Search

High intra-patient variability (IPV) of tacrolimus trough concentrations is increasingly recognized as a predictor of poor long-term outcomes in kidney transplant. However, there is a lack of information regarding the association between tacrolimus IPV and graft outcomes according to immunological risk. We analyzed tacrolimus IPV using the coefficient of variability from months 6-12 after transplantation in 1080 kidney transplant recipients. Patients were divided into two immunological risk groups based on pre-transplant panel reactive antibodies and donor-specific antibodies. High immunological risk was defined as panel reactive antibodies ≥ 20% or the presence of donor-specific antibodies. The effects of tacrolimus IPV on graft outcomes were significantly different between low and high immunological risk patients. A multivariable Cox regression model confirmed that high tacrolimus IPV was an independent risk factor for graft failure in the high risk group (HR, 2.90; 95% CI, 1.42-5.95, P = 0.004). In the high risk group, high tacrolimus IPV was also significantly associated with increased risk of antibody-mediated rejection (P = 0.006). In contrast, death-censored graft survival and antibody-mediated rejection in the low immunological risk group was not significantly different by tacrolimus IPV. High tacrolimus IPV significantly increases the risk of graft failure and antibody-mediated rejection in patients with high immunological risk.

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Serum bilirubin, a potent endogenous antioxidant, has been associated with decreased risks of cardiovascular disease, diabetes, and kidney disease. However, the effects of serum bilirubin on kidney transplant outcomes remain undetermined. We analyzed 1628 patients who underwent kidney transplantations between 2003 and 2017. Patients were grouped into sex-specific quartiles according to mean serum bilirubin levels, 3-12 months post-transplantation. Median bilirubin levels were 0.66 mg/dL in males and 0.60 mg/dL in females. The intra-individual variability of serum bilirubin levels was low (9%). Serum bilirubin levels were inversely associated with graft loss, death-censored graft failure, and all-cause mortality, independent of renal function, donor status, and transplant characteristics. Multivariable analysis revealed that the lowest serum bilirubin quartile was associated with increased risk of graft loss (HR 2.64, 95% CI 1.67-4.18, P < 0.001), death-censored graft failure (HR 2.97, 95% CI 1.63-5.42, P < 0.001), and all-cause mortality (HR 2.07, 95% CI 1.01-4.22, P = 0.046). Patients with lower serum bilirubin were also at greater risk of rejection and exhibited consistently lower glomerular filtration rates than those with higher serum bilirubin. Serum bilirubin levels were significantly associated with transplantation outcomes, suggesting that bilirubin could represent a therapeutic target for improving long-term transplant outcomes.

Background: The diagnostic criteria of antibody-mediated rejection (ABMR) has been significantly changed since Banff 2013. The most important revision was adopting microvascular inflammation (MVI) as immunopathologic evidence for ABMR even in C4d-negative cases. In this study, we retrospectively reviewed previous allograft biopsy results and evaluated the impact of this change., Methods: We reviewed results of 536 renal allograft biopsies at Severance Hospital during 2011 to 2013, which were diagnosed according to the Banff 2009 criteria. All biopsy results were reassessed according to the Banff 2017 criteria., Results: According to the Banff 2009 criteria, antibody-mediated changes were observed in 48 cases out of the 536 allograft biopsies (9.0%). According to the Banff 2017 criteria, 28 additional cases (5.2%) were reclassified as antibody-mediated changes. Twenty-six of these cases were C4d-negative ABMR. The most frequent diagnostic finding in these cases was MVI comprising glomerulitis and peritubular capillaritis. Donor-specific antibodies were investigated in 14 of these cases, which revealed positive results in 12 cases., Conclusion: The incidence rate of ABMR has increased after the recent revision of the Banff criteria. The MVI in C4d-negative ABMR cases is the major cause for this increase., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The significance of proinflammatory M1 (classically activated) and profibrotic M2 (alternatively activated) macrophages in antibody-mediated rejection (ABMR) after kidney transplantation has not been investigated., Methods: Fifty-five biopsy-confirmed ABMR samples were stained with MRP 8/14 (a marker of M1 macrophages) and CD163 (a marker of M2 macrophages), and positive cells were counted in glomeruli and the tubulointerstitium, respectively. Patients were classified into M1 and M2 polarization groups according to the glomerular and tubulointerstitial M1:M2 ratio, and the results were compared with Banff scores, serum creatinine level, estimated glomerular filtration rate (eGFR), and graft survival., Results: The glomerular M2 polarization group showed significantly higher chronic glomerulopathy scores, serum creatinine levels, and lower eGFR at the time of biopsy (P = .019 and P = .015, respectively) and 3-month postbiopsy (P = .016 and P = .032, respectively) than the M1 polarization group. The tubulointerstitial M2 polarization group had significantly lower glomerulitis, arteritis, peritubular capillaritis, and glomerulitis + peritubular capillaritis scores than the M1 polarization group, but there was no significant difference in renal function. Long-term graft survival was not associated with macrophage polarization., Conclusion: Glomerular M2 polarization in ABMR biopsy samples is associated with chronic glomerular injury and poorer graft function, but without graft survival., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Rationale: Human leukocyte antigen (HLA) is the major immunologic barrier in kidney transplantation (KT). Various desensitization protocols to overcome the HLA barrier have increased the opportunity for transplantation in sensitized patients. In addition, technological advances in solid-phase assays have permitted more comprehensive assessment of donor-specific antibodies. Although various desensitization therapies and immunologic techniques have been developed, the final transplantation decision is still based on the classic complement-dependent cytotoxicity (CDC) crossmatch (XM) technique. Some patients who fail to achieve negative XM have lost their transplant opportunities, even after receiving sufficient desensitization therapies., Patient Concerns: A 57-year-old male with end-stage renal disease secondary to chronic glomerulonephritis was scheduled to have a second transplant from his son, but CDC XM was positive., Diagnoses: Initial CDC XM (Initial T-AHG 1:32) and flow-cytometry XM were positive. Anti-HLA-B59 donor specific antibody was detected by Luminex single antigen assay., Interventions: Herein, we report a successful case of KT across a positive CDC XM (T-AHG 1:8 at the time of transplantation) by using C1q assay-directed, bortezomib-assisted desensitization. After confirming a negative conversion in the C1q donor-specific antibody, we decided to perform KT accepting a positive AHG-CDC XM of 1:8 at the time of transplantation., Outcomes: The posttransplant course was uneventful and a protocol biopsy at 3 months showed no evidence of rejection. The patient had excellent graft function at 12 months posttransplant., Lessons: The results of XM test and solid-phase assay should be interpreted in the context of the individual patient.

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 Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

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., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Purpose: Recently, bortezomib has been used to treat antibody-mediated rejection (AMR) refractory to conventional treatment such as plasmapheresis, intravenous immunoglobulin, and rituximab. The authors aimed to describe their experiences when bortezomib was used to treat refractory AMR., Materials and Methods: Eleven refractory AMR episodes treated with bortezomib were included in this study. The patients received one or two cycles of bortezomib (1.3 mg/m²) on days 1, 4, 8, and 11., Results: Bortezomib effectively reduced antibodies against various targets, including human leukocyte antigen (HLA) class I and II, ABO blood group antigen, and angiotensin II type 1 receptor. Antibodies were depleted or reduced significantly in eight AMR episodes. Overall, there was a significant improvement in the mean estimated glomerular filtration rate (eGFR) at 3 months after therapy (36.91±22.15 mL/min/1.73 m²) versus eGFR at time of AMR diagnosis (17.00±9.25 mL/min/1.73 m²; p=0.007). All six early-onset AMR episodes (within 6 months post-transplantation) showed full recovery of allograft function. Additionally, three of the five late-onset AMR episodes (>6 months post-transplantation) showed improved allograft function., Conclusion: Anti-humoral treatment based on bortezomib might be an effective strategy against refractory AMR caused by various types of antibodies. Notably, this treatment could be more effective in early-onset AMR than in late-onset AMR.

The optimal immunosuppressive strategy for renal transplant recipients at high immunologic risk remains a topic of investigation. This prospective single arm pilot study was undertaken to evaluate the safety and efficacy of a combined tacrolimus and sirolimus regimen in recipients at immunological high risk and to compare outcomes with a contemporaneous control group received tacrolimus and mycophenolate mofetil. Patients that received a renal allograft between 2010 and 2011 at high risk (defined as panel reactive antibodies > 50%, 4 or more human leukocyte antigen mismatches, or retransplantation) were enrolled. All patients received basiliximab induction and corticosteroids. A total of 28 recipients treated with tacrolimus and sirolimus were enrolled in this study and 69 recipients were retrospectively reviewed as a control group. The sirolimus group showed a higher, but not statistically significant, incidence of biopsy proven acute rejection and a lower glomerular filtration rate than the control group. Furthermore, sirolimus group was associated with significant increases in BKV infection (P = 0.031), dyslipidemia (P = 0.004), and lymphocele (P = 0.020). The study was terminated prematurely due to a high incidence of adverse events. A de novo tacrolimus/sirolimus combination regimen may not be an ideal choice for recipients at high immunological risk.

Background: Solid-phase immunoassays have improved detection sensitivity for donor-specific HLA antibody (DSHA) and permitted the accurate diagnosis of antibody-mediated rejection (AMR). However, DSHA is not always sufficient to explain the cause of AMR. Consequently, a means of assessing non-HLA antibodies is required to determine the cause of AMR. The aim of the present study was to evaluate the clinical implications of antibodies (Abs) targeting angiotensin II type I receptor (AT1R) in recipients with AMR but without serum DSHA., Methods: Non-HLA AMR cases diagnosed between January 2011 and June 2014 were included. Levels of anti-AT1R Abs (U/mL) were quantified by using AT1R assay kits (One Lambda, Calif, United States) with collected sera pretransplantation and at biopsy (cut-off value: 15 U/mL)., Results: Seventy-two patients were diagnosed with AMR during the above-mentioned period. Of them, 12 recipients (16.7%) had no DSHA. The sera of these 12 patients were tested (2 patients were only checked at time of biopsy). Nine patients (9/10) were presensitized for anti-AT1R Abs (median, 25.0 U/mL; range, 12.9 to 50.0 U/mL). Ten patients (10/12) were anti-AT1R- positive at time of biopsy (median, 23.2 U/mL; range, 11.4 to 50.0 U/mL). The mean time from transplantation to biopsy was 73 months. Eight patients experienced acute AMR, and 4 developed chronic AMR. Four patients showed negative C4d staining in peritubular capillaries (4/12). Patients were treated with plasmapheresis, low-dose intravenous immunoglobulin, and/or rituximab., Conclusions: AT1R Abs may play a significant role in AMR without detectable DSHA. Pretransplantation detection of AT1R Abs may be helpful for assessing the risk for non-HLA AMR., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Everolimus and cyclosporine A (CsA) exhibit synergistic immunosuppressive activity when used in combination. We examined the safety and efficacy of the use of everolimus with a cyclosporine-sparing strategy in de novo renal transplant recipients., Methods: A comparative, parallel, randomized, open-label 1-year study has been performed in 148 patients from five transplant centers to compare the efficacy and tolerability of everolimus and reduced exposure CsA (the investigational group) or enteric-coated mycophenolate sodium and standard-exposure CsA (the control group) in combination with basiliximab and steroids. The eligible subjects were randomly assigned at 1 month after transplantation. Efficacy failure (biopsy-proven acute rejection, death, graft loss, or loss to follow-up), safety, and renal function were evaluated., Results: One graft loss has been reported in the control group and no patient death were reported in either group. The incidence of biopsy-proven acute rejection until 12 months after transplantation of the investigational group was 7.5%, compared to 11.1% of the control group (P=0.565). The mean estimated glomerular filtration rates of the investigational group at 12 months after transplantation was significantly higher (68.1 ± 16.8 ml/min/1.73 m(2)) than that of the control group (60.6 ± 15.8 ml/min/1.73 m(2); P=0.016). There was no significant difference (P>0.05) in the incidence of discontinuations and serious adverse events between the groups., Conclusion: The results of this study provide the evidences that (1) the calcineurin inhibitor (CNI) minimization by the introduction of everolimus after 1-month posttransplantation keeps the incidences of acute rejection and additional risks as low as the conventional immunosuppression; (2) it allows minimizing CNI exposure, consequently reducing CNI nephrotoxicity and preserving renal function.

This study was designed to evaluate whether sirolimus (SRL) conversion effectively improves renal function and histopathology in calcineurin inhibitor (CNI)-treated renal recipients with mild to moderate renal insufficiency. SRL conversion from CNI was performed in patients who underwent kidney transplantation from 6 months to 5 yr prior to screening. Forty-five patients were enrolled. The effect of SRL conversion on graft function was evaluated, and protocol biopsies were performed preconversion and 1 yr after conversion. Overall graft function after SRL conversion gradually improved, and the improvement in renal function was closely associated with the shorter duration of CNI exposure. When we divided the patients by the duration of CNI exposure, the patients with less than 1 yr of CNI exposure demonstrated significant improvement, but patients with a greater than 1 yr CNI exposure did not exhibit significant improvement. In contrast, protocol biopsies demonstrated no significant improvements in the modified "ah" score or other Banff scores after SRL conversion. Furthermore, the duration of CNI treatment prior to SRL conversion was not associated with histological findings 1 yr after SRL conversion. SRL conversion improved graft function in renal recipients with mild to moderate renal insufficiency, but this effect is not accompanied by histological improvement.

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.

Recently, Luminex-crossmatch (LumXm) was introduced. The aim of this study was to evaluate clinical outcomes in sensitized recipients with a positive Luminex-crossmatch (LumXm (+)) and a negative complement-dependent cytotoxicity crossmatch (CDCXm (-)) after renal transplantation. Fifty-five renal transplant recipients with a CDCXm (-) and PRA class I or II ≥20% were enrolled in this study between February 2008 and December 2010 at Severance Hospital. Eighteen patients displayed LumXm (+) defined as LumXm positive class I or II and 37 patients displayed LumXm (-). Mean duration of follow-up was 18.9 ± 8.3 months. During this period, no patient death or graft loss occurred. The incidence of biopsy-proven or clinically presumed rejection was higher in the LumXm (+) group (n = 12, 66.7%) than in the LumXm (-) group (n = 6, 18.2%) (P = 0.001). All biopsy-proven acute rejections (n = 12) were diagnosed as acute cellular rejection. No significant difference in mean serum creatinine level or eGFR was observed between the groups at 18 months post-transplantation. The short-term outcome of renal transplantation in sensitized patients with a LumXm (+) and a CDCXm (-) may be considered to be acceptable. However, patients with a LumXm (+) have a substantially higher immunological risk for the development of acute cellular rejection., (© 2012 The Authors. Transplant International © 2012 European Society for Organ Transplantation.)

Introduction: The number of end-stage renal disease (ESRD) patients with preformed antibodies waiting for a kidney transplant has been increasing lately. We conducted a nationwide study on the outcomes of kidney transplantation after desensitization in Korea., Methods: Six transplant centers have run desensitization programs. The patients who underwent living donor kidney transplantation after desensitization from 2002 to 2010 were retrospectively analyzed., Results: A total of 86 cases were enrolled. Thirty-five of these were cases of re-transplantation (40.7 %). Indications of desensitization were positive complement-dependent cytotoxicity (CDC) cross-match responses (CDC(+), 36.0 %), positive flow-cytometric cross-match responses (FCX(+), 54.7 %), and positive donor-specific antibodies (DSA(+), 8.1 %). The desensitization protocols used pre-transplant plasmapheresis (95.3 %), intravenous immunoglobulin (62.8 %), and rituximab (67.4 %). Acute rejection occurred in 18 patients (20.9 %), graft failure occurred in 4 patients, and the 3-year graft survival rate was 93.8 %. The presence of DSA increased the acute rejection rate (P = 0.015) and decreased the 1-year post-transplant estimated glomerular filtration rate (P = 0.006). Although rejection-free survival rates did not differ significantly between the CDC(+) and FCX(+) groups, the 1-year estimated glomerular filtration rate was lower in the CDC(+) group (P = 0.010). Infectious and significant bleeding complications occurred in 15.5 % and 4.7 % of cases, respectively., Conclusion: Kidney transplantation after desensitization had good graft outcomes and tolerable complications in Korea, and therefore, this therapy can be recommended for sensitized ESRD patients.

Introduction: The role of lymphocyte cross-matches (LCM) remains controversial in the liver transplant field. The aim of this study was to correlate the risk for acute rejection episodes and graft survival in liver transplantation with pretransplant LCM results., Patients and Methods: We enrolled 184 adult liver transplantation patients, excluding pediatric and second grafts. The 129 living donor and 55 deceased donor liver transplantations were divided into 2 groups: LCM (+); (n=20) and LCM (-); (n=164)., Results: There were no differences in the demographic features, such as gender and recipient age, original disease, Model for End-Stage Liver Disease score, donor type, number of human leukocyte antigen mismatches, and cold ischemia times. There were no hyperacute rejection episodes in the LCM (+) group. Also, posttransplant complications such as acute rejection episode, biliary complication, or hepatic artery thrombosis were not different. Acute rejection episodes occurred in 5.0% of the LCM (+) group and 15.2% of the LCM (-) group (P=.317). Bile duct complications after transplantation arose in 20.0% of the LCM (+) group and in 32.9% of the LCM (-) group (P=.312). The 2 groups showed no difference in graft survival rate analyzed by the Kaplan-Meier method according to LCM results., Conclusion: Pretransplant LCM results were not associated with overall graft survival or acute rejection episodes in this study., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: AEB071 (sotrastaurin) is a specific inhibitor of protein kinase C that prevents T-cell activation. Our previous study demonstrated that AEB071 monotherapy could prevent acute cardiac allograft rejection in rats. Herein, we investigated the effects of AEB071 combined with various doses of tacrolimus (Tac) on the allograft rejection and survival in a rat heart transplantation model., Materials and Methods: Heterotopic cardiac transplantation from Brown-Norway to Lewis rats was performed. Cardiac allograft survival was assessed by monitoring heartbeats in six recipients of each experimental group. Another four recipient rats were selectively sacrificed in each group at d 7 post-transplantation for histologic examination. Serum transaminases, blood urea nitrogen, and creatinine concentrations were measured., Results: AEB071 monotherapy prolonged allograft mean survival time (MST) compared with the untreated control group. Also a combination of AEB071 and Tac prolonged MST compared with monotherapy groups with higher dose of Tac. In the cardiac graft histology, AEB071 combined with Tac 0.6 mg/kg/d significantly decreased the rejection grade as indicative of decreased inflammatory cell infiltration into the graft. No experimental group was found with any abnormal histologic or serologic evidence of liver and kidney toxicity., Conclusion: AEB071 combined with a smaller dosage of Tac may be clinically possible to establish calcineurin inhibitor (CNI) minimization protocol in solid organ transplantation., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: We measured donor kidney weight (D-KW), functional renal volume (D-FRV), and single-kidney glomerular filtration rate (D-SKGFR), and then evaluated the impact of the indices to recipient body weight (R-BW) on graft function., Methods: This study included 44 recipients of live donor transplants without delayed graft function or acute rejection within 2 years of transplantation., Results: There was a statistically significant difference in serum creatinine between recipients with a D-KW/R-BW ratio of 4.25, D-FRV/R-BW ratio of >5.14, or D-SKGFR/R-BW ratio of >1.06, respectively. D-KW/R-BW, D-FRV/R-BW, and D-SKGFR/R-BW strongly correlated with serum creatinine at 1 year and 2 years post-transplantation. In multivariate analysis, D-FRV and donor age were statistically significant risk factors which influenced serum creatinine at 1 year and 2 years post-transplantation., Conclusion: D-FRV/R-BW and donor age have significant impact on graft function. D-FRV/R-BW can be measured ahead of surgery. Therefore, measuring the D-FRV is useful to select a more optimal donor kidney among otherwise similar candidates during preoperative evaluation to improve posttransplant graft function., ((c) 2009 S. Karger AG, Basel.)