Influence of Long-term Oral Steroid Intake on Glaucoma and Ocular Hypertension

Purpose@#The aim of this study was to evaluate the risk factors associated with glaucoma or ocular hypertension (OHT) in patients taking oral corticosteroids for extended periods, and to aid in managing intraocular pressure (IOP) in patients with these risk factors. @*Methods@#A cross-sectional study was performed involving 690 patients who visited a tertiary referral hospital and had been using oral corticosteroids for more than six months. Patients' demographics, tonometry results, drug type, dosage, duration, ophthalmic history, and the use of glaucoma eye drops were analyzed to determine the risk factors associated with glaucoma or OHT. @*Results@#In a generalized linear model analysis comparing patients' eyes diagnosed with glaucoma or ocular hypertension to those without such diagnoses, no statistical difference was observed between the two groups in terms of drug type, age, and duration of oral corticosteroid use. However, the dosage was found to be statistically significant (odds ratio 1.09, p = 0.0294). @*Conclusions@#No difference in the incidence of glaucoma or OHT was found based on the type of oral steroid, age, or duration of use. However, a higher incidence of glaucoma and OHT was observed among patients taking higher doses of oral steroids. Therefore, it is suggested that using lower doses of oral steroids may be more beneficial for managing IOP.

The Immunomodulating Effects of Thalidomide and Dexamethasone in a Murine Cardiac Allograft Transplantation Model

Purpose@#The immunomodulatory effects of thalidomide (TM) and dexamethasone (DX) on immune cells and their co-stimulatory, co-inhibitory molecules in vitro and in vivo have been previously reported. The current study investigated the effects of TM and the combinatorial treatment with DX on immune cells using a murine cardiac allograft transplantation model. @*Materials and Methods@#Intraabdominal transplant of cardiac allografts from BALB/c (H-2d ) donors to C57BL/6 (H-2b ) recipients was performed. After transplantation, mice were injected daily with TM or DX or a combination of both TM and DX (TM/DX) by intraperitoneal route until the time of graft loss. CD4+ T cell subsets and CD11c+ cells in the peripheral blood mononuclear cells and spleen were examined and quantified with flow cytometry. Serum IL-6 levels were measured by enzyme-linked immunosorbent assay on day 7. @*Results@#The mean graft survivals were 6.86 days in the untreated group, and 10.0 days in the TM/DX group (p<0.001). The TM/DX treatment affected the CD4+ T cell subsets without suppressing the total CD4+ T cell population. The CD4 + FOXP3+ /CD4+ CD44hi T cell ratio increased. Increase in cell counts and median fluorescence intensity on CD11c+ CD85k+ with TM/DX were observed. The inhibition of pro-inflammatory cytokine interleukin-6 was also observed. @*Conclusion@#These outcomes suggest the immunomodulating effect of the TM/DX combinatorial treatment. In conclusion, TM/ DX combination may be a promising immunomodulatory approach for preventing allograft rejection and improving graft survival by inducing tolerance in transplantation.

Systemic Immunomodulatory Effects of Combinatorial Treatment of Thalidomide and Dexamethasone on T Cells and Other Immune Cells

Purpose@#In organ transplantation, the need for immune modulation rather than immune suppression has been emphasized. In this study, we investigated whether combinatorial treatments of with thalidomide (TM) and dexamethasone (DX) might be new approaches to induce systemic immunomodulation on T cells and other immune cells that regulate the expression of co-inhibitory molecules. @*Materials and Methods@#Naïve splenic T cells from C57BL/6 mice were sort-purified and cultured in vitro for CD4+ T cell proliferation and regulatory T cell (Treg) conversion in the presence of TM or/and DX. Expression of cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed death-1 (PD-1) in proliferated and converted T cells was quantified by flow cytometry. We also quantified in vivo expression of CTLA-4 and PD-1 on splenic CD4+ T cells and other immune cells isolated from TM- or/and DX-treated mice. Mixed lymphocytes reactions (MLR) were performed to evaluate the capacity of immune cells in carrying out immune responses. @*Results@#CTLA-4 expressions in effector T cells in vivo and in Tregs in vivo/vitro significantly increased upon TM/DX combinatorial treatment. Corresponding to increased CTLA-4 expression in T cells, the expression of ligand molecules for CTLA-4 significantly increased in splenic dendritic cells in TM/DX-treated groups. In addition, MLR results demonstrated that splenocytes isolated from TM/DX-treated mice significantly suppressed the proliferation of T cells isolated from other strains. @*Conclusion@#Based on these results, we suggest that TM/DX combinatorial treatments might be efficient immunomodulatory methods for regulating T cell immunity.

The Impact of Perioperative Factors on Changes in Diastolic Function after Kidney Transplantation: A Retrospective Analysis

PURPOSE: Cardiac changes in end-stage renal disease are the most common causes of death after kidney transplantation (KT). Chronic kidney disease presents a major risk factor for the development and progression of diastolic dysfunction. The purpose of this study was to identify the association between changes in left ventricular (LV) diastolic function and perioperative clinical factors in patients with preserved ejection fraction following KT. MATERIALS AND METHODS: We reviewed 115 patients who underwent KT between January 2011 and December 2015 with both preand post-transplant echocardiograms; patients with LV systolic dysfunction were excluded. LV diastolic function was measured using the ratio of early transmitral flow velocity to early diastolic velocity of the mitral annulus (E/e′). RESULTS: Patients with normal pre-operative LV systolic function (n=97) showed improvement in E/e′ after KT (11.9±4.4 to 10.5±3.8, p=0.023). Additionally, post-KT estimated glomerular filtration ratio was associated with changes in E/e′ (odds ratio, −0.056; 95% confidence interval, −0.014 to −0.007; p=0.026). Among patients with preexisting diastolic dysfunction (20/97 patients), the amount of intraoperative fluid administration was related to E/e′ changes (odds ratio, 0.003; 95% confidence interval, 0.000 to 0.005; p=0.029). CONCLUSION: KT is associated with improved diastolic function. Post-KT renal function was significantly related to changes in LV diastolic function. The amount of intraoperative fluid was a risk factor for worsening diastolic function after KT in patients with preexisting diastolic dysfunction.

Sirolimus Combination with Tacrolimus in Kidney Transplant Recipients at High Immunological Risk: Observational Results 3 Years after Transplantation / 대한이식학회지

BACKGROUND: The optimal immunosuppressive strategy for renal transplant recipients at high immunological risk requires clarification. We compared the 3 year outcomes of a sirolimus group (tacrolimus plus sirolimus) to those of a control group (tacrolimus plus mycophenolate mofetil). METHODS: This observational study was an extension of a prospective pilot study. We assessed acute rejection, glomerular filtration rate, adverse events, graft, and patient survival. RESULTS: Overall, 43% of the sirolimus group versus 78% of the control group were still on the initial immunosuppressive regimen at 3 years (P=0.005), and most discontinuations in each group were due to adverse events. No differences were observed between two groups with respect to acute rejection. The mean glomerular filtration rate at 36 months was greater in the sirolimus group than in the control group, but this was not statistically significant (64.0±6.8 mL/min/1.73 m² vs. 61.8±17.1 mL/min/1.73 m², P=0.576). Graft and patient survival were similar in both groups. Importantly, mean tacrolimus through levels were significantly lower in the sirolimus group than in the control group at each time point. No neoplasm was reported in the sirolimus group. In the control group, three cases of neoplasms developed during the study period. CONCLUSIONS: The sirolimus group had a greater number of discontinuations, particularly related to adverse events. Nevertheless, optimal concentration of sirolimus allowed reduced calcineurin inhibitor exposure in high immunologic risk patients, without increasing the risk of acute rejection and graft failure.

Adult Kidney Transplantation of Pediatric En bloc Kidneys Using a Partial Bladder Wall / 대한이식학회지

Kidney transplantation is a treatment of choice which improves survival and quality of life for patients with end-stage renal disease. Due to the growing waiting list for kidney transplantation, expansion of the donor pool to use of deceased pediatric kidneys is of critical importance. However, the use of pediatric kidneys has been limited due to concerns about early graft failure, hyperfiltration injury, and technical difficulties. Performing ureteroneocystostomy using small pediatric en bloc kidneys is sometimes difficult due to the small diameter and short length of the ureter in the adult kidney recipient. We hereby report on a partial bladder wall transplantation using pediatric en bloc kidneys. Pediatric en bloc kidneys and partial bladder wall from a 12-month-old female donor who weighed 9.13 kg was transplanted into a 49-year-old male recipient. The urinary tract was reconstructed with a partial bladder wall of the donor. At 12 months post-transplantation, Doppler ultrasonograpy and renogram showed stable graft renal function without urological complications. Pediatric en bloc kidney transplantation with a partial bladder wall can be a safe and feasible surgical technique to reduce urological complications.

A 12-Month Single Arm Pilot Study to Evaluate the Efficacy and Safety of Sirolimus in Combination with Tacrolimus in Kidney Transplant Recipients at High Immunologic Risk

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.

The Effect of Bortezomib on Antibody-Mediated Rejection after Kidney Transplantation

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.

Successful Pediatric ABO-Incompatible Kidney Transplantation without Pretransplant Plasmapheresis: Report of a Case / 대한이식학회지

Immunologic responses of infants and younger children differ from those of adults. Therefore, application of different pretransplant strategies for antibody depletion in younger ABO-incompatible transplant recipients is appropriate. A 12-month-old male infant with end stage renal disease after acute tubular necrosis was scheduled to undergo kidney transplantation from an ABO-incompatible living donor. He did not undergo pretransplant plasmapheresis, as the titer of the anti-ABO antibody was less than 1:4. After kidney transplantation, posttransplant renal function and anti-ABO titers were stable until posttransplant 2 years.

Sirolimus Conversion Efficacy for Graft Function Improvement and Histopathology in Renal Recipients with Mild to Moderate Renal Insufficiency

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.

Safety and Efficacy of Conversion from Twice-Daily Tacrolimus to Once-Daily Tacrolimus One Month after Transplantation: Randomized Controlled Trial in Adult Renal Transplantation

PURPOSE: The purpose of this study was to compare once-daily tacrolimus with twice-daily tacrolimus in terms of safety, efficacy, and patient satisfaction. MATERIALS AND METHODS: This prospective, randomized, open-label, multicenter study was conducted at three institutes. Patients in the investigational group were converted from tacrolimus twice daily to the same dose of extended-release tacrolimus once daily at 1 month post-transplantation, while patients in the control group were maintained on tacrolimus twice daily. The efficacies, safeties, and patient satisfaction for the two drugs at 6 months post-transplantation were compared. RESULTS: Sixty patients were enrolled and randomized to the investigational group (28 of 29 patients completed the study) or the control group (26 of 31 patients completed the study). At 6 months post-transplantation, composite efficacy failure rates including the incidences of biopsy-confirmed acute rejection in the investigational and control groups were 0% and 10.7%, respectively; patient survival was 100% in each group. No difference in estimated glomerular filtration rate values were observed at 6 months post-transplantation (p=0.97). The safety and satisfaction profile (immunosuppressant therapy barrier scale) of once-daily tacrolimus was comparable with that of twice-daily tacrolimus (p=0.35). CONCLUSION: Conversion from twice-daily tacrolimus to once-daily tacrolimus one month after transplantation is safe and effective.

Changes of Kidney Injury Molecule-1 Expression and Renal Allograft Function in Protocol and for Cause Renal Allograft Biopsy / 대한이식학회지

BACKGROUND: Kidney injury molecule-1 (KIM-1) is known as a good ancillary marker of acute kidney injury (AKI) and its expression has also been observed in acute rejection and chronic graft dysfunction. We tested usefulness of KIM-1 as an indicator of acute and chronic renal graft injury by correlating KIM-1 expression with renal graft function and histology. METHODS: A total of 133 zero-time biopsies and 42 follow-up biopsies obtained within 1 year posttransplantation were selected. Renal tubular KIM-1 staining was graded semiquantitatively from 0 to 3 and the extent of staining was expressed as the ratio of KIM-1 positive/CD10 positive proximal tubules using Image J program. RESULTS: KIM-1 was positive in 39.8% of zero-time biopsies. KIM-1 positive cases were predominantly male and had received grafts from donors with older age, deceased donors, and poor renal function at the time of donation, compared with KIM-1 negative cases. KIM-1 expression showed correlation with delayed graft function and acute tubular necrosis. In comparison of KIM-1 expression between stable grafts (n=23) and grafts with dysfunction (n=19) at the time of repeated biopsy, the intensity/extent of KIM-1 staining and renal histology at zero-time did not differ significantly between the two groups. Histologically, KIM-1 expression was significantly increased with both acute and chronic changes of glomeruli, tubules and interstitium, peritubular capillaritis, and arteriolar hyalinosis. CONCLUSIONS: KIM-1 can be used as an ancillary marker of AKI and a nonspecific indicator of acute inflammation and tubulointerstitial fibrosis. However, KIM-1 expression at zero-time is not suitable for prediction of long-term graft dysfunction.

Clinical Characteristics and Risk Factors for Renal Cell Carcinoma after Kidney Transplantation / 대한이식학회지

BACKGROUND: The occurrence of malignancy following kidney transplantation has been estimated three to five times the incidence compared to that of the general population. It is estimated that particularly in renal cell carcinoma (RCC), the relative risk increases. The aim of this study was to analyze the characteristics, risk factors, and prognosis of RCC following kidney transplantation. METHODS: Total number of 3,272 kidney recipients who underwent transplantation from April 1979 to December 2012 and patients who had RCC following kidney transplantation were retrospectively reviewed and analyzed. RESULTS: We found that among 232 cases of posttransplant malignancies, 25 recipients were diagnosed with RCC. We have observed in our study that it took an average of 175.2+/-71.0 months to develop RCC after their first kidney transplantation. However, with longer follow up period, interval incidence of RCC increased. Fourteen patients (56%) were diagnosed with RCC 15 years after transplantation. We also found that with reference to the risk factor analysis for posttransplant RCC, the long-term follow-up period was the only independent risk factor. In our study, 21 patients with RCC were treated with radical nephrectomy. Of them, 16 patients survived, and four RCC-related deaths occurred. Furthermore, the patient survival rate of RCC recipients was lower than that of the nonmalignancy group despite the graft survival rate were not different. CONCLUSIONS: We conclude that the incidence of RCC increased in a time-dependent manner following kidney transplantation. Therefore, we strongly recommend the procedure of regular-interval screening for the patients who are on compulsive long-term immunosuppression.

Posttransplant Lymphoproliferative Disorder without Epstein-Barr Virus Presented as Small Bowel Perforation in Renal Transplant Recipient: A Case Report / 대한이식학회지

Posttransplant lymphoproliferative disorder (PTLD) is documented as one of the serious complications leading to mortality particularly in organ transplant recipients receiving immunosuppressive therapy. Extant literature confirms beyond doubt that the most common site of involvement of PTLD is lymph nodes, and rarely involved is the gastrointestinal tract. It is a well-known fact that Epstein-Barr virus (EBV) is a risk factor for PTLD development. In this study, we report a case of PTLD presented as small bowel perforation without EBV infection after long-term immunosuppressive therapy in a renal transplant recipient.

Clinical Implications for Graft Function of a New Equation Model for the Ratio of Living Donor Kidney Volume to Recipient Body Surface Area

PURPOSE: We propose an equation that predicts graft function after kidney transplantation by using donated kidney volume and recipient body surface area (BSA). MATERIALS AND METHODS: Included were 261 cases of living kidney transplantation between 2007 and 2009. Preoperative computed tomography scans were performed and the donated kidney volume was measured by use of a three-dimensional reconstruction program (Ripidia). The estimated glomerular filtration rate (eGFR) was calculated by using the modification of diet in renal disease formula. Donated kidney volume, preoperative renal function, and demographic factors of both donors and recipients were evaluated as predictors. RESULTS: The mean ages of the donors and recipients were 40.8 and 41.6 years, respectively. The mean donated kidney volume and donated kidney volume/recipient BSA ratio were 153.4 mL and 96.9 mL/m2, respectively. Mean preoperative and postoperative 12-month eGFR of recipients were 7.1 and 59.7 mL/min, respectively, and the mean preoperative eGFR of donors was 92.2 mL/min. Donated kidney volume/recipient BSA ratio, donor age, and recipient gender were the significant predictors of eGFR level (p<0.001) and eGFR<45 mL/min at postoperative 12 months (p=0.005, p<0.001, and p=0.006). From the multiple linear regression equation and predicted probability from logistic regression, we could calculate the equation for the ratio of living donor kidney volume to recipient BSA on graft function. CONCLUSIONS: Graft kidney volume/recipient BSA ratio, donor age, and recipient gender were predictors of graft function 12 months after kidney transplantation. Although we are concerned only with the preoperative, this equation model could help physicians to counsel patients concerning their postoperative prognosis and to avoid insufficient volume donations.

Waiting Time for Deceased Donor Kidney Allocation in Korea: A Single Center Experience / 대한이식학회지

BACKGROUND: The kidney recovery rate associated with deceased donors has increased after the establishment of the Korean Network for Organ Sharing (KONOS). And the KONOS organ allocation system gives priority to candidates affiliated with a Hospital based Organ Procurement Organization (HOPO) and/or donor recovery hospital. Regardless of whether or not this organ allocation system is fair, it can make an important impact on the waiting time for an organ transplant. METHODS: A total of 157 deceased donor kidney transplantations were performed at Severance Hospital between January 2006 and April 2011. The recipients of these transplantations were retrospectively divided into five groups according to their allocation types; general allocation group (GA, n=54), HOPO priority group (HP, n=65), zero antigen mismatching group (ZM, n=23), marginal donor allocation group (MD, n=7), and the combined organ transplant allocation group (CT, n=8). The five groups were assessed in terms of their waiting time for organ allocation, cold ischemia time, and post-transplant graft outcome. RESULTS: Mean waiting time for organ allocation of the HP group (69.5+/-27.4 months) was significantly shorter than for the GA group (90.0+/-34.0 months)(P<0.05). However, the degree of HLA mismatching was not different between each group. The cold ischemia time for the HP group (301.5+/-133.9 min) was significantly shorter than all other groups, except for the ZM group. There were no differences between groups in terms of acute rejection episodes, delayed graft function events or graft survival rates. CONCLUSIONS: Our retrospective analysis of the kidney allocation pattern showed that there were disparities in distribution by priority of allocation. We should make a consensus within the Korean transplant society in order to further develop the allocation system to decease donor kidney transplantation time.

Impact of pretransplant rituximab induction on highly sensitized kidney recipients: comparison with non-rituximab group / 대한외과학회지

PURPOSE: Highly sensitized patients with a high level of panel reactive antibody (PRA) experience more episodes of antibody-mediated rejection (AMR) and poorer graft survival than non-sensitized patients. Rituximab is a well-known monoclonal anti-CD20 antibody that causes the depletion of B lymphocytes. The aim of this study was to compare a rituximab-administered and a non-administered group of highly sensitized recipients. METHODS: Forty-three kidney recipients with a PRA level of > or =50% were included. Sixteen (group R) received one dose of rituximab at 2 days prior to transplantation and 27 patients (group NR) did not. RESULTS: Patients' demographics, such as age, sex, dialysis duration, and type of immunosuppressive agent were not different in the two groups. No side effects due to rituximab administration were observed in group R. Class I PRA of group R (75.6 +/- 37.7%) was higher than that of group NR (45.7 +/- 35.8%, P = 0.013). More acute rejection episodes occurred within 1 year after transplantation in group NR but the difference between the groups was not significant (18.8% in group R vs. 29.6% in group NR, P = 0.631). However, two AMR episodes occurred only in group NR. Renal functions were not different in the two groups. In group R, CD19 and CD20 rapidly decreased 2 days after rituximab infusion. Furthermore, the administration of rituximab was not linked to acute rejection. CONCLUSION: To confirm the long-term anti-rejection and beneficial effects of rituximab, further studies should be performed with a larger cohort. In conclusion, rituximab administration 2 days prior to transplantation is both effective and safe.

Severity of End-stage Liver Disease in Liver Transplant Candidate; Comparison of KONOS Status with MELD Score / 대한이식학회지

BACKGROUND: We have allocated liver according to the Korean Network Organ Sharing (KONOS) status. However, it was necessary to change the system to a more adequate and objective system. We analyzed the correlation between KONOS status and MELD score under the current status of organ allocation. METHODS: We reviewed medical records of 70 liver recipients as KONOS status 2A and 2B between September 2005 and December 2010. We analyzed their KONOS status, MELD score, clinical characteristics, waiting time, Child-Turcotte-Pugh (CTP) score and clinical symptoms accorded to KONOS status 2A. RESULTS: Mean MELD and CTP score of the 2A group was significantly higher than the 2B group (P<0.001). In the 2B group, the blood types of all recipients were identical to those of the donors. However, 2A group included 7 cases (23.3%) of non-identical blood types. The MELD score of all recipients were correlated with CTP score (R=0.798, P<0.001). However, there was an overlapping area between the 2B group and the 2A group that was registered by the condition of intractable ascites. Those who had hepatorenal syndrome and hepatic encephalopathy showed high MELD score over 20. However, 36.4% of the patients who had only intractable ascites showed a MELD score of less than 20. CONCLUSIONS: CTP score was highly correlated with MELD score. However, KONOS status showed some overlapping area of the MELD score between 2A and 2B groups. We should make an effort to improve KONOS allocation system to meet the Korean situation.

Role of Plasma Exchange in ABO-incompatible Kidney Transplantation

BACKGROUND: In the past, ABO incompatibility was an absolute contraindication for solid organ transplantation. However, multiple recent trials have suggested strategies for overcoming the reactions between graft antigens and recipient antibodies that cause graft rejection. In this study, we determined the usefulness of plasma exchange (PE) for removing anti-A/B antibodies that cause hyperacute/acute humoral graft rejection in patients undergoing ABO-incompatible kidney transplantation. METHODS: In our study, 12 patients underwent ABO-incompatible kidney transplantation. All recipients received pre-transplantation conditioning by PE or intravenous immunoglobulin (IVIG) administration. After pre-transplantation conditioning, anti-A/B antibody titers were evaluated, and transplantation was performed when the titer was below 1:8. To assess the transplantation outcome, anti-A/B antibody titers, creatinine level, estimated glomerular filtration rate (eGFR), and proteinuria levels were measured. RESULTS: Anti-A/B antibody titers were below 1:8 in all patients at the time of transplantation. eGFR measured on post-transplant day 14 showed that 10 patients had immediate recovery of graft function, while 2 patients had slow recovery of graft function. Short-term outcomes of ABO-incompatible kidney transplantation (measured as creatinine levels) after reducing anti-A/B antibody titers were similar to those of ABO-compatible kidney transplantation. After transplantation, the anti-A/B antibody titers were below 1:8 in 7 patients, but the remaining 5 patients required post-transplantation PE and IVIG treatment to prevent antigen-antibody reactions. CONCLUSIONS: With the increasing demand for kidney donations, interest in overcoming the ABO incompatibility barrier has increased. PE may be an important breakthrough in increasing the availability of kidneys for transplantation.

Changes in Serum Cytokine Profile after AEB071 (Sotrastaurin) or Tacrolimus versus Their Combinations in Rat Heterotopic Cardiac Allografts / 대한이식학회지

BACKGROUND: AEB071, an orally available PKC inhibitor, prevents organ rejection after transplantation in rodents and man. Furthermore, pro-inflammatory cytokines and inflammatory processes are important mediators of transplanted organ rejection. We therefore examined whether single or combination therapies of AEB071 and/or tacrolimus affect cytokine profiles in a rat cardiac allograft model. METHODS: AEB071 (60 mg/kg twice a day) and tacrolimus (0.6 or 1.2 mg/kg once a day) were orally administered daily after cardiac transplantation. Interferon (IFN)-gamma, interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-10, and tumor necrosis factor (TNF)-alpha levels in serum were subsequently measured 5 days after cardiac transplantation using a multiplex protein assay system. RESULTS: All cytokine levels were significantly depressed in cardiac transplanted rats treated with AEB071, whereas tacrolimus only reduced IFN-gamma, IL-2, IL-4, IL-6, and IL-10 levels. When administered in combination, AEB071 and low- or high-dose tacrolimus had additive effects on IFN-gamma, IL-4, IL-6, and TNF-alpha. CONCLUSIONS: These results suggest that AEB071 inhibits T cell activation by blocking the production of proinflammatory cytokines, and that tacrolimus combined with AEB071 can effectively regulate inflammatory cytokines in the transplantation setting.