Adult Renal Transplant Recipients Research Articles

Effects of CYP3A5 Genetic Polymorphisms on the Weight-adjusted through Concentration of Sirolimus in Renal Transplant Recipients: A Systematic Review and Meta-analysis.

Sirolimus, one of the immunosuppressive drugs administered to renal transplant recipients, is metabolized by cytochrome P450 (CYP) 3A5. Accordingly, CYP3A5 polymorphism is a genetic factor affecting sirolimus pharmacokinetics (PK). Therefore, we conducted a systematic review and meta-analysis on the association between sirolimus PK and CYP3A5*3 polymorphism. We searched for studies published up to 13 June 2024 from PubMed, Embase, Cochrane Library, and Web of Science. We reviewed studies on the relationship between CYP3A5*3 polymorphism and weightadjusted trough concentration/dose (C/D) ratio and dosage of sirolimus in renal transplant recipients, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We evaluated mean differences (MDs) and 95% confidence intervals (CIs). A total of seven studies were included. The weight-adjusted C/D ratio of sirolimus was significantly higher in patients with the CYP3A5*3/*3 rather than CYP3A5*1/*1 or CYP3A5*1/*3 genotype (MD 95.27 ng/mL per mg/kg; 95% CI: 58.06, 132.47; I2 = 74%; p < 0.00001). Also, the weight-adjusted dosage of sirolimus was significantly lower in patients with the CYP3A5*3/*3 rather than CYP3A5*1/*1 or CYP3A5*1/*3 genotype (MD -2.60 × 10-3 mg/kg; 95% CI: -4.52, -0.69; I2 = 44%; p = 0.008). Our meta-analysis showed a significant effect for the CYP3A5*3 genotype on weight-adjusted C/D ratio and dosage of sirolimus in adult renal transplant recipients.

Pulmonary Nocardiosis in Renal Transplant Recipients From Pakistan: Risk Factors, Clinical Presentation, and Mortality.

Nocardia is an opportunistic infection among renal transplant recipients with an incidence of <1% but high mortality. Data from Pakistan are scarce. Our aim was to find the risk factors, clinical and radiographic findings, antimicrobial sensitivity, and outcomes of Nocardia infection among renal transplant recipients in Pakistan. All adult renal transplant recipients diagnosed with nocardiosis between 2013 and 2020 were included. The cases were matched 1:2 with controls based on sex, age (±1 year), and transplant date (±1 year). Risk factors, clinical features, antibiotic sensitivities and outcomes were analyzed. A total of 48 patients developed nocardiosis. Around 25% of patients presented with disseminated disease. Median time from transplant to disease development was 2.68 years. High-dose methylprednisolone and presence of cytomegalovirus infection within 90 days of disease development were independent risk factors for Nocardia infection. The mortality rate was 20%. Central nervous system disease and cytomegalovirus infection within 90 days were significantly associated with mortality. The most susceptible drugs were co-trimoxazole and linezolid. Imipenem susceptibility was only 20%. High-dose methylprednisolone and cytomegalovirus infection were independent risk factors for Nocardia infection. Central nervous system disease was associated with mortality. Nocardia species were highly resistant to ceftriaxone and imipenem in our patient population.

Hypomagnesaemia, an independent risk factor for the development of post-transplant diabetes mellitus in liver and renal transplant recipients? A systematic review.

Post-transplantation diabetes mellitus (PTDM) is common after solid organ transplantation. In the past decade, there has been increasing interest in the association between hypomagnesaemia and the development of PTDM. This systematic review aimed to investigate the current knowledge regarding the association between hypomagnesaemia and PTDM in adult liver and renal transplant recipients. A literature search of five databases, Medline, Embase, ProQuest, Scopus and Google Scholar, as well as article reference lists, was performed. Eligible studies that focused on adult liver and renal transplant recipients without pretransplantation hyperglycaemia or diabetes were included. Other eligibility criteria included quantitative studies which reported magnesium concentrations, studies with at least 6 months of follow-up, and studies published in English. The Newcastle-Ottawa Assessment Tool was used for the quality assessment. In total, 12 studies were included in the final analysis. Eleven focused on renal transplantation and one on liver transplantation. All studies were medium to high quality with eight out of 12 achieving the highest rating of nine. Eight studies found a negative association between either pretransplant or early post-transplant serum magnesium concentration and the risk of PTDM, three studies found no association between these two variables, and one study found a positive association between the magnesium concentration at 8 weeks after transplantation and glycosylated haemoglobin A1C. Further large-scale prospective studies with at least 6 months of follow-up are needed to confirm these findings, particularly in liver transplantation, to further clarify and explore the relationship between hypomagnesaemia and PTDM.

A joint population pharmacokinetic model to assess the high variability of whole-blood and intracellular tacrolimus in early adult renal transplant recipients

Tacrolimus (TAC) has high pharmacokinetic (PK) variability during the early transplantation period. The relationships between whole-blood and intracellular TAC concentrations and clinical outcomes remain controversial. This study identifies the factors affecting the PK variability of TAC and characterizes the relationships between whole-blood and intracellular TAC concentrations. Data regarding whole-blood TAC concentrations of 1,787 samples from 215 renal transplant recipients (<90 days postoperative) across two centers and intracellular TAC concentrations (648 samples) digitized from previous studies were analyzed using nonlinear mixed-effects modeling. The effects of potential covariates were screened, and the distribution of whole-blood to intracellular TAC concentration ratios (RWB:IC) was estimated. The final model was evaluated using bootstrap, goodness of fit, and prediction-corrected visual predictive checks. The optimal dosing regimens and target ranges for each type of immune cell subsets were determined using Monte Carlo simulations. A two-compartment model adequately described the data, and the estimated mean TAC CL/F was 23.6 L·h−1 (relative standard error: 11.5 %). The hematocrit level, CYP3A5*3 carrier status, co-administration with Wuzhi capsules, and tapering prednisolone dose may contribute to the high variability of TAC PK variability during the early post-transplant period. The estimated RWB:IC of all TAC concentrations in peripheral blood mononuclear cells (PBMCs) was 4940, and inter-center variability of PBMCs was observed. The simulated TAC target range in PBMCs was 20.2–85.9 pg·million cells−1. Inter-center variability in intracellular concentrations should be taken into account in further analyses. TAC dosage adjustments can be guided based on PK/PD variability and simulated intracellular concentrations.

#1776 Distinct changes in gut microbiota of patients with kidney graft rejection

Abstract Background and Aims Kidney graft rejection still represents the major cause of graft loss in kidney transplant recipients. Of growing interest is the bidirectional relationship between gut microbiome and immune system suggesting that gut microbiota can affect allograft outcome. Method In this cross-sectional case control study, we characterized the gut microbial profile of adult renal transplant recipients with and without graft rejection in order to define a cohort-specific microbial fingerprint through 16S rRNA gene sequencing. We used very strict inclusion and exclusion criteria to address confounder of microbiota composition. Results Different relative abundances in several gut microbial taxa were detectable in control patients compared to patients with kidney allograft rejection. Alpha diversity was lower in the rejection group and beta diversity revealed dissimilarity between patients with and without kidney graft rejection (P &amp;lt; .01). When the rejection group was stratified according to different types of allograft rejection, major changes were identified between patients with chronic T cell mediated rejection (cTCMR) and controls. Changes in alpha diversity within the gut microbiome were related to the probability of cTCMR (P &amp;lt; .05). Kidney transplant patients without rejection showed significant enrichment of rather anti-inflammatory taxa whereas in the rejection group bacteria well known for their role in chronic inflammation were increased. For example, ASV 362 belonging to the genus Bacteroides and ASV 312 belonging to Tanerrelaceae were enriched in no rejection (P &amp;lt; .001 and P &amp;lt; .01) whereas ASV 365 was enriched in patients with allograft rejection (P = .04). Looking at metagenomic functions, a higher abundance of genes coding for enzymes involved in bacterial multidrug resistance and processing of short chain fatty acids was found in patients without rejection but an increase in enzymes involved in NADPH production was seen in patients with allograft rejection. Conclusion A distinct microbial fingerprint of patients with allograft rejection might serve as non-invasive biomarker in the future.

Clinical Features and Prognostic Predictors in Patients with Renal Transplant Complicated by SARS-CoV-2 Infection, a Retrospective Single-Center Study.

This study examines the clinical outcomes and prognostic factors of COVID-19 in renal transplant recipients. Given their immunosuppressed status, these patients are at higher risk of severe complications from COVID-19. The study aims to provide healthcare professionals with critical insights for diagnosing and managing this vulnerable population. This retrospective cohort study included adult renal transplant recipients diagnosed with COVID-19. Data on demographics, medical history, laboratory results, and patient outcomes were analyzed to identify clinical characteristics and prognostic factors. This study included 115 renal transplant recipients with COVID-19, predominantly male, with a mortality rate of 10.4% (12 deaths). The overall vaccination rate was 20%. Univariate analysis showed significant differences between survivors and non-survivors in initial serum creatinine levels, and percentages of neutrophils, monocytes, and lymphocytes, along with CRP levels on day 3. Additionally, CRP levels, hemoglobin, and platelet counts on day 7 also differed significantly. Multivariate analysis identified CRP levels on days 3 and 7, day 7 hemoglobin and platelet counts, and concurrent bacterial infections as independent risk factors for mortality. Elevated CRP levels, renal impairment, and bacterial co-infections play a significant role in the outcomes of COVID-19 in kidney transplant recipients. This study highlights the importance of monitoring these factors for early identification and management of high-risk patients.

The Efficacy and Safety of Roxadustat for the Treatment of Posttransplantation Anemia: A Randomized Study

IntroductionRoxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, can stimulate erythropoiesis. Our objective was to evaluate the efficacy and safety of roxadustat for the treatment of post-transplantation anemia (PTA). MethodsA total of 150 adult renal transplant recipients who underwent PTA were randomized to either the experimental group or the control group. During the 12-week randomized phase, the experimental group was randomized to oral iron and roxadustat treatment, and the control group was randomized to oral iron treatment only. The randomized phase was followed by a 12-week extended treatment period in which all participants were prescribed roxadustat treatment according to hemoglobin (Hb) levels. All the participants were followed up every 4 weeks. The primary endpoints were the change in Hb levels and response rate throughout the randomized period. ResultsA total of 128 participants completed the randomized treatment period (90 in the experimental group and 38 in the control group). The mean Hb concentration at week 12 was 12.20 g/dL in the experimental group and 11.19 g/dL in the control group. A significantly higher proportion of participants who achieved Hb responses were in the experimental group than in the control group. Differences in serum iron, total iron-binding capacity (TIBC) and transferrin from baseline to week 8-12 were significant between the two groups. The adverse event profiles were comparable between the two groups. ConclusionsRoxadustat increased Hb in adult renal transplant recipients who underwent PTA, with an adverse event profile comparable to that of the control group.

Utility of a fusion protein T-cell co-stimulation blocker Belatacept in heart transplant recipients: Real world experience from a high volume center.

Belatacept (BTC), a fusion protein, selectively inhibits T-cell co-stimulation by binding to the CD80 and CD86 receptors on antigen-presenting cells (APCs) and has been used as immunosuppression in adult renal transplant recipients. However, data regarding its use in heart transplant (HT) recipients are limited. This retrospective cohort study aimed to delineate BTC's application in HT, focusing on efficacy, safety, and associated complications at a high-volume HT center. A retrospective cohort study was conducted of patients who underwent HT between January 2017 and December 2021 and subsequently received BTC as part of their immunosuppressive regimen. Twenty-one HT recipients were identified. Baseline characteristics, history of rejection, and indication for BTC use were collected. Outcomes included renal function, graft function, allograft rejection and mortality. Follow-up data were collected through December 2023. Among 776 patients monitored from January 2017 to December 2021 21 (2.7%) received BTC treatment. Average age at transplantation was 53 years (±12 years), and 38% were women. BTC administration began, on average, 689 [483, 1830] days post-HT. The primary indications for BTC were elevated pre-formed donor-specific antibodies in highly sensitized patients (66.6%) and renal sparing (23.8%), in conjunction with reduced calcineurin inhibitor dosage. Only one (4.8%) patient encountered rejection within a year of starting BTC. Graft function by echocardiography remained stable at 6 and 12 months posttreatment. An improvement was observed in serum creatinine levels (76.2% of patients), decreasing from a median of 1.58 to 1.45 (IQR [1.0-2.1] to [1.1-1.9]) over 12 months (p=.054). eGFR improved at 3 and 6 months compared with 3 months pre- BTC levels; however, this was not statistically significant (p=.24). Treatment discontinuation occurred in seven patients (33.3%) of whom four (19%) were switched back to full dose CNI. Infections occurred in 11 patients (52.4%), leading to BTC discontinuation in 4 patients (19%). In this cohort, BTC therapy was used as alternative immunosuppression for management of highly sensitized patients or for renal sparing. BTC therapy when combined with CNI dose reduction resulted in stabilization in renal function as measured through renal surrogate markers, which did not, however, reach statistical significance. Patients on BTC maintained a low rejection rate and preserved graft function. Infections were common during BTC therapy and were associated with medication pause/discontinuation in 19% of patients. Further randomized studies are needed to assess the efficacy and safety of BTC in HT recipients.

Acute pancreatitis as a complication of acute COVID-19 in kidney transplant recipients.

Acute pancreatitis is a rare extrapulmonary manifestation of coronavirus disease 2019 (COVID-19) but its full correlation with COVID-19 infection remains unknown. To identify acute pancreatitis' occurrence, clinical presentation and outcomes in a cohort of kidney transplant recipients with acute COVID-19. A retrospective observational single-centre cohort study from a transplant centre in Croatia for all adult renal transplant recipients with a functioning kidney allograft between March 2020 and August 2022 to record cases of acute pancreatitis during acute COVID-19. Data were obtained from hospital electronic medical records. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was proven by a positive SARS-CoV-2 real-time reverse transcriptase-polymerase chain reaction on the nasopharyngeal swab. Four hundred and eight out of 1432 (28.49%) patients who received a renal allograft developed COVID-19 disease. The analyzed cohort included 321 patients (57% males). One hundred and fifty patients (46.7%) received at least one dose of the anti-SARS-CoV-2 vaccine before the infection. One hundred twenty-five (39.1%) patients required hospitalization, 141 (44.1%) developed pneumonia and four patients (1.3%) required mechanical ventilation. Treatment included immunosuppression modification in 233 patients (77.1%) and remdesivir in 53 patients (16.6%), besides the other supportive measures. In the study cohort, only one transplant recipient (0.3%) developed acute pancreatitis during acute COVID-19, presenting with abdominal pain and significantly elevated pancreatic enzymes. She survived without complications with a stable kidney allograft function. Although rare, acute pancreatitis may complicate the course of acute COVID-19 in kidney transplant recipients. The mechanism of injury to the pancreas and its correlation with the severity of the COVID-19 infection in kidney transplant recipients warrants further research.

Distinct Changes in Gut Microbiota of Patients With Kidney Graft Rejection.

Kidney graft rejection still represents the major cause of graft loss in kidney transplant recipients. Of growing interest is the bidirectional relationship between gut microbiome and immune system suggesting that gut microbiota can affect allograft outcome. In this cross-sectional case-control study, we characterized the gut microbial profile of adult renal transplant recipients with and without graft rejection to define a cohort-specific microbial fingerprint through 16S ribosomal RNA gene sequencing. We used very strict inclusion and exclusion criteria to address confounder of microbiota composition. Different relative abundances in several gut microbial taxa were detectable in control patients compared with patients with kidney allograft rejection. Alpha diversity was lower in the rejection group and beta diversity revealed dissimilarity between patients with and without kidney graft rejection (P < 0.01). When the rejection group was stratified according to different types of allograft rejection, major changes were identified between patients with chronic T-cellular-mediated rejection and controls. Changes in alpha diversity within the gut microbiome were related to the probability of chronic T-cellular-mediated rejection (P < 0.05). Kidney transplant patients without rejection showed significant enrichment of rather anti-inflammatory taxa whereas in the rejection group bacteria well known for their role in chronic inflammation were increased. For example, amplicon sequence variant (ASV) 362 belonging to the genus Bacteroides and ASV 312 belonging to Tannerellaceae were enriched in no rejection (P < 0.001 and P < 0.01), whereas ASV 365 was enriched in patients with allograft rejection (P = 0.04). Looking at metagenomic functions, a higher abundance of genes coding for enzymes involved in bacterial multidrug resistance and processing of short-chain fatty acids was found in patients without rejection but an increase in enzymes involved in nicotinamide adenine dinucleotide phosphate production was seen in patients with allograft rejection. A distinct microbial fingerprint of patients with allograft rejection might serve as noninvasive biomarker in the future.

One-year Body Mass Index Change in Adult Renal Transplant Recipients and Its Relationship with Glomerular Filtration Rate and Creatinine Level: A Retrospective Study

One-year Body Mass Index Change in Adult Renal Transplant Recipients and Its Relationship with Glomerular Filtration Rate and Creatinine Level: A Retrospective Study

Sarcopenia, an overlooked diagnosis inkidney transplant recipients.

Most studies of sarcopenia in renal transplant recipients (RTRs) have been hampered by a lack of standardization in the definitions of sarcopenia. In this study, we aimed to investigate the prevalence of sarcopenia and the associated factors in RTRs using the recently proposed criteria of the European Working Group on Sarcopenia in Older People 2018 (EWGSOP2), which included a standardized definition of sarcopenia. We examined 93 consecutive adult RTRs, 46 chronic kidney disease patients, and 46 healthy controls. We assessed the muscle strength with a hand grip test using a dynamometer and with a chair stand test. We used bioimpedance analysis to estimate appendicular skeletal mass using the Sergi formula. Finally, we conducted a 2-minute walking test to assess endurance. Sarcopenia and probable sarcopenia were determined according to the revised criteria of the EWGSOP2. Probable sarcopenia was found in 29 RTR patients (31.2%), of them 14 (15.1%) were diagnosed with sarcopenia. Multivariate logistic regression analysis showed that presence of diabetes mellitus, increased uric acid level, and statin use were risk factors for probable sarcopenia. On the other hand, longer dialysis vintage was a risk factor for sarcopenia in RTRs. We found that probable sarcopenia and sarcopenia were highly prevalent in our relatively young RTRs. We recommend active screening for the presence of sarcopenia in RTRs, especially in the cadaveric ones. Furthermore, caution seems warranted regarding the myopathic side effects in RTRs who use statins.

Humoral and Cellular Immunity Are Significantly Affected in Renal Transplant Recipients, following Vaccination with BNT162b2.

Renal transplant recipients (RTRs) tend to mount weaker immune responses to vaccinations, including vaccines against the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Humoral immunity was assessed using anti-receptor binding domain (RBD) and neutralizing antibodies (NAb) serum levels measured by ELISA, and cellular immunity was assessed using T-, B-, NK, natural killer-like T (NKT)-cell subpopulations, and monocytes measured by flow cytometry, and also specific T-cell immunity, at predefined time points after BNT162b2 vaccination, in 57 adult RTRs. Administration of three booster doses was necessary to achieve anti-RBD and NAb protective levels in almost all patients (92.98%). Ab production, at several time points, was positively correlated with the corresponding renal function and inversely correlated with hemodialysis vintage (HDV) and treatment with mycophenolic acid (MPA). A gradual rise in several cell subpopulations, including total lymphocytes (p = 0.026), memory B cells (p = 0.028), activated CD4 (p = 0.005), and CD8 cells (p = 0.001), was observed even after the third vaccination dose, while a significant reduction in CD3+PD1+ (p = 0.002), NKT (p = 0.011), and activated NKT cells (p = 0.034) was noted during the same time interval. Moreover, SARS-CoV-2-specific T-cells were present in 41% of the patients who were unable to develop Nabs, and their positivity rates four months after the second dose were in inverse correlation with monocytes (p = 0.045) and NKT cells (p = 0.01). SARS-CoV-2-specific T-cell responses preceded the humoral ones, while two booster doses were needed for this group of immunocompromised patients to mount a protective immune response.

Prospective cohort study of Torque Teno Virus (TTV) viral load kinetics and the association with graft rejection in renal transplant patients.

Graft survival is mainly determined by rejections and infectious complications in transplant recipients. Torque Teno Virus (TTV), a nonpathogenic and ubiquitous single-stranded DNA virus, has been proposed as a biomarker of the immune status in transplant patients. This study aimed to determine the correlation between a Home-Brew TTV PCR and R-GENE®PCR; the TTV viral load kinetics in renal transplant recipients and the association with graft rejection. Prospective cohort study on 107 adult renal transplant recipients. TTV viral load was determined in 746 plasma samples collected before and after renal transplantation by a Home-Brew PCR and a commercial PCR (R-GENE®PCR). Associations of TTV viral load with graft rejections were analyzed. Agreement of both PCR assays was 93.2% and Pearson correlation coefficient was r: 0.902 (95%CI: 0.8881-0.9149, p<0.0001). TTV viral load kinetics showed an initial gradual increase reaching a peak at 3 months. This highest value was followed by a slight decrease, reaching a plateau significantly higher than the initial baseline at 6 months (p<0.0001). Between (181-270) days post-transplantation, TTV median viral load in patients with graft rejection was significantly lower, 3.59 Log10 copies/mL (by Home-Brew PCR) and 3.10 Log10 copies/mL (by R-GENE®PCR) compared to patients without graft rejection (6.14 and 5.96 Log10 copies/mL, respectively). Significantly lower TTV viral load was observed in patients with renal rejection occurring at a median of 243 days post-transplantation. Given the dynamic behavior of TTV viral load post-transplantation, cut-off values for risk stratification to predict rejection might be determined in relation to the post-transplant period.

COVID-19 Vaccine Seroresponse Based on The Timing of The Primary Series; Pre- versus Post-Renal Transplantation.

Coronavirus disease 2019 (COVID-19) poses a serious risk to patients with chronic kidney disease (CKD) and renal transplant. While COVID-19 vaccination is recommended before transplant, there are limited data comparing vaccine timing. Our aim is to evaluate serological responses to COVID-19 vaccines pre- and post-renal transplant and the durability of antibody levels. We retrospectively evaluated the antibody response of adult renal transplant recipients who had received at least a primary series of the COVID-19 vaccine. The patients were divided into two groups based on the timing; pre- or post-transplant. Antibody titer levels were evaluated at least 4weeks after vaccination for each group. Titer durability was assessed by calculating the median titer level of individuals. A total of 139 patients were identified between January 2019 and April 2022. Twenty-nine patients were excluded because of previous COVID-19 infection, and 15 patients were excluded each for insufficient vaccine doses and lack of titer data. Forty patients were included for the pre-transplant group and 40 for post-transplant. The number of pre-transplant patients who developed antibodies (39 patients, 97.5%) was significantly greater than the number of post-transplant patients (21 patients, 52.5%) with p<.01. The median post-vaccination titer levels were significantly greater in the pre-transplant group up to 5months after vaccination (p<.05). The pre-transplant group's titers seemed sustained even after renal transplantation. Vaccinating renal transplant patients before transplant results in increased achievement of seroresponse, higher levels of antibody titers, and sustained titers following transplant. Larger and prospective studies are warranted to confirm the findings.

Lymphoproliferative disorders after renal transplantation along 2 decades: a large longitudinal study of 21.546 recipients

IntroductionPost transplant lymphoproliferative disorders (PTLD) are heterogeneous lymphoid proliferations in recipients of solid organs which seem to be related to Epstein Barr Virus (EBV). The use of antilymphocyte antibodies, EBV seronegativity in the recipient,acute rejection and CMV infection have been identified as classical risk factors. Material y methodsWe have studied in a retrospective observational study, the incidence of PTLD in a period of 22 years, its relationship with EBV, presence of classical risk factors and outcome in 21546 simple adult renal transplant recipients from cadaveric and living donors, transplanted in 21 hospitals from 1990 to 2009. ResultsA total of 275 recipients developed PTLD (1,2%),195 males (70,9%), 80 females (29,1%) aged 59.2 (p25 44.7 p75 68)years. Two hundred forty-five (89.0%) were 1st transplant recipients and 269 (97,8%) from cadaveric donors. EBV in the tissue was reported in 94 out of the 155 studied recipients (60.6%) and 86.0% of the proliferations were due to B lymphocytes. PTLD median appearance after transplant were 42.months (p25, 75, 12, 77, 5). One hundred eighty-eight recipients out of 275 patients (68.3%) had any classical risk factor and the use of antilymphocyte antibodies was the most frequent.During the follow-up, 172 patients died (62,5%) and 103 (37,5%) had a complete remission. The main cause of death was PTLD progression (n = 91, 52,9%), followed by sepsis (n = 24, 13,9%). The follow-up period post-transplant of the recipients was between 3 and 22 years.The incidence was 0,14% during the first year post-trasplant and 0.98% the cumulative incidence at 10 years.Patient survival after diagnosis was 51%, 44% and 39% after 1, 2 and 5 years, respectively. Finally, overall graft survival was 48%, 39% and 33% at the same periods. ConclusionPTLD has a low incidence in renal transplant recipients. Most of the proliferations are due to B lymphocytes and seem to have a close relationship with EBV. PTLD can develop in the absence of classical risk factors. The prognosis is poor, mainly due to PTLD progression, but the survivors can even maintain their grafts.

Evaluation of Eculizumab Use in Renal Transplant Recipients.

Introduction: Eculizumab is a monoclonal antibody that binds to complement protein C5, inhibiting complement-mediated thrombotic microangiopathy. It is approved for several indications including atypical hemolytic uremic syndrome. Additionally, eculizumab is used off-label for antibody-mediated rejection and C3 glomerulopathy in renal transplant recipients. Due to limited data available, the purpose of this study was to describe the use of eculizumab treatment in renal transplant recipients. Design: This retrospective single-center study evaluated the safety and efficacy of eculizumab for on- and off-label indications in renal transplant recipients. Adult renal transplant recipients receiving at least 1 dose of eculizumab posttransplant between October 2018 and September 2021 were included. The primary outcome evaluated was graft failure in patients treated with eculizumab. Results: Forty-seven patients were included in analysis. The median age at eculizumab initiation was 51 years [IQR 38-60], with 55% being female. Indications for eculizumab included atypical hemolytic uremic syndrome/thrombotic microangiopathy (63.8%), antibody-mediated rejection (27.7%), C3 glomerulopathy (4.3%), and other (4.3%). Graft failure occurred in 10 patients (21.3%) with a median of 2.4 weeks [IQR 0.5-23.3] from transplant to graft failure. At last follow-up (median 56.1 weeks), 44 (93.6%) patients were alive. After eculizumab initiation, renal function improved at 1 week, 1 month, and last follow-up. Conclusion: Eculizumab treatment demonstrated a benefit on graft and patient survival compared to reported incidence in thrombotic microangiopathy and antibody-mediated rejection. Due to the small sample size and retrospective design, further research is warranted to confirm these results.

Optimal Glomerular Filtration Rate Equations for Various Age Groups, Disease Conditions and Ethnicities in Asia: A Systematic Review.

(1) Background: The performance of estimated glomerular filtration rate (eGFR) equations in the Asian population has been widely questioned. The primary objective of this study was to gather evidence regarding optimal GFR equations in Asia for various age groups, disease conditions, and ethnicities. The secondary objective was to see whether the equations based on the combination of creatinine and cystatin C biomarkers if employed are satisfactory across different age groups and disease conditions in various ethnicities in Asia compared to those based on either of the single biomarkers. (2) Methods: Validation studies that had both creatinine and cystatin C-based equations either alone or in combination, validated in specific disease conditions, and those which compared the performance of these equations with exogenous markers were eligible only. The bias, precision, and 30% accuracy (P30) of each equation were recorded accordingly. (3) Results: Twenty-one studies consisting of 11,371 participants were included and 54 equations were extracted. The bias, precision, and P30 accuracies of the equations ranged from -14.54 to 9.96 mL/min/1.73 m2, 1.61 to 59.85 mL/min/1.73 m2, and 4.7% to 96.10%. The highest values of P30 accuracies were found for the JSN-CKDI equation (96.10%) in Chinese adult renal transplant recipients, for the BIS-2 equation (94.5%) in Chinese elderly CKD patients, and Filler equation (93.70%) also in Chinese adult renal transplant recipients. (4) Conclusions: Optimal equations were identified accordingly and it was proven that combination biomarker equations are more precise and accurate in most of the age groups and disease conditions. These can be considered equations of choice for the specific age groups, disease conditions, and ethnicities within Asia.

The Educational Needs of Adolescent and Young Adult Renal Transplant Recipients-A Scoping Review.

Renal transplantation is the gold-standard treatment for adolescents and young adults with end-stage renal disease. Despite enjoying excellent short-term outcomes, they suffer the worst rates of premature transplant function loss. Health behaviors: such as lack of adherence to immunosuppressive medications, are felt to be the major contributory factor. Understanding the educational needs of young renal transplant recipients allows healthcare practitioners to better support patients in managing their chronic disease. The aim of this scoping review was to understand what is known about their educational needs. A scoping review methodology was followed. Following an online search, study titles, and abstracts were screened for eligibility, followed by full-text assessment and data extraction. Data were qualitatively analyzed using thematic analysis. A total of 29 studies were included in the scoping review. In young people who struggled with self-management, three themes were identified (1) the Needs of the disrupted youth, (2) the Needs of the disorganized youth (3) the Needs of the distressed youth. There was a paucity of research to identify the protective factors that enable young recipients to successfully manage their health. This review outlines current knowledge of the patient education needs of young transplant recipients. It also highlights remaining research gaps that will need to be addressed with future research.

Envarsus XR® pharmacokinetics in adolescents post-kidney transplantation - A pilot study.

Envarsus XR® (LCPT), a once daily dosage formulation of tacrolimus, is an FDA-approved medication in adult renal transplant recipients (RTRs). There are limited data on its pharmacokinetics (PK) in adolescent RTRs. We report here the PK profile of LCPT in adolescent RTRs. The dose of LCPT was determined using a dose conversion ratio targeting 0.7 relative to the total daily immediate-release tacrolimus (IR-Tac) dose. On day 7 after converting to LCPT, patients had an abbreviated PK assessment with sampling at: 0 h (pre-dose), 8-, and 12-h post-dose. The PK data analysis was performed using Bayesian estimators. Our results were compared to those of published adult PK data for LCPT and pediatric PK data for IR-Tac and extended release tacrolimus (ER-Tac) formulation (Advagraf). PK data from three adolescent patients on LCPT were evaluated. The mean (±SD) area under the time-concentration curve (AUC) was 240 (±20.22) h*ng/mL. The mean Tmax was 9.01 ± 2.12h, and the % fluctuation was 77.71 ± 3.96%. The AUC, Tmax , and % fluctuation were similar to reported results in adult patients taking LCPT. The AUC was higher and the Tmax was longer than what has been reported in pediatric patients taking IR-Tac and ER-Tac. In addition, the LCPT group showed a lower % fluctuation than patients receiving ER-Tac. The PK evaluation of LCPT in adolescent RTRs showed similar results to adults. Adolescents taking LCPT had a higher AUC, a more attenuated Tmax , and a lower fluctuation than that seen with ER-Tac in pediatrics.