Pediatric Renal Transplant Recipients Research Articles

Health-related quality of life of pediatric renal transplant recipientsand their parents: the role of associated factors and clinical counseling.

This study evaluates the health-related quality of life (HRQoL) of pediatric renal transplant recipients and their parents and investigates the effects of clinical, socioeconomic, and psychological factors as well as continuous counseling on the HRQoL. Patients aged 8-17 years (mean: 14.9 ± 2.9) were enrolled. Clinical and demographic data were noted. The Beck Depression Inventory (BDI), Rosenberg Self-Esteem Scale (RSES), and Turkish version of the Kinder Lebensqualität Fragebogen (KINDL) questionnaire for children and the BDI, RSES, parent-proxy version of KINDL, and Short-Form 36 (SF-36) for parents were applied (step 1). Following a 1-year counseling program, the tests were repeated (step 2). Child-self and parent-proxy KINDL scores were optimal with no difference between periods (for child-self and parent-proxy scores, P > 0.05). Parent SF-36 scores indicated optimal results. Parent RSES scores decreased in step 2 (P < 0.05). The BDI scores were higher in parents than children in both periods (P < 0.05 for step 1 and P < 0.01 for step 2). Higher creatinine levels, lower monthly income, and urological comorbidities modified the HRQoL negatively in step 1. Continuous education with psychosocial counseling carries importance in improving HRQoL in the posttransplant period.

Cytomegalovirus transmission in pediatric renal transplant recipients during the window period

We report two CMV naïve children who received deceased donor renal transplants from a CMV IgG-negative single donor. CMV IgG in both recipients and the donor were negative immediately prior to transplant. Both recipients had early recurrences of their original disease in their transplants, requiring multiple sessions of plasmapheresis. All blood products used were leukoreduced or CMV seronegative. A few days post-transplant, both recipients developed significant positive CMV viremia. Both required initiation of oral valganciclovir. Case 1 responded to oral valganciclovir only while the case 2 had a delayed response to it and hence required intravenous ganciclovir with good response. When checked retrospectively, CMV IgM in the donor was positive along with positive CMV DNA PCR from the white cells. Here we describe a very unusual scenario of CMV transmission in two pediatric renal transplant recipients from a single donor during the CMV window period.

Long-term effects of paediatric kidney transplantation.

Renal transplantation in paediatric patients usually provides excellent short-term and medium-term results. Early diagnosis of chronic kidney disease and active therapy of end-stage renal disease before and after transplantation enables the majority of children to grow and develop normally. The adverse effects of immunosuppressive medication and reduced graft function might, however, hamper long-term outcomes in these patients and can lead to metabolic complications, cardiovascular disease, reduced bone health, and malignancies. The neurocognitive development and quality of life of paediatric transplant recipients largely depend on the primary diagnosis and on graft function. Poor adherence to immunosuppression is an important risk factor for graft loss in adolescents, and controlled transition to adult care is of utmost importance to ensure a continued normal life. In this Review, we discuss the outcomes and long-term effects of renal transplantation in paediatric recipients, including consequences on growth, development, bone, metabolic, and cardiovascular disorders. We discuss the key problems in the care of paediatric renal transplant recipients and the remaining challenges that should be the focus of future research.

Coincidence of late‐onset cytomegalovirus‐induced myositis and gastritis in a pediatric renal transplant recipient

An 8-year-old girl with a renal transplant was admitted for myalgia and muscle weakness in both legs over the previous 2 weeks. She also had fever and intermittent epigastric pain. Based on these clinical manifestations, and laboratory and histopathological findings, the diagnosis was coincidence of late-onset cytomegalovirus (CMV)-induced myositis and gastritis in an immunocompromised child with a renal transplant. After administration of intravenous ganciclovir for 3 weeks, her symptoms resolved, with normalization of abnormal muscle enzymes, including lactate dehydrogenase, creatine kinase, aspartate aminotransferase, and the disappearance of CMV viremia.

Improved cardiovascular risk factors in pediatric renal transplant recipients on steroid avoidance immunosuppression: A study of the Midwest Pediatric Nephrology Consortium.

Several centers have examined the implementation of immunosuppression protocols that minimize steroid exposure. This study retrospectively examined cardiovascular risk factors in 70 pediatric renal transplant recipients on steroid avoidance-based immunosuppression over three yr compared to matched pediatric patients maintained on chronic corticosteroids. Although higher rates of acute rejection were noted in the steroid-avoidant group (22% vs. 16%, p = 0.034), graft function was similar (67 + 10 mL/min/1.73 m(2) vs. 72 + 12 mL/min/1.73 m(2)) (p = 0.053). The steroid-avoidant group demonstrated improved growth (height z-score -0.41 + 5.9 vs. -1.1 + 0.041) with a decrease in the prevalence of obesity (24% vs. 34%, p = 0.021). Indexed systolic blood pressures were lower beginning at six months post-transplant in the steroid-avoidant group (1.21 + 0.15 vs. 1.51 + 0.22, p = 0.020). Indexed diastolic blood pressures were lower beginning at 12 months post-transplant (0.91 + 0.11 vs. 1.12 + 0.18, p = 0.037). Differences in total serum cholesterol values and serum glucose values were not statistically significant. Beginning at 12 months, a statistically significant decrease in left ventricular mass index (39.2 + 11.3 vs. 49.4 + 14.5, p = 0.014) was noted in patients on steroid-avoidant immunosuppression, which corresponded to a significant decrease in the prevalence of left ventricular hypertrophy in these patients by two yr post-transplant (35% vs. 48%, p = 0.012). Systolic blood pressure and BMI were independent predictors of left ventricular hypertrophy.

Incidence, risk factors, and outcomes of opportunistic infections in pediatric renal transplant recipients

OIs present significant risks to patients following solid organ transplantation. The purpose of this study was to identify risk factors for the development of OIs after kidney transplantation in pediatric patients and to evaluate the impact of OIs on outcomes in this patient population. A single-center retrospective longitudinal cohort analysis including pediatric patients 21 yr of age or younger transplanted from July 1999 to June 2013 at an academic medical center was conducted. Patients were excluded if they received multi-organ transplant. A total of 175 patients were included in the study. Patients who developed OIs were more likely to be female and younger at the time of transplant. A six-factor risk model for OI development was developed. Death, disease recurrence, and PTLD development were similar between groups but trended toward increased incidence in the OI group. Incidence of rejection was significantly higher in the OI group (p = 0.04). Patients who developed OIs had several important risk factors, including younger age, EBV-negative serostatus, CMV donor (+)/recipient (-), biopsy-proven acute rejection, ANC <1000, MMF dose >500 mg/m(2), and any infection. Incidence of rejection was higher in the OI group, but rate of graft loss was not statistically different.

Low-Grade Persistent Hyperparathyroidism After Pediatric Renal Transplant.

Hyperparathyroidism, a frequent complication of chronic kidney disease, persists after renal transplant. Our aims were to examine the status of parathyroid hormone levels and to determine the clinical and biochemical risk factors of persistent hyperparathyroidism after transplant. Our study included 44 pediatric renal transplant recipients with stable graft function. Median follow-up after transplant was 17.5 months (range, 12-126 mo). Patients did not receive routine vitamin D or calcium supplements after transplant, and none had undergone previous parathyroidectomy. Bone mineral densitometry of the lumbar spine was measured. Fifteen patients (34%) had parathyroid hormone levels greater than 70 pg/mL (normal range, 10-70 pg/mL). Duration of dialysis before transplant was longer in patients with persistent hyperparathyroidism. Mean serum bicarbonate levels were significantly lower in patients with persistent hyperparathyroidism than in patients without persistent hyperparathyroidism after transplant. A significant negative correlation was noted between parathyroid hormone level and serum bicarbonate level. Another significant negative correlation was shown between parathyroid hormone level and z score. We found that persistent hyperparathyroidism is related to longer dialysis duration, lower serum bicarbonate level, and lower z score. Pretransplant dialysis duration is an important predictor of persistent hyperparathyroidism. Early identification of factors that contribute to persistent hyperparathyroidism after transplant could lead to treatment strategies to minimize or prevent its detrimental effects on bone health and growth in pediatric transplant recipients.

Can pre-implantation biopsies predict renal allograft function in pediatric renal transplant recipients?

Objectives:To determine the utility of pre-implantation renal biopsy (PIB) to predict renal allograft outcomes.Methods:This is a retrospective review of all patients that underwent PIB from January 2003 to December 2011 at the Great Ormond Street Hospital for Children in London, United Kingdom. Thirty-two male patients (56%) aged 1.5-16 years (median: 10.2) at the time of transplantation were included in the study and followed-up for 33 (6-78) months. The results were compared with 33 controls.Results:The PIB showed normal histopathological findings in 13 patients (41%), mild chronic vascular changes in 8 (25%), focal tubular atrophy in one, moderate to severe chronic vascular change in 3, mild to moderate acute tubular damage in 6, and tissue was inadequate in one subject. Delayed graft function (DGF) was observed in 3 patients; 2 with vascular changes in PIB, and one with normal histopathological findings. Two subjects with PIB changes lost their grafts. The estimated glomerular filtration rate at 3-, and 6-months post-transplantation was lower in children with abnormal PIB changes compared with those with normal PIB. There was one case of DGF in the control group, and 4 children lost their grafts including the one with DGF.Conclusion:Pre-implantation renal biopsy can provide important baseline information of the graft with implications on subsequent medical treatment for pediatric renal transplant recipients.

Efficacy and Safety of an Everolimus- vs. a Mycophenolate Mofetil-Based Regimen in Pediatric Renal Transplant Recipients

IntroductionData on the efficacy and safety of everolimus in pediatric renal transplantation compared to other immunosuppressive regimens are scarce.Patients/MethodsWe therefore performed a multicenter, observational, matched cohort study over 4 years post-transplant in 35 patients on everolimus plus low-dose cyclosporine, who were matched (1:2) with a control group of 70 children receiving a standard-dose calcineurin-inhibitor- and mycophenolate mofetil-based regimen.ResultsCorticosteroids were withdrawn in 83% in the everolimus vs. 39% in the control group (p<0.001). Patient and graft survival were comparable. The rate of biopsy-proven acute rejection episodes Banff score ≥ IA during the first year post-transplant was 6% in the everolimus vs. 13% in the control group (p = 0.23). The rate of de novo donor-specific HLA antibodies (11% in everolimus, 18% in controls) was comparable (p = 0.55). At 4 years post-transplant, mean eGFR in the everolimus group was 56±33 ml/min per 1.73 m² vs. 63±22 ml/min per 1.73 m² in the control group (p = 0.14). Everolimus therapy was associated with less BK polyomavirus replication (3% vs. 17% in controls; p = 0.04), but with a higher percentage of arterial hypertension and more hyperlipidemia (p<0.001).ConclusionIn pediatric renal transplantation, an everolimus-based regimen with low-dose cyclosporine yields comparable four year results as a standard regimen, but with a different side effect profile.

Anti-HLA antibodies in pediatric renal transplant recipients – Analysis of potential triggers

Aim HLA antigen sensitization poses a challenge both before and after renal transplantation (KTx). Its etiology and clinical importance in pediatric transplant recipients is not well understood. The aim of the study was to examine potential causes of HLA antibody formation in children pre- and post KTx. Methods A retrospective chart review of pediatric renal allograft recipients ages 1–18 years and transplanted between January 2009 and December 2014 was performed. Data extracted included potential sensitizing events (transfusion, rejection, infection, vaccination) and anti-HLA antibody (Ab) status. Ab were detected by flow cytometry-based single antigen bead assays. A mean fluorescence intensity (MFI) > 1000 was considered positive. Other events such as delayed graft function were not included in the analysis. Results Of a total of 20 transplanted patients (8 females), 5 received a living-related and 15 a de-ceased donor graft. The median age at KTx was 9.2 years. Eleven of the 20 patients (55%) had detectable HLA Ab during a median follow-up of 3.1 years. Two patients had de-novo donor-specific antibodies (DSA) and two had self-antibodies. Major possible causes of HLA sensitization were blood and platelet transfusions, infections and vaccinations (Table). Mono-specific HLA Ab were identified in 5, multi-specific Ab in 3, and mono- and multi-specific Ab (at discrete occasions) in 3 children. A possible sensitizing immunological trigger was noted in 1 patient with mono-specific, 6 patients with multi-specific, and 1 patient with sequential detection of mono- and multi-specific HLA Ab. Conclusion Our results demonstrate that transfusions, infections and/or immunizations may sensitize pediatric graft recipients leading to mono- or multi-specific HLA Ab. Their clinical significance, specifically concerning antibody-mediated rejection and graft outcome, remains to be established. Download : Download full-size image

Donor-specific anti-HLA antibodies in pediatric renal transplant recipients with creeping creatinine: Prevalence, histological correlations, and impact on patient and graft survival.

Donor-specific anti-HLA antibodies (DSA) causing CAMR are responsible for a high proportion of long-term graft failures after RTX. We studied the prevalence of DSA in RTX children biopsied for creeping Cr, its relationship with NA, and patient and graft survival according to histopathology. Between 2008 and 2013, 92 children were biopsied at a median of 38 months post-RTX. At biopsy, the prevalence of DSA was 49% and C4d 70%. NA rate was 45%, higher in adolescents (60%). Most frequent diagnoses were CAMR (72%) and interstitial fibrosis with tubular atrophy (IFTA) (28%). Forty-five of 66 patients with CAMR (68%) had detectable DSA. Twenty-one DSA-negative patients with CAMR had histological damage (IFTA + C4d positivity). C4d was detected in 64 of 66 biopsies with CAMR. Recipients with IFTA alone had neither C4d, nor detectable DSA, and were adherent. Graft survival at five yr was 89% in patients with CAMR, 79% in those with CAMR + TCMR Banff I, 33% in those with CAMR + TCMR Banff II, and 96% in those with IFTA. ABMR and complement activation were frequent in children biopsied for creeping Cr. Recipients with DSA were more likely to be non-adherent and have CAMR or CAMR + TCMR and worse graft survival.

Clinical efficacy and pharmacokinetics of tacrolimus in children with steroid-resistant nephrotic syndrome.

Tacrolimus has gained acceptance in the management of steroid-resistant nephrotic syndrome (SRNS) in children. Due to limited data, therapeutic range is extrapolated from pediatric renal transplant recipients. This study was designed to assess therapeutic efficacy of tacrolimus in children with SRNS and its correlation with inter-dose area under concentration curve (AUC0-12 h) and trough concentration (C0). Pre dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3, 4, 8, and 12 h after drug administration blood samples were collected in 25 children who were on tacrolimus for a minimum of 3 months and AUC0-12 h was calculated. There was an 80% (20/25) response rate with 64% (16/25) children achieving complete remission. Median C0 in remission was higher than in relapse group (2.95 ng/ml, versus 1.20 ng/ml, p = 0.005). Median AUC0-12 h in remission was higher compared to those in relapse group (79.75 versus 35.15 μg × h/l; p = 0.025). Maximum concentration after drug administration (Cmax) among the groups was not significantly different. There was a significant correlation between C0 and AUC0-12 h (r = 0.79); and Cmax and AUC0-12 h (r = 0.84). Five patients had a rise in serum creatinine, of which four were still proteinuric and had lower C0 and AUC0-12 h. No other adverse effect was noted. Tacrolimus had beneficial clinical response in SRNS. Target C0 and AUC0-12 h level for treatment remission was higher than those in relapse in children with SRNS but was lower than required in transplant recipient.

Sexually transmitted infections in pediatric renal transplant recipients: Time to take notice!

We sought to assess the prevalence of STIs, contraception use, and unintentional pregnancy in our pediatric renal transplant recipients. We performed a retrospective chart review. Forty-nine of 65 patients in our program are currently in the high-risk age window of 13 yr or older (34 men, 15 women; mean age 17 yr old, range 13-23 yr old). There was a disproportionate difference in sexual behavior among the men and women, such that while only 15% of the men reported being sexually active, 53% of the women were sexually active. Among high-risk age-group women, 40% were on hormonal contraception. This increased to 75% in sexually active women. There were no cases of unintentional pregnancy. Thirty percent of sexually active recipients had at least one STI. This was higher among sexually active women (37.5%) compared to men (20%). STIs identified included gonococcal and chlamydial urethritis/cervicitis, Trichomonas vaginitis, HSV-2 genital sores, pelvic inflammatory disease, and HIV. In conclusion, STIs are a realistic public health concern in our pediatric renal transplant recipients. Consensus guidelines on STI screening and reproductive health counseling are needed to address this understudied problem.

Vitamin D insufficiency and deficiency in pediatric renal transplant recipients

Vitamin D deficiency is prevalent in the pediatric CKD population. Recognizing that renal transplant recipients have CKD, we assessed the prevalence of vitamin D insufficiency and deficiency in pediatric renal transplant recipients, compared to a healthy pediatric population. We prospectively studied 25(OH)D levels in 29 pediatric renal transplant recipients and 45 control patients over one yr. The overall prevalence of vitamin D insufficiency and deficiency was common in both populations, at 76% (95% CI: 61, 87%) in the pediatric renal transplant recipients and 91% (95% CI: 80, 98%) in the control group. In the paired renal transplant samples, the mean 25(OH)D level was 52.3 ± 17.9 nmol/L in the winter and 65.6 ± 18.8 nmol/L in the summer (95% CI diff.: 3.9, 22.7), in keeping with a significant seasonal difference. The mean dietary intake of vitamin D in the renal transplant recipients, assessed by three-day dietary record, was 5.7 μg/day, with a vitamin D intake below the EAR in the majority. We did not find an association between vitamin D intake and 25(OH)D levels in this study, likely due to the low dietary intake of vitamin D within the transplant population, identifying a potential area for intervention and improvement.

A high-performance liquid chromatography – tandem mass spectrometry – based targeted metabolomics kidney dysfunction marker panel in human urine

BackgroundPrevious studies have examined and documented fluctuations in urine metabolites in response to disease processes and drug toxicity affecting glomerular filtration, tubule cell metabolism, reabsorption, oxidative stress, purine degradation, active secretion and kidney amino acylase activity representative of diminished renal function. However, a high-throughput assay that incorporates metabolites that are surrogate markers for such changes into a kidney dysfunction panel has yet to be described. MethodsA high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) assay for the quantification of ten metabolites associated with the Krebs cycle, purine degradation, and oxidative stress in human urine was developed and validated. Normal values were assessed in healthy adult (n=120) and pediatric (n=36) individuals. In addition, 9 pediatric renal transplant recipients patients were evaluated before and after initial dosing of the immunosuppressant tacrolimus in a proof-of-concept study. ResultsThe assay met all predefined acceptance criteria. The lower limit of quantification ranged from 0.1 to 1000 μmol/l. Inter-day trueness and imprecisions ranged from 91.4–112.9% and 1.5–12.4%, respectively. The total assay run time was 5.5 minutes.Concentrations of glucose, sorbitol, and trimethylamine oxide (TMAO) were elevated in pediatric renal transplant patients (n=9) prior to transplantation as well as before and immediately after initial dosing of tacrolimus. One month post-transplant urine metabolite patterns matched those of healthy children (n=36). ConclusionsThe LC-MS/MS assay will provide the basis for further large-scale clinical studies to explore these analytes as molecular markers for the patients with renal insufficiency.

G487(P) Improving renal allograft survival by introducing a multicomponent transition programme for paediatric renal transplant recipients

Background Adolescence is a vulnerable period for paediatric renal transplant recipients (RTR), with many losing their allografts within years of transferring to adult care. A transition programme was developed to better equip RTR for adulthood. It features a five-year education framework with a phased-handover to the adult team over two years via joint-clinics. Aims To evaluate the impact of the transition programme on post-transfer renal allograft survival and to evaluate the patient education arm of the transition programme. Methods A retrospective cohort study of RTR who transferred from a paediatric centre before the transition programme was introduced (non-transition cohort) and RTR who transferred via the transition programme (transition cohort). RTR who transferred to one of four adult centres between January 1999 and January 2014 were followed up to their first four years in adult care. Data on renal allograft survival and therapeutic drug monitoring of immunosuppressive medications were collected. Additionally, RTR currently on the programme approaching transfer completed a questionnaire to indicate self-care competencies they possessed and post-transfer RTR were asked if the transition programme helped them develop said competencies. Results 106 (69 non-transition, 37 transition) RTR were followed-up. Non-transition RTR were 2.76 times more likely to lose their allografts during their first four years in adult care; when controlling for donor type (live/deceased), prior number of renal transplants and the time (days) post–transplant prior transferring (95% CI = 0.808 – 9.51; p = 0.1). The transition cohort also had on average 21% (65% vs. 44%) more of their trough levels within their therapeutic target levels (95% CI = 2.5–38.4%; p = 0.03). 41 RTR at the paediatric centre and 7 post-transfer RTR completed the questionnaire. Responses indicated patients possessed most competencies, except for managing administrative tasks relating to their care. Over 50% of post-transfer RTR reported the programme helped them develop all, but one, competencies they possessed. Conclusion We report the largest follow-up to-date of RTR from a single centre evaluating a novel, multicomponent transition programme. Our data indicates a longitudinal transition programme with a phased-handover via joint–clinics is positively associated with post-transfer renal allograft survival.

Elevated urinary CXCL10-to-creatinine ratio is associated with subclinical and clinical rejection in pediatric renal transplantation.

Subclinical and clinical T cell-mediated rejection (TCMR) has significant prognostic implications in pediatric renal transplantation. The goal of this study was to independently validate urinary CXCL10 as a noninvasive biomarker for detecting acute rejection in children and to extend these findings to subclinical rejection. Urines (n = 140) from 51 patients with surveillance or indication biopsies were assayed for urinary CXCL10 using enzyme-linked immunosorbent assay and corrected with urinary creatinine. Median urinary CXCL10-to-creatinine (Cr) ratio (ng/mmol) was significantly elevated in subclinical TCMR (4.4 [2.6, 25.4], P < 0.001, n = 17); clinical TCMR (24.3 [11.2, 44.8], P < 0.001, n = 9); and antibody-mediated rejection (6.0 [3.3, 13.7], P = 0.002, n = 9) compared to noninflamed histology (1.4 [0.4, 4.2], normal and interstitial fibrosis and tubular atrophy, n = 52), and borderline tubulitis (3.3, [1.3, 4.9], n = 36). Elevated urinary CXCL10:Cr was independently associated with t scores (P < 0.001) and g scores (P = 0.006) on multivariate analysis. The area under receiver operating curve for subclinical and clinical TCMR was 0.81 (P = 0.045) and 0.88 (P = 0.019), respectively. This corresponded to a sensitivity-specificity of 0.59-0.67 and 0.77-0.60 for subclinical and clinical TCMR at cutoffs of 4.82 and 4.72 ng/mmol, respectively. This study demonstrates that urinary CXCL10:Cr corresponds with microvascular inflammation and is a sensitive and specific biomarker for subclinical and clinical TCMR in children. This may provide a noninvasive monitoring tool for posttransplant immune surveillance for pediatric renal transplant recipients.

G473 Outcomes of abo incompatible kidney transplantation in children

Objective ABO blood group incompatible transplantation (ABOi) has become increasingly common over the last decade, in part due to a shortage of suitable deceased donor allografts. Whilst encouraging data is emerging on short and medium term graft outcomes in adults, ABOi in children is rare; pre-transplant conditioning in paediatric patients remains challenging and concerns persist about an increased risk of rejection. Encouraged by good results in a large number of adult ABOi transplants, we extended our programme to paediatric recipients, and here report the largest European cohort. Methods A retrospective analysis of all ABOi paediatric renal transplant recipients in the 2 largest centres in the UK sharing the same tailored desensitisation protocol. Patients with pre-transplant titres 1 in 8 or above received rituximab one month prior to transplant; tacrolimus and mycophenolate mofetil were started one week pre-op. Antibody removal was performed to reduce titres to 1 in 8 or less at surgery. No routine post-op removal was performed. Results Ten children (age 2–14 years) underwent an ABOi kidney transplant (Figures 1 and 2 and Table 1). Graft and patient survival was 100%. Baseline titres, tailored desensitisation and graft outcomes are shown in table. One patient developed grade IIa rejection after 2 weeks successfully treated with anti-thymocyte globulin;no histological evidence of rejection in other 9 patients. Another patient had a rise in titre of 2 dilutions at week one treated with 2 immunoadsorption sessions. Nine patients had good graft function (eGFR 30–130 mls/min/1.73m2) at last follow up (range 1–36 months); one patient had eGFR 22 ml/min/1.73m2. One patient developed CMV and BK; another EBV and BK. Conclusion ABOi transplantation in children appears to have an optimal outcome with good graft survival, low risk of rejection and infectious complications.

Mineral Metabolism in European Children Living with a Renal Transplant

Data on mineral metabolism in pediatric renal transplant recipients largely arise from small single-center studies. In adult patients, abnormal mineral levels are related to a higher risk of graft failure. This study used data from the European Society for Paediatric Nephrology/European Renal Association-European Dialysis and Transplant Association Registry to study the prevalence and potential determinants of mineral abnormalities, as well as the predictive value of a disturbed mineral level on graft survival in a large cohort of European pediatric renal transplant recipients. This study included 1237 children (0-17 years) from 10 European countries, who had serum calcium, phosphorus, and parathyroid hormone measurements from 2000 onward. Abnormalities of mineral metabolism were defined according to European guidelines on prevention and treatment of renal osteodystrophy in children on chronic renal failure. Abnormal serum phosphorus levels were observed in 25% (14% hypophosphatemia and 11% hyperphosphatemia), altered serum calcium in 30% (19% hypocalcemia, 11% hypercalcemia), and hyperparathyroidism in 41% of the patients. A longer time since transplantation was associated with a lower risk of having mineral levels above target range. Serum phosphorus levels were inversely associated with eGFR, and levels above the recommended targets were associated with a higher risk of graft failure independently of eGFR. Abnormalities in mineral metabolism are common after pediatric renal transplantation in Europe and are associated with graft dysfunction.

Use of pharmacogenomics in pediatric renal transplant recipients.

Transplant recipients receive potent immunosuppressive drugs in order to prevent graft rejection. Therapeutic drug monitoring is the current approach to guide the dosing of calcineurin inhibitors, mammalian target of rapamycin inhibitors (mTORi) and mofetil mycophenolate. Target concentrations used in pediatric patients are extrapolated from adult studies. Gene polymorphisms in metabolizing enzymes and drug transporters such as cytochromes CYP3A4 and CYP3A5, UDP-glucuronosyl transferase, and P-glycoprotein are known to influence the pharmacokinetics and dose requirements of immunosuppressants. The implications of pharmacogenomics in this patient population is discussed. Genetic information can help with achieving target concentrations in the early post-transplant period, avoiding adverse drug reactions and drug-drug interactions. Evidence about genetic studies and transplant outcomes is revised.