Pediatric Renal Transplant Research Articles

Use of a donor-derived cell-free DNA assay to monitor treatment response in pediatric renal transplant recipients with allograft rejection.

Detection of donor-derived cell-free DNA (dd-cfDNA) reliably identifies allograft rejection in pediatric and adult kidney transplant (KT) recipients. Here, we evaluate the utility of dd-cfDNA for monitoring response to treatment among pediatric renal transplant recipients suffering graft rejection. 58 pediatric transplant recipients were enrolled between April 2018 and March 2020 and underwent initial dd-cfDNA testing to monitor for rejection. Allograft biopsy was performed for dd-cfDNA scores >1.0%. Patients with histologically proven rejection formed the study cohort and underwent appropriate treatment. Results of dd-cfDNA, serum creatinine (SCr), biopsy findings, and treatment outcomes were evaluated. Standard statistical analyses were applied. Nineteen of 58 (31%) patients had dd-cfDNA score >1.0%, of which 18 (94.7%) had biopsy-proven rejection. Median dd-cfDNA value was 1.90% (interquartile range 1.43%-3.23%), and biopsy results showed 11 patients (61.1%) with antibody-mediated rejection (AMR), 2 patients (11.1%) with T-cell mediated rejection (TCMR), and 5 patients (27.7%) with mixed AMR/TCMR. SCr at time of biopsy was 1.28±1.09mg/dl. Following treatment, dd-cfDNA scores decreased for all types of rejection but still remained >1.0% in both AMR (1.50% [0.90%-3.10%]) and mixed (1.40% [0.95%-4.15%]) groups. Repeat dd-cfDNA values were <1.0% for patients with TCMR (0.20%-0.28%). SCr showed minimal change from pre-treatment levels regardless of rejection subtype. Patients with TCMR may be reliably followed by dd-cfDNA; however, it remains unclear whether persistently elevated dd-cfDNA levels in AMR is a reflection of ongoing subclinical rejection or an inherent limitation of the assay's utility.

Hospitalization following pediatric kidney transplantation: An international comparison among a Canadian pediatric transplant center, North American Pediatric Renal Trials and Collaborative Studies, and Cooperative European Pediatric Renal Transplant Initiative registry data

There are several databases across the world that collect pediatric KT data. We compare the hospitalization outcomes for pediatric KT recipients from a large Canadian transplant center (SickKids database; The Hospital for Sick Children Kidney Transplantation Institutional Database), United States (NAPRTCS), and Europe (CERTAIN registry). An institutional retrospective review of KT was performed between 2000 and 2015. Baseline characteristics, duration of initial hospitalization/readmission at 1-5 and 6- to 11-month posttransplant, and 1-year graft survival data were collected. Corresponding data from the NAPRTCS 2014 Annual Transplant Report and CERTAIN registry were compared. Posttransplant, patients from NAPRTCS had the shortest duration of hospitalization within the first month (10.4days, SE 0.2), followed by SickKids (20.3days, SE 0.7) and CERTAIN (25.5days, SE 0.7). For both living and deceased donor populations, patients from SickKids were most likely to be hospitalized at 1- to 5-month posttransplant (82.4% [89/108]; 72.1% [98/136]), followed by Europe (52.1% [198/380]; 61.6% [501/813]) and United States (45.4% [2379/5241]; 51.4% [2517/4896]). Patients from Europe were most likely to be hospitalized at 6- to 12-month posttransplant (42.1% [160/380]; 51.7% [420/813]), followed by SickKids (35.2% [38/108]; 37.5% [51/136]) and United States (28.3% [1387/4901]; 31.6% [1411/4465]). Across all databases, the most commonly addressed issues during readmissions were infectious complications. The differences observed in this investigation may reflect the local reimbursement models, resources for outpatient management, and practice variations across a large Canadian transplant center, United States, and European countries.

COVID-19 Infections in Pediatric Renal Transplant Recipients.

The new coronavirus SARS-CoV-2 (COVID-19) first appeared in Turkey in March 2020, spread rapidly, and caused many deaths. Although COVID-19 is mostly a respiratory disease, it can cause kidney and multiorgan failure in some cases. We believe that by sharing information about the course and effects of COVID-19 infection in kidney transplant recipients receiving long-term immunosuppressive therapy our understanding will improve. Between March 2020 and October 2021, COVID-19 was researched in kidney transplant recipients under the age of 20 years who were followed at the Başkent University Transplantation Center. We documented the clinical characteristics and prognosis of pediatric kidney transplant recipients with COVID-19 disease. Our study group included 23 patients with COVID-19 infection from 215 pediatric kidney transplant recipients. The mean age of the patients was 14.6 ± 4.7 years; there were 9 female patients. The mean follow-up time posttransplant was 62.3 ± 43.2 months. In 13 patients (56.5%), fever was the most frequent symptom. Most patients (n = 18, 78%) had minor symptoms and recovered completely after receiving supportive treatment. Four patients (17%) required hospitalization. One was diagnosed with COVID-19 infection 1 week after being treated with rituximab for acute antibody-mediated rejection. That patient died because of significant lung disease and multiorgan failure. Despite the fact that most of our pediatric transplant recipients had mild symptoms of COVID-19, we believe that particular caution should be observed in patients who have recently received intensive immunosuppressive medications. As a result of potential new vaccines, national immunization programs, and the emergence of novel virus strains, the clinical picture may change in the future. We believe that, as information sharing increases, we will learn more about COVID-19 in renal transplant recipients.

Cystinosis in Pediatric Renal Transplant Recipients: A Case-Control Study From Kuwait.

Cystinosis is the most frequent cause of the inherited renal Fanconi syndrome and is also potentially treatable. In this study, we have reported our single-center experience of the longterm outcomes of kidney transplant in patients with cystinosis. Pediatric patients with cystinosis (n = 17) were compared with a matched control group without cystinosis (n = 126). The 2 groups were compared with regard to demographic data, posttransplant complications, and graft and patient outcomes. Most patients with cystinosis were male teenagers (52.9%) with comparable mean age (12.4 ± 4.1 vs 14 ± 3.1 years) versus the group without cystinosis. The 2 study groups were comparable with regard to type of dialysis, type of donor, blood group, and pretransplant comorbidities (P > .05). Patients with cystinosis received significantly more potent induction therapy (P < 0.05), but both groups were maintained on comparable immunosuppressive regimens (mostly tacrolimus based) (P > .05). Most grafts in both groups displayed immediate graft function. The percentage of patients with cystinosis with primary graft function was significantly higher than the percentage of those patients without cystinosis who had primary graft function (P = .024); this was associated with a relatively lower baseline creatinine level, although this was not significant (P > .05). Posttransplant complications, especially posttransplant diabetes, cytomegalovirus viremia, or BK nephropathy, were comparable (P > .05). Moreover, patient and graft survival rates were similar in the 2 groups (P > .05). Under standard immunosuppression, renal transplant and cysteamine therapy were safe with good long-term outcomes in patients with cystinosis. Studies that can include more patients and that have longer follow-up are needed to better understand the nature of this genetic disease and to discover the best treatment options.

Primary Focal Segmental Glomerulosclerosis Recurrence After Pediatric Renal Transplantation.

Focal segmental glomerulosclerosis recurrence after renal transplant occurs frequently in pediatric patients and is associated with poor graft survival when patients reach adulthood. We investigated recurrence rates, recurrence risk factors, management strategies, and long-term graft function among pediatric renal transplant recipients with focal segmental glomerulosclerosis as primary disease. We retrospectively evaluated medical records of 34 pediatric patients with primary focal segmental glomerulosclerosis who had undergone renal transplant between 2004 and 2019 at our center. Focal segmental glomerulosclerosis recurrence was diagnosed by the presence of nephrotic range proteinuria after transplant and confirmed by graft biopsy. Preoperative prophylactic plasma exchange was administered to pediatric renal transplant recipients with primary focal segmental glomerulosclerosis. Plasma exchange was also used to treat focal segmental glomerulosclerosis recurrence, with rituximab added if the patient did not respond to plasma exchange. All patients (male-to-female ratio of 19:15) in our group underwent renal transplant. Mean patient age at the time of transplant was 12.72 ± 5.46 years. Twenty-nine patients received living- related donor allografts (85.3%) and 5 received organs from deceased donors (14.7%). We identified focal segmental glomerulosclerosis recurrence in 5 recipients (14.7%). Time from focal segmental glomerulosclerosis diagnosis to end-stage renal disease and duration of dialysis were shorter in the recurrence group than in the nonrecurrence group (48.4 months [range, 2-90 mo] vs 65.1 months [range, 8-123 mo] and 1.41 ± 0.82 vs 3.18 ± 1.88 years, respectively; P < .05). Donor type and transplant age were similar in both groups. Of those with recurrence who had received plasma exchange and rituximab, 3 patients (75%) had complete remission and 1 patient (25%) had partial remission. Prophylactic plasma exchange and the combined plasma exchange-rituximab regimen for treatment of focal segmental glomerulosclerosis recurrence resulted in low recurrence and good remission rates in our pediatric cohort.

Safe Renal Transplantation to the Extraperitoneal Cavity in Children Weighing Less Than 15 kg

Pediatric renal transplantation is associated with various surgical complications due to the complexity of the technique and the often-fragile condition of patients with end-stage renal disease. We evaluated the surgical complications associated with renal transplantation via the extraperitoneal approach in pediatric recipients. This retrospective study enrolled 280 patients younger than 16 years old who underwent renal transplantation via the extraperitoneal approach: 216 patients underwent transplant placement in the iliac fossa like in adults, and 64 underwent transplant placement in the distal part of the original renal lower pole (the extraperitoneal cavity). On the basis of the Clavien-Dindo classification, 30 patients (10.7%) showed grade 2 complications and 12 patients (4.3%) showed grade 3 or higher complications. None of the patients showed gastrointestinal complications. In a Cox regression analysis, grade 2 or higher complications were significantly associated with weight less than 15 kg (P=.027) and operative times longer than 245 minutes (P=.029). Among the 49 patients weighing less than 15 kg with an allograft placed in a distal portion of the original renal lower pole, only 3 patients (6.1%) developed surgical complications. Thus, allograft placement in the extraperitoneal cavity can be performed safely in children weighing less than 15 kg.

A0791 - The use of Tutoplast® fascia lata assisting fascial closure of pediatric renal transplant recipients with donor size discrepancy

A0791 - The use of Tutoplast® fascia lata assisting fascial closure of pediatric renal transplant recipients with donor size discrepancy

Pediatric renal transplantation in Southern Saudi Arabia: A single-center retrospective study

Background: The outcome of pediatric renal transplantation (RT) has improved over the last decades. Aims and Objectives: To study the outcome of pediatric transplantation at our center including patient and graft survival, acute rejection, and surgical complications. Materials and Methods: A retrospective review of pediatric RT outcomes at the only transplant center in Southern Saudi Arabia. Results: between 11/2013 till 03/2020, 63 RT were performed in pediatric recipients 2 through 18 years of age (mean 11.7 ± 3.75) including 43 patients (68.2%) aged 14 and younger. Average BMI-height-age-z were 66.05 ± 6.65 percentile. 49 patients (77.7%) received kidneys from adult living donors (LD), 8(16%) were unrelated donors.41% had preemptive KT. The commonest known etiologies of ESRD were focal segmental glomerulosclerosis, Post Urethral valve, and dysplastic kidney (9.5% each). Thymoglobulin and Basiliximab were used as induction therapy in 37 (58.7%) and 26 (41.3%) patients respectively. With a mean follow-up of 80 months, 1-year and 5-year graft survival rates for LD and deceased donors were (97.2%, 86.4%) and (96.4%, 76%) respectively. 1-year and 5-year patients survival rates were 100%. Conclusions: pediatric renal transplantation outcome at our center, despite the low volume of cases, is encouraging.

Treatment of Acute Antibody-Mediated Rejection in Children Post-Kidney Transplantation: A Single Center’s Experience

Introduction Acute antibody-mediated rejection (aAMR) can negatively impact renal allografts outcomes. To date, there has not been a consistent therapeutic approach to manage aAMR. The aim of the study is to evaluate the tolerance and efficacy of an institutional protocol of methylprednisolone, intravenous gamma globulin (IVIG), rituximab, and bortezomib used to treat aAMR in pediatric renal transplant recipients (pRTRs). Methods A retrospective chart review was performed on 10 pediatric renal transplant recipients (pRTRs) who were diagnosed with aAMR on a renal biopsy performed between January 2014 and November 2015. Results Over the study period, 9.5% of pRTRs had aAMR. Sixty percent of whom had concurrent acute cellular rejection (ACR). Renal allografts survival was 100% during the the first post-aAMR. At the time of diagnosis of aAMR, estimated glomerular filtration rate (eGFR) had decreased by 42% (mean at baseline eGFR=67.2±19.5 mL/min/1.73 m2 vs mean at aAMR eGFR=38.9±14.2 mL/min/1.73 m2; p=0.002). At 1-year post rejection, eGFR had increased by 26% as compared eGFR at the time of rejection (mean eGFR=49.0±13.2 mL/min/1.73 m2; p=0.006). Immuno-dominant donor-specific anti-HLA antibody titers (iDSAs) class I and class II decreased by 69% and 15% at 6-month follow-up visit. No serious opportunistic infections nor malignancy were reported in our subjects. Conclusion Our study suggests that our protocol improved kidney function with 100% graft survival at 1-year post aAMR episode. The percentage decline in iDSAs class I titers was more significant than class II. Furthermore, our treatment protocol was well-tolerated with no life threatening complications.

Emergency Department Utilization and Serious Bacterial Infection Rates in Children With Renal Transplants.

Emergency department (ED) visits by children with solid organ transplants have increased significantly. Our objectives were to describe the common complaints, diagnosis, types, and rates of serious bacterial infection (SBI) in children with renal transplant (RT) who present to the hospital. We conducted a retrospective study from 2012 to 2016 of RT children up to 18 years who presented to the ED or were directly admitted. We excluded patients who presented for a procedure. We collected demographics, transplant type, immunosuppressive data, chief complaints, diagnostic testing with results, interventions performed, and final diagnosis. We analyzed 131 visits in 29 patients during the study period. Most common chief complaints were infectious (34.4%) and gastrointestinal (26%). Infection was proven in 42.0% of visits with only 3.1% being organ rejection. Serious bacterial infection was diagnosed in 34 visits (26.0%) with urinary tract infection (UTI) being the most common (20.6%). Of the 33 visits for fever, SBI occurred in 16 (48.5%) patients with the most common SBI being UTI 10 (30.3%). Bacteremia occurred in 1 patient and hypotension in 4 patients. Antibiotic administration was the most common intervention performed (78; 59.5%). Significant interventions were uncommon (2 patients). Logistic regression revealed no factors to be associated with SBI. Our cohort of children with RT presented most commonly with infections to the hospital with UTI being the most common SBI. Bacteremia and significant interventions were rare. Future studies are needed to identify subgroups of low-risk pediatric RT patients who can possibly be safely discharged home from the ED.

Follow-Up of Blood Pressure, Arterial Stiffness, and GFR in Pediatric Kidney Transplant Recipients.

Pediatric renal transplant recipients (RTx) were studied for longitudinal changes in blood pressure (BP), arterial stiffness by pulse wave velocity (PWV), and graft function.Patients and Methods: 52 RTx patients (22 males) were included; office BP (OBP) and 24 h BP monitoring (ABPM) as well as PWV were assessed together with glycemic and lipid parameters and glomerular filtration rate (GFR) at 2.4[1.0–4.7] (T1) and 9.3[6.3–11.8] years (T2) after transplantation (median [range]).Results: Hypertension was present in 67 and 75% of patients at T1 and T2, respectively. Controlled hypertension was documented in 37 and 44% by OBP and 40 and 43% by ABPM. Nocturnal hypertension was present in 35 and 30% at T1 and T2; 24 and 32% of the patients had masked hypertension, while white coat hypertension was present in 16 and 21% at T1 and T2, respectively. Blood pressure by ABPM correlated significantly with GFR and PWV at T2, while PWV also correlated significantly with T2 cholesterol levels. Patients with uncontrolled hypertension by ABPM had a significant decrease in GFR, although not significant with OBP. Anemia and increased HOMAi were present in ~20% of patients at T1 and T2.Conclusion: Pediatric RTx patients harbor risk factors that may affect their cardiovascular health. While we were unable to predict the evolution of renal function based on PWV and ABPM at T1, these risk factors correlated closely with GFR at follow-up suggesting that control of hypertension may have an impact on the evolution of GFR.

Pediatric renal transplantation; 10 years experience.

Although renal transplantation (RT) is the first treatment option for children with end-stage renal failure, the number of transplanted chil- dren remains low compared to adults. Experience of the individual pediatric transplant center is very important in the prognosis of pediatric transplant recipients. In this study, our pediatric RT experience was presented. We retrospectively analyzed the data of 27 patients who had RT in our clinic between April 2009 and April 2019. Fifteen of the patients were males, and mean age of all patients was 12.36 ± 4.18 years (range 4-17 years). The most frequent etiology for end- stage renal disease (ESRD) was vesicourethral reflux. Eighteen (66.7%) of the transplanted kidneys came from cadaveric donors and 9 (33.3%) from live donors. One patient had preemptive RT and one patient had a re-RT. Twenty-two patients were on peritoneal dialysis program and four patients were on hemodialysis program. Mean dialysis time before transplantation was 29 (3-104) months. Bleeding was the most common surgical complication. Delayed graft function developed in four patients, and all of their grafts were from cadaveric donors. Rejection developed in 12 of our patients, graft loss was observed in only four of them. Considering all patients, graft survival rates were 100% in the 1st and 3rd years, and 92% in the 5th year. Pediatric RT program is difficult to establish, maintain and develop. Complications after transplantation are not uncommon; therefore, early detection and appropriate management are needed. Strategies are still needed to increase post-transplant success.

EBV, CMV, and BK viral infections in pediatric kidney transplantation: Frequency, risk factors, treatment, and outcomes.

Improved short- and long-term outcomes of kidney transplantation have been achieved over the past decades due to improved immunosuppression. This may have increased the risk for infections and, particularly, for the viral infections: cytomegalovirus (CMV), Epstein-Barr virus (EBV), and polyoma BK virus (BKV). A retrospective review of viremic CMV, EBV, and BKV infections in pediatric renal transplant recipients treated and followed by a national referral center over a 10-year period. Sixty-seven patients (68% males) received 68kidney grafts (62% from living donors) during the study period; the mean follow-up period was 5.2±2.4years. Twenty-seven viremic episodes were documented (CMV: 13, EBV: 6, BKV: 8) in 24 patients (35.2%). The median time (interquartile range) to viremia post-transplant was 11 (4-38) months. The viral infection rate was significantly higher in the years 2014-2015 than in previous years (61% vs. 29%, p=.017). Compared to patients who did not develop viremia, patients with viremias were younger at the time of transplantation, were more likely to receive thymoglobulin induction pre-transplant and to develop an acute rejection. Multiple logistic regression modeling identified transplant year and recipient's age as significant risk factors for viremia. Graft outcome and eGFR at the last follow-up was similar between patients who did and did not develop viremia. Viral infections continue to be a major cause of morbidity in pediatric kidney transplant recipients. However, with close monitoring and prompt intervention, patient and renal outcomes remain favorable.

Short-term Outcomes of Pediatric Renal Transplantation in Nigeria; A Single-Center Experience :

Introduction This case-series describes a short term follow-up of Renal Transplantation (RT) in three children at the Zenith Medical and Kidney Centre (ZMKC), Abuja, Nigeria. Methods The immediate allograft function (IAF) and recipients’ survival at 6-24 months of follow-up from January 2018 to January 2020 were described. RT involved the use of basiliximab and thymoglobulin for induction therapy and oral prednisolone, tacrolimus and mycophenolate mofetil for maintenance immunosuppressive therapy. Results Recipients were 9 years to 17 years (average age of 12 years) of age. Primary steroid-resistant focal segmental glomerulosclerosis nephrotic syndrome, congenital posterior urethral stricture and lupus nephritis were the causes of the end-stage kidney diseases. The IAF was excellent in all the cases. All the 3 children are alive with good allograft functions at 6-24 months of the follow-up period. Conclusion This case series shows that a successful paediatric RT programme is feasible in a resource-constrained setting like Nigeria

Maternal versus paternal living kidney transplant donation is associated with lower rejection in young pediatric recipients: A Collaborative Transplant Study report.

Approximately 1700 children per year with end-stage kidney disease undergo kidney transplantation in Europe and the United States of America; 30%-50% are living donor kidney transplantations. There may be immunological differences between paternal and maternal donors due to transplacental exchange of cells between the mother and fetus during pregnancy leading to microchimerism. We investigated whether the outcome of living-related kidney transplantation in young children is different after maternal compared with paternal organ donation. Using the international Collaborative Transplant Study (CTS) database, we analyzed epidemiological data of 7247 children and adolescents aged <18years who had received a kidney transplant from either mother or father. Risk of treated rejection episodes and death-censored graft failure were computed using the Kaplan-Meier method and multivariable Cox regression. In the recipient age group 1-4years, the rate of treated rejection episodes in recipients of kidneys from maternal donors (N=195) during the first 2years post-transplant was significantly lower (hazard ratio HR=0.47, p=.004) than in patients receiving kidneys from paternal donors (N=179). This association between donor sex and risk of treated rejections was not observed in children aged 5-9years. The 5-year death-censored graft survival in children aged 1-4years with a maternal or paternal donor was comparable. Maternal kidney donation in young pediatric renal transplant recipients is associated with an approximately 50% lower rate of treated rejection than paternal kidney donation. Whether this phenomenon is due to maternal microchimerism-induced donor-specific hyporesponsiveness must be evaluated in prospective mechanistic studies.

Subclinical Rejection and Immunosuppression in Pediatric Kidney Transplant Recipients : Single Centre Study

Background: By the time of histological confirmation of rejection is achieved, renal scarring may for treatment as a realistic option . This study aims to study the subclinical pathological graft data and to evaluate the histopathological impact of different immunosuppression protocols in pediatric renal transplant recipients. Methods: This is a case series that included twenty living donor renal transplant recipients. All included cases received the classic triple immunotherapy for at least one month post-transplantation [Steroids, calconurine inhibitors (CNI), and mycofenlolic mofetile (MMF)]. Based on their immunological risk stratification; included cases were divided into 2 groups: group (A) continued on CNI based triple therapy protocol; group (B) shifted to evirolimus /low dose CNI protocol. Surveillance biopsies were done for all cases at one and four month post-transplantation. Results: One and four month biopsies revealed subclinical rejection (including borderline changes) in 4 (20%) cases and 6 (30%) cases respectively. The number of patients received tacrolimus/MMF therapy significantly increased (p=0.02) while that of patients on everloimus/low dose CNI significantly decreased (p=0.014) due to drug modifications based on four month surveillance biopsy data. Conclusion: Subclinical rejection is not uncommon in pediatric renal graft recipients which makes surveillance biopsy might be of help. Early usage of evirolimus/low CNI protocol is associated with higher rejection rate than triple therapy.

Clinical practice guidelines standardisation of immunosuppressive and anti-infective drug regimens in UK paediatric renal transplantation: the harmonisation programme

Clinical practice guidelines standardisation of immunosuppressive and anti-infective drug regimens in UK paediatric renal transplantation: the harmonisation programme

Clinical impact of complement deposition findings on biopsies in acute rejection episodes of pediatric renal transplant patients

IntroductionRejection is the most important problem for renal graft function and survival. Complement system plays a key role in immune responses from host to graft. It was demonstrated that complement system activation is related with renal fibrosis. We evaluate clinical impact of complement deposition findings on biopsies in acute rejection episodes of pediatric renal transplant patients. MethodDemographics of the patients, graft functions, acute rejection episodes and graft loss were recorded from data files of 165 pediatric renal transplant patients. Findings of 98 renal biopsies were retrospectively evaluated. ResultsThirty three patients with kidney transplant had 44 acute rejection episodes (32 pure cellular acute rejection episodes / 1 pure humoral acute rejection episode / 11 combined acute cellular and acute humoral rejection episodes) proven by biopsy. C1q staining was positive in 7 biopsies, C3 staining in 15 biopsies and, C4d staining in 15 biopsies. 26 patients had graft fibrosis. All patients with a rejection history had a significant decrease in GFR value during follow-up. Patients who did not have fibrotic changes in first biopsy had same level of deterioration of GFR when compared with patients who had fibrotic changes in first biopsy. ConclusionWe could not demonstrate a significant relation between complement deposition and renal fibrosis, and between complement deposition and GFR values. Our data demonstrated that graft outcomes and graft loss after acute rejection episodes cannot be predicted only with complement deposition on graft or only with graft fibrosis.

A Systematic Review of Multiple Linear Regression-Based Limited Sampling Strategies for Mycophenolic Acid Area Under the Concentration–Time Curve Estimation

Background and ObjectiveOne approach of therapeutic drug monitoring in the case of mycophenolic acid (MPA) is a limited sampling strategy (LSS), which allows the evaluation of the area under the concentration–time curve (AUC) based on few concentrations. The aim of this systematic review was to review the MPA LSSs and define the most frequent time points for MPA determination in patients with different indications for mycophenolate mofetil (MMF) administration.MethodsThe literature was comprehensively searched in July 2021 using PubMed, Scopus, and Medline databases. Original articles determining multiple linear regression (MLR)-based LSSs for MPA and its free form (fMPA) were included. Studies on enteric-coated mycophenolic sodium, previously established LSS, Bayesian estimator, and different than twice a day dosing were excluded. Data were analyzed separately for (1) adult renal transplant recipients, (2) adults with other than renal transplantation indication, and (3) for pediatric patients.ResultsA total of 27, 17, and 11 studies were found for groups 1, 2, and 3, respectively, and 126 MLR-based LSS formulae (n = 120 for MPA, n = 6 for fMPA) were included in the review. Three time-point equations were the most frequent. Four MPA LSSs: 2.8401 + 5.7435 × C0 + 0.2655 × C0.5 + 1.1546 × C1 + 2.8971 × C4 for adult renal transplant recipients, 1.783 + 1.248 × C1 + 0.888 × C2 + 8.027 × C4 for adults after islet transplantation, 0.10 + 11.15 × C0 + 0.42 × C1 + 2.80 × C2 for adults after heart transplantation, and 8.217 + 3.163 × C0 + 0.994 × C1 + 1.334 × C2 + 4.183 × C4 for pediatric renal transplant recipients, plus one fMPA LSS, 34.2 + 1.12 × C1 + 1.29 × C2 + 2.28 × C4 + 3.95 × C6 for adult liver transplant recipients, seemed to be the most promising and should be validated in independent patient groups before introduction into clinical practice. The LSSs for pediatric patients were few and not fully characterized. There were only a few fMPA LSSs although fMPA is a pharmacologically active form of the drug.ConclusionsThe review includes updated MPA LSSs, e.g., for different MPA formulations (suspension, dispersible tablets), generic form, and intravenous administration for adult and pediatric patients, and emphasizes the need of individual therapeutic approaches according to MMF indication. Five MLR-based MPA LSSs might be implemented into clinical practice after evaluation in independent groups of patients. Further studies are required, e.g., to establish fMPA LSS in pediatric patients.

Abstract 35 - The Paediatric Renal Transplant Recipient: A retrospective review of the changing trends of transplantation in Ireland

Abstract 35 - The Paediatric Renal Transplant Recipient: A retrospective review of the changing trends of transplantation in Ireland