Adult outcomes of childhood kidney replacement therapy in Europe from 2008 to 2019: an ERA Registry study.

BACKGROUND AND HYPOTHESIS: Young adults starting kidney replacement therapy (KRT) during childhood and reaching their 18th birthday (i.e. adult survivors of childhood KRT) form a challenging population of interest to nephrologists treating adults, as during this period there will be a transition to adult renal centres. Nonetheless, few studies have focused on the epidemiology of KRT in this group. We aimed to provide an update on these patients' characteristics, treatment history, graft and patient survival, to report their 5-year prognosis, and expected remaining lifetime. METHODS: Data on KRT patients reaching their 18th birthday in 2008-2019 were collected from 21 European countries/regions providing individual patient data to the European Renal Association (ERA) Registry. Patient characteristics and treatment trajectories were examined before and after turning 18 years. Kaplan-Meier and Cox proportional hazards regression were used for patient and graft survival analyses. RESULTS: In total, 2944 patients were included. The proportion of adult survivors initiating KRT at a very young age (0-4 years), and undergoing pre-emptive kidney transplantation increased. Unadjusted 5-year patient survival was 96.9% (95% CI: 96.2-97.5). Dialysis patients had a higher risk of death than kidney transplant recipients (adjusted hazard ratio 5.44 (95% CI: 3.34-8.86)). Between ages 18 and 23 years, about 21% of the adult survivors lost their kidney transplant and 34% of the dialysis patients continued this treatment. Compared with the general population, life expectancy for eighteen-year-old kidney transplant and dialysis patients was 17 and 40 years shorter, respectively. CONCLUSION: Life expectancy of 18-year-old kidney transplant recipients was lower compared with the general population. Yet, having a functioning kidney graft at age 18 years resulted in better outcomes than being on dialysis. Nevertheless, between ages 18 and 23 years, about one-fifth of the kidney grafts failed and one-third of the patients remained on dialysis.

Associations of longitudinal height and weight with clinical outcomes in pediatric kidney replacement therapy: results from the ESPN/ERA Registry.

BACKGROUND: Associations between anthropometric measures and patient outcomes in children are inconsistent and mainly based on data at kidney replacement therapy (KRT) initiation. We studied associations of height and body mass index (BMI) with access to kidney transplantation, graft failure, and death during childhood KRT. METHODS: We included patients < 20 years starting KRT in 33 European countries from 1995-2019 with height and weight data recorded to the ESPN/ERA Registry. We defined short stature as height standard deviation scores (SDS) < -1.88 and tall stature as height SDS > 1.88. Underweight, overweight and obesity were calculated using age and sex-specific BMI for height-age criteria. Associations with outcomes were assessed using multivariable Cox models with time-dependent covariates. RESULTS: We included 11,873 patients. Likelihood of transplantation was lower for short (aHR: 0.82, 95% CI: 0.78-0.86), tall (aHR: 0.65, 95% CI: 0.56-0.75), and underweight patients (aHR: 0.79, 95%CI: 0.71-0.87). Compared with normal height, patients with short and tall statures showed higher graft failure risk. All-cause mortality risk was higher in short (aHR: 2.30, 95% CI: 1.92-2.74), but not in tall stature. Underweight (aHR: 1.76, 95% CI: 1.38-2.23) and obese (aHR: 1.49, 95% CI: 1.11-1.99) patients showed higher all-cause mortality risk than normal weight subjects. CONCLUSIONS: Short and tall stature and being underweight were associated with a lower likelihood of receiving a kidney allograft. Mortality risk was higher among pediatric KRT patients with a short stature or those being underweight or obese. Our results highlight the need for careful nutritional management and multidisciplinary approach for these patients. A higher resolution version of the Graphical abstract is available as Supplementary information.

Growth in children on kidney replacement therapy: a review of data from patient registries.

Growth retardation is a major complication in children with chronic kidney disease (CKD) and on kidney replacement therapy (KRT). Conversely, better growth in childhood CKD is associated with an improvement in several hard morbidity-mortality endpoints. Data from pediatric international registries has demonstrated that improvements in the overall conservative management of CKD, the search for optimal dialysis, and advances in immunosuppression and kidney transplant techniques have led to a significant improvement of final height over time. Infancy still remains a critical period for adequate linear growth, and the loss of stature during the first years of life influences final height. Preliminary new original data from the European Society for Paediatric Nephrology/European Renal Association-European Dialysis and Transplant Association (ESPN/ERA-EDTA) Registry confirm an association between the final height and the height attained at 2 years in children on KRT.

Ten-year trends in epidemiology and outcomes of pediatric kidney replacement therapy in Europe: data from the ESPN/ERA-EDTA Registry.

BACKGROUND: For 10 consecutive years, the ESPN/ERA-EDTA Registry has included data on children with stage 5 chronic kidney disease (CKD 5) receiving kidney replacement therapy (KRT) in Europe. We examined trends in incidence and prevalence of KRT and patient survival. METHODS: We included all children aged <15 years starting KRT 2007-2016 in 22 European countries participating in the ESPN/ERA-EDTA Registry since 2007. General population statistics were derived from Eurostat. Incidence and prevalence were expressed per million age-related population (pmarp) and time trends studied with JoinPoint regression. We analyzed survival trends using Cox regression. RESULTS: Incidence of children commencing KRT <15 years remained stable over the study period, varying between 5.5 and 6.6 pmarp. Incidence by treatment modality was unchanged over time: 2.0 for hemodialysis (HD) and peritoneal dialysis (PD) and 1.0 for transplantation. Prevalence increased in all age categories and overall rose 2% annually from 26.4 pmarp in 2007 to 32.1 pmarp in 2016. Kidney transplantation prevalence increased 5.1% annually 2007-2009, followed by 1.5% increase/year until 2016. Prevalence of PD steadily increased 1.4% per year over the entire period, and HD prevalence started increasing 6.1% per year from 2011 onwards. Five-year unadjusted patient survival on KRT was around 94% and similar for those initiating KRT 2007-2009 or 2010-2012 (adjusted HR: 0.98, 95% CI:0.71-1.35). CONCLUSIONS: We found a stable incidence and increasing prevalence of European children on KRT 2007-2016. Five-year patient survival was good and was unchanged over time. These data can inform patients and healthcare providers and aid health policy makers on future resource planning of pediatric KRT in Europe.

Results in the ESPN/ERA-EDTA Registry suggest disparities in access to kidney transplantation but little variation in graft survival of children across Europe.

One of the main objectives of the European health policy framework is to ensure equitable access to high-quality health services across Europe. Here we examined country-specific kidney transplantation and graft failure rates in children and explore their country- and patient-level determinants. Patients under 20 years of age initiating kidney replacement therapy from January 2007 through December 2015 in 37 European countries participating in the ESPN/ERA-EDTA Registry were included in the analyses. Countries were categorized as low-, middle-, and high-income based on gross domestic product. At five years of follow-up, 4326 of 6909 children on kidney replacement therapy received their first kidney transplant. Overall median time from kidney replacement therapy start to first kidney transplantation was 1.4 (inter quartile range 0.3-4.3) years. The five-year kidney transplantation probability was 48.8% (95% confidence interval: 45.9-51.7%) in low-income, 76.3% (72.8-79.5%) in middle-income and 92.3% (91.0-93.4%) in high-income countries and was strongly associated with macro-economic factors. Gross domestic product alone explained 67% of the international variation in transplantation rates. Compared with high-income countries, kidney transplantation was 76% less likely to be performed in low-income and 58% less likely in middle-income countries. Overall five-year graft survival in Europe was 88% and showed little variation across countries. Thus, despite large disparities transplantation access across Europe, graft failure rates were relatively similar. Hence, graft survival in low-risk transplant recipients from lower-income countries seems as good as graft survival among all (low-, medium-, and high-risk) graft recipients from high-income countries.

Association between timing of dialysis initiation and clinical outcomes in the paediatric population: an ESPN/ERA-EDTA registry study.

BACKGROUND: There is no consensus regarding the timing of dialysis therapy initiation for end-stage kidney disease (ESKD) in children. As studies investigating the association between timing of dialysis initiation and clinical outcomes are lacking, we aimed to study this relationship in a cohort of European children who started maintenance dialysis treatment. METHODS: We used data on 2963 children from 21 different countries included in the European Society of Pediatric Nephrology/European Renal Association-European Dialysis and Transplant Association Registry who started renal replacement therapy before 18 years of age between 2000 and 2014. We compared two groups according to the estimated glomerular filtration rate (eGFR) at start: eGFR ≥8 mL/min/1.73 m2 (early starters) and eGFR <8 mL/min/1.73 m2 (late starters). The primary outcomes were patient survival and access to transplantation. Secondary outcomes were growth and cardiovascular risk factors. Sensitivity analyses were performed to account for selection- and lead time-bias. RESULTS: The median eGFR at the start of dialysis was 6.1 for late versus 10.5 mL/min/1.73 m2 for early starters. Early starters were older [median: 11.0, interquartile range (IQR): 5.7-14.5 versus 9.4, IQR: 2.6-14.1 years]. There were no differences observed between the two groups in mortality and access to transplantation at 1, 2 and 5 years of follow-up. One-year evolution of height standard deviation scores was similar among the groups, whereas hypertension was more prevalent among late initiators. Sensitivity analyses resulted in similar findings. CONCLUSIONS: We found no evidence for a clinically relevant benefit of early start of dialysis in children with ESKD. Presence of cardiovascular risk factors, such as high blood pressure, should be taken into account when deciding to initiate or postpone dialysis in children with ESKD, as this affects the survival.

Hemodialysis vascular access and subsequent transplantation: a report from the ESPN/ERA-EDTA Registry.

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.

Mortality risk disparities in children receiving chronic renal replacement therapy for the treatment of end-stage renal disease across Europe: an ESPN-ERA/EDTA registry analysis.

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.

Survival in children requiring chronic renal replacement therapy.

Survival in the pediatric end-stage renal disease (ESRD) population has improved substantially over recent decades. Nonetheless, mortality remains at least 30 times higher than that of healthy peers. Patient survival is multifactorial and dependent on various patient and treatment characteristics and degree of economic welfare of the country in which a patient is treated. In this educational review, we aim to delineate current evidence regarding mortality risk in the pediatric ESRD population and provide pediatric nephrologists with up-to-date information required to counsel affected families.

Outcomes of renal replacement therapy in boys with prune belly syndrome: findings from the ESPN/ERA-EDTA Registry.

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.

Infants Requiring Maintenance Dialysis: Outcomes of Hemodialysis and Peritoneal Dialysis.

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.

Racial variation in cardiovascular disease risk factors among European children on renal replacement therapy-results from the European Society for Paediatric Nephrology/European Renal Association - European Dialysis and Transplant Association Registry.

BACKGROUND: Racial differences in overall mortality rates have been found in children on renal replacement therapy (RRT). We used data from the European Society for Paediatric Nephrology/European Renal Association - European Dialysis and Transplant Association Registry to study racial variation in the prevalence of cardiovascular disease (CVD) risk factors among European children on RRT. METHODS: We included patients aged <20 years between 2006-13 who (i) initiated dialysis treatment or (ii) had a renal transplant vintage of ≥1 year. Racial groups were defined as white, black, Asian and other. The CVD risk factors assessed included uncontrolled hypertension, obesity, hyperphosphataemia and anaemia. Differences between racial groups in CVD risk factors were examined using generalized estimating equation (GEE) models while adjusting for potential confounders. RESULTS: In this study, 1161 patients on dialysis and 1663 patients with a transplant were included. The majority of patients in both groups were white (73.8% and 79.9%, respectively). The crude prevalence of the CVD risk factors was similar across racial groups. However, after adjustment for potential confounders, Asian background was associated with higher risk of uncontrolled hypertension both in the dialysis group [odds ratio (OR): 1.27; 95% confidence interval (CI): 1.01-1.64] and the transplant group (OR: 1.37; 95% CI: 1.11-1.68) compared with white patients. Patients of Asian and other racial background with a renal transplant had a higher risk of anaemia compared with white patients (OR: 1.50; 95% CI: 1.15-1.96 and OR: 1.45; 95% CI: 1.01-2.07, respectively). Finally, the mean number of CVD risk factors among dialysis patients was higher in Asian patients (1.83, 95% CI: 1.64-2.04) compared with white patients (1.52, 95% CI: 1.40-1.65). CONCLUSIONS: We found a higher prevalence of modifiable CVD risk factors in Asian children on RRT. Early identification and management of these risk factors could potentially improve long-term outcomes.

The association of donor and recipient age with graft survival in paediatric renal transplant recipients in a European Society for Paediatric Nephrology/European Renal Association-European Dialysis and Transplantation Association Registry study.

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.

Mortality risk in European children with end-stage renal disease on dialysis.

We aimed to describe survival in European pediatric dialysis patients and compare the differential mortality risk between patients starting on hemodialysis (HD) and peritoneal dialysis (PD). Data for 6473 patients under 19 years of age or younger were extracted from the European Society of Pediatric Nephrology, the European Renal Association, and European Dialysis and Transplant Association Registry for 36 countries for the years 2000 through 2013. Hazard ratios (HRs) were adjusted for age at start of dialysis, sex, primary renal disease, and country. A secondary analysis was performed on a propensity score-matched (PSM) cohort. The overall 5-year survival rate in European children starting on dialysis was 89.5% (95% confidence interval [CI] 87.7%-91.0%). The mortality rate was 28.0 deaths per 1000 patient years overall. This was highest (36.0/1000) during the first year of dialysis and in the 0- to 5-year age group (49.4/1000). Cardiovascular events (18.3%) and infections (17.0%) were the main causes of death. Children selected to start on HD had an increased mortality risk compared with those on PD (adjusted HR 1.39, 95% CI 1.06-1.82, PSM HR 1.46, 95% CI 1.06-2.00), especially during the first year of dialysis (HD/PD adjusted HR 1.70, 95% CI 1.22-2.38, PSM HR 1.79, 95% CI 1.20-2.66), when starting at older than 5 years of age (HD/PD: adjusted HR 1.58, 95% CI 1.03-2.43, PSM HR 1.87, 95% CI 1.17-2.98) and when children have been seen by a nephrologist for only a short time before starting dialysis (HD/PD adjusted HR 6.55, 95% CI 2.35-18.28, PSM HR 2.93, 95% CI 1.04-8.23). Because unmeasured case-mix differences and selection bias may explain the higher mortality risk in the HD population, these results should be interpreted with caution.

Kidney Versus Combined Kidney and Liver Transplantation in Young People With Autosomal Recessive Polycystic Kidney Disease: Data From the European Society for Pediatric Nephrology/European Renal Association-European Dialysis and Transplant (ESPN/ERA-EDTA) Registry.

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.

Timing of renal replacement therapy does not influence survival and growth in children with congenital nephrotic syndrome caused by mutations in NPHS1: data from the ESPN/ERA-EDTA Registry.

BACKGROUND: Congenital nephrotic syndrome (CNS) of the Finnish type, NPHS1, is the most severe form of CNS. Outcomes of renal replacement therapy (RRT) in NPHS1 patients in Europe were analysed using data from the ESPN/ERA-EDTA Registry. As NPHS1 is most prevalent in Finland and the therapeutic approach differs from that in many other countries, we compared outcomes in Finnish and other European patients. METHODS: NPHS1 mutations were confirmed in 170 children with CNS who initiated RRT (dialysis or renal transplantation) between 1991 and 2012. Finnish (n = 66) and non-Finnish NPHS1 patients (n = 104) were compared with respect to treatment policy, age at first RRT and renal transplantation (RTX), patient and graft survival, estimated glomerular filtration rate (eGFR) and growth. Age-matched patients with congenital anomalies of the kidney and urinary tract (CAKUT) served as controls. RESULTS: Finnish NPHS1 patients were significantly younger than non-Finnish patients, both at the start of RRT and at the time of RTX. We found similar overall 5-year patient survival on RRT (91 %) and graft survival (89 %) in both NPHS1 groups and CAKUT controls. At the start of RRT, height standard deviation score (SDS) was higher in Finnish patients than in non-Finnish patients (mean [95 % CI]: -1.31 [-2.13 to -0.49] and -3.0 [-4.22 to -1.91], p < 0.01 respectively), but not at 5 years of age. At 5 years of age height and body mass index (BMI) SDS were similar to those of CAKUT controls. CONCLUSIONS: Overall, 5-year patient and graft survival of both Finnish and non-Finnish NPHS1 patients on RRT were excellent and comparable with CAKUT patients with equally early RRT onset and was independent of the timing of RRT initiation and RTX.

Lessons learned from the ESPN/ERA-EDTA Registry.

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.

Anemia in children following renal transplantation-results from the ESPN/ERA-EDTA Registry.

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.

Dyslipidaemia in children on renal replacement therapy.

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 m(2), 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 m(2) (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.