Renal Transplantation In Children Research Articles

Commentary on Long-term Growth Following Renal Transplantation in Children.

Commentary on Long-term Growth Following Renal Transplantation in Children.

Population pharmacokinetics of ganciclovir after valganciclovir in renal transplant children.

Valganciclovir, the ganciclovir prodrug, is an antiviral agent administered orally to prevent or treat cytomegalovirus infection in solid organ transplant recipients. Dosing regimen of valganciclovir is still controversial in children, as the number of patients reaching the Area Under the Curve at steady state (AUCss) target (40 - 60 mg.h/L) remains highly variable. The aim of this study was to determine the population pharmacokinetics of valganciclovir in paediatric renal transplant recipients and propose an appropriate dosing regimen. Renal transplant children who received valganciclovir to prevent or treat cytomegalovirus infection at Robert Debré University Hospital were included. Plasma ganciclovir concentrations were determined by high performance liquid chromatography and ultraviolet detection. Population pharmacokinetic analysis was performed with NONMEM software. 104 patients, aged 2 to 20 years, treated with valganciclovir administered at a mean dose of 17.3 ± 6.1 mg/kg to prevent and/or treat cytomegalovirus infection after renal transplantation were included. A total of 1212 samples were available. A two-compartment model with first-order elimination best fitted the data: ganciclovir clearance increased with body surface area, was 15% higher in boys and decreased with increasing creatinine concentration. Central volume of distribution increased with body surface area and was 14% higher in boys. According to the personalized dosing regimen, 65.7% and 65.4% of children were predicted to achieve the AUCss target for cytomegalovirus prophylaxis and treatment, respectively. A new pharmacokinetic model was built allowing to propose individualised dose adapted to renal transplanted paediatric patients characteristics.

Cardiometabolic correlates of sleep-disordered breathing in renal transplant children.

Sleep-disordered breathing, a prevalent condition among adult renal transplant (RTx) recipients, has become an established independent risk factor of MetS, and furthermore, it might contribute to increased CV risk. Despite the proven correlations in adults, there is a lack of evidence for its significance in the pediatric RTx population. In this study, we aimed at assessing the prevalence and the clinical correlates of SDB in RTx children. Data of 13 patients (age [mean±SD]: 14.2±2.7years) were analyzed. SDB was evaluated by PSG, as severity score OAHI was applied. Carbohydrate metabolism was characterized by OGTT, whereas CV status was studied by ABPM. Three composite end-points were calculated as sum of z-scores: daytime systolic and diastolic BP; nighttime systolic and diastolic BP; and glucose and insulin levels at 120minutes. Eight patients (61.5%) were diagnosed with SDB of whom five patients (38.5%) had moderate or severe SDB. In linear regression analysis, OAHI during REM was associated with the CV variables (daytime BP P=0.032, ß=0.748; nighttime BP P=0.041, ß=0.715), and the correlations remained significant after adjustments for BMI. However, we did not confirm a significant association with the metabolic variables. The prevalence of SDB was high, and its severity during REM was a predictor of the BP suggesting that RTx children with SDB might be at risk of developing CV complications, especially HTN similarly to adults.

GCV/VCVG prophylaxis against CMV DNAemia in pediatric renal transplant patients: A systematic review and meta-analysis.

CMV disease continues to stand as a significant threat to the longevity of renal transplants in children. More pediatric recipients are CMV-negative with CMV-positive donor serologies resulting in a HR mismatch. The length of prophylaxis with GCV or VGCV required to optimally prevent recurrence of CMVDNAemia remains unknown. This study is a meta-analysis comparing GCV/VGCV prophylaxis regimens provided for <6months, from 6 to <12months, and ≥12months after transplant in order to prevent CMVDNAemia. The search conducted involved PubMed, EMBASE, ISI Web of Science, and Cochrane Central Register from inception through December 2017. Search terms Kidney Transplantation, CMV, GCV, and VGCV provided 204 studies for abstract review. Studies excluded were those which did not itemize pediatric data separately, single case reports, and duplicate studies. Pooled analysis of five retrospective studies and one prospective study identified that there is no statistically significant difference in the incidence of CMV DNAemia when comparing <6months of prophylaxis and >12months of prophylaxis (23% and 15%, respectively, P=0.23). Regardless of the length of prophylaxis, there was no statistical difference in the incidence of CMV DNAemia in the HR patients (6 to <12months vs <6months, P=0.62; 6 to <12months vs ≥12months, P=0.78; ≥12months vs <6months, P=0.83). This study identifies no optimal length of prophylaxis for HR mismatch pediatric renal transplant patients as many develop CMV DNAemia.

Renal Transplantation in Children

Renal Transplantation in Children

Pediatric Renal Transplantation in Children with Weight 20kg or Less: A Single-Center Experience

Pediatric Renal Transplantation in Children with Weight 20kg or Less: A Single-Center Experience

Translating nutritional guidelines for post renal transplant children into practice

Translating nutritional guidelines for post renal transplant children into practice

Health-related quality of life changes following renal transplantation in children.

Studies of HRQoL after kidney transplant have yielded conflicting results. We sought to assess the impact of kidney transplant on HRQoL. We performed a retrospective study using the PedsQL3.0ESRD module during dialysis and at 3 and 12months following kidney transplant in 56 recipients. For the entire cohort, we described HRQoL scores at each time point and used ANOVA models to test for associations between demographic and transplant-related factors and post-transplant scores. We used linear mixed models to investigate interactions between transplant and demographic and transplant-related factors and to estimate differences between mean pre- and post-transplant scores. Longitudinal changes in HRQoL were assessed by t test. We found increases in all mean total scores, including subscales, at each assessed time period from dialysis to 3months post-transplant to 12months post-transplant. Post-transplant total scores did not differ by gender, race, proximity to hospital, allograft source, or dialysis modality, but did differ by recipient age. Among participants with both pre- and post-transplant observations, total scores increased for both recipients and parent-proxies. This study affirms the association between kidney transplant and improvement in HRQoL in the first year following transplant. Future research should further explore outcomes over the longer-term and factors contributing to HRQoL among this population.

GINGIVAL ENLARGEMENT IN RENAL TRANSPLANT PATIENTS: A META-ANALYSIS

Severe gingival enlargement (GE) is one of the most common observed effects in renal transplant patients due to the usage of cyclosporine A. GE causes pain, aesthetic problems, gingival bleeding and periodontal diseases. The databases of PubMed, Web of Science were searched for relevant studies from January 1990 to January 2018. Summary incidence rates, and 95% confidence intervals (CIs) were calculated by using random effects models. A total of 595 patients from 10 studies were included. The incidences of GE was 62.6% (95% CI: 41.9–79.5%) in patients using cyclosporine with or without any other drugs. Sub-group analysis according to diagnostic criteria showed that the incidence of GE was lower when a well defined diagnostic criteria or scoring system was implemented. The incidences of GE was 88.2% (95% CI: 80.9–93.0%) in patients using cyclosporine with nifedipine. Cyclosporine A without nifedipine was associated with a significantly decreased risk of GE incidence in comparison to cyclosporine A with nifedipine combination (Odds Ratio: 0.198; 95% CI, 0.083- 0.473; P < 0.001). It is important to know effects of these drugs which cause gingival enlargement and the treatment options for all clinicians. The dental evaluation in a service would be helpful for renal transplant children. The aim of this study was to gain more insight into the prevalence of gingival enlargement in renal transplant patiens.

Successful ABO and HLA Incompatible Renal Transplantation in Children in the United Kingdom over the Last Decade

Successful ABO and HLA Incompatible Renal Transplantation in Children in the United Kingdom over the Last Decade

Longitudinal Study of the Role of Epidermal Growth Factor on the Fractional Excretion of Magnesium in Children: Effect of Calcineurin Inhibitors.

Background: It was shown in animal models and adults that the epidermal growth factor (EGF) is involved in the pathophysiology of calcineurin inhibitor (CNI) induced renal magnesium loss. In children, however, the exact mechanism remains unclear, which was set as the purpose of the present study. Methods: Children with nephrotic syndrome and renal transplant children treated with CNI (n = 50) and non-CNI treated children (n = 46) were included in this study. Urine and serum samples were collected at three time points to determine magnesium, creatinine, and EGF. The magnesium intake was calculated from a food frequency questionnaire. Results: Serum Mg2+ and urinary EGF/creatinine were significantly lower in the CNI treated children, with significantly more CNI-treated children developing hypomagnesaemia. In the latter patients, the fractional excretion of magnesium (FE Mg2+) was significantly higher. Urinary EGF, age, renal function, and serum magnesium were independent predictors of the FE Mg2+. Only 29% of the children reached the recommended daily intake of magnesium. The magnesium intake did not differ between hypomagnesemic and normomagnesemic patients and was not a predictor of the FE Mg2+. Conclusions: In CNI-treated children who developed hypomagnesemia, the FE Mg2+ was increased. The urinary EGF concentration, age, and renal function are independent predictors of the FE Mg2+.

The choice between deceased- vs living-donor renal transplantation in children: Analysis of data from a Belgian tertiary center.

Pediatric renal transplantation with a living donor (LD) has superior outcome, but there is a paucity of studies analyzing the reasons for not undertaking living donation in West-European countries. The aim of this study was to retrospectively review the choice of donor source in our center. We also aimed to identify factors which prevented transplantation with a LD. This retrospective study was performed including children aged 2-19years who underwent kidney transplantation (KT) at the Ghent University Hospital between 1996 and 2016. Relevant data were collected from medical files to identify the main medical, psychological, and socio-economic factors influencing the choice of the donor source. There were 48 patients (boys n=33) who underwent KT. Thirty-nine patients received a deceased donor (DD) kidney and nine patients received a LD kidney. Sixteen of 48 transplantations were preemptive. The reasons for DD KT included socio-economic factors such as single caregiver families, one or both parents with a criminal record or convictions and religious or cultural constraints (n=15), medical considerations (n=13), refusal of the close relatives/parents to donate (n=7), and acceptance of an organ from a DD while prospective donor was undergoing medical screening (n=4). The low incidence of living kidney donation can be explained by socio-economic and medical factors. Refusal to donate is a potentially modifiable factor and strategies aimed at education and guidance of the families might contribute to a higher incidence of living donation in our setting.

Renal transplantation in children under 3years of age: Experience from a single-center study.

RTx remains challenging in children under 3years of age. This single-center study reviewed the medical records of children <3years transplanted since 1987 (N=32, Group 1). They were matched for donor type and RTx period with children aged 3-13years (N=32, Group 2) and 13-18years (N=32, Group 3). There were no between-group significant differences regarding distributions of gender, primary renal disease, proportion of dialysis before RTx, and growth (SDS). Compared to Groups 2 and 3, Group 1 had more peritoneal dialyses (P<.001), more EBV mismatches (P=.04), and longer warm ischemia times (P<.001). The risk of graft loss was not significantly different among age groups (hazard ratio, 2.4 in Group 2 and 2.0 in Group 3 vs Group 1; P=.2). Death occurred in four patients (3 in Group 1 and 1 in Group 2) and graft loss occurred in 28 patients, mainly due to chronic allograft nephropathy. In recipients <3years of age, the outcomes of RTx are close to those obtained in older pediatric age groups. Thus, young patients may be transplanted in experienced multidisciplinary teams without additional risks provided that particular attention is paid to donor selection and prevention/early diagnosis of comorbidities and complications.

Transient abnormal liver enzyme level in the early stage after renal transplantation in children

Aim: The study aim was to evaluate the prevalence, risk factors, and clinical importance of abnormal elevation in liver enzyme levels in children after renal transplantation. Materials and Methods: The files of all 62 patients (mean age 10.2 years), who underwent renal transplantation at a tertiary pediatric medical center in 2001-2013, were reviewed for clinical data, including: Postoperative liver function, tacrolimus level, and serology for cytomegalovirus (CMV) and hepatitis B and C viruses. Results: The most common indication for transplantation (53%) was dysplastic hypoplastic kidney. Liver enzyme levels were abnormal in 7 patients (11%) before transplantation and 42 (67.7%) during the first 6 months following, with a peak on day 14 (P

Indications for renal transplantation in children: What a pediatrician should know ?

Renal transplantation is the best modality of treatment for end stage renal disease in children when compared to chronic dialysis. The growth, development and quality of life in these children are significantly better after transplantation. There has been a marked increase in the number of children undergoing renal transplantation in the recent years. The short term graft survival rates have increased with improved immunosuppression, but the long term outcome is still poor due to chronic graft rejection and opportunistic infections. In developing countries renal transplantation is not accessible to many children due to economic issues, lack of expertise and the absence of a strong deceased donor program. This article is a brief review of the indications and other aspects of pre-operative evaluation of pediatric renal transplant recipients.

Prevalence of Gastrointestinal Symptoms in Renal Transplant Children Receiving Mofetil Mycophenolate

Prevalence of Gastrointestinal Symptoms in Renal Transplant Children Receiving Mofetil Mycophenolate

Risk factors for urological complications following living donor renal transplantation in children.

The aim of this study was to detect possible risk factors for UC and UTI following pediatric renal Tx and effect of these complications on outcome. One hundred and eight children who underwent living donor Tx between 2009 and 2015 were retrospectively included. Extraperitoneal approach was used with stented tunneled extravesical procedure. Mean recipient age was 9.89±3.46years while mean weight was 25.22±10.43kg. Seventy-three (67.6%) recipients were boys while 92 (85.2%) were related to donors. Urological causes of ESRD were present in 33 (30.6%) recipients (14 [13%] posterior urethral valve, 16 [14.8%] VUR, and 3 [2.8%] neurogenic bladder). Augmentation ileocystoplasty was performed in 9 (8.3%) patients. Mean follow-up was 39.3±17.33months. UC were detected in 10 (9.3%) children (leakage 4 [3.7%], obstruction 3 [2.8%], and VUR 3 [2.8%]) while UTIs were reported in 40 (37%) children. After logistic regression analysis, UC were significantly higher in children with cystoplasty (44.4% vs 6.1%; P=.001). UTIs were significantly higher in girls (51.4% vs 30.1%; P=.001) and in children with urological causes of ESRD (51.5% vs 30.7%; P=.049). UC and UTI were not significantly associated with increased graft loss or mortality. UC were significantly higher in children with cystoplasty while UTIs were significantly higher in girls and children with urological causes of ESRD. Presence of UC did not affect the rate of graft loss or mortality due to its early detection and proper management.

Renal Transplantation in Children with Lower Urinary Tract Dysfunction: A Single-Center Experience

Aim: To evaluate patient and graft survival, as well as the surgical risks of LUTD patients treated at Gazi University Transplantation Center. Renal transplantation in patients with lower urinary tract dysfunction (LUTD) of various origins remains challenging in the field of pediatric transplantation. Patients and Methods: Of 42 pediatric transplantation recipients treated since 2006, LUTD developed in five (12%). Videourodynamic tests were performed on all patients preoperatively, and postoperatively if required. The causes of urological disorders were: Posterior urethral valve (PUV) (n=3), PUV with a neurogenic bladder (n=1), and a meningiomyocele plus a neurogenic bladder (n=1). Continual intermittent catheterization (CIC) was required by three patients for bladder emptying. Three patients received kidneys from deceased donors and two patients received kidneys from living donors. All patients underwent calcineurine-based triple immunosuppressive therapy. No patient underwent pre-transplantation augmentation. Only one patient (with PUV and a neurogenic bladder) underwent an augmentation operation during transplantation surgery. We used the Haberal corner-saving suture technique for ureteral stenting combined with ureteroneocystostomic anastomosis. Results: The mean age at transplantation was 12.2±1.6 years (10-14 years). The median follow-up duration after transplantation was 101 months (68 to 110 months). Two of the five recipients developed BK virus nephropathy (BK). One of the grafts was lost to BK but the other retained normal functioning. No recipient developed urological or surgical complications after transplantation. Three grafts were lost [BK (n=1); chronic allograft nephropathy (n=2)] but the remaining two patients are doing well with median creatinine levels 1.1 mg/dL. The 1-, 3-, and 5-year patient and graft survival rates were: 100%, 100%, 100% and 100%, 100%, 60% respectively. Conclusion: Renal transplantation in children with a LUTD can yield long-term successful outcomes comparable to those in children with non-LUTD. Because of the high complication rates associated with these transplants, careful evaluation, surveillance, and management of pre/post-transplantation periods are essential to optimize these outcomes.

O-19 Incidence and risk factors of adverse events during immunosuppressive therapy after renal transplantation in children

Background Transplantation has become an important treatment option in children with end-stage renal dis-ease. In the last decades progress in immunosuppressive treatment options and surgical techniques have reduced the frequency of acute rejection, graft loss and mortality. However, adverse events occur in patients treated with immunosuppressive therapy. These adverse events are well described for adults but few data are available for children. Our objective was to describe the frequency of adverse events (AEs) under different immunosuppres-sive regimen including either ciclosporin or tacrolimus in children after renal transplantation. Secondary objectives include comparison of AEs with known adverse drug re-actions (ADRs) as described in the Summary of Product Characteristics. Furthermore, risk factors for AEs will be examined. Methods Children receiving a renal transplant at our institution between 2002 to 2015 were included in the study. Initial immunosuppression was obtained by thy-moglobulin or monoclonal antibody, calcineurin inhib-itors (tacrolimus or ciclosporin), mycophenolate mofetil, and corticoids. AEs reported after transplantation were collected from medical reports and coded using Med-DRA (version 19.1). Descriptive statistical analyses were performed using SAS 9.4. Data were stratified by tacrolim-us or ciclosporin treatment schedule at the time of the AE. Results A total of 164 children fulfilled the inclusion cri-teria. Finally, complete medical records were available for 125 children (53 girls and 72 boys). The median age was 12 (2 – 19) years old. The indication for renal transplan-tation included congenital, familial and genetic disorders for 61% of the patients and renal and urinary disorders for 39% (including 30% of nephritis). The median time of observation until last follow up was 2.7 (0.6–4.3) years. Initially, 91 patients were treated with tacrolimus and 34 with ciclosporin. During the observation period 6 patients switched from tacrolimus to ciclosporin and 14 switched from ciclosporin to tacrolimus. A total of 1520 AEs were reported. For patients receiving tacrolimus 1122 AEs (233.6 person-years of exposure) were reported and 372 AEs (71.4 person-years of expo-sure) for those treated with ciclosporin. Twenty-six AEs were reported in patients not receiving any calcineurin inhibitor. The most frequent medical AEs reported for pa-tients treated with tacrolimus and ciclosporin by system organ class were renal and urinary disorders (0.3 vs 0.3 AEs per person-year of exposure), infections (0.3 vs 0.4 AEs per person-year of exposure), vascular disorders (0.2 vs 0.3 AEs per person-year of exposure) and gastrointestinal disor-ders (0.2 vs 0.2 AEs per person-year of exposure). For 46 patients at least one episode of transplant rejection was reported. Conclusion This study describes AEs up to 4 years after renal transplantation in children treated with immuno-suppressive therapy. Our findings will contribute to the understanding of the benefit-risk balance of immuno-suppressive therapy following renal transplantation in children.

Renal Transplantation in Children: Current Status and Challenges

Abstract Renal transplantation is the treatment of choice for children with end-stage renal disease (ESRD) since it decreases morbidity and mortality and improves quality of life. Potent immunosuppressive medications have significantly improved the short and medium-term outcomes while long-term outcomes continue to remain a challenge. This article reviews the current practices involved in the care of pediatric renal transplant recipients and challenges faced by them. Here, we provide a brief overview of various aspects of care for pediatric renal transplant recipients that include indications and contraindications, immunologic workup, pre-transplant evaluation, currently used immunosuppressive therapies, long-term complications and graft survival.