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Recurrence of primary disease is one of the major risks for allograft loss after pediatric RTx. The risk of recurrence of FSGS/SRNS after pediatric RTx in particular can be up to 86% in idiopathic cases. There is a need for consensus recommendations on its prevention and treatment. The CERTAIN study group has therefore performed a thorough literature search based on the PICO model of clinical questions to formulate educated statements to guide the clinician in the process of decision-making. A set of educated statements on prevention and treatment of FSGS/SRNS after pediatric RTx has been generated after careful evaluation of available evidence and thorough panel discussion. We do not recommend routine nephrectomy prior to transplantation; neither do we recommend abstaining from living donation. Special attendance needs to be given to those patients who had already experienced graft loss due to FSGS/SRNS recurrence. Early PE or IA with or without high-dose CsA and/or rituximab seems to be most promising to induce remission. The educated statements presented here acknowledge that FSGS/SRNS recurrence after pediatric RTx remains a major concern and is associated with shorter graft survival or even graft loss. The value of any recommendation needs to take into account that evidence is based on cohorts that differ in ethnicity, pre-transplant history, immunosuppressive regimen, definition of recurrence (eg, clinical and/or histological diagnosis) and treatment modalities of recurrence., (© 2020 Wiley Periodicals LLC.)

Background and Aims: This multicenter trial compared immediate-release tacrolimus (IR-T) vs prolonged-release tacrolimus (PR-T) in de novo kidney, liver, and heart transplant recipients aged <16 years. Each formulation had similar pharmacokinetic (PK) profiles. Follow-up efficacy and safety results are reported herein., Materials and Methods: Patients, randomized 1:1, received once-daily, PR-T or twice-daily, IR-T within 4 days of surgery. After a 4-week PK assessment, patients continued randomized treatment for 48 additional weeks. At Year 1, efficacy assessments included the number of clinical acute rejections, biopsy-confirmed acute rejection (BCAR) episodes (including severity), patient and graft survival, and efficacy failure (composite of death, graft loss, BCAR, or unknown outcome). Adverse events were assessed throughout., Results: The study included 44 children. At Year 1, mean ± standard deviation tacrolimus trough levels were 6.6 ± 2.2 and 5.4 ± 1.6 ng/mL, and there were 2 and 7 acute rejection episodes in the PR-T and IR-T groups, respectively. No cases of graft loss or death were reported during the study. The overall efficacy failure rate was 18.2% (PR-T n = 1; IR-T n = 7)., Conclusions: In pediatric de novo solid organ recipients, the low incidence of BCAR and low efficacy failure rate suggest that PR-T-based immunosuppression is effective and well tolerated to 1-year post-transplantation., (© 2019 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)

Objective: There are no specific recommendations for therapeutic plasma exchange (TPE) in children after renal transplantation. The purpose of this study was to report the experience with TPE in a pediatric transplant setting., Materials and Methods: 59 patients (mean age 12.5 ± 4.5 years) undergoing renal transplantation. Indications for TPE included the recurrence of nephrotic syndrome (NS; n = 30) and atypical hemolytic uremic syndrome (n = 6), chronic antibody-mediated rejection (cAMR; n = 20), sensitization (n = 2), and immune thrombocytopenia (n = 1). The single-filtration TPE was performed in all cases. In 74.7% of patients, fresh frozen plasma was used as a replacement fluid. In 25.3% of patients, 4% albumin solution was used as a replacement fluid. Criteria for TPE efficacy included a decrease of proteinuria and normalization of renal function in NS; a normalization of platelet count, C3, and hemoglobin concentration in aHUS; improvement in renal function; and reduction of donor-specific antibodies in cAMR; and removal of antiplatelet antibodies in immune thrombocytopenia., Results: Efficacy results for patients with NS: 59.3% achieved remission, 25.9% achieved partial remission, and 14.8% achieved no remission, respectively. For patients with atypical hemolytic uremic syndrome there was remission in 66.6% and no remission in 33.4%. For patients with cAMR there was remission in 75% and no remission in 25%. Antiplatelet antibodies disappeared after TPE in 1 patient. In 9% of TPE procedures, minor complications were noted. All patients were on posttransplant maintenance immunosuppression and several children received additional treatment (intravenous immunoglobulin therapy or rituximab) during TPE therapy., Conclusion: TPE therapy (combined with immunosuppression) was an effective tool in most pediatric cases after renal transplantation with low incidence of minor adverse events., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Infants with a body weight of less than 10 kg are often not considered to be suitable candidates for renal transplantation (RTx). The objective of this study was to evaluate this arbitrary weight threshold for pediatric RTx., Methods: We conducted a multicenter, retrospective, match-controlled cohort study on infants weighing less than 10 kg at time of engrafting (low-weight group [LWG], n = 38) compared to a matched control group (n = 76) with a body weight of 10-15 kg, using data from the first 2 years post-transplant derived from the CERTAIN Registry., Results: Patient survival was 97 and 100% in the LWG and control groups, respectively (P = 0.33), and death-censored graft survival was 100 and 95% in the LWG and control groups, respectively (P = 0.30). Estimated glomerular filtration rate at 2 years post-transplant was excellent and comparable between the groups (LWG 77.6 ± 34.9 mL/min/1.73 m 2 ; control 74.8 ± 29.1 mL/min/1.73 m 2 ; P = 0.68). The overall incidences of surgery-related complications (LWG 11%, control 23%; P = 0.12) and medical outcome measures (LWG 23%, control 36%, P = 0.17) were not significantly different between the groups. The medical outcome measures included transplant-related viral diseases (LWG 10%, control 21%; P = 0.20), acute rejection episodes (LWG 14%, control 29%; P = 0.092), malignancies (LWG 3%, control 0%; P = 0.33) and arterial hypertension (LWG 73%, control 67%; P = 0.57)., Conclusions: These data suggest that RTx in low-weight children is a feasible option, at least in selected centers with appropriate surgical and medical expertise.

Unlabelled: Pediatric patients with end-stage renal failure due to severe drug-resistant nephrotic syndrome are at risk of rapid recurrence after renal transplantation. Treatment options include plasmapheresis, high-dose of cyclosporine A/methylprednisolone and more recently-rituximab (anti-B CD20 monoclonal depleting antibody). We report five patients with immediate (1-2 days) post-transplant recurrence of nephrotic syndrome, treated with this kind of combined therapy including 2-4 weekly doses of 375 mg/m(2) of rituximab. Only two (of five) patients have showed full long-term remission, while the partial remission was seen in two cases, and no clinical effect at all was achieved in one patient. The correlation between B CD19 cells depletion and clinical effect was present in two cases only. Severe adverse events were present in two patients, including one fatal rituximab-related acute lung injury., Conclusion: The anti-CD20 monoclonal antibody may be not effective in all pediatric cases of rapid post-transplant recurrence of nephrotic syndrome, and benefit/risk ratio must be carefully balanced on individual basis before taking the decision to use this protocol., What Is Known: • nephrotic syndrome may recur immediately after renal transplantation • plasmapheresis combined with pharmacotherapy is used as rescue management • rituximab was reported as effective drug both in primary and post-transplant nephrotic syndrome What is New: • rituximab may not be effective is several cases of post-transplant nephrotic syndrome due to variety of underlying mechanisms of the disease, which may be or not be responsive to this drug • there may be no correlation between drug-induced depletion of specific B cells and clinical effect; this might suggest B-cell independent manner of rituximab action., Competing Interests: Compliance with ethical standards All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Funding The study did not receive fundings. Conflict of interest The authors declare that they have no conflict of interest. Informed consent Informed consent was obtained from all individual participants included in this study.

Background: Some kidney diseases tend to recur in the renal allograft after transplantation. We studied the risk of graft loss among primary renal diseases known for their high risk of recurrence and compared it with that of patients with hypoplasia and/or dysplasia., Methods: Within the European Society of Paediatric Nephrology and European Renal Association and European Dialysis and Transplant Association (ESPN/ERA-EDTA) registry, we studied children from 33 countries who received a kidney transplant before the age of 20 between 1990 and 2009. Patients were censored after 5 years of follow-up and cumulative incidence competing risk analysis was used to calculate survival curves., Results: Patients with focal and segmental glomerulosclerosis (FSGS), haemolytic uraemic syndrome (HUS), membranoproliferative glomerulonephritis Type I or II (MPGN), IgA nephropathy or Henoch Schönlein Purpura (HSP/IgA) or systemic lupus erythomatosus (SLE) underwent pre-emptive transplantation significantly less often than patients with hypoplasia and/or dysplasia. The rate of living donation was lower among patients with FSGS and SLE than in patients with hypoplasia and/or dysplasia. In comparison with hypoplasia and/or dysplasia patients with a risk of 14.4%, the 5-year risk of graft loss was significantly increased in patients with FSGS (25.7%) and MPGN (32.4%) while it was not significantly increased in children with HUS (18.9%), HSP/IgA (16.3%) or SLE (20.3%). One-year graft survival strongly improved among HUS patients from 17.1% in 1995-1999 to 3.6% in 2005-2009 and was not accompanied by a decrease in the number of transplantations., Conclusion: The risk of graft loss is increased among specific causes of renal failure with a high risk of post-transplant recurrence. It seems likely that, due to anticipation of such risk, physicians perform less pre-emptive transplantation and provide fewer grafts from living related donors in patients with these conditions. Improved risk stratification by physicians, resulting in the identification of patients with HUS at higher or lower risk of recurrence, might explain the much improved graft survival rates.

Background: Systemic complications in patients after renal or liver transplantation may be localized in the oral cavity. Calcium-phosphate disturbances may affect the structure and metabolism of mandible bones, promote calcification of dental pulp, and in children may cause developmental defects of teeth. The aim of this study was to evaluate the incidence of dental and bone abnormalities in children and adolescents after kidney and liver transplantation with respect to the type of the transplanted organ and maintenance immunosuppression., Material/methods: Overall, 23 kidney and 25 liver recipients (mean age: 13.95±4.2 yrs) were evaluated. Twenty patients received ciclosporin A (CsA) and 28 tacrolimus (TAC). Twenty-one kidney and 14 liver recipients were treated with steroids. Mean time after transplantation was 3.62±2.98 years., Results: The severity of caries and percentage of odontogenic abnormalities (76.0% vs. 60.86%) was higher in liver transplant recipients. Positive correlations were found between discoloration of the deciduous teeth and liver transplantation, between enamel hypoplasia and kidney transplantation, and between treatment with CsA and its dose and blood concentration (p<0.05). Pulp stones were present in 13.04% of kidney vs. 8.0% in liver recipients, more often in those treated with CsA than with TAC. Jaw bone abnormalities were present in 30.43% kidney recipients vs. 12% liver recipients., Conclusions: Both kidney and liver recipients present dental and bone abnormalities. The incidence of specific types of oral lesions is different in renal and liver graft recipients; however, it is also correlated with specific immunosuppression.

Purpose: Candidiasis is an infectious complication in organ transplant recipients resulting from the patients' immunodeficiency and virulence of fungi pathogens. The purpose of this study was to evaluate the frequency of Candida spp. and identify their presence in the oral lesions of graft recipients., Methods: This study included 185 patients, 1.5 to 25.2 years of age (mean = 13.1 +/- 4.2 years) who were receiving combined immunosuppression treatment after kidney or liver transplantation and 70 control subjects. Evaluation included clinical oral examination, mycology, and statistical analysis., Results: Candida spp. colonies were found in the oral mucosa of 63 (34%) graft recipients and in 19 (27%) control subjects. Candida albicans was the most prevalent species. This study showed that, regardless of the type of the organ transplant and immunosuppression, frequent, regular oral follow-up and mycologic tests are recommended. Diagnosing increased density of Candida spp. colonies in the oral cavity will help initiate early antifungal treatment., Conclusions: Candida spp. prevalence in the oral cavity in transplant recipients was higher than in immunocompetent control subjects. Kidney or liver transplantation predisposes one to the development of an increased density of Candida spp. colonies.