Rejection-free Survival Rates Research Articles

Early CYP3A5 Genotype-Based Adjustment of Tacrolimus Dosage Reduces Risk of De Novo Donor-Specific HLA Antibodies and Rejection among CYP3A5-Expressing Renal Transplant Patients.

Our previous retrospective single-center cohort study found, at 3-year follow-up, a trend toward low tacrolimus trough levels and an increased risk of de novo donor-specific anti-HLA antibodies (DSAs) and of antibody-mediated rejection (ABMR) in CYP3A5-expressing patients. Determining CYP3A5-expression status immediately after renal transplant would allow early genotype-based dosage adjustment of tacrolimus and might prevent the occurrence of de novo DSAs and ABMR, improving transplant outcome. 160 renal allograft recipients who underwent renal transplant at the University Hospital Essen between May 2019 and May 2022 were genotyped for the CYP3A5 rs776746 polymorphism within the first two weeks after transplant, and genotype-based dose adjustment of tacrolimus was performed for the follow-up of 2 years. CYP3A5 expression was detected in 33 (21%) of the 160 patients. Tacrolimus trough levels were similar in CYP3A5 expressers and nonexpressers over the entire 2-year follow-up period. However, we observed a trend toward slightly higher tacrolimus trough levels in CYP3A5 expressers, who, as expected, required tacrolimus dosages twice as high as did nonexpressers during follow-up. Calcineurin inhibitor (CNI) nephrotoxicity-free survival rates were comparable between CYP3A5 expressers and nonexpressers (p = 0.49). Rejection-free survival rates (p = 0.89), de novo anti-HLA antibody-free survival rates (p = 0.57) and de novo DSA-free survival rates (p = 0.61) did not differ between the two groups. Early detection of CYP3A5-expression status and resultant genotype-based adjustment of tacrolimus dosage after renal transplant protected patients from transplant rejection and de novo DSA formation and was not associated with increased incidence of CNI toxicity among CYP3A5 expressers.

Human leukocyte antigen compatibility and incidence of donor-specific antibodies in pediatric liver transplant recipients.

Antibody-mediated rejection following liver transplantation (LT) has been increasingly recognized, particularly with respect to the emergence of de novo donor-specific antibodies (DSAs) and their impact on graft longevity. While substantial evidence for adult populations exists, research focusing on pediatric LT outcomes remains limited. To investigate the prevalence of human leukocyte antigen (HLA) mismatches and DSA and evaluate their association with rejection episodes after pediatric LT. A cohort of pediatric LT recipients underwent HLA testing at Santa Casa de Porto Alegre, Brazil, between December 2013 and December 2023. Only patients who survived for > 30 days after LT with at least one DSA analysis were included. DSA classes I and II and cross-matches were analyzed. The presence of de novo DSA (dnDSA) was evaluated at least 3 months after LT using the Luminex® single antigen bead method, with a positive reaction threshold set at 1000 MFI. Rejection episodes were confirmed by liver biopsy. Overall, 67 transplanted children were analyzed; 61 received grafts from living donors, 85% of whom were related to recipients. Pre-transplant DSA (class I or II) was detected in 28.3% of patients, and dnDSA was detected in 48.4%. The median time to DSA detection after LT was 19.7 [interquartile range (IQR): 4.3-35.6] months. Biopsy-proven rejection occurred in 13 patients at follow-up, with C4d positivity observed in 5/13 Liver biopsies. The median time to rejection was 7.8 (IQR: 5.7-12.8) months. The presence of dnDSA was significantly associated with rejection (36% vs 3%, P < 0.001). The rejection-free survival rates at 12 and 24 months were 76% vs 100% and 58% vs 95% for patients with dnDSA anti-DQ vs those without, respectively. Our findings highlight the importance of incorporating DSA assessment into pre- and post-transplantation protocols for pediatric LT recipients. Future implications may include immunosuppression minimization strategies based on this analysis in pediatric LT recipients.

Deep Anterior Lamellar Keratoplasty-Treated Keratoconic Eyes With Descemet Membrane Rupture.

The aim of this study was to evaluate the outcomes of deep anterior lamellar keratoplasty (DALK) and compare it with penetrating keratoplasty (PKP) in keratoconic eyes with Descemet membrane (DM) rupture. In this comparative retrospective case series, 33 keratoconic eyes with a history of hydrops underwent DALK and 27 received PKP. Baseline and postoperative visual acuity, corneal astigmatism, mean keratometry, endothelial cell density, and complication rates were measured. The median follow-up of patients who underwent DALK was 45 months (range, 4-76 months) and that of patients who underwent PKP was 84 months (range, 4-136 months). Both procedures had comparable postoperative visual acuity, astigmatism, and mean keratometry. Significantly higher endothelial cell densities were observed in DALK than in PKP at 2, 3, and 5 years postsurgery (2043 ± 767 vs. 1165 ± 683 cell/mm 2 , P = 0.007, n = 12 in both groups at 2 years). Intra-DALK, 15 perforations occurred (44.12%) and 1 (2.94%) was converted to PKP. Graft rejection was diagnosed in 1 (3.03%) DALK procedure versus 8 (29.63%) PKP ( P = 0.008), and other long-term complication rates were equivalent. Kaplan-Meier survival analysis also revealed a higher rejection-free survival rate for the DALK group ( P = 0.012). Subgroup analysis within both groups based on the severity of preoperative DM rupture revealed no significant difference in any major 2-year outcomes. DALK showed similar beneficial visual outcome and safety but significantly better endothelial protection over PKP in eyes with keratoconus and previous hydrops. Therefore, DALK is recommended in posthydrops cases irrespective of the DM rupture severity.

235.6: The Impact of Extended Release Tacrolimus and Everolimus Based Immunosuppressive Regimen on Living Donor Kidney Transplantation

Introduction: The efficacy of extended release tacrolimus (TACER) and everolimus (EVR) in kidney transplantation have been demonstrated independently. However, there is few reports on the efficacy of extended release tacrolimus and everolimus based immunosuppressive regimen in KT. We investigated the impact of TACER and EVR based immunosuppressive (IS) regimen on living donor kidney transplantation (LDKT). Methods: A total 160 recipients underwent LDKT were included in this study. Steroids, TACER and mycophenolate mofetil (MMF) based IS regimen was administered in 77 recipients (MMF group). Steroids, TACER and EVR based IS regimen was administered in 83 recipients (EVR group). The primary outcomes were the estimated glomerular filtration rate (eGFR), de novo donor specific antibody (DSA), rejection, graft survival, and recipient survival. The secondary outcome was the findings of calcineurin inhibitor (CNI) toxicity by the protocol biopsy at 1 month and 12 months after LDKT and incidences of cytomegalovirus infection and all infectious diseases requiring treatment. Inverse probability of treatment weighting analysis was used. Results: The eGFR changes over time, de novo DSA free survival rate (P=0.413), rejection free survival rate (P=0.385), graft loss free survival rate (0.692), and recipient survival rate (0.570) were similar between 2 groups. the findings of calcineurin inhibitor (CNI) toxicity by the protocol biopsy at 1 month and 12 months after LDKT were more frequent in the EVR group (P=0.059 and P=0.006). Incidences of cytomegalovirus infection (P=0.896) and all infectious diseases requiring treatment (P=0.524) were similar between 2 groups. Conclusion: The efficacy of TACER and EVR based IS regimen was similar to that of TACER and MMF based IS regimen except for frequent findings of CNI toxicity.

Outcome of ABO-Incompatible Kidney Transplantation According to ABO Type of Transfused Plasma: Comparative Analysis Between "Universal" AB and Donor-Type Plasma.

We compared the clinical outcomes of recipients of ABO-incompatible (ABOi) kidney transplantation (KT) according to the blood group of the plasma transfused. We retrospectively analyzed the data of 60 recipients of ABOi-KT with blood type O and A or B donors. Demographic and clinical characteristics were compared between 2 groups of recipients: 1 group received AB plasma regardless of the donor's blood type (n = 30), and the other group received donor-type plasma (n = 30). There were no significant differences between the groups in terms of demographic characteristics. Transfusion of donor-type plasma was noninferior to transfusion of type AB plasma in terms of both rejection-free survival and rejection rate (P = .455, P = .335). There was no significant prognostic difference between the 2 groups. In terms of blood supply and inventory management, we suggest that the blood group of the plasma should match the donor's type.

Outcomes following tacrolimus systemic immunosuppression for penetrating keratoplasty in infants and young children.

To report outcomes of tacrolimus immunosuppression after penetrating keratoplasty (PK) in very young children. Retrospective, consecutive, cohort study of children undergoing PK at a tertiary children's hospital between 2005 and 2016. Oral tacrolimus immunosuppression was given for 2 years, followed by topical tacrolimus. Fourteen children (20 eyes) had 24 PKs; nineteen eyes had primary PKs, five eyes had repeat PKs. Mean age at primary graft was 95 days (3.1 months) for anterior segment dysgenesis (ASD), 430 days (14.3 months) for non-ASD children. Eleven children (15 eyes) had ASD. Three children (five eyes) had non-ASD: two children (three eyes) had glaucoma-related corneal opacity and one child (two eyes) had congenital hereditary endothelial dystrophy (CHED). One-year rejection-free survival rates following primary PK was 80% for ASD (n = 15) and 100% for non-ASD (n = 4). At final review, 5/15 of primary grafts for ASD were clear. 10/15 failed after a mean of 19 months, specifically attributable to infection (n = 2), rejection (n = 2) and glaucoma (n = 2). 4/4 primary non-ASD grafts are clear at final review (mean follow-up = 77 months). All repeat grafts (n = 5), failed after a mean of 38.25 months. Considering all grafts, 15/24 (62.5%) failed: 5/15 due to infection, 2/15 due to rejection, 8/15 due to glaucoma, phthisis, perforation or vascularised with no rejection. At last review (mean = 58.1 months, range 28-84), overall cohort survival is 37.5%. Final visual acuities range between 0.86 and 2.4 LogMAR. We compare our results to published literature: 1-year graft survival was higher than previously reported, with lower failure due to rejection. Overall infection rates did not increase, however, proportionally, severe infections were higher. Overall graft survival is at least comparable to reported literature.

Topical corticosteroids with topical cyclosporine A versus topical corticosteroids alone for immunological corneal graft rejection.

To assess the efficacy and safety of supplementing topical cyclosporine A (CsA) to topical corticosteroids (CS), in the prophylaxis and treatment of corneal graft rejection following penetrating keratoplasty (PK). Meta-analysis. Search was performed in PubMed, CENTRAL, ClinicalTrials.gov, reference lists of articles and conference proceedings. Primary outcomes: 1-year rejection-free survival rate (prophylaxis); resolution rate of rejection episodes (treatment). Secondary outcomes: 6- and 24-month rejection-free graft survival rate, number of rejection episodes during follow-up, time-to-resolution of rejection episode, 12- and 24-months graft survival rate, adverse events. Subgroup analyses were planned for high-risk grafts; primary vs. secondary prophylaxis of graft rejection episodes; and CsA concentrations of 0.05%, 1%, and 2%. Five studies of moderate methodological quality were included (one retrospective, four RCT), assessing 459 eyes (CS + CsA 226, CS 233). In the prophylaxis setting, supplemental CsA was associated with a higher rejection-free survival rate at 12-months (RR 1.25, 95% CI: 1.00-1.56, p = 0.05) and 24-months post-PK (RR 1.56, 95% CI: 1.15-2.11, p < 0.01), though no differences were found at the 6-months timepoint (p = 0.93). This effect was mostly verified using CsA 2% in the high-risk subset of patients. In the treatment setting, no differences were found in the resolution rate of rejection episodes (p = 0.23). No differences existed on drug-related adverse events. In the prophylaxis of rejection episodes post-PK, the combined regimen of CS + CsA was associated with a higher 1- and 2-year rejection-free graft survival rate. Subgroup analysis mostly supported the use of CsA 2% for high-risk grafts. Further studies are needed to validate these results.

Intestinal Transplantation at a Single Institution in Japan

This study aimed to compare the clinical outcomes of intestinal transplantation (ITX) between 2 groups by using medications for induction treatment and assess the utility of the current protocol. From 2003 to 2020, 11 patients underwent ITX. Recipients were classified into 2 groups: group IL-2Ra (interleukin-2 receptor antagonist therapy, n=6) and ATG (rabbit antithymocyte globulin therapy, n=5). We conducted a retrospective review of patient and graft survival rates and the postoperative course. The 1-, 5-, and 10-year patient and graft survival rates of the 11 primary grafts in the 11 recipients were 100%, 88.9%, 62.2% and 90.0%, 78.8%, 56.3%, respectively. The median duration of follow-up for the IL-2Ra and ATG groups was 197.3 and 87.3 months, respectively. The 1-, 5-, and 10-year patient survival rates were 100%, 83.3%, 50% and 100%, 100%, 100% for the IL-2Ra and ATG groups, respectively (P=.25) and 83.3%, 66.7%, 33.3% and 100%, 100%, 100% for graft survival in the IL-2Ra and ATG groups, respectively (P=.08). The incidence of moderate and severe acute rejection was 100% and 20% in the IL-2Ra and ATG groups, respectively (P=.02). The 1- and 5-year moderate and severe rejection-free survival rates were 33.3%, 0% and 80%, 80% in the IL-2Ra and ATG groups, respectively (P=.04). ATG significantly suppressed moderate and severe acute rejection compared with IL-2Ra, thereby showing better short- and mid-term rejection-free survival rates. Additional clinical experience is needed to determine the optimal regimen for the management of ITX recipients.

Outcomes of kidney transplantation over a 16-year period in Korea: An analysis of the National Health Information Database.

This study investigated the outcomes of kidney transplantation (KT) over a 16-year period in Korea and identified risk factors for graft failure using a nationwide population-based cohort. We investigated the Korean National Health Insurance Service-National Health Information Database. Health insurance claims for patients who underwent KT between 2002 and 2017 were analyzed. The data from 18,331 patients who underwent their first KT were reviewed. The percentage of antithymocyte globulin (ATG) induction continuously increased from 2.0% in 2002 to 23.5% in 2017. Rituximab began to be used in 2008 and had increased to 141 patients (9.6%) in 2013. Acute rejection occurred in 17.3% of all patients in 2002 but decreased to 6.3% in 2017. The rejection-free survival rates were 78.8% at 6 months after KT, 76.1% after 1 year, 67.5% after 5 years, 61.7% after 10 years, and 56.7% after 15 years. The graft survival rates remained over 80% until 12 years after KT, and then rapidly decreased to 50.5% at 16 years after KT. In Cox's multivariate analysis, risk factors for graft failure included being male, more recent KT, KT from deceased donor, use of ATG, basiliximab, or rituximab, tacrolimus use as an initial calcineurin inhibitor, acute rejection history, and cytomegalovirus infection. ATG and rituximab use has gradually increased in Korea and more recent KT is associated with an increased risk of graft failure. Therefore, meticulous preoperative evaluation and postoperative management are necessary in the case of recent KT with high risk of graft failure.

Topical 0.03% tacrolimus versus systemic mycophenolate mofetil as adjuncts to systemic corticosteroids for preventing graft rejection after repeat keratoplasty: one-year results of a randomized clinical trial.

To compare the efficacy of topical 0.03% tacrolimus in combination with systemic corticosteroids versus systemic mycophenolate mofetil (MMF) and corticosteroids in preventing corneal allograft rejection after repeat keratoplasty. This prospective, randomized clinical trial enrolled 63 consecutive eyes of 63 patients who underwent repeat keratoplasty after a failed penetrating keratoplasty. Group 1 (32 eyes) received MMF orally 1 g twice daily for the first 6 months and then 1 g daily for the next 6 months, and group 2 (31 eyes) received topical 0.03% tacrolimus four times a day for 12 months. All patients were treated with topical and oral corticosteroids postoperatively. The participants were observed closely for signs of graft rejection, and the rates of rejection-free graft survival were calculated and compared between the two groups at postoperative month 12. The groups were balanced in patient's age and risk factors for graft rejection (e.g., original diagnosis, number of previous grafts, and quadrants of corneal vascularization). Endothelial graft rejection occurred in 5 eyes (15.6%) of group 1 and 6 eyes (19.4%) of group 2 (P = 0.75). Irreversible endothelial graft rejection resulting in graft failure occurred in 3 eyes of each group (P = 0.99). The rate of rejection-free graft survival was 84.4% in group 1 and 80.6% in group 2 at postoperative month 12 (P = 0.74). Topical 0.03% tacrolimus was as effective as systemic MMF as adjuncts to topical and systemic corticosteroids in reducing endothelial graft rejection with 12 months follow up after repeat keratoplasty.

THE KOREAN ORGAN TRANSPLANTATION REGISTRY (KOTRY): FIRST OFFICIAL KIDNEY TRANSPLANTATION REPORT

Korean Organ Transplantation Registry Study Group. Korean Organ Transplantation Registry (KOTRY), a first prospective-deigned national transplantation registry in Korea, was launched in 2014. This is an initial report on the status of patients received kidney transplants over the past 4 years. A total of 4839 kidney transplants (KTs) from 32 transplant centers were collected from April 2014 to December 2018. Among these, 3039 patients received kidneys from living donors, and 1800 patients received kidneys from deceased donors. We analyzed baseline characteristics of recipients and donors, and short-term post-transplantation outcomes. Among 4839 KTs, 3039 patients (62.8%) received kidneys from living donors (LDs), and 1800 patients (37.2%) received kidneys from deceased donors (DDs). The average recipient age was 48 years; there were 1774 (58.4%) male recipients. The mean age of patients undergoing LD kidney transplantation was 4 years younger than that of patients undergoing DD kidney transplantation. Even though glomerulonephritis was the most common cause of end-stage renal disease (33.3%), the number of diabetic nephropathy was increasing. At the time of transplantation, 10.9% and 29.8% of KTs had cardiovascular disease and diabetes, respectively. The average donor age was 47 years; there was 2593 (53.6%) male donors. The mean age of LD was 2 years younger than that of DD. Expanded criteria donors (30.8%) were frequently used. During follow-up period, new-onset cardiac events and NODAT were identified in 9.4% and 8.4% of the recipients, respectively. The overall 1- and 4-year patient survival rates were 98.4% and 96.9%, respectively. During the follow-up period, 84 KTs died, and the most common cause of death was infection (47.6%). The overall 1- and 4-year graft survival rates were 97.1% and 93.0%, respectively, and the most common cause of graft loss was rejection (43.5%). The overall 1- and 4-year rejection-free survival rates were 81.8% and 72.2%, respectively. In multivariate analysis, older recipients, history of cardiovascular disease, an increasing number of HLA mismatch, bortezomib induction, cyclosporine use at discharge, no anti-metabolite at discharge, an increase serum creatinine at discharge, and long cold ischemic time were significantly associated with death after transplantation. And no anti-metabolite at discharge, an increase serum creatinine at discharge and long cold ischemic time were significantly associated with graft loss after transplantation. With the establishment of KOTRY, it is possible to present the first nationwide epidemiological data of Korean kidney transplantation. KOTRY will provide better understanding regarding nationwide epidemiological data for kidney transplantation in Korea. Novartis Korea, Ltd.. Research of Korea Centers for Disease Control and Prevention (2014-ER6301-00, 2014-ER6301-01, 2014-ER6301-02, 2017-ER6301-00, 2017-ER6301-01).

Serum N-glycan profiling can predict biopsy-proven graft rejection after living kidney transplantation.

To evaluate whether serum N-glycan profile can be used as a diagnostic marker of graft rejection after living-donor kidney transplants (KT). We retrospectively examined 174 KT recipients at five medical centers. N-Glycan levels were analyzed in postoperative serum samples using glycoblotting combined with mass spectrometry. We developed an integrated score to predict graft rejection based on a combination of age, gender, immunological risk factors, and serum N-glycan levels at post-KT day D1 and D7. Rejection-free survival rates stratified by the sum of integrated scores (D1 + D7) were evaluated using Kaplan-Meier curves. Of 174, 52 showed graft rejection (Rejection-pos. group) and 122 recipients did not show graft rejection (Rejection-neg. group). The integrated scores were significantly higher in the Rejection-pos. group than those of the Rejection-neg. group. Area-under-curve (AUC) value of integrated scores at post-KT D1, and D7 were 0.84 and 0.84, respectively. The sum of integrated scores (D1 + D7) ≥ 0.50 identified graft rejection with 81% sensitivity and 80% specificity; with an AUC value of 0.87. Recipients with higher sum of integrated scores (D1 + D7 ≥ 0.5) had significantly shorter rejection-free survival than those with lower scores. Evaluation of serum N-glycosylation profiles can identify recipients who are prone to rejection.

Clinical significance of isoagglutinin titre with the current desensitization protocol in ABO-incompatible kidney transplantation.

ABO-incompatible (ABOi) kidney transplantation (KT) has become a routine procedure with graft survival rates comparable to those of ABO-compatible KT. However, the clinical significance of the isoagglutinin titre in ABOi KT remains uncertain. Therefore, in this study, we analysed the clinical outcomes of ABOi KT according to the baseline and post-operative isoagglutinin titre. All patients who received ABOi KT between 2009 and 2013 were reviewed and followed up until December 2016. The patients were classified according to baseline (<1:128 or ≥1:128) and post-operative rebound isoagglutinin titre (<1:16 or ≥1:16), and the clinical outcomes of KT were compared. Patients with a high baseline isoagglutinin titre showed a poor titre reduction rate (1.48 ± 0.41 vs 1.32 ± 0.34, P = 0.008), and more patients experienced titre rebound ≥1:16 after KT (15.0% vs 35.8%, P = 0.002). The occurrence of both T-cell-mediated rejection and antibody-mediated rejection did not show a significant difference (P = 0.805 and 0.714, respectively). The rate of rejection-free survival was not different among groups (P = 0.680, log-rank test). Furthermore, the rate of death-censored graft survival was not different among groups (P = 0.701, log-rank test). Urinary tract infection was the most frequently reported infectious complication overall. The incidence of urinary tract infection, pneumonia and viral infections (BK virus and cytomegalovirus) was not different among groups. In conclusion, high baseline isoagglutinin titre was associated with a high rebound isoagglutinin titre, low titre reduction rates and more sessions of plasmapheresis. However, the isoagglutinin titre may not be as important as it was in the past in ABOi KT if appropriate desensitization is performed.

Rapid Discontinuation of Prednisone in Kidney Transplant Recipients: 15-Year Outcomes From the University of Minnesota.

Short- and intermediate-term results have been reported after rapid discontinuation of prednisone (RDP) in kidney transplant recipients. Yet there has been residual concern about late graft failure in the absence of maintenance prednisone. From October 1, 1999, through June 1, 2015, we performed a total of 1553 adult first and second kidney transplants-1021 with a living donor, 532 with a deceased donor-under our RDP protocol. We analyzed the 15-year actuarial overall patient survival (PS), graft survival (GS), death-censored GS (DCGS), and acute rejection-free survival (ARFS) rates for RDP compared with historical controls on maintenance prednisone. For living donor recipients, the actuarial 15-year PS rates were similar between groups. But RDP was associated with increased GS (P = 0.02) and DCGS (P = 0.01). For deceased donor recipients, RDP was associated with significantly better PS (P < 0.01), GS (P < 0.01) and DCGS (P < 0.01). There was no difference between groups in the rate of acute or chronic rejection, or in the mean estimated glomerular filtration rate at 15 years. However, RDP-treated recipients had significantly lower rates of avascular necrosis, cytomegalovirus, cataracts, new-onset diabetes after transplant, and cardiac complications. Importantly, for recipients with GS longer than 5 years, there was no difference between groups in subsequent actuarial PS, GS, and DCGS. In summary, at 15 years postkidney transplant, RDP did not lead to decreased in PS or GS, or an increase in graft dysfunction but as associated with reduced complication rates.

Severe intellectual disability is not a contraindication to kidney transplantation in children

Renal transplantation in children with ID is controversial. Acceptability of these children as candidates varies between programs. Limited outcome data in pediatric renal TXP recipients with cognitive impairment diminish their access to TXP. A retrospective chart review was performed of all children who underwent renal transplantation between January 1, 2002 and June 30, 2012 (N=72). Patients were divided into two groups, those with ID prior to transplantation (n=10) and those without (non-ID; n=62). Graft survival and BPAR episodes were compared between the two groups using Kaplan-Meier estimates. Graft survival rates at 3years post-TXP were 100% in the ID group and 80% in the non-ID group (P=.13). Rates of BPAR at 3years post-TXP were 10% in the ID group and 27% in the non-ID group (P=.29). Graft survival and acute rejection-free survival rates are similar between children with ID and those without. Based on midterm outcomes, there is no apparent contraindication to renal transplantation in pediatric patients with ID. Children with ID should be considered as TXP candidates provided that they have an adequate social support network.

Penetrating Keratoplasty for Keratoconus With and Without Resolved Corneal Hydrops: Long-term Results

To evaluate the long-term risk of endothelial rejection, graft survival, and associated factors following penetrating keratoplasty (PK) for keratoconus, with and without prior resolved corneal hydrops. Retrospective cohort study. Primary outcome measures were endothelial rejection-free survival and failure-free survival. Secondary outcome measures were corneal neovascularization following hydrops and complications following PK. A total of 245 eyes underwent PK for keratoconus with mean follow-up of 5.6 ± 3.6 years. Eyes with prior hydrops (n= 74) had lower endothelial rejection-free survival rates compared with eyes without prior hydrops: 86.5% ± 4.0% vs 86.5% ± 2.6% at 1 year, 61.0% ± 6.2% vs 76.9% ± 3.3% at 5 years, and 45.8% ± 10.1% vs 70.9% ± 4.3% at 10 years, respectively (P= .023). Multivariate analysis identified factors associated with endothelial rejection as age ≤25 years (P= .017), corneal neovascularization (P= .001), donor trephination size >8mm (P= .017), and poor clinic attendance (P= .015). There was no difference in the failure-free survival rates with and without prior hydrops: 98.6% ± 1.3% vs 97.1% ± 1.3% at 1 year, 97.3% ± 1.9% vs 95.1% ± 1.9% at 5 years, and 97.3% ± 1.9% vs 92.2% ± 2.7% at 10 years, respectively (P= .42). Corneal neovascularization was present at the time of PK in 44.6% of eyes with prior hydrops and 7.6% without prior hydrops (P < .001). Corneal neovascularization, a frequent complication of corneal hydrops, was associated with increased risk of endothelial rejection following PK. However, allograft survival was similar in eyes with and without prior hydrops.

Effect of Pretransplant Rituximab Use on Posttransplant Clinical Outcomes in Patients with High Panel Reactive Antibody Scores

Background/Aims: Whether desensitization treatment is needed before kidney transplant (KT) in patients with high panel reactive antibody (PRA) scores but negative cross-matching (XM) tests remains controversial. This study aimed to investigate the effect of pretransplant rituximab (RTX) treatment on clinical outcomes in these patients. Methods: The study included 52 patients with PRA >50% but negative XM tests before transplantation. A single dose of RTX was administered before KT in 32 patients (RTX group). The 20 patients without RTX treatment were considered as controls (CON group). We compared the development of acute antibody-mediated rejection (AMR), rejection-free survival, allograft function, allograft and patients' survival rates and infection rates between the 2 groups. Results: The rate of acute AMR development was significantly lower in the RTX group than in the CON group (p = 0.009), and rejection-free survival in the RTX group was higher than in the CON group (p = 0.042). The 3-year graft and patient survival rates were higher in the RTX group than in the CON group (p = 0.007 and p = 0.037, respectively). There were no significant differences in infection rates between the groups. Conclusions: Pretransplant use of RTX improved the post-transplant clinical outcomes in patients with high PRAs but negative XM tests.

Safety of reduced dose of mycophenolate mofetil combined with tacrolimus in living-donor liver transplantation.

Background/AimsThe dose of mycophenolate mofetil (MMF) has been reduced in Asia due to side effects associated with the conventional fixed dose of 2-3 g/day. We aimed to determine the pharmacokinetics of a reduced dose of MMF and to validate its feasibility in combination with tacrolimus in living-donor liver transplantation (LDLT).MethodsTwo sequential studies were performed in adult LDLT between October 2009 and 2011. First, we performed a prospective pharmacokinetic study in 15 recipients. We measured the area under the curve from 0 to 12 hours (AUC0-12) for mycophenolic acid at postoperative days 7 and 14, and we performed a protocol biopsy before discharge. Second, among 215 recipients, we reviewed 74 patients who were initially administered a reduced dose of MMF (1.0 g/day) with tacrolimus (trough, 8-12 ng/mL during the first month, and 5-8 ng/mL thereafter), with a 1-year follow-up. We performed protocol biopsies at 2 weeks and 1 year post-LDLT.ResultsIn the first part of study, AUC0-12 was less than 30 mgh/L in 93.3% of cases. In the second, validating study, 41.9% of the recipients needed dose reduction or cessation due to side effects within the first year after LDLT. At 12 months post-LDLT, 17.6% of the recipients were administered a lower dose of MMF (0.5 g/day), and 16.2% needed permanent cessation due to side effects. The 1- and 12-month rejection-free survival rates were 98.6% and 97.3%, respectively.ConclusionsA reduced dose of MMF was associated with low blood levels compared to the existing recommended therapeutic range. However, reducing the dose of MMF combined with a low level of tacrolimus was feasible clinically, with an excellent short-term outcome in LDLT.

Surviving 20 Years After Heart Transplantation: A Success Story

We report the long-term outcomes of patients who survived 20 years or greater after heart transplantation. From 1985 to 2012, 386 patients underwent heart transplantation at our institution. Patient data were analyzed retrospectively for transplants performed from 1985 to 1991. The Kaplan-Meier method was used for survival analyses. In total, 133 patients were included. The mean age of the 20-year survivors at transplant was 43.6±11.4 years. The mean ischemic time was 71.2±34.0 minutes. The overall actuarial survival rates at 1, 10, and 20 years were 82.7%, 63.9%, and 55.6%, respectively. The most common causes of death were graft rejection (21%), malignancy (21%), infection (15%), and cardiac allograft vasculopathy (CAV, 14%). After 1, 10, and 20 years, the rejection-free survival rates were 19%, 13%, and 13%, respectively, and the malignancy-free survival rates were 99%, 67%, and 61%. The CAV-free survival rates were 97%, 48%, and 42%, respectively, and the infection-free survival rates were, respectively, 70%, 15%, and 14%. The actuarial diabetes-free survival rates at 1, 10, and 20 years were 85%, 80%, and 79%, respectively. Actuarial hypertension-free survival was 56% after 1 year and 26% after 10 and 20 years. Two patients received a second heart transplant. A remarkable number of patients survived 20 years or greater after heart transplantation, confirming the procedure as the gold standard for end-stage heart failure. Complications resulting from immunologic events and immunosuppressive therapy determine post-transplant mortality and morbidity. Due to improvements in immunosuppressive management in recent years, long-term survival is likely to increase.

Clinical Outcomes in Kidney Transplantation Patients From Deceased Donors With Acute Kidney Injury

BackgroundThis single-center study sought to examine the clinical outcomes of kidney transplant recipients from donors displaying acute kidney injury (AKI). MethodsWe analyzed retrospectively the medical records of the donors and recipients of 54 deceased-donor kidney transplantations performed in our center between March 2009 and March 2012. ResultsAmong the 54 deceased donors, 36 (66.7%) experienced AKI as determined by the final mean serum creatinine levels measured before graft harvest of 2.66 ± 1.62 mg/dL versus 0.82 ± 0.28 mg/dL among non-AKI donors. The risks of delayed graft function and slow graft function were increased among the AKI versus non-AKI groups in the early post-transplantation period. However, the renal function status of recipients at 3, 6, and 12 months after transplantation was not significantly different between the two groups. Moreover, rejection-free survival rates during the study period were similar. Multivariate analysis revealed an acute rejection episodes (P = .047) and a lower body mass index in the donor relative to the recipient (P = .011) to be independent risk factors predicting poor graft function defined as a 1-year estimated glomerular filtration rate less than 50 mL/min/l.73 m2. Donor AKI with either a high level (>4.0 mg/dL), an increasing trend of creatinine, or greater severity by the Risk, Injury, Failure, Loss, and End-stage kidney disease (RIFLE) classification was not a significant risk factor. ConclusionTransplantation of kidneys from the AKI donors, namely, patients with severely decreased renal function, displayed excellent short-term outcomes. Accordingly, kidney transplantations from deceased donors with AKI should be considered more actively to expand the donor pool in Korea.