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Background: Children requiring kidney replacement therapy experience high burden of cardiovascular (CV) disease leading to increased mortality. Intima-media thickness (IMT) indicating atherosclerosis is a validated surrogate marker for future CV events., Methods: We investigated the effect of different treatment modalities (dialysis, preemptive kidney transplantation (KTx), late KTx after dialysis) on IMT by multivariable linear mixed-effect modeling. Patients were enrolled in a prospective cohort study., Results: A total of 261 analyzed children had a mean follow-up of 3 y. Children after preemptive and late KTx had lower levels of IMT when compared with dialysis. Using an interaction term, a significant progression of IMT over time was seen during dialysis (β = 0.0053 mm/y, P   =  0.004). IMT before the start of therapy was the most influential determinant in all models. Low IMT was associated with maintenance steroid treatment after preemptive KTx. High IMT on dialysis was associated with higher systolic blood pressure, lower body mass index, lower serum albumin, and lower bicarbonate., Conclusions: IMT remained rather stable in children several years after KTx. In contrast, children on dialysis had higher IMT values, which increased over time. In these children, blood pressure control, calorie and protein intake, and acid-base homeostasis seem important. Taken together, children might profit from early transplantation to limit accumulation of CV risk., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Focal segmental glomerular sclerosis (FSGS) is 1 of the primary causes of nephrotic syndrome in both pediatric and adult patients, which can lead to end-stage kidney disease. Recurrence of FSGS after kidney transplantation significantly increases allograft loss, leading to morbidity and mortality. Currently, there are no consensus guidelines for identifying those patients who are at risk for recurrence or for the management of recurrent FSGS. Our work group performed a literature search on PubMed/Medline, Embase, and Cochrane, and recommendations were proposed and graded for strength of evidence. Of the 614 initially identified studies, 221 were found suitable to formulate consensus guidelines for recurrent FSGS. These guidelines focus on the definition, epidemiology, risk factors, pathogenesis, and management of recurrent FSGS. We conclude that additional studies are required to strengthen the recommendations proposed in this review., (Copyright © 2023 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: We assessed the effect of blood pressure (BP) control on left ventricular mass index (LVMI) and left ventricular hypertrophy (LVH)., Methods: Ninety-six patients (64 males) ≥9 months post-kidney transplantation from the 4C-T (Cardiovascular Comorbidity in Children with Chronic Kidney Disease and Transplantation) study were analyzed longitudinally (mean follow-up, 2.6±1.3 years). Cumulative systolic blood pressure (SBP)/diastolic BP exposure was calculated as a time-averaged area under the curve and categorized: ≤50th, 50th to ≤75th, 75th to ≤90th, and >90th percentile (pct). We performed adjusted linear and logistic mixed models for LVMI and LVH, respectively., Results: At baseline, LVMI was 49.7±12.7g/m 2.16 with 64% (n=61) kidney transplantation recipients displaying LVH. Compared with patients with cumulative SBP exposure >90th pct, patients with cumulative SBP of 50th to ≤75th showed a significant LVMI reduction of -5.24g/m 2.16 ( P =0.007). A similar tendency was seen for cumulative SBP≤50th (β=-3.70 g/m 2.16 ; P =0.067), but patients with cumulative SBP of 75th to ≤90th pct showed no reduction. A post hoc analysis in patients with cumulative SBP≤75th revealed that median SBP exposure was at 57.5th pct. For cumulative diastolic BP, a significant LVMI reduction was seen in all 3 categories ≤90th pct compared with patients >90th pct. Patients with cumulative SBP of ≤50th or 50th to ≤75th pct showed 79% or 83% lower odds of developing LVH, respectively. Patients with cumulative diastolic BP ≤50th showed a tendency of 82% lower odds for LVH (95% CI, 0.03-1.07)., Conclusions: Stricter BP control led to regression of LVMI and LVH. Our data suggest a BP target below the 60th pct, which needs to be substantiated in a randomized controlled trial., Competing Interests: Disclosures None.

Mortality in children with kidney failure is higher in girls than boys with cardiovascular complications representing the most common causes of death. Pulse wave velocity (PWV), a measure of vascular stiffness, predicts cardiovascular mortality in adults. Here, PWV in children with kidney failure undergoing kidney replacement therapy was investigated to determine sex differences and potential contributing factors. Two-hundred thirty-five children (80 girls; 34%) undergoing transplantation (150 pre-emptive, 85 with prior dialysis) having at least one PWV measurement pre- and/or post-transplantation from a prospective cohort were analyzed. Longitudinal analyses (median/maximum follow-up time of 6/9 years) were performed for PWV z-scores (PWVz) using linear mixed regression models and further stratified by the categories of time: pre-kidney replacement therapy and post-transplantation. PWVz significantly increased by 0.094 per year and was significantly higher in girls (PWVz +0.295) compared to boys, independent of the underlying kidney disease. During pre-kidney replacement therapy, an average estimated GFR decline of 4 ml/min/1.73 m 2 per year was associated with a PWVz increase of 0.16 in girls only. Higher diastolic blood pressure and low density lipoprotein were independently associated with higher PWVz during pre-kidney replacement therapy in both sexes. In girls post-transplantation, an estimated GFR decline of 4ml/min/1.73m 2 per year pre-kidney replacement therapy and a longer time (over 12 months) to transplantation were significantly associated with higher PWVz of 0.22 and of 0.57, respectively. PWVz increased further after transplantation and was positively associated with time on dialysis and diastolic blood pressure in both sexes. Thus, our findings demonstrate that girls with advanced chronic kidney disease are more susceptible to develop vascular stiffening compared to boys, this difference persist after transplantation and might contribute to higher mortality rates seen in girls with kidney failure., (Copyright © 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: The International Pediatric Nephrology Association (IPNA) Global Kidney Replacement Therapy (KRT) Registry was established to evaluate the incidence and outcomes of kidney replacement therapy (dialysis and transplantation) provided to children worldwide. Analysis of registry data for separate regions is feasible., Methods: Three centers located in Shanghai, Guangzhou, and Zhengzhou, which have the greatest number of pediatric kidney transplantation cases in China, participated in this analysis of transplant data. Data were registered by each center for patients under the age of 19 years who received a single-organ kidney transplant for the first time between 2011 and 2018., Results: In total, 415 patients (59.8% male) aged 1.4-18.7 (median 12.1) years were followed for 0.3-97.1 (median 27.7) months. The number of kidney transplants increased from a total of 129 during 2011-2014 to 286 cases during 2015-2018. 85.8% of patients received the transplanted kidney from a pediatric (age < 19 years) donor, and deceased donors accounted for 94% of all donors. 8.0% of grafts were lost. One and 5-year patient survival rates were 97.6% and 95.5%, respectively. The major cause of death was infection (7/14). Similar graft and patient survival rates were observed for organs from pediatric and adult donors in 6-11 and 12-18 year recipient age groups, whereas recipients < 6 years showed inferior patient and graft survival., Conclusions: Pediatric kidney transplantation shows favorable short-term and medium-term outcomes in China. Our experience supports use of pediatric donors in pediatric kidney transplantation, but attention directed to the outcome of recipients aged under 6 is necessary. Graphical abstract.

Background: Current guidelines advocate use of arteriovenous fistula (AVF) over central venous catheter (CVC) for children starting hemodialysis (HD). European data on current practice, determinants of access choice and switches, patient survival, and access to transplantation are limited., Methods: We included incident patients from 18 European countries who started HD from 2000 to 2013 for whom vascular access type was reported to the ESPN/ERA-EDTA Registry. Data were evaluated using descriptive statistics, logistic and Cox regression models, and cumulative incidence competing risk analysis., Results: Three hundred ninety-three (55.1%) of 713 children started HD with a CVC and were more often females, younger, had more often an unknown diagnosis, glomerulonephritis, or vasculitis, and lower hemoglobin and height-SDS at HD initiation. AVF patients were 91% less likely to switch to a second access, and two-year patient survival was 99.6% (CVC, 97.2%). Children who started with an AVF were less likely to receive a living donor transplant (adjusted HR, 0.30; 95% CI, 0.16-0.54) and more likely to receive a deceased donor transplant (adjusted HR, 1.50; 95% CI, 1.17-1.93), even after excluding patients who died or were transplanted in the first 6 months., Conclusions: CVC remains the most frequent type of vascular access in European children commencing HD. Our results suggest that the choice for CVC is influenced by the time of referral, rapid onset of end-stage renal disease, young age, and an expected short time to transplantation. The role of vascular access type on the pattern between living and deceased donation in subsequent transplantation requires further study.

Background: As outcome data for prune belly syndrome (PBS) complicated by end-stage renal disease are scarce, we analyzed characteristics and outcomes of children with PBS using the European Society for Pediatric Nephrology/European Renal Association-European Dialysis and Transplant Association (ESPN/ERA-EDTA) Registry data., Methods: Data were available for 88 male PBS patients aged <20 years who started renal replacement therapy (RRT) between 1990 and 2013 in 35 European countries. Patient characteristics, survival, and transplantation outcomes were compared with those of male patients requiring RRT due to congenital obstructive uropathy (COU) and renal hypoplasia or dysplasia (RHD)., Results: Median age at onset of RRT in PBS was lower [7.0; interquartile range (IQR) 0.9-12.2 years] than in COU (9.6; IQR: 3.0-14.1 years) and RHD (9.4; IQR: 2.7-14.2 years). Unadjusted 10-year patient survival was 85% for PBS, 94% for COU, and 91% for RHD. After adjustment for country, period, and age, PBS mortality was similar to that of RHD but higher compared with COU [hazard ratio (HR) 1.96, 95% confidence interval (CI) 1.03-3.74]. Seventy-four PBS patients (84%) received a first kidney transplant after a median time on dialysis of 8.4 (IQR 0.0-21.1) months. Outcomes with respect to time on dialysis before transplantation, chance of receiving a first transplant within 2 years after commencing RRT, and death-censored, adjusted risk of graft loss were similar for all groups., Conclusions: This study in the largest cohort of male patients with PBS receiving RRT to date demonstrates that outcomes are comparable with other congenital anomalies of the kidney and urinary tract, except for a slightly higher mortality risk compared with patients with COU.

Background: The impact of donor age in paediatric kidney transplantation is unclear. We therefore examined the association of donor-recipient age combinations with graft survival in children., Methods: Data for 4686 first kidney transplantations performed in 13 countries in 1990-2013 were extracted from the ESPN/ERA-EDTA Registry. The effect of donor and recipient age combinations on 5-year graft-failure risk, stratified by donor source, was estimated using Kaplan-Meier survival curves and Cox regression, while adjusting for sex, primary renal diseases with a high risk of recurrence, pre-emptive transplantation, year of transplantation and country., Results: The risk of graft failure in older living donors (50-75 years old) was similar to that of younger living donors {adjusted hazard ratio [aHR] 0.74 [95% confidence interval (CI) 0.38-1.47]}. Deceased donor (DD) age was non-linearly associated with graft survival, with the highest risk of graft failure found in the youngest donor age group [0-5 years; compared with donor ages 12-19 years; aHR 1.69 (95% CI 1.26-2.26)], especially among the youngest recipients (0-11 years). DD age had little effect on graft failure in recipients' ages 12-19 years., Conclusions: Our results suggest that donations from older living donors provide excellent graft outcomes in all paediatric recipients. For young recipients, the allocation of DDs over the age of 5 years should be prioritized., (© The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: The impact of different dialysis modalities on clinical outcomes has not been explored in young infants with chronic kidney failure., Study Design: Cohort study., Setting & Participants: Data were extracted from the ESPN/ERA-EDTA Registry. This analysis included 1,063 infants 12 months or younger who initiated dialysis therapy in 1991 to 2013., Factor: Type of dialysis modality., Outcomes & Measurements: Differences between infants treated with peritoneal dialysis (PD) or hemodialysis (HD) in patient survival, technique survival, and access to kidney transplantation were examined using Cox regression analysis while adjusting for age at dialysis therapy initiation, sex, underlying kidney disease, and country of residence., Results: 917 infants initiated dialysis therapy on PD, and 146, on HD. Median age at dialysis therapy initiation was 4.5 (IQR, 0.7-7.9) months, and median body weight was 5.7 (IQR, 3.7-7.5) kg. Although the groups were homogeneous regarding age and sex, infants treated with PD more often had congenital anomalies of the kidney and urinary tract (CAKUT; 48% vs 27%), whereas those on HD therapy more frequently had metabolic disorders (12% vs 4%). Risk factors for death were younger age at dialysis therapy initiation (HR per each 1-month later initiation, 0.95; 95% CI, 0.90-0.97) and non-CAKUT cause of chronic kidney failure (HR, 1.49; 95% CI, 1.08-2.04). Mortality risk and likelihood of transplantation were equal in PD and HD patients, whereas HD patients had a higher risk for changing dialysis treatment (adjusted HR, 1.64; 95% CI, 1.17-2.31)., Limitations: Inability to control for unmeasured confounders not included in the Registry database and missing data (ie, comorbid conditions). Low statistical power because of relatively small number of participants., Conclusions: Despite a widespread preconception that HD should be reserved for cases in which PD is not feasible, in Europe, we found 1 in 8 infants in need of maintenance dialysis to be initiated on HD therapy. Patient characteristics at dialysis therapy initiation, prospective survival, and time to transplantation were very similar for infants initiated on PD or HD therapy., (Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

End-stage renal disease (ESRD) in children is a medically challenging condition. Due to its rarity and special features, methodologically sound collaborative studies are required. In 2007, a new European registry of pediatric renal replacement therapy (RRT), the ESPN/ERA-EDTA Registry, was launched. In recent years, the Registry has provided comprehensive data on incidence, prevalence, patient characteristics, RRT modalities, and mortality in pediatric ESRD, along with relevant insights into cardiovascular risk, anemia, nutrition and growth, transplantation outcomes, and rare diseases. In this review, we describe the study design and structure underlying the ESPN/ERA-EDTA Registry, summarize the major research findings from more than 20 publications, and discuss current limitations and the future challenges to overcome.

Background: The choice for either kidney or combined liver-kidney transplantation in young people with kidney failure and liver fibrosis due to autosomal recessive polycystic kidney disease (ARPKD) can be challenging. We aimed to analyze the characteristics and outcomes of transplantation type in these children, adolescents, and young adults., Study Design: Cohort study., Setting & Participants: We derived data for children, adolescents, and young adults with ARPKD with either kidney or combined liver-kidney transplants for 1995 to 2012 from the ESPN/ERA-EDTA Registry, a European pediatric renal registry collecting data from 36 European countries., Factor: Liver transplantation., Outcomes & Measurements: Transplantation and patient survival., Results: 202 patients with ARPKD aged 19 years or younger underwent transplantation after a median of 0.4 (IQR, 0.0-1.4) years on dialysis therapy at a median age of 9.0 (IQR, 4.1-13.7) years. 32 (15.8%) underwent combined liver-kidney transplantation, 163 (80.7%) underwent kidney transplantation, and 7 (3.5%) were excluded because transplantation type was unknown. Age- and sex-adjusted 5-year patient survival posttransplantation was 95.5% (95% CI, 92.4%-98.8%) overall: 97.4% (95% CI, 94.9%-100.0%) for patients with kidney transplantation in contrast to 87.0% (95% CI, 75.8%-99.8%) with combined liver-kidney transplantation. The age- and sex-adjusted risk for death after combined liver-kidney transplantation was 6.7-fold (95% CI, 1.8- to 25.4-fold) greater than after kidney transplantation (P=0.005). Five-year death-censored kidney transplant survival following combined liver-kidney and kidney transplantation was similar (92.1% vs 85.9%; P=0.4)., Limitations: No data for liver disease of kidney therapy recipients., Conclusions: Combined liver-kidney transplantation in ARPKD is associated with increased mortality compared to kidney transplantation in our large observational study and was not associated with improved 5-year kidney transplant survival. Long-term follow-up of both kidney and liver involvement are needed to better delineate the optimal transplantation strategy., (Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Identification of patient groups by risk of renal graft loss might be helpful for accurate patient counselling and clinical decision-making. Survival tree models are an alternative statistical approach to identify subgroups, offering cut-off points for covariates and an easy-to-interpret representation., Methods: Within the European Society of Pediatric Nephrology/European Renal Association-European Dialysis and Transplant Association (ESPN/ERA-EDTA) Registry data we identified paediatric patient groups with specific profiles for 5-year renal graft survival. Two analyses were performed, including (i) parameters known at time of transplantation and (ii) additional clinical measurements obtained early after transplantation. The identified subgroups were added as covariates in two survival models. The prognostic performance of the models was tested and compared with conventional Cox regression analyses., Results: The first analysis included 5275 paediatric renal transplants. The best 5-year graft survival (90.4%) was found among patients who received a renal graft as a pre-emptive transplantation or after short-term dialysis (<45 days), whereas graft survival was poorest (51.7%) in adolescents transplanted after long-term dialysis (>2.2 years). The Cox model including both pre-transplant factors and tree subgroups had a significantly better predictive performance than conventional Cox regression (P < 0.001). In the analysis including clinical factors, graft survival ranged from 97.3% [younger patients with estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m(2) and dialysis <20 months] to 34.7% (adolescents with eGFR <60 mL/min/1.73 m(2) and dialysis >20 months). Also in this case combining tree findings and clinical factors improved the predictive performance as compared with conventional Cox model models (P < 0.0001)., Conclusions: In conclusion, we demonstrated the tree model to be an accurate and attractive tool to predict graft failure for patients with specific characteristics. This may aid the evaluation of individual graft prognosis and thereby the design of measures to improve graft survival in the poor prognosis groups., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Racial disparities in kidney transplantation in children have been found in the United States, but have not been studied before in Europe., Study Design: Cohort study., Setting & Participants: Data were derived from the ESPN/ERA-EDTA Registry, an international pediatric renal registry collecting data from 36 European countries. This analysis included 1,134 young patients (aged ≤19 years) from 8 medium- to high-income countries who initiated renal replacement therapy (RRT) in 2006 to 2012., Factor: Racial background., Outcomes & Measurements: Differences between racial groups in access to kidney transplantation, transplant survival, and overall survival on RRT were examined using Cox regression analysis while adjusting for age at RRT initiation, sex, and country of residence., Results: 868 (76.5%) patients were white; 59 (5.2%), black; 116 (10.2%), Asian; and 91 (8.0%), from other racial groups. After a median follow-up of 2.8 (range, 0.1-3.0) years, we found that black (HR, 0.49; 95% CI, 0.34-0.72) and Asian (HR, 0.54; 95% CI, 0.41-0.71) patients were less likely to receive a kidney transplant than white patients. These disparities persisted after adjustment for primary renal disease. Transplant survival rates were similar across racial groups. Asian patients had higher overall mortality risk on RRT compared with white patients (HR, 2.50; 95% CI, 1.14-5.49). Adjustment for primary kidney disease reduced the effect of Asian background, suggesting that part of the association may be explained by differences in the underlying kidney disease between racial groups., Limitations: No data for socioeconomic status, blood group, and HLA profile., Conclusions: We believe this is the first study examining racial differences in access to and outcomes of kidney transplantation in a large European population. We found important differences with less favorable outcomes for black and Asian patients. Further research is required to address the barriers to optimal treatment among racial minority groups., (Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Our aim was to determine the prevalence of sub-target hemoglobin (Hb) levels in children with a renal allograft and to identify potential determinants associated with these Hb levels., Methods: Data from 3669 children with a functioning renal allograft, aged <18 years between 1 January 2000 and 31 December 2012, from 20 European countries were retrieved from the ESPN/ERA-EDTA Registry, providing 16,170 Hb measurements., Results: According to the NKF/KDOQI classification and the UK-NICE guidelines, 49.8 and 7.8% of the patients, respectively, were anemic. Hb levels were strongly associated with graft function, with Hb levels of 12.6 g/dl in children with chronic kidney disease (CKD) stage 1, declining to 10.7 g/dl in children with CKD stage 5 (P < 0.001). Higher Hb levels were associated with the use of tacrolimus compared to ciclosporin (0.14 g/dl; 95% confidence interval 0.02-0.27; P = 0.002). Low Hb levels were associated with an increased risk of graft failure (P = 0.01) or combined graft failure and death (P < 0.01), but not with death alone (not significant)., Conclusions: Anemia is present in a significant proportion of European pediatric kidney transplant recipients and is associated with renal allograft dysfunction and type of immunosuppressants used. In our patient cohort, higher Hb levels were associated with better graft and patient survival and less hypertension.

Background: Considerable disparities exist in the provision of paediatric renal replacement therapy (RRT) across Europe. This study aims to determine whether these disparities arise from geographical differences in the occurrence of renal disease, or whether country-level access-to-care factors may be responsible., Methods: Incidence was defined as the number of new patients aged 0-14 years starting RRT per year, between 2007 and 2011, per million children (pmc), and was extracted from the ESPN/ERA-EDTA registry database for 35 European countries. Country-level indicators on macroeconomics, perinatal care and physical access to treatment were collected through an online survey and from the World Bank database. The estimated effect is presented per 1SD increase for each indicator., Results: The incidence of paediatric RRT in Europe was 5.4 cases pmc. Incidence decreased from Western to Eastern Europe (-1.91 pmc/1321 km, P < 0.0001), and increased from Southern to Northern Europe (0.93 pmc/838 km, P = 0.002). Regional differences in the occurrence of specific renal diseases were marginal. Higher RRT treatment rates were found in wealthier countries (2.47 pmc/€10 378 GDP per capita, P < 0.0001), among those that tend to spend more on healthcare (1.45 pmc/1.7% public health expenditure, P < 0.0001), and among countries where patients pay less out-of-pocket for healthcare (-1.29 pmc/11.7% out-of-pocket health expenditure, P < 0.0001). Country neonatal mortality was inversely related with incidence in the youngest patients (ages 0-4, -1.1 pmc/2.1 deaths per 1000 births, P = 0.10). Countries with a higher incidence had a lower average age at RRT start, which was fully explained by country GDP per capita., Conclusions: Inequalities exist in the provision of paediatric RRT throughout Europe, most of which are explained by differences in country macroeconomics, which limit the provision of treatment particularly in the youngest patients. This poses a challenge for healthcare policy makers in their aim to ensure universal and equal access to high-quality healthcare services across Europe., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background and Objectives: 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., Design, Setting, Participants, & Measurements: 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., Results: 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., Conclusions: Abnormalities in mineral metabolism are common after pediatric renal transplantation in Europe and are associated with graft dysfunction., (Copyright © 2015 by the American Society of Nephrology.)

Background: Registry data can be used to assess associations between medical and health-policy factors and the likelihood of children on renal replacement therapy (RRT) to live with a functioning kidney transplant in Europe., Methods: A survey questionnaire was distributed among renal registry representatives in 38 European countries, and additional data was obtained from the European Society for Pediatric Nephrology/European Renal Association-European Dialysis and Transplant Association (ESPN/ERA-EDTA) registry., Results: Thirty-two countries with a pediatric RRT program responded. The median percentage of children by country on RRT with a functioning transplant was 62 % (interquartile range 39-77). One per million population increase in donation rate from deceased donors was associated with a 5 % increase in the percentage of functioning transplants; the existence of an intermediate and high pediatric priority policy doubled and tripled this percentage, respectively, compared with no priority, whereas an increase in living donor pediatric kidney transplant rate of one per million children was associated with a 14 % higher percentage of functioning transplants. The percentage of functioning transplants was also strongly associated with the gross domestic product (GDP)., Conclusion: Considerable variations exist in the percentages of prevalent pediatric RRT populations with functioning renal transplants across Europe. A macroeconomic indicator such as GDP is the most important determinant of these international differences. Efforts should be made for living donation programs and pediatric allocation priority to increase access to kidney transplantation for children.

Background: The prevalence of childhood overweight is rising worldwide, but in children on renal replacement therapy (RRT) a poor nutritional status is still the primary concern. We aimed to study the prevalence of, and factors associated with, underweight and overweight/obesity in the European paediatric RRT population. Moreover, we assessed the evolution of body mass index (BMI) after the start of RRT., Methods: We included 4474 patients younger than 16 years from 25 countries of whom BMI data, obtained between 1995 and 2010, were available within the European Society for Paediatric Nephrology/European Renal Association-European Dialysis and Transplant Association Registry. Prevalence estimates for under- and overweight/obesity were calculated using age and sex-specific criteria of the World Health Organization (WHO, 0-1 year olds) and the International Obesity Task Force cut-offs (2-15 year olds)., Results: The prevalence of underweight was 3.5%, whereas 20.8% of the patients were overweight and 12.5% obese. Factors associated with being underweight were receiving dialysis treatment and infant age. Among transplanted recipients, a very short stature (OR: 1.64, 95% CI: 1.40-1.92) and glucocorticoid treatment (OR: 1.23, 95% CI: 1.03-1.47) were associated with a higher risk of being overweight/obese. BMI increased post-transplant, and a lower BMI and a higher age at the start of RRT were associated with greater BMI changes during RRT treatment., Conclusions: Overweight and obesity, rather than underweight, are highly prevalent in European children on RRT. Short stature among graft recipients had a strong association with overweight, while underweight appears to be only a problem in infants. Our findings suggest that nutritional management in children receiving RRT should focus as much on the prevention and treatment of overweight as on preventing malnutrition.

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: ABO-incompatible renal transplantation (ABOi-RTx) following preconditioning with immunoadsorption (IA) and rituximab is a promising approach to facilitate living-related RTx. However, clinical experience is limited in pediatric patients., Methods: Three patients underwent living-related ABOi-RTx in our center. Preoperative IA was performed six, ten and 11 times in patient one, two and three, respectively, to achieve isoagglutinin titers of ≤1:8 on the day of transplantation; rituximab was administered once. The immunosuppressive regimen further comprised tacrolimus, mycophenolate, methylprednisolone and basiliximab; immunoglobulin G (IgG) was infused on the day of ABOi-RTx., Results: All three patients achieved normal renal function within 2-6 days post-RTx. Major postoperative bleeding occurred in two patients, with one requiring repeated blood transfusions and the other a surgical revision 4 h after RTx, despite local citrate anticoagulation use during the preoperative IA procedures in the latter patient. A pyelonephritis-associated increase of the isoagglutinin IgG/IgM titers to 1:64/1:128 led to a biopsy-proven acute humoral rejection in the third patient, which was treated successfully with plasma exchange and methylprednisolone pulses. The estimated glomerular filtration rate at 18, 8 and 23 months post-RTx was 96, 52 and 74 ml/min/1.73 m(2), respectively., Conclusions: ABOi-RTx can successfully be performed in pediatric patients after preconditioning with quadruple immunosuppression, rituximab and IA. Caution is required regarding bleeding complications, which are most likely due to the unspecific binding of coagulation factors during repeated IA.

Background: The biological properties of oxidized and non-oxidized PTH are substantially different. Oxidized PTH (oxPTH) loses its PTH receptor-stimulating properties, whereas non-oxidized PTH (n-oxPTH) is a full agonist of the receptor. This was described in more than 20 well published studies in the 1970(s) and 80(s). However, PTH oxidation has been ignored during the development of PTH assays for clinical use so far. Even the nowadays used third generation assay systems do not consider oxidation of PTH We recently developed an assay to differentiate between oxPTH and n-oxPTH. In the current study we established normal values for this assay system. Furthermore, we compare the ratio of oxPTH to n-oxPTH in different population with chronic renal failure: 620 children with renal failure stage 2-4 of the 4C study, 342 adult patients on dialysis, and 602 kidney transplant recipients. In addition, we performed modeling of the interaction of either oxPTH or n-oxPTH with the PTH receptor using biophysical structure approaches., Results: The children had the highest mean as well as maximum n-oxPTH concentrations as compared to adult patients (both patients on dialysis as well as kidney transplant recipients). The relationship between oxPTH and n-oxPTH of individual patients varied substantially in all three populations with renal impairment. The analysis of n-oxPTH in 89 healthy control subjects revealed that n-oxPTH concentrations in patient with renal failure were higher as compared to healthy adult controls (2.25-fold in children with renal failure, 1.53-fold in adult patients on dialysis, and 1.56-fold in kidney transplant recipients, respectively). Computer assisted biophysical structure modeling demonstrated, however, minor sterical- and/or electrostatic changes in oxPTH and n-oxPTH. This indicated that PTH oxidation may induce refolding of PTH and hence alters PTH-PTH receptor interaction via oxidation induced three-dimensional structure alteration of PTH., Conclusion: A huge proportion of circulating PTH measured by current state-of-the-art assay systems is oxidized and thus not biologically active. The relationship between oxPTH and n-oxPTH of individual patients varied substantially. Non-oxidized PTH concentrations are 1.5 - 2.25 fold higher in patients with renal failure as compared to health controls. Measurements of n-oxPTH may reflect the hormone status more precise. The iPTH measures describes most likely oxidative stress in patients with renal failure rather than the PTH hormone status. This, however, needs to be demonstrated in further clinical studies. © 2013 S. Karger AG, Basel.

Background and Objectives: Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of ESRD in children, but the proportion of patients with individual CAKUT entities progressing to ESRD during adulthood and their long-term clinical outcomes are unknown. This study assessed the age at onset of renal replacement therapy (RRT) and patient and renal graft survival in patients with CAKUT across the entire age range., Design, Setting, Participants, & Measurements: Patients with CAKUT were compared with age-matched patients who were undergoing RRT for other renal disorders on the basis of data from the European Renal Association-European Dialysis and Transplant Association Registry. Competing risk and Cox regression analyses were conducted., Results: Of 212,930 patients commencing RRT from 1990 to 2009, 4765 (2.2%) had renal diagnoses consistent with CAKUT. The proportion of incident RRT patients with CAKUT decreased from infancy to childhood and then increased until age 15-19 years, followed by a gradual decline throughout adulthood. Median age at RRT start was 31 years in the CAKUT cohort and 61 years in the non-CAKUT cohort (P<0.001). RRT was started earlier (median, 16 years) in patients with isolated renal dysplasia than in those with renal hypoplasia and associated urinary tract disorders (median, 29.5-39.5 years). Patients with CAKUT survived longer than age- and sex-matched non-CAKUT controls because of lower cardiovascular mortality (10-year survival rate, 76.4% versus 70.7%; P<0.001)., Conclusions: CAKUT leads to ESRD more often at adult than pediatric age. Treatment outcomes differ from those of acquired kidney diseases and vary within CAKUT subcategories.

Background and Objectives: Primary hyperoxaluria (PH) as a cause of ESRD in children is believed to have poor outcomes. Data on management and outcomes of these children remain scarce., Design, Setting, Participants, & Measurements: This study included patients aged <19 years who started renal replacement therapy (RRT) between 1979 and 2009 from 31 countries providing data to a large European registry., Results: Of 9247 incident patients receiving RRT, 100 patients had PH. PH children were significantly younger than non-PH children at the start of RRT. The median age at RRT of PH children decreased from 9.8 years in 1979-1989 to 1.5 years in 2000-2009. Survival was 86%, 79%, and 76% among PH patients at 1, 3, and 5 years after the start of RRT, compared with 97%, 94%, and 92% in non-PH patients, resulting in a three-fold increased risk of death over non-PH patients. PH and non-PH patient survival improved over time. Sixty-eight PH children received a first kidney (n=13) or liver-kidney transplantation (n=55). Although the comparison was hampered by the lower number of kidney transplantations primarily derived from the earlier era of RRT, kidney graft survival in PH patients was 82%, 79%, and 76% at 1, 3, and 5 years for liver-kidney transplantation and 46%, 28%, and 14% at 1, 3, and 5 years for kidney transplantation alone, compared with 95%, 90%, and 85% in non-PH patients., Conclusions: The outcomes of PH children with ESRD are still poorer than in non-PH children but have substantially improved over time.

Background: Controversy exists concerning the timing of the first kidney transplantation for children who need to start renal replacement therapy (RRT). Our aim was to estimate the effect of timing of the first transplantation on patient survival in children, for the first time also taking into account the mortality on dialysis before transplantation., Methods: We included 2091 patients who started RRT between the age of 3 and 18 years in the period 1988-2007, from 13 European renal registries. A multistate model was used to simulate patient survival assuming (i) pre-emptive transplantation, (ii) transplantation after 1 or 2 years on dialysis and (iii) remaining on dialysis., Results: Over the 20-year period, the highest 8-year survival probabilities were achieved in children transplanted pre-emptively {living donor (LD): 95.9% [95% confidence interval (CI): 93.1-98.8], deceased donor (DD): 95.3% (95% CI: 90.9-99.9)} rather than after 2 years of dialysis [LD: 94.2% (95% CI: 91.6-96.8), DD: 93.4% (95% CI: 91.0-95.9)], although these differences were not statistically significant., Conclusions: Even after taking mortality on dialysis into account, the potentially negative effect of postponing transplantation for 1 or 2 years was relatively small and not statistically significant. Therefore, if pre-emptive transplantation is not possible, starting RRT with a short period of dialysis and receiving a transplant thereafter seems an acceptable alternative from the perspective of patient survival.

Background and Objectives: Nephropathic cystinosis (NC) is an autosomal recessive disorder occurring in one to two per 100,000 newborns. Because of the rarity of NC, long-term outcome data are scarce., Design, Setting, Participants, & Measurements: 245 NC patients from 18 countries provided data to the ESPN/ERA-EDTA registry. We matched NC patients on renal replacement therapy (RRT) to non-NC children on RRT., Results: Between 1979 and 2008, mean age at the start of RRT among NC children increased by 0.15 year per calendar year (95% confidence interval, 0.10 to 0.21) from 8.8 to 12.7 years, whereas we did not observe this in non-NC children. Five-year survival after the start of RRT improved in NC patients from 86.1% (before 1990) to 100% (since 2000) as compared with the control population (89.6% and 94.0%). NC patients received a renal allograft more often (relative risk, 1.09; 95% confidence interval, 1.00 to 1.17) as compared with matched RRT children, and 5-year graft survival was better (94.0% versus 84.0%). NC dialysis patients were less often hypertensive than non-NC children matched for age, country, and dialysis modality (42.7% versus 51.7%) and had lower parathyroid hormone levels (median, 56 versus 140 pg/ml). Although height at start of RRT slightly improved during the past decade, children with NC remained significantly shorter than non-NC children at the start of RRT., Conclusions: We demonstrated improved survival of the renal function as well as better patient and graft survival after the start of RRT in a large European cohort of NC patients over the last two decades.

Transplant tourism is a necessity for children with end-stage renal disease living in regions without established local transplantation programs. The use of kidneys from living unrelated donors (LURDs) was common practice in Asia prior to the recent global condemnation of commercial organ transplantation. Objective information on the outcomes of pediatric transplant tourism is scarce. Here, we report the Dubai experience with 45 renal allograft transplantations performed outside the United Arab Emirates (UAE) between 1993 and 2009. Transplantation from 33 LURDs, ten living related donors (LRDs) and two deceased donors was performed in 14 different countries. The mean number of human leukocyte antigen (HLA) A/B/DR allele matches was 1.4 +/- 0.8 in the LURD graft recipients and 3.9 +/- 0.7 in the LRD recipients. Outcomes were compared with those of a matched group of 3,150 pediatric LRD transplantations from the Collaborative Transplant Study (CTS). Ten-year patient survival was 100% in the LRD patients, 91.2% in the LURD patients, and 92% in the CTS patients. The three deaths in the LURD group occurred within the first 4 months after transplantation and were related to acute rejection. One-year and 10-year graft survival was 100% in the LRD group and 94.8% and 66.7% in the CTS-LRD groups, vs 87.8% and 43.4% in the LURD group. Major viral infections [Epstein-Barr virus (EBV), cytomegalovirus (CMV), varicella zoster (VZV)] were four-times more common in patients that had received LURD grafts than in those that had received LRD grafts. In conclusion, whereas LRD kidney transplantation performed abroad yields excellent long-term results, transplantation of LURD kidneys is fraught with a high complication rate affecting graft and even early patient survival.

Mutations in the NPHS2 gene, which encodes podocin, are associated with steroid-resistant nephrotic syndrome in childhood. Renal histology frequently presents focal segmental glomerulosclerosis (FSGS). Post-transplant recurrence of proteinuria in patients affected by homozygous or compound heterozygous NPHS2 mutation is encountered rarely (1-2%) compared to 30% recurrence in nonhereditary FSGS. We report on a pediatric kidney transplant recipient with NPHS2-associated nephrotic syndrome and FSGS, who developed biopsy-proven recurrence of FSGS 10 years post-transplant in temporal association with conversion from cyclosporin A (CsA)- to sirolimus (SRL)-based immunosuppression, due to histological evidence of severe CsA-induced nephrotoxicity. Reswitch of the immunosuppressive regimen from SRL to CsA led to a noticeable decrease of proteinuria and to stabilization of graft function. We conclude that patients with hereditary FSGS are not entirely protected from post-transplant recurrence of proteinuria, even in the long term. The close temporal relationship of FSGS recurrence with CsA withdrawal and conversion to SRL suggests that caution should be exercised in the use of CsA-free immunosuppression also in patients with NPHS2-associated FSGS.

Increased intima-media thickness of the carotid arteries (cIMT) has been found in young adults with childhood-onset chronic kidney disease (CKD). The disease stage at which these patients first develop abnormalities of arterial texture is unknown. The objective of this study was to determine the onset and character of arterial changes in children aged 10 to 20 yr with different stages of CKD and to identify risk factors for early arteriopathy. High-resolution ultrasonography was conducted of common cIMT and femoral superficial artery IMT. Fifty-five children with stages 2 to 4 CKD (GFR 51 +/- 31 ml/min per 1.73 m2), 37 on dialysis, and 34 after renal transplantation (Rtx; GFR 73 +/- 31 ml/min per 1.73 m2) were studied. Control subjects were 270 healthy children, matched for age and gender. Compared with control subjects, cIMT, femoral superficial artery IMT (both as absolute values and as SD score of median of normal value), wall cross-sectional area, and lumen cross-sectional area of carotid artery were significantly increased in all patient groups and most markedly abnormal in dialysis patients. cIMT in CKD and Rtx patients was significantly lower in comparison with dialysis patients. cIMT correlated with mean past serum Ca x P product, the cumulative dose of calcium-based phosphate binders, and the time-averaged mean calcitriol dose. The cumulative phosphate binder intake, time-averaged Ca x P product, and young age were independent predictors of an increased cIMT. In children with CKD, thickening of IMT occurs early in the course of disease and is most marked in dialyzed patients. The changes may be partly reversible after Rtx.

Background: The kidney is central for maintaining water balance. As a corollary, patients with impaired kidney function are prone to pathological fluid volumes. Total body water (TBW) is distributed between the extracellular (ECW) and intracellular fluid compartments (ICW). In clinical practice, the judgment of hydration status does not allow to distinguish between ECW and ICW. Here, we evaluate the hydration status in children with chronic kidney disease by analyzing TBW, ECW, and ICW. Methods: Hydration was quantified using whole-body bioimpedance spectroscopy (BCM) in 128 outpatients (1–25 years, 52 girls). Forty-two were transplanted (TPL), 43 suffered from chronic kidney disease without kidney replacement therapy (CKD), 21 were on peritoneal dialysis (PD), and 22 on hemodialysis (HD). HD patients were investigated before, after, and sequentially during dialysis. Results: The ECW and ICW values obtained by BCM were of the same magnitude as those from the literature using isotope dilution. When compared with a healthy control group, TBW was increased in 9 TPL, 9 CKD, 1 PD, and 11 HD patients before but in none after dialysis. The decline of overhydration during dialysis (p < 0.001, n = 22) correlated with the change in body weight (R2 = 0.62). The kinetics of fluid compartment changes assessed twice in six HD patients revealed a reproducible linear decay of the ECW/ICW ratio due to an increase of ICW and a decrease of ECW. Conclusion: BCM quantifies TBW and acute changes of ECW and ICW in children with chronic kidney failure. The clinical utility of measuring TBW, ECW, and ICW should be defined in the future. [ABSTRACT FROM AUTHOR]

Background The burden of chronic kidney disease (CKD) and its treatment may severely limit the ability of children with CKD to do daily tasks and participate in family, school, sporting and recreational activities. Life participation is critically important to affected children and their families; however, the appropriateness and validity of available measures used to assess this outcome are uncertain. The aim of this study was to identify the characteristics, content and psychometric properties of existing measures for life participation used in children with CKD. Methods We searched MEDLINE, Embase, PsychINFO, Cumulative Index to Nursing and Allied Health Literature and the Cochrane Kidney and Transplant register to August 2019 for all studies that used a measure to report life participation in children with CKD. For each measure, we extracted and analyzed the characteristics, dimensions of life participation and psychometric properties. Results From 128 studies, we identified 63 different measures used to assess life participation in children with CKD. Twenty-five (40%) of the measures were patient reported, 7 (11%) were parent proxy reported and 31 (49%) had both self and parent proxy reports available. Twenty-two were used in one study only. The Pediatric Quality of Life Inventory version 4.0 generic module was used most frequently in 62 (48%) studies. Seven (11%) were designed to assess ability to participate in life, with 56 (89%) designed to assess other constructs (e.g. quality of life) with a subscale or selected questions on life participation. Across all measures, the three most frequent activities specified were social activities with friends and/or family, leisure activities and self-care activities. Validation data in the pediatric CKD population were available for only 19 (30%) measures. Conclusions Life participation is inconsistently measured in children with CKD and the measures used vary in their characteristics, content and validity. Validation data supporting these measures in this population are often incomplete and are sparse. A meaningful and validated measure for life participation in children with CKD is needed. [ABSTRACT FROM AUTHOR]

Background: We explored the variation in country mortality rates in the paediatric population receiving renal replacement therapy across Europe, and estimated how much of this variation could be explained by patient-level and country-level factors.Methods: In this registry analysis, we extracted patient data from the European Society for Paediatric Nephrology/European Renal Association-European Dialysis and Transplant Association (ESPN/ERA-EDTA) Registry for 32 European countries. We included incident patients younger than 19 years receiving renal replacement therapy. Adjusted hazard ratios (aHR) and the explained variation were modelled for patient-level and country-level factors with multilevel Cox regression. The primary outcome studied was all-cause mortality while on renal replacement therapy.Findings: Between Jan 1, 2000, and Dec 31, 2013, the overall 5 year renal replacement therapy mortality rate was 15·8 deaths per 1000 patient-years (IQR 6·4-16·4). France had a mortality rate (9·2) of more than 3 SDs better, and Russia (35·2), Poland (39·9), Romania (47·4), and Bulgaria (68·6) had mortality rates more than 3 SDs worse than the European average. Public health expenditure was inversely associated with mortality risk (per SD increase, aHR 0·69, 95% CI 0·52-0·91) and explained 67% of the variation in renal replacement therapy mortality rates between countries. Child mortality rates showed a significant association with renal replacement therapy mortality, albeit mediated by macroeconomics (eg, neonatal mortality reduced from 1·31 [95% CI 1·13-1·53], p=0·0005, to 1·21 [0·97-1·51], p=0·10). After accounting for country distributions of patient age, the variation in renal replacement therapy mortality rates between countries increased by 21%.Interpretation: Substantial international variation exists in paediatric renal replacement therapy mortality rates across Europe, most of which was explained by disparities in public health expenditure, which seems to limit the availability and quality of paediatric renal care. Differences between countries in their ability to accept and treat the youngest patients, who are the most complex and costly to treat, form an important source of disparity within this population. Our findings can be used by policy makers and health-care providers to explore potential strategies to help reduce these health disparities.Funding: ERA-EDTA and ESPN. [ABSTRACT FROM AUTHOR]

World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood. [ABSTRACT FROM AUTHOR]

Background Information on lipid abnormalities in end-stage renal disease (ESRD) mainly originates from adult patients and small paediatric studies. We describe the prevalence of dyslipidaemia, and potential determinants associated with lipid measures in a large cohort of paediatric ESRD patients. Methods In the ESPN/ERA-EDTA registry, lipid measurements were available for 976 patients aged 2–17 years from 19 different countries from the year 2000 onwards. Dyslipidaemia was defined as triglycerides >100 mg/dL (2–9 years) or >130 mg/dL (9–17 years), high-density lipoprotein (HDL) cholesterol <40 mg/dL or non-HDL cholesterol >145 mg/dL. Missing data were supplemented using multiple imputation. Results The prevalence of dyslipidaemia was 85.1% in peritoneal dialysis (PD) patients, 76.1% in haemodialysis (HD) patients and 55.5% among renal allograft recipients. Both low and high body mass index (BMI) were associated with a less favourable lipid profile. Younger age was associated with a worse lipid profile among PD patients. HDL levels significantly improved after transplantation, whereas no significant improvements were found for triglyceride and non-HDL levels. In transplant recipients, use of cyclosporin was associated with significantly higher non-HDL and HDL levels than tacrolimus usage (P < 0.01). In transplant patients with eGFR < 29 mL/min/1.73 m2, the mean triglyceride level was 137 mg/dL (99% confidence interval (CI): 119–159) compared with 102 mg/dL among those with eGFR > 90 mL/min/1.73 m2 (P < 0.0001). Conclusions Dyslipidaemia is common among paediatric ESRD patients in Europe. Young age and PD treatment are associated with worse lipid profiles. Although lipid levels generally improve after transplantation, dyslipidaemia may persist due to decreased graft function, high BMI or to the use of certain immunosuppressants. [ABSTRACT FROM PUBLISHER]

Focal segmental glomerulosclerosis (FSGS) is a cause of proteinuric kidney disease, compromising both native and transplanted kidneys. Treatment is limited because of a complex pathogenesis, including unknown serum factors. Here we report that serum soluble urokinase receptor (suPAR) is elevated in two-thirds of subjects with primary FSGS, but not in people with other glomerular diseases. We further find that a higher concentration of suPAR before transplantation underlies an increased risk for recurrence of FSGS after transplantation. Using three mouse models, we explore the effects of suPAR on kidney function and morphology. We show that circulating suPAR activates podocyte ?3 integrin in both native and grafted kidneys, causing foot process effacement, proteinuria and FSGS-like glomerulopathy. Our findings suggest that the renal disease only develops when suPAR sufficiently activates podocyte ?3 integrin. Thus, the disease can be abrogated by lowering serum suPAR concentrations through plasmapheresis, or by interfering with the suPAR-?3 integrin interaction through antibodies and small molecules targeting either uPAR or ?3 integrin. Our study identifies serum suPAR as a circulating factor that may cause FSGS. [ABSTRACT FROM AUTHOR]

Background. Few studies have investigated the determinants of glomerular filtration rate (GFR) in paediatric patients starting on dialysis or with a transplant.Methods. Data were collected as part of the European Society of Paediatric Nephrology/European Renal Association–European Dialysis and Transplant Association registry from 14 European countries and referred to incident paediatric patients starting on renal replacement therapy (RRT) between 2002 and 2007 under the age of 18 years. Estimated glomerular filtration rate (eGFR) was calculated using the Schwartz formula. Data were adjusted for age, gender, treatment modality at start, primary cause of renal failure (PRD) and regions in Europe (eGFRadj).Results. Median eGFR in the 938 patients starting RRT was 10.4 mL/min/1.73 m2 (5th and 95th percentile: 4.0–26.9). Twenty-six patients (2.8%), mainly infants with Finnish-type nephropathy, started with eGFR levels >50 mL/min/1.73 m2. Younger age, female gender, starting on dialysis and having a short time between the first visit to a paediatric nephrologist (PN) and start of RRT were associated with lower eGFR at start of RRT. Gender differences were only present during adolescent age and disappeared when using the same K value for both genders. The various PRDs showed large differences in the rate of decline in eGFR between the first visit to a PN and start of RRT; however, this did not result in differences in eGFRadj at start of RRT.Conclusions. The main determinants of eGFR at start of RRT were age, gender, treatment modality at start, and the time between the first visit to a PN and start of RRT. Research is needed to determine the consequences of these differences. [ABSTRACT FROM AUTHOR]

Background In recent years, increased efforts have been undertaken to address the needs of patients with rare diseases by international initiatives and consortia devoted to rare disease research and management. However, information on the overall prevalence of rare diseases within the end-stage renal disease (ESRD) population is limited. The aims of this study were (i) to identify those rare diseases within the ERA–EDTA Registry for which renal replacement therapy (RRT) is being provided and (ii) to determine the prevalence and incidence of RRT for ESRD due to rare diseases, both overall and separately for children and adults. Methods The Orphanet classification of rare disease was searched for rare diseases potentially causing ESRD, and these diagnosis codes were mapped to the corresponding ERA–EDTA primary renal disease codes. Thirty-one diagnoses were defined as rare diseases causing ESRD. Results From 1 January 2007 to 31 December 2011, 7194 patients started RRT for a rare disease (10.6% children). While some diseases were exclusively found in adults (e.g. Fabry disease), primary oxalosis, cystinosis, congenital anomalies of the kidney and urinary tract (CAKUT) and medullary cystic kidney disease affected young patients in up to 46%. On 31 December 2011, 20 595 patients (12.4% of the total RRT population) were on RRT for ESRD caused by a rare disease. The point prevalence was 32.5 per million age-related population in children and 152.0 in adults. Only 5.8% of these patients were younger than 20 years; however, 57.7% of all children on RRT had a rare disease, compared with only 11.9% in adults. CAKUT and focal segmental glomerulosclerosis were the most prevalent rare disease entities among patients on RRT. Conclusions More than half of all children and one of nine adults on RRT in the ERA–EDTA Registry suffer from kidney failure due to a rare disease, potentially with a large number of additional undiagnosed or miscoded cases. Comprehensive diagnostic assessment and the application of accurate disease classification systems are essential for improving the identification and management of patients with rare kidney diseases. [ABSTRACT FROM AUTHOR]

To mark World Kidney Day 2016, Nature Reviews Nephrology invited six leading researchers to highlight the key advances and challenges within their specialist field of paediatric nephrology. Here, advances and remaining challenges in the fields of prenatal patterning, acute kidney injury, renal transplantation, genetics, cardiovascular health, and growth and nutrition, are all discussed within the context of paediatric and neonatal patients with kidney disease. Our global panel of researchers describe areas in which further studies and clinical advances are needed, and suggest ways in which research in these areas should progress to optimize renal care and long-term outcomes for affected patients. [ABSTRACT FROM AUTHOR]

At least 10% of adults and nearly all children who receive renal-replacement therapy have an inherited kidney disease. These patients rarely die when their disease progresses and can remain alive for many years because of advances in organ-replacement therapy. However, these disorders substantially decrease their quality of life and have a large effect on health-care systems. Since the kidneys regulate essential homoeostatic processes, inherited kidney disorders have multisystem complications, which add to the usual challenges for rare disorders. In this review, we discuss the nature of rare inherited kidney diseases, the challenges they pose, and opportunities from technological advances, which are well suited to target the kidney. Mechanistic insights from rare disorders are relevant for common disorders such as hypertension, kidney stones, cardiovascular disease, and progression of chronic kidney disease. [ABSTRACT FROM AUTHOR]