Pediatric Renal Transplant Recipients Research Articles

248.10: COVID-19 Infections in Pediatric Renal Transplant Recipients

248.10: COVID-19 Infections in Pediatric Renal Transplant Recipients

332.3: Preoperative Systemic Immune-Inflammation Index, Platelet-Lymphocyte Ratio and Neutrophil-Lymphocyte Ratio in Predicting the Delayed Graft Function in Pediatric Renal Transplant Recipients: A Single Centre Study

332.3: Preoperative Systemic Immune-Inflammation Index, Platelet-Lymphocyte Ratio and Neutrophil-Lymphocyte Ratio in Predicting the Delayed Graft Function in Pediatric Renal Transplant Recipients: A Single Centre Study

243.4: Evolution of Polyomavirus BK and JC Viral Load in Pediatric Renal Transplant Recipients

Introduction: Polyomavirus-associated nephropathy (PVAN) occurs in 5% of renal transplant recipients (RTR) and is caused by Polyomavirus BK (BKPyV) and JC (JCPyV), at a very low rate. This disease causes a progressive impairment of renal function and ultimate graft loss. Monitoring of viral load with pre-emptive reduction of immunosuppression is the only proved preventive strategy to reduce the risk of PVAN. The aim of this study was to describe the evolution of BKPyV and JCPyV viral load in de novo pediatric RTR. Method: A prospective observational study was carried out in a pediatric RTR. Paired samples of serum and urine were collected at baseline (on the day of transplantation), then monthly for at least 9 months post transplantation (PostTx). Viral load of BKPyV and JCPyV was determined by a Multiplex Real Time PCR assay (transferred by Fedele CG,2012). Results: Fourteen patients were enrolled, the median age of the group was 13 years old (8-19) and 11 were male. The monitoring period was from 9 to 20 months (media 16). None of the patients developed PVAN during the study, but 11 (78%) of them tested positive, which were divided into three groups: 1.BKPyV positive (n=7) - they showed a pattern of viruria with a maximum between the 2nd and 7th month PostTx (median 8.5.108copies/ml), after this peak viral load diminished significantly over the time getting undetectable in 4 cases. Two patients had higher values at the maximum in coincidence with impairment of renal function. Viremia was detectable in all cases, but with intermittences and it has not shown a well-defined profile, the highest values were around 104copies/ml. 2.JCPyV positive (n=2) - both cases had JCPyV viruria without viremia with similar patterns: viral load was detectable from 2nd month PostTx and continued along the time with tendency to increase. 3.BKPyV and JCPyV dual positive (n=2) - BKPyV viruria and viremia were detected at low rates at the beginning, then appeared JCPyV viruria simultaneously but with higher viral load, and from 10th month PostTx to the end (17th month) only JCPyV viruria was detectable with the same upward trend as group two. Conclusion: We detected active infection of BKPyV in 64% (9/14) of the cases, although there was no occurrence of any case of PVAN. However, in cases with impair renal function it were observed a significant increase of viruria. There are different proposed algorithms for monitoring BKPyV viral load to identify patients at risk of PVAN. We found a characteristic pattern of BKPyV viral shedding in urine. Based on this finding we would recommend to strengthen controls between 2nd to 7th month PostTx to be more sensitive to detect patients with viruria higher than 107copies/ml, thus at more risk to develop viremia and consequently PVAN. Finaly, when PVAN is suspected and BKPyV is undetectable, JCPyV diagnose should be made, since it can cause PVAN as well although with low frequency, and we demonstrated its presence in 29% of the cases. Cesare Giovanni Fedele.

Incidence and outcome of SARS-CoV-2 infection in a pediatric kidney transplant recipient cohort from a single center in Northern Italy.

BackgroundConcern about SARS‐CoV‐2 infection has increased over the possible effects on immunocompromised patients. Among them, recipients of solid organ transplantation deserve special attention. Data from the adult population suggest they may be at high risk for developing severe COVID‐19, but little data are available for pediatric solid organ transplantation recipients.MethodsFrom March 2020 to April 2021, KT recipients aged <21 years, routinely managed at our center, who underwent RT‐PCR testing with nasopharyngeal swabs to detect SARS‐CoV‐2 infection, were studied. Tests were performed according to clinical and/or epidemiological criteria.ResultsOne hundred one transplanted patients were managed at our center during the observation period. Among this population, 57 patients were tested for SARS‐CoV‐2 infection with a RT‐PCR test and were subsequently enrolled. A total of 111 swabs were performed. Twelve out of the 57 patients tested (21.1%) had a positive RT‐PCR test result. Among the positive patients, eight were symptomatic (66.7%). Median duration of symptoms and RT‐PCR positivity was two days (IQR 1–2.25) and 17 days (IQR 11–27.25), respectively. No patients required specific treatment or IS therapy reduction; no one was admitted to hospital.ConclusionsOur data show that pediatric renal transplant recipients are at low risk of clinically relevant COVID‐19, as is the healthy age‐related population. On the contrary, our results differed substantially from those seen in adult SOT recipient populations that have a high incidence and an even earlier and higher mortality rate.

Long term tolerability and clinical outcomes associated with tocilizumab in the treatment of refractory antibody mediated rejection (AMR) in pediatric renal transplant recipients.

Treatment options for antibody-mediated rejection (AMR) are limited. Recent studies have shown that inhibition of interleukin-6 (IL-6)/interleukin-6 receptor (IL-6R) signaling can reduce inflammation and slow AMR progression. We report our experience using monthly tocilizumab (anti-IL6R) in 25 pediatric renal transplant recipients with AMR, refractory to IVIg/Rituximab. From January 2013 to June 2019, a median (IQR) of 12 (6.019.0) doses of tocilizumab were given per patient. Serial assessments of renal function, biopsy findings, and HLA DSA (by immunodominant HLA DSA [iDSA] and relative intensity score [RIS]) were performed. Median (IQR) time from transplant to AMR was 41.4 (24.367.7) months, and time from AMR to first tocilizumab was 10.6 (8.317.6) months. At median (IQR) follow up of 15.8 (8.435.7) months post-tocilizumab initiation, renal function was stable except for 1 allograft loss. There was no significant decrease in iDSA or RIS. Follow up biopsies showed reduction in peritubular capillaritis (p=.015) and C4d scoring (p=.009). The most frequent adverse events were cytopenias. Tocilizumab in pediatric patients with refractory AMR was well tolerated and appeared to stabilize renal function. The utility of tocilizumab in the treatment of AMR in this population should be further explored.

Pharmacokinetics of free and total mycophenolic acid in paediatric and adult renal transplant recipients: Exploratory analysis of the effects of clinical factors and gene variants.

Clinical and genetic influencing factors on free fraction of mycophenolic acid (MPA) have rarely been discussed. The present study investigated whether the clinical and genetic factors could explain the variability in the pharmacokinetics of free MPA (fMPA) and total MPA (tMPA) in Chinese paediatric and adult renal transplant recipients. Twenty-eight paediatric and 31 adult patients were enrolled, and the concentrations of tMPA and fMPA were determined at 0 h (predose) and 0.5, 1, 1.5, 2, 4, 5, 8, 9, 10 and 12 h after mycophenolate mofetil administration. Genetic polymorphisms of UGTs (rs671448, rs1042597, rs2741049, rs62298861, rs7439366, rs12233719) and ABCC2 (rs717620) were simultaneously determined. The clinical and genetic data were analysed and reported. tMPA and fMPA concentrations adjusted for dose per body weight were consistently higher in adults than in paediatric patients. In the paediatric group, only albumin and time after transplantation correlated significantly with the MPA-free fraction variation, which could explain 32.4% of the variability. Besides, ABCC2 polymorphism, albumin and time after transplantation correlated significantly with the MPA-free fraction variation in adults, which could explain 56.9% of the variability. The influencing factors in the paediatric group are different from those in adults, which may be due to age-related transporter expression.

The Role of Platelet-Lymphocyte Ratio and Neutrophil-Lymphocyte Ratio in Predicting the Delayed Graft Function in Pediatric Renal Transplant Patients.

Delayed graft function is a common adverse outcome after renal transplant. Attempts for early prediction and prevention of delayed graft function are often challenging and misleading. Herein, we investigated for the first time the correlation between delayed graft function and preoperative noninvasive hematologic parameters to predict the possible adverse outcomes for renal transplant in pediatric patients. In this study, preoperative hematologic parameters of 51 pediatric renal transplant recipients followed between 2015 and 2021 were analyzed retrospectively. The selected 16 renal transplant patients with delayed graft function and 35 patients without delayed graft function had no concomitant comorbidities. The cutoff values for platelet-to-lymphocyte ratio of <5 and neutrophilto- lymphocyte ratio of <175 were considered low. We retrospectively evaluated a total of 51 (male/female, 33/18) pediatric kidney transplant recipients with a median age of 12 (interquartile range, 8-18) years. Median level of circulating lymphocytes was significantly higher in patients with delayed graft function compared with patients without delayed graft function (2 vs 1, P = .040). The preoperative low values for platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio were more prevalent in recipients who developed delayed graft function versus those who did not develop delayed graft function (68.8% vs 31.4% [P = .014] and 68.8% vs 34.3% [P = .023], respectively). Pretransplant low platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte were associated with increased number of delayed graft dysfunction. These novels and noninvasive inflammatory biomarkers may contribute to an early prediction of delayed graft function in pediatric kidney transplant recipients.

Effects of tacrolimus intrapatient variability and CYP3A5 polymorphism on the outcomes of pediatric kidney transplantation.

The intrapatient variability (IPV) of tacrolimus (Tac) is associated with the long-term outcome of kidney transplantation. The CYP3A single-nucleotide polymorphism (SNP) may affect the IPV of Tac. We investigated the impact of IPV and genetic polymorphism in pediatric patients who received kidney transplantation. A total of 202 pediatric renal transplant recipients from 2000 to 2016 were analyzed retrospectively. The IPV was calculated between 6 and 12months after surgery. Among these patients, CYP3A5 polymorphism was analyzed in 67 patients. The group with high IPV had a significantly higher rate of de novo donor-specific human leukocyte antigen antibodies (dnDSA) development (35.7% vs. 16.7%, p=.003). The high IPV group also had a higher incidence of T-cell-mediated rejection (TCMR; p<.001). The high IPV had no significant influence on Epstein-Barr virus, cytomegalovirus, and BK virus viremia but was associated with the incidence of posttransplant lymphoproliferative disorders (p=.003). Overall, the graft survival rate was inferior in the high IPV group (p<.001). The CYP3A5 SNPs did not significantly affect the IPV of Tac. In the CYP3A5 expressor group, however, the IPV was significantly associated with the TCMR-free survival rate (p<.001). The IPV of Tac had a significant impact on dnDSA development, occurrence of acute TCMR, and graft failure in pediatric patients who received renal transplantation. CYP3A5 expressors with high IPV of Tac showed worse outcomes, while the CYP3A5 polymorphism had no impact on IPV of Tac.

Treatment of post-transplant recurrent FSGS in children using plasmapheresis and augmentation of immunosuppression

BackgroundUp to 60% of pediatric renal transplant recipients with end-stage renal disease due to primary focal and segmental glomerulosclerosis (FSGS) may develop recurrent disease. Such recurrence is associated with poor prognosis if no remission is achieved. We report a single center experience with a protocol based on plasmapheresis and increased immunosuppression that resulted in a high long-lived remission rate.MethodsThis retrospective cohort study included consecutive pediatric renal transplant patients with recurrent FSGS treated with a standardized protocol using plasmapheresis and cyclophosphamide to supplement usual post-transplant immunosuppression with calcineurin inhibitors and steroids. Relapse was defined as urinary protein/creatinine ratio > 1.0 g/g and remission as < 0.5 g/g.ResultsSeventeen patients with FSGS recurrence post-transplant were treated. All had therapy resistant FSGS in native kidneys and had been on dialysis from 4 to 10 years. Of the 17, one died perioperatively from a pulmonary thromboembolism. Fifteen others achieved a complete remission within 3 months of treatment for FSGS recurrence. After a median follow-up period of 4 years, there were no recurrences of significant proteinuria. One patient achieved remission with rituximab.ConclusionThe addition of plasmapheresis and cyclophosphamide to a calcineurin- and steroid-based immunosuppression regime was highly successful in inducing high remission rates with recurrent FSGS. Prospective trials are needed to evaluate further the efficacy of increased immunosuppression along with plasmapheresis in this setting.

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.

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.

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

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.

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.

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.

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.

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.