The KNOW-KT, the first large-scale cohort study in Asian KT patients, is expected to represent the Asian KT population and provide information on their natural course, complications, and risk factors for complications.

Background: Renal transplant candidates with extended indications, such as older age and advanced atherosclerosis, are currently accepted onto the waiting list., Methods: We retrospectively evaluated the clinical outcomes of simultaneous kidney transplantation and angioplasty compared with transplantation alone., Results: We included 748 patients who underwent living-donor kidney transplant because of end-stage renal disease during a 5-year period, consisting of 27 kidney transplants with simultaneous angioplasty and 721 without additional vascular procedures. As candidates for simultaneous angioplasty and transplant, we considered patients with TransAtlantic Inter-Society Consensus type A and B aorto-iliac disease. We compared transplant outcomes in patients who did or did not receive simultaneous angioplasty. Although simultaneous iliac artery angioplasty was significantly related to recipient age, diabetes mellitus, hypertension, and coronary artery disease, it was not associated with graft (uncensored, P=0.937; death censored, P=0.981) or patient (P=0.804) survival during the follow-up period. In addition, simultaneous angioplasty was not associated with a higher risk of delayed graft function (P=0.099) or a longer hospital stay (P=0.790). There was no significant difference in mortality due to a cardiovascular event between the two groups (P=0.199)., Conclusions: Simultaneous iliac artery angioplasty and kidney transplantation in carefully selected patients can be performed safely with equivalent graft and patient survival to transplantation alone.

Background: Although the therapeutic potential of regulatory T lymphocytes (Tregs) in preventing allograft rejection has been well documented, accumulating evidence indicates that supplemental measures, such as concomitant use of immunosuppressive agents, are essential for effective application of Treg cell therapy in clinical transplantation. Thus, it is important to know the effect of immunosuppressive agents on Treg cell therapy., Methods: We examined the impact of various immunosuppressive agents on the in vivo proliferation and therapeutic efficacy of in vitro-expanded Tregs using the murine graft-versus-host reaction and skin allograft model (BDF1 [H-2] to C57BL/6 [H-2]), respectively., Results: All six immunosuppressive agents tested inhibited the alloantigen-stimulated proliferation of Tregs as efficiently as they inhibited the proliferative response of conventional CD3 T cells. We further show that blockade of the CD40-CD40L interaction by treatment with a MR-1 antibody significantly increased the therapeutic efficacy of Tregs, a synergistic effect that seemed to be related to the strong regulatory activity of adoptively transferred Tregs together with effector T-cell hyporesponsiveness. Although concomitant use of rapamycin marginally augmented the therapeutic effectiveness of Tregs, mycophenolate mofetil and cyclosporine A at their full therapeutic doses exerted an antagonistic effect on Treg cell therapy., Conclusion: These results demonstrate that inhibition of CD40-CD40L interaction or treatment with rapamycin could be successfully combined with in vitro-expanded Treg cell therapy, but the concomitant use of mycophenolate mofetil or cyclosporine A in this type of Treg cell therapy should be carefully considered.

The necessity to transplant islet tissue without the need for immunosuppressant therapy has led to the development of materials for immune modulation. Pegylation makes islets antigenically silent, protecting them from the adsorption of foreign protein and thus avoiding immune injury. The aim of this study is to determine whether pegylation of islets prolongs islet survival and function both during tissue culture and posttransplantation. We used cyanuric chloride-activated methoxy-polyethylene glycol for cell surface modification. To detect the pegylation effect on splenocytes, we measured antibody binding inhibition and abrogation of lymphocyte proliferation. To detect the pegylation effect on islet grafts, we performed rodent islet transplantation. Islet viability and function were maintained after pegylation. Pegylated islets showed a 90% decrease in antibody binding and decreased lymphocyte proliferation in a mixed lymphocyte culture. However, when pegylated islets were transplanted, no prolongation of graft survival was observed. When a subtherapeutic dose of immunosuppressant was given at the time of transplantation of pegylated islets, islet graft survival was significantly prolonged. In addition, when rats were sensitized with donor splenocytes, graft survival was prolonged by pegylation. We observed that pegylation of islets, combined with a subtherapeutic dose of immunosuppressant, protects the graft from rejection. Prolonged graft survival in sensitized recipients showed that pegylation of islets shifted the pattern of rejection from an acute humoral response to a less aggressive cellular alloresponse.