The medical cost and outcome of desensitization protocol in kidney transplantation recipients with high immunological risks.

BACKGROUND: Kidney transplantation is a well-established alternative in renal replacement therapy. Compared with hemodialysis, low-immunological-risk kidney transplantation can reduce the medical treatment costs associated with end-stage renal disease. However, there are few reports on whether high-immunological-risk kidney transplantation reduces the financial burden on governments. We investigated the medical costs of high-immunological-risk kidney transplantation in comparison with the cost of hemodialysis in Japan. METHODS: We compared the medical costs of high-immunological-risk kidney transplantation with those of hemodialysis. 15 patients who underwent crossmatch-positive and/or donor-specific antibody-positive kidney transplantations between 2020 and 2021 were enrolled in this study. The patients received intravenous immunoglobulin, plasmapheresis, and rituximab as desensitizing therapy. RESULTS: Acute antibody-mediated rejection was detected in nine (60%) recipients, while there were no indications of graft function deterioration during the follow-up. For each patient, the transplant hospitalization cost was 38 428 ± 8789 USD. However, the cumulative costs were 59 758 ± 10 006 USD and 79 781 ± 16 366 USD, at 12 and 24 months, respectively. Compared with hemodialysis (34 286 USD per year), high-immunological-risk kidney transplantation tends to be expensive in the first year, but the cost is likely to be lower than that of hemodialysis after 3 years. CONCLUSIONS: Although kidney transplantation is initially expensive compared with hemodialysis, the medical cost becomes advantageous after 3 years even in kidney transplant recipients with high immunological risk.

Very Low Dose Anti-Thymocyte Globulins Versus Basiliximab in Non-Immunized Kidney Transplant Recipients.

The choice between Basiliximab (BSX) or Anti-Thymocyte Globulin (ATG) as induction therapy in non-immunized kidney transplant recipients remains uncertain. Whilst ATG may allow steroid withdrawal and a decrease in tacrolimus, it also increases infectious complications. We investigated outcomes in non-immunized patients receiving a very low dosage of ATG versus BSX as induction. Study outcomes were patient/graft survival, cumulative probabilities of biopsy proven acute rejection (BPAR), infectious episode including CMV and post-transplant diabetes (PTD). Cox, logistic or linear statistical models were used depending on the studied outcome and models were weighted on propensity scores. 100 patients received ATG (mean total dose of 2.0 mg/kg) and 83 received BSX. Maintenance therapy was comparable. Patient and graft survival did not differ between groups, nor did infectious complications. There was a trend for a higher occurrence of a first BPAR in the BSX group (HR at 1.92; 95%CI: [0.77; 4.78]; p = 0.15) with a significantly higher BPAR episodes (17% vs 7.3%, p = 0.01). PTD occurrence was significantly higher in the BSX group (HR at 2.44; 95%CI: [1.09; 5.46]; p = 0.03). Induction with a very low dose of ATG in non-immunized recipients was safe and associated with a lower rate of BPAR and PTD without increasing infectious complications.

Immunological risk and complement genetic evaluations in early onset de novo thrombotic microangiopathy after living donor kidney transplantation: A Japanese multicenter registry.

BACKGROUND: Thrombotic microangiopathy (TMA) after kidney transplantation (KTx), particularly early onset de novo (dn) TMA, requires immediate interventions to prevent irreversible organ damage. This multicenter study was performed to investigate the allogeneic clinical factors and complement genetic background of dnTMA after KTx. METHODS: Perioperative dnTMA after KTx within 1 week after KTx were diagnosed based on pathological or/and hematological criteria at each center, and their immunological backgrounds were researched. Twelve aHUS-related gene variants were examined in dnTMA cases. RESULTS: Seventeen recipients (15 donors) were enrolled, and all dnTMA cases were onset within 72-h of KTx, and 16 of 17 cases were ABO incompatible. The implementation rate of pre-transplant plasmaphereses therapies were low, including cases with high titers of anti-A/anti-B antibodies. Examination of aHUS-related gene variants revealed some deletions and variants with minor allele frequency (MAF) in Japan or East Asian genome databases in genes encoding alternative pathways and complement regulatory factors. These variants was positive in 8 cases, 6 of which were positive in both recipient and donor, but only in one graft loss case. CONCLUSIONS: Although some immunological risks were found for dnTMA after KTx, only a few cases developed into TMA. The characteristic variations revealed in the present study may be novel candidates related to dnTMA in Japanese or Asian patients, but not pathogenic variants of aHUS. Future studies on genetic and antigenic factors are needed to identify factors contributing to dnTMA after KTx.

Treatment of early borderline lesions in low immunological risk kidney transplant patients: a Spanish multicenter, randomized, controlled parallel-group study protocol: the TRAINING study.

BACKGROUND: Subclinical inflammation, including borderline lesions (BL), is very common (30-40%) after kidney transplantation (KT), even in low immunological risk patients, and can lead to interstitial fibrosis/tubular atrophy (IFTA) and worsening of renal function with graft loss. Few controlled studies have analyzed the therapeutic benefit of treating these BL on renal function and graft histology. Furthermore, these studies have only used bolus steroids, which may be insufficient to slow the progression of these lesions. Klotho, a transmembrane protein produced mainly in the kidney with antifibrotic properties, plays a crucial role in the senescence-inflammation binomial of kidney tissue. Systemic and local inflammation decrease renal tissue expression and soluble levels of α-klotho. It is therefore important to determine whether treatment of BL prevents a decrease in α-klotho levels, progression of IFTA, and loss of kidney function. METHODS: The TRAINING study will randomize 80 patients with low immunological risk who will receive their first KT. The aim of the study is to determine whether the treatment of early BL (3rd month post-KT) with polyclonal rabbit antithymocyte globulin (Grafalon®) (6 mg/kg/day) prevents or decreases the progression of IFTA and the worsening of graft function compared to conventional therapy after two years post-KT, as well as to analyze whether treatment of BL with Grafalon® can modify the expression and levels of klotho, as well as the pro-inflammatory cytokines that regulate its expression. DISCUSSION: This phase IV investigator-driven, randomized, placebo-controlled clinical trial will examine the efficacy and safety of Grafalon® treatment in low-immunological-risk KT patients with early BL. TRIAL REGISTRATION: clinicaltrials.gov : NCT04936282. Registered June 23, 2021, https://clinicaltrials.gov/ct2/show/NCT04936282?term=NCT04936282&draw=2&rank=1 . Protocol Version 2 of 21 January 2022. SPONSOR: Canary Isles Institute for Health Research Foundation, Canary Isles (FIISC). mgomez@fciisc.org .

Decreased incidence of acute rejection without increased incidence of cytomegalovirus (CMV) infection in kidney transplant recipients receiving rabbit anti-thymocyte globulin without CMV prophylaxis - a cohort single-center study.

Induction therapy with rabbit anti-thymocyte globulin (rATG) in low-risk kidney transplant recipients (KTR) remains controversial, given the associated increased risk of cytomegalovirus (CMV) infection. This natural experiment compared 12-month clinical outcomes in low-risk KTR without CMV prophylaxis (January/3/13-September/16/15) receiving no induction or a single 3 mg/kg dose of rATG. We used logistic regression to characterize delayed graft function (DGF), negative binomial to characterize length of hospital stay (LOS), and Cox regression to characterize acute rejection (AR), CMV infection, graft loss, death, and hospital readmissions. Recipients receiving 3 mg/kg rATG had an 81% lower risk of AR (aHR 0.14 0.190.25 , P < 0.001) but no increased rate of hospital readmissions because of infections (0.68 0.911.21 , P = 0.5). There was no association between 3 mg/kg rATG and CMV infection/disease (aHR 0.86 1.101.40 , P = 0.5), even when the analysis was stratified according to recipient CMV serostatus positive (aHR 0.94 1.251.65 , P = 0.1) and negative (aHR 0.28 0.571.16 , P = 0.1). There was no association between 3 mg/kg rATG and mortality (aHR 0.51 1.253.08 , P = 0.6), and graft loss (aHR 0.34 0.731.55 , P = 0.4). Among low-risk KTR receiving no CMV pharmacological prophylaxis, 3 mg/kg rATG induction was associated with a significant reduction in the incidence of AR without an increased risk of CMV infection, regardless of recipient pretransplant CMV serostatus.

Early Antibody-Mediated Kidney Transplant Rejection Associated With Anti-Vimentin Antibodies: A Case Report.

Improving precision in predicting alloreactivity is an important unmet need and may require individualized consideration of non-HLA antibodies. We report a 21-year-old man with kidney failure from immunoglobulin A nephropathy who met all traditional criteria for a "low-risk" transplant for immune memory. He was unsensitized and received a haplotype-matched living donor kidney transplant from his mother. There were no anti-HLA donor-specific antibodies and flow cross-match was negative. After immediate function, he developed delayed graft function on postoperative day 2. The transplant biopsy specimen was suggestive of antibody-mediated rejection and acute tubular injury with increased vimentin proximal tubular expression compared to the implantation biopsy specimen. He had a history of juvenile idiopathic arthritis, and non-HLA antibody screening demonstrated preformed anti-vimentin antibody. He was successfully treated with plasmapheresis, intravenous immunoglobulin, antithymocyte globulin, and methylprednisolone, with renal recovery. The follow-up biopsy specimen demonstrated decreased vimentin expression with decreased alloinflammation, and graft function remains stable at 1 year posttransplantation (estimated glomerular filtration rate, 62mL/min/1.73m2). We postulate that preformed anti-vimentin autoantibodies bound to vimentin expressed on apoptotic tubular epithelial cells induced by ischemia-reperfusion injury and to constitutively expressed vimentin on peritubular capillaries and podocytes. Our case is suggestive of the involvement of anti-vimentin antibody, for which the pathogenic epitopes may be exposed during ischemia-reperfusion injury.

Early protocol biopsies in pediatric renal transplantation: interest for the adaptation of immunosuppression.

GPB are often performed in PRT to detect subclinical acute rejection or IF/TA. Reducing immunosuppression side effects without increasing rejection is a major concern in PRT. We report the results of GPB in children transplanted with a steroid-sparing protocol adapted to immunological risk. Children under 18 yr who received a renal transplantation between April 1, 2009 and May 31, 2012 were included. Immunosuppression consisted of an antibody induction therapy, tacrolimus, and MMF for all recipients. CSs were administered to children under five yr old, or receiving a second allograft. Twenty-eight children were included, 50% were CSs free. GPB were performed between three and six months. IF/TA was documented in seven biopsies; four of these seven children were CS free. One child, with CSs, presented a borderline rejection, and another child, steroid free, with significant inflammatory interstitial infiltrate, considered as a subclinical rejection, was treated with CSs pulses. The median eGFR was stable (74, 67.5, and 82 mL/min/1.73 m² at, respectively, seven days, three months, and one yr). Patient and graft survival were 100%. These results have to be confirmed in a larger cohort, with long-term follow-up.

Splenectomy Before Kidney Transplantation for Hypersplenism: A Case Report.

Hypersplenism, although a rare hematological complication seen in chronic kidney disease patients, poses a significant challenge for successful kidney transplantation due to potential complications such as cytopenias and inadequate immunosuppressive therapy. We present a 40-year old end-stage kidney disease patient on dialysis with hypersplenism who underwent a laparoscopic splenectomy prior to high immunological risk renal transplantation. Post-splenectomy, there was a remarkable improvement in cytopenias, and effective immunosuppressive therapy could be administered prior to renal transplantation. Splenectomy remains a valuable strategy for managing hypersplenism, ensuring correction of cytopenias, for optimal immunosuppression prior to kidney transplantation. Pre-transplant vaccination further mitigates the risk infections with capsulated organisms. Our case underscores the importance of a multidisciplinary approach in decision-making and highlights splenectomy as a safe and effective intervention to address cytopenias due to hypersplenism prior to renal transplantation.

Standardized, risk-adapted induction therapy in kidney transplantation.

BACKGROUND: The choice of induction therapy in kidney transplantation is often non-standardized and centre-specific. Clinicians can choose between depleting and non-depleting antibodies, which differ in their immunosuppressive capacity and the concomitant risk of infection. We herein present a standardized risk-stratified algorithm for induction therapy that might help to balance the risk of rejection and/or serious infection. METHODS: Prior to kidney transplantation, patients were stratified into low-risk, intermediate-risk or high-risk according to our protocol based on immunologic risk factors. Depending on their individual immunologic risk, patients received basiliximab (low risk), antithymocyte globulin (intermediate risk) or low-dose alemtuzumab (high risk) for induction therapy. We analysed the results after 3 years of implementation of our risk-stratified induction therapy protocol at our kidney transplant centre. RESULTS: Between 01/2017 and 05/2020, 126 patients were stratified in accordance with our protocol (low risk/intermediate risk/high risk: 69 vs. 42 vs. 15 patients). The median follow-up time was 1.9 [1.0-2.5] years. No significant difference was observed in rejection rate and allograft survival (low risk/intermediate risk/high risk: 90.07% vs. 80.81% vs. 100% after 3 years (p > 0.05)) among the groups. The median eGFR at follow-up was (low risk/intermediate risk/high risk) 47 [33-58] vs 58 [46-76] vs 44 [22-55] ml/min/1.73 m2. Although the rate of viral and bacterial infections did not differ significantly, we observed a higher rate of opportunistic fungal infections with alemtuzumab induction. CONCLUSIONS: Our strategy offers facilitated and individualized choice of induction therapy in kidney transplantation. We propose further evaluation of our algorithm in prospective trials.

The impact of induction therapy in low-immunological risk kidney transplant recipients regardless of HLA matching.

BACKGROUND: Induction agents have proved to reduce the rate of acute rejection (AR) in kidney transplant recipients (KTRs) without improving long-term graft and patient survival (PS). OBJECTIVE: This study evaluates the utility of induction therapy in low immunological risk KTRs regardless of donor-to-recipient HLA matching. METHODS: We retrospectively reviewed the records of 218 patients undergoing kidney transplantation (KT). These patients were divided into two groups according to the usage of induction therapy: 82 did not receive any induction therapy (Group I), and 136 patients received either Anti-IL2 receptor antibodies or anti-thymocyte globulin (Group II). All patients had panel reactive antibody (PRA) < 20% and absence of donor-specific antibodies (DSA). The difference in outcomes were assessed at different intervals following KT. RESULTS: The rate of bacterial infections at one year (p-value = 0.032) and the frequency of CMV disease (p-value = 0.044) were significantly higher in Group II (with induction therapy). The duration of hospital stay, the rate and severity of acute rejection, the occurrence of delayed graft function, the rate and type of surgical complications at one year, and the graft function and survival at one and three years were similar between the two groups (p-value = NS). In addition, the financial burden is much less in Group I (without induction therapy), reducing the total cost of the transplant procedure. CONCLUSION: We conclude that induction therapy in low-immunological risk kidney transplant patients is not a must regardless of donor-to-recipient HLA matching. Therefore, induction therapy did not yield significant health results, but had negative financial consequences.

Immunosuppression of HLA identical living-donor kidney transplant recipients: A systematic review.

BACKGROUND: Kidney transplant (KT) recipients of HLA identical siblings (HLAid) have lower immunological risk, but there are no specific recommendations for immunosuppression. Our aim was to analyze evidence about results from HLAid living-donor recipients under different immunosuppression in the current era of immunological risk assessment. METHODS: Systematic review of studies describing associations between outcomes of HLAid living-donor KT recipients according to their immunological risk and applied immunosuppression. RESULTS: From 1351 studies, 16 (5636 KT recipients) were included in the analysis. All studies were retrospective, ten comparing immunosuppression strategies, and six immunological risk strata. Of those ten, six studies were published in 1990 or earlier and only three included tacrolimus. The evidence is poor, and the inclusion of calcineurin inhibitors does not demonstrate better results. Furthermore, only few studies describe different immunosuppression regimens according to the patient immunological risk and, in general, they do not include the assessment with new solid phase assays. CONCLUSIONS: There are no studies analyzing the association of outcomes of HLAid KT recipients with current immunological risk tools. In the absence of evidence, no decision or proposal of immunosuppression adapted to modern immunological risk assessment can be made currently by the Descartes Working Group.

Predicting Immunological Risk for Stage 1 and Stage 2 Diabetes Using a 1-Week CGM Home Test, Nocturnal Glucose Increments, and Standardized Liquid Mixed Meal Breakfasts, with Classification Enhanced by Machine Learning.

Background: Predicting the risk for type 1 diabetes (T1D) is a significant challenge. We use a 1-week continuous glucose monitoring (CGM) home test to characterize differences in glycemia in at-risk healthy individuals based on autoantibody presence and develop a machine-learning technology for CGM-based islet autoantibody classification. Methods: Sixty healthy relatives of people with T1D with mean ± standard deviation age of 23.7 ± 10.7 years, HbA1c of 5.3% ± 0.3%, and body mass index of 23.8 ± 5.6 kg/m2 with zero (n = 21), one (n = 18), and ≥2 (n = 21) autoantibodies were enrolled in an National Institutes of Health TrialNet ancillary study. Participants wore a CGM for a week and consumed three standardized liquid mixed meals (SLMM) instead of three breakfasts. Glycemic outcomes were computed from weekly, overnight (12:00-06:00), and post-SLMM CGM traces, compared across groups, and used in four supervised machine-learning autoantibody status classifiers. Classifiers were evaluated through 10-fold cross-validation using the receiver operating characteristic area under the curve (AUC-ROC) to select the best classification model. Results: Among all computed glycemia metrics, only three were different across the autoantibodies groups: percent time >180 mg/dL (T180) weekly (P = 0.04), overnight CGM incremental AUC (P = 0.005), and T180 for 75 min post-SLMM CGM traces (P = 0.004). Once overnight and post-SLMM features are incorporated in machine-learning classifiers, a linear support vector machine model achieved the best performance of classifying autoantibody positive versus autoantibody negative participants with AUC-ROC ≥0.81. Conclusion: A new technology combining machine learning with a potentially self-administered 1-week CGM home test can help improve T1D risk detection without the need to visit a hospital or use a medical laboratory. Trial registration: ClinicalTrials.gov registration no. NCT02663661.

Kidney Transplantation in a Patient Affected by Sickle Cell Trait: A Case Report and State-of-the-Art Review.

Chronic kidney disease (CKD) is a common feature of sickle cell disease (SCD). The awareness of the clinical presentation and renal involvement in patients affected by hemoglobinopathies is greatly needed. Patient management is particularly complex, especially with kidney transplantation. We, therefore, report the case of a 56-year-old patient affected by sickle cell trait who underwent kidney transplantation. This case will underline all the various challenges the nephrologist must face in this clinical setting and their management.

Determination of unacceptable HLA antigen mismatches in kidney transplant recipients.

With the introduction of the virtual allocation crossmatch in the Eurotransplant (ET) region in 2023, the determination of unacceptable antigen mismatches (UAM) in kidney transplant recipients is of utmost importance for histocompatibility laboratories and transplant centers. Therefore, a joined working group of members from the German Society for Immunogenetics (Deutsche Gesellschaft für Immungenetik, DGI) and the German Transplantation Society (Deutsche Transplantationsgesellschaft, DTG) revised and updated the previous recommendations from 2015 in light of recently published evidence. Like in the previous version, a wide range of topics is covered from technical issues to clinical risk factors. This review summarizes the evidence about the prognostic value of contemporary methods for HLA antibody detection and identification, as well as the impact of UAM on waiting time, on which these recommendations are based. As no clear criteria could be determined to differentiate potentially harmful from harmless HLA antibodies, the general recommendation is to assign all HLA against which plausible antibodies are found as UAM. There is, however, a need for individualized solutions for highly immunized patients. These revised recommendations provide a list of aspects that need to be considered when assigning UAM to enable a fair and comprehensible procedure and to harmonize risk stratification prior to kidney transplantation between transplant centers.

B-cell activating factor BAFF as a novel alert marker for the immunological risk stratification after kidney transplantation.

The B cell activating factor BAFF has gained importance in the context of kidney transplantation due to its role in B cell survival. Studies have shown that BAFF correlates with an increased incidence of antibody-mediated rejection and the development of donor-specific antibodies. In this study, we analyzed a defined cohort of kidney transplant recipients who were treated with standardized immunosuppressive regimens according to their immunological risk profile. The aim was to add BAFF as an awareness marker in the course after transplantation to consider patient's individual immunological risk profile. Included patients were transplanted between 2016 and 2018. Baseline data, graft function, the occurrence of rejection episodes, signs of microvascular infiltration, and DSA kinetics were recorded over 3 years. BAFF levels were determined 14 d, 3 and 12 months post transplantation. Although no difference in graft function could be observed, medium-risk patients showed a clear dynamic in their BAFF levels with low levels shortly after transplantation and an increase in values of 123% over the course of 1 year. Patients with high BAFF values were more susceptible to rejection, especially antibody-mediated rejection and displayed intensified microvascular inflammation; the combination of high BAFF + DSA puts patients at risk. The changing BAFF kinetics of the medium risk group as well as the increased occurrence of rejections at high BAFF values enables BAFF to be seen as an awareness factor. To compensate the changing immunological risk, a switch from a weaker induction therapy to an intensified maintenance therapy is required.

Impact of HLA Mismatching on Early Subclinical Inflammation in Low-Immunological-Risk Kidney Transplant Recipients.

The impact of human leukocyte antigen (HLA)-mismatching on the early appearance of subclinical inflammation (SCI) in low-immunological-risk kidney transplant (KT) recipients is undetermined. We aimed to assess whether HLA-mismatching (A-B-C-DR-DQ) is a risk factor for early SCI. As part of a clinical trial (Clinicaltrials.gov, number NCT02284464), a total of 105 low-immunological-risk KT patients underwent a protocol biopsy on the third month post-KT. As a result, 54 presented SCI, showing a greater number of total HLA-mismatches (p = 0.008) and worse allograft function compared with the no inflammation group (48.5 ± 13.6 vs. 60 ± 23.4 mL/min; p = 0.003). Multiple logistic regression showed that the only risk factor associated with SCI was the total HLA-mismatch score (OR 1.32, 95%CI 1.06-1.64, p = 0.013) or class II HLA mismatching (OR 1.51; 95%CI 1.04-2.19, p = 0.032) after adjusting for confounder variables (recipient age, delayed graft function, transfusion prior KT, and tacrolimus levels). The ROC curve illustrated that the HLA mismatching of six antigens was the optimal value in terms of sensitivity and specificity for predicting the SCI. Finally, a significantly higher proportion of SCI was seen in patients with >6 vs. ≤6 HLA-mismatches (62.3 vs. 37.7%; p = 0.008). HLA compatibility is an independent risk factor associated with early SCI. Thus, transplant physicians should perhaps be more aware of HLA mismatching to reduce these early harmful lesions.

Effect of donor-to-recipient HLA matching in low-immunological risk kidney transplant recipients without induction therapy on acute rejection, graft survival, infections, and surgical complications at 3 years: The road towards new recommendations.

BACKGROUND: Donor-to-recipient human leukocyte antigen mismatching is considered one of the strongest determinants for graft and patient survival in kidney transplant recipients (KTR). OBJECTIVE: This retrospective study discusses the impact of HLA matching as low immunological risk KTR without induction therapy. MATERIAL AND METHODS: Records of 80 adult kidney transplant patients were reviewed with three years of the follow-up. All patients had panel reactive antibodies (PRA) < 20%, absence of donor-specific antibodies (DSA) and did not receive the induction therapy. These patients were divided into two groups according to their HLA matching between donor and recipient: 55 patients with ≥ 3 HLA matches (Group I; low immunogenicity) were compared to 25 patients with <3 HLA matches (Group II; high immunogenicity). The primary endpoints included the rate and severity of acute rejection (AR) episodes, graft function (creatinine level), and survival at 1, 3, 6, 12, and 36 months. Secondary endpoints include the rate and type of infections at one-year, surgical complications at one-year, and patient survival at 1, 6, 12, and 36 months after kidney transplantation. Baseline demographic characteristics were comparable between the two groups except for recipient age, donor gender, and pre-transplant dialysis time. RESULTS: There was no significant difference observed between two groups at one-year in infection rate, the length of hospital stay, AR severity, the rate of cytomegalovirus infection, and the occurrence of delayed graft function. However, the rate of AR, the graft function upon discharge, and the rate and type of surgical complications at one-year were significantly higher in Group II (high immunogenicity). The patient and graft survival at three years, the death-censored graft survival, and the serum creatinine levels at 1, 3, 6, 12, and 36 months were similar between two groups. Two deaths occurred in each group (NS). CONCLUSION: In our center, the donor-to-recipient HLA mismatch is not considered an immunological risk factor in low-risk kidney transplant recipients (PRA < 20% and absence of DSA).

Immunological Risk Factors in Paediatric Kidney Transplantation.

PURPOSE: The aim of this study was to identify factors impacting recipient sensitization rates and paediatric renal transplant patient outcomes. PATIENTS AND METHODS: For this purpose, a retrospective analysis of 143 paediatric renal transplants was carried out. This included the evaluation of patient's and donor's demographic data, HLA mismatches, immunosuppressive therapy, rejection episodes, panel reactive antibody (PRA) and post-transplant lymphoproliferative disease (PTLD). RESULTS: The mean patient age at the point of transplant receival was 11.5 years with a mean follow up time of 9.33±5.05 years. It was noted that graft survival rates for donors over 59 years had the worst outcome. HLA match did not show statistically significant influence on graft outcome. Graft survival for more than one biopsy-proven rejection was also significantly shorter (p=0.008). PRA were found in 28% of the recipient's post-transplantation and showed association with lower graft survival rates (p<0.001). In the present study, 22.7% (5/22) of the patients with EBV infections presented a PTLD. CONCLUSION: In conclusion, good graft survival with reduced sensitization for future transplantations and minimize the risk of PTLD, can be ensured through a balance between donor age, HLA match and condition of the recipient should be sought. Furthermore, paediatric patients should preferably receive organs from donors between the age of 10 and 59. EBV infection could be a relevant factor for developing PTLD.

Clinical Relevance of Corticosteroid Withdrawal on Graft Histological Lesions in Low-Immunological-Risk Kidney Transplant Patients.

The impact of corticosteroid withdrawal on medium-term graft histological changes in kidney transplant (KT) recipients under standard immunosuppression is uncertain. As part of an open-label, multicenter, prospective, phase IV, 24-month clinical trial (ClinicalTrials.gov, NCT02284464) in low-immunological-risk KT recipients, 105 patients were randomized, after a protocol-biopsy at 3 months, to corticosteroid continuation (CSC, n = 52) or corticosteroid withdrawal (CSW, n = 53). Both groups received tacrolimus and MMF and had another protocol-biopsy at 24 months. The acute rejection rate, including subclinical inflammation (SCI), was comparable between groups (21.2 vs. 24.5%). No patients developed dnDSA. Inflammatory and chronicity scores increased from 3 to 24 months in patients with, at baseline, no inflammation (NI) or SCI, regardless of treatment. CSW patients with SCI at 3 months had a significantly increased chronicity score at 24 months. HbA1c levels were lower in CSW patients (6.4 ± 1.2 vs. 5.7 ± 0.6%; p = 0.013) at 24 months, as was systolic blood pressure (134.2 ± 14.9 vs. 125.7 ± 15.3 mmHg; p = 0.016). Allograft function was comparable between groups and no patients died or lost their graft. An increase in chronicity scores at 2-years post-transplantation was observed in low-immunological-risk KT recipients with initial NI or SCI, but CSW may accelerate chronicity changes, especially in patients with early SCI. This strategy did, however, improve the cardiovascular profiles of patients.