Publications by authors named "Augustina Jankauskiene"

65 Publications

A cross-sectional study of screening for coronavirus disease 2019 (COVID-19) at the pediatric emergency department in Vilnius during the first wave of the pandemic.

Eur J Pediatr 2021 Feb 25. Epub 2021 Feb 25.

Clinic of Children's Diseases, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.

Screening for COVID-19 is based on clinical and epidemiological factors. Children infected with SARS-CoV-2 may have a few or many non-specific symptoms or may be asymptomatic. The aim of this study was to analyze clinical features and exposure to SARS-CoV-2 characteristics of children screened for COVID-19 at the pediatric emergency department in Vilnius during the first 3 months (March-May) of the COVID-19 pandemic in Lithuania. SARS-CoV-2 PCR was positive for 0.6% (8/1348) of all screened children and for 0.9% (7/811) of symptomatic patients, more among children with fever and cough (2.6%, 4/154). There were also COVID-19 cases among children without cough but with other respiratory symptoms (0.5%, 2/409) or gastrointestinal symptoms (1.2%, 3/257). Only one child with positive SARS-CoV-2 did not meet COVID-19 clinical criteria-he presented with vomiting and dehydration only. All COVID-19 cases (n = 8) had a contact with a confirmed COVID-19 family member. There were no COVID-19 cases among children without known exposure to SARS-CoV-2 or among asymptomatic children.Conclusion: Screening for COVID-19 in children is exceptionally challenging due to the diverse and non-specific symptoms of infection they present. Testing strategies should not only focus on the typical COVID-19 symptoms of fever or cough, but also include other symptoms, especially gastrointestinal symptoms, which are also important. The greatest attention should be paid to known exposure to SARS-CoV-2, especially in family clusters. Screening of asymptomatic children with no known exposure should be weighed for medical necessity and cost-effectiveness. What is Known: • Diagnosis of COVID-19 in children is challenging because the disease does not always manifest with typical symptoms. What is New: • Children in our study who did not have symptoms of acute infection and contact with another person infected with COVID-19 were not diagnosed with COVID-19, so the benefit of PCR testing is questionable. Such testing may only be useful for infection control purposes, and to limit intra-hospital transmission.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00431-021-03999-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906570PMC
February 2021

Countermeasures against COVID-19: how to navigate medical practice through a nascent, evolving evidence base - a European multicentre mixed methods study.

BMJ Open 2021 02 17;11(2):e043015. Epub 2021 Feb 17.

Division of Pediatric Nephrology and Gastroenterology, Department of Pediatrics and Adolescent Medicine, Comprehensive Center for Pediatrics, Medical University of Vienna, Vienna, Austria

Objectives: In a previously published Delphi exercise the European Pediatric Dialysis Working Group (EPDWG) reported widely variable counteractive responses to COVID-19 during the first week of statutory public curfews in 12 European countries with case loads of 4-680 infected patients per million. To better understand these wide variations, we assessed different factors affecting countermeasure implementation rates and applied the capability, opportunity, motivation model of behaviour to describe their determinants.

Design: We undertook this international mixed methods study of increased depth and breadth to obtain more complete data and to better understand the resulting complex evidence.

Setting: This study was conducted in 14 paediatric nephrology centres across 12 European countries during the COVID-19 pandemic.

Participants: The 14 participants were paediatric nephrologists and EPDWG members from 12 European centres.

Main Outcome Measures: 52 countermeasures clustered into eight response domains (access control, patient testing, personnel testing, personal protective equipment policy, patient cohorting, personnel cohorting, suspension of routine care, remote work) were categorised by implementation status, drivers (expert opinion, hospital regulations) and resource dependency. Governmental strictness and media attitude were independently assessed for each country and correlated with relevant countermeasure implementation factors.

Results: Implementation rates varied widely among response domains (median 49.5%, range 20%-71%) and centres (median 46%, range 31%-62%). Case loads were insufficient to explain response rate variability. Increasing case loads resulted in shifts from expert opinion-based to hospital regulation-based decisions to implement additional countermeasures despite increased resource dependency. Higher governmental strictness and positive media attitude towards countermeasure implementation were associated with higher implementation rates.

Conclusions: COVID-19 countermeasure implementation by paediatric tertiary care centres did not reflect case loads but rather reflected heterogeneity of local rules and of perceived resources. These data highlight the need of ongoing reassessment of current practices, facilitating rapid change in 'institutional behavior' in response to emerging evidence of countermeasure efficacy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2020-043015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893209PMC
February 2021

Influenza and pneumococcus vaccination rates in pediatric dialysis patients in Europe: Recommendations vs reality A European Pediatric Dialysis Working Group and European Society for Pediatric Nephrology Dialysis Working Group Study.

Turk J Med Sci 2021 Feb 4. Epub 2021 Feb 4.

Background: Children on dialysis are under increased risk of influenza and invasive pneumococcal disease. Although, vaccination against these microorganisms are recommended in dialysis patients and despite the fact that these vaccines can reduce disease burden and rates of hospitalization due to infection, vaccination rates are below expected and desired. We aimed to evaluate influenza and pneumococcal vaccination and infection rates in European pediatric dialysis centers.

Methods: In 16 centers from 11 countries, 357 pediatric dialysis patients were evaluated retrospectively during one year of observation period between 01.01.2014 and 01.01.2015.

Results: In all centers, vaccination policy included immunization of dialysis patients with inactive influenza vaccine and pneumococcal conjugate vaccine (PCV). 50% of centers recommended pneumococcal polysaccharide vaccine following routine PCV series. Significantly higher pneumococcal vaccination rate (43.9 %) was seen in PD patients compared to those on HD (32.9 %) (p=0.035), while the rates for influenza were similar (42.4 % and 46.1 respectively, p=0.496). Among all dialysis patients, 2,2 % (n=8) developed pneumonia and 6.4 % (n=23) infected by influenza. Pneumococcic pneumonia rate was 5 % for 140 patients who received anti-pneumococcal vaccine, while only one pneumonia episode was recorded out of 217 unvaccinated patients (p=0.007). The influenza virus infection rates were similar for patients vaccinated and non-vaccinated (7 % and 6 %, respectively).

Conclusions: Although influenza and pneumococcal vaccines are highly recommended in pediatric dialysis patients, vaccination rates were lower than expected. Pneumococcal vaccination rates were higher in PD compared to the patients on HD. The rate of children with influenza infection was higher than pneumonia. The efficacy of influenza and pneumococcal vaccines was highlighted by the low infection rates. Higher pneumonia rates in patients vaccinated against pneumococcus compared to unvaccinated ones might be due to coexisting risk factors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3906/sag-2012-26DOI Listing
February 2021

Epidemiology of Chronic Kidney Disease in Children: A Report from Lithuania.

Medicina (Kaunas) 2021 Jan 26;57(2). Epub 2021 Jan 26.

Vilnius University Hospital Santaros Klinikos, LT-08406 Vilnius, Lithuania.

The data on the prevalence of chronic kidney disease (CKD) in the pediatric population are limited. The prevalence of CKD ranges from 56 to 74.7 cases per million of the age-related population (pmarp). The most common cause of CKD among children is congenital anomalies of the kidney and urinary tract (CAKUT). With progressing CKD, various complications occur, and end-stage renal disease (ESRD) can develop. The aim of the study was to determine the causes, stage, prevalence, and clinical signs of CKD and demand for RRT (renal replacement therapy) among Lithuanian children in 2017 and to compare the epidemiological data of CKD with the data of 1997 and 2006. The data of 172 Lithuanian children who had a diagnosis of CKD (stage 2-5) in 1997 ( = 41), in 2006 ( = 65), and in 2017 ( = 66) were retrospectively analyzed. Physical development and clinical signs of children who had CKD (stage 2-5) in 2017 were assessed. The prevalence of CKD stages 2-5 was 48.0 pmarp in 1997; 88.7 in 2006; and 132.1 in 2017 ( < 0.01). Congenital and hereditary diseases of the kidney in 1997 accounted for 66% of all CKD causes; in 2006, for 70%; and in 2017, for 79%. In 2017, children with CKD stages 4 or 5 (except transplanted children) had hypertension (87.5%) and anemia (50%) ( < 0.01). Children under ≤2 years with CKD were at a 3-fold greater risk of having elevated blood pressure (OR = 3.375, 95% CI: 1.186-9.904). There was no change in the number of children with CKD in Lithuania; however, the prevalence of CKD increased due to reduced pediatric population. CAKUT remains the main cause of CKD at all time periods. Among children with CKD stages 4 or 5, there were more children with hypertension and anemia. In children who were diagnosed with CKD at an early age hypertension developed at a younger age.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/medicina57020112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912265PMC
January 2021

Serum indoxyl sulfate concentrations associate with progression of chronic kidney disease in children.

PLoS One 2020 27;15(10):e0240446. Epub 2020 Oct 27.

Division of Pediatric Nephrology, Center of Pediatric and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany.

The uremic toxins indoxyl sulfate (IS) and p-cresyl sulfate (pCS) accumulate in patients with chronic kidney disease (CKD) as a consequence of altered gut microbiota metabolism and a decline in renal excretion. Despite of solid experimental evidence for nephrotoxic effects, the impact of uremic toxins on the progression of CKD has not been investigated in representative patient cohorts. In this analysis, IS and pCS serum concentrations were measured in 604 pediatric participants (mean eGFR of 27 ± 11 ml/min/1.73m2) at enrolment into the prospective Cardiovascular Comorbidity in Children with CKD study. Associations with progression of CKD were analyzed by Kaplan-Meier analyses and Cox proportional hazard models. During a median follow up time of 2.2 years (IQR 4.3-0.8 years), the composite renal survival endpoint, defined as 50% loss of eGFR, or eGFR <10ml/min/1.73m2 or start of renal replacement therapy, was reached by 360 patients (60%). Median survival time was shorter in patients with IS and pCS levels in the highest versus lowest quartile for both IS (1.5 years, 95%CI [1.1,2.0] versus 6.0 years, 95%CI [5.0,8.4]) and pCS (1.8 years, 95%CI [1.5,2.8] versus 4.4 years, 95%CI [3.4,6.0]). Multivariable Cox regression disclosed a significant association of IS, but not pCS, with renal survival, which was independent of other risk factors including baseline eGFR, proteinuria and blood pressure. In this exploratory analysis we provide the first data showing a significant association of IS, but not pCS serum concentrations with the progression of CKD in children, independent of other known risk factors. In the absence of comorbidities, which interfere with serum levels of uremic toxins, such as diabetes, obesity and metabolic syndrome, these results highlight the important role of uremic toxins and accentuate the unmet need of effective elimination strategies to lower the uremic toxin burden and abate progression of CKD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240446PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591021PMC
December 2020

Safety and efficacy of sucroferric oxyhydroxide in pediatric patients with chronic kidney disease.

Pediatr Nephrol 2020 Oct 27. Epub 2020 Oct 27.

Children's National Hospital, The George Washington University, Washington, DC, USA.

Background: Pediatric patients with advanced chronic kidney disease (CKD) are often prescribed oral phosphate binders (PBs) for the management of hyperphosphatemia. However, available PBs have limitations, including unfavorable tolerability and safety.

Methods: This phase 3, multicenter, randomized, open-label study investigated safety and efficacy of sucroferric oxyhydroxide (SFOH) in pediatric and adolescent subjects with CKD and hyperphosphatemia. Subjects were randomized to SFOH or calcium acetate (CaAc) for a 10-week dose titration (stage 1), followed by a 24-week safety extension (stage 2). Primary efficacy endpoint was change in serum phosphorus from baseline to the end of stage 1 in the SFOH group. Safety endpoints included treatment-emergent adverse events (TEAEs).

Results: Eighty-five subjects (2-18 years) were randomized and treated (SFOH, n = 66; CaAc, n = 19). Serum phosphorus reduction from baseline to the end of stage 1 in the overall SFOH group (least squares [LS] mean ± standard error [SE]) was - 0.488 ± 0.186 mg/dL; p = 0.011 (post hoc analysis). Significant reductions in serum phosphorus were observed in subjects aged ≥ 12 to ≤ 18 years (LS mean ± SE - 0.460 ± 0.195 mg/dL; p = 0.024) and subjects with serum phosphorus above age-related normal ranges at baseline (LS mean ± SE - 0.942 ± 0.246 mg/dL; p = 0.005). Similar proportions of subjects reported ≥ 1 TEAE in the SFOH (75.8%) and CaAc (73.7%) groups. Withdrawal due to TEAEs was more common with CaAc (31.6%) than with SFOH (18.2%).

Conclusions: SFOH effectively managed serum phosphorus in pediatric patients with a low pill burden and a safety profile consistent with that reported in adult patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00467-020-04805-yDOI Listing
October 2020

Phenotypes and Baseline Risk Factors of Acute Kidney Injury in Children After Allogeneic Hematopoietic Stem Cell Transplantation.

Front Pediatr 2020 27;8:499. Epub 2020 Aug 27.

Clinic of Pediatrics, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.

Acute kidney injury (AKI) is a frequent and widely recognized complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Despite relatively high prevalence, AKI after allo-HSCT and its risk factors in children remain obscure. The aim of this study was to describe the prevalence and course of AKI during the first 100 days after allo-HSCT in children and to investigate its associations with baseline characteristics. Retrospective single-center chart review of all patients under 18 who underwent allo-HSCT during 2011-2017 was performed. AKI was defined using the pediatric RIFLE criteria and only the patients with pRIFLE stage I (eGFR decrease by 50% or more) or higher were considered for the analysis. Recurrent AKI and acute kidney disease (AKD) were defined according to the Acute Disease Quality Initiative consensus. Demographic, clinical, and procedure-related characteristics were recorded at the day of HSCT. Fifty-one patients (68.6% boys) with a median age of 9 years (range: 0.25-17) were included. During a median follow-up of 82 (IQR, 60-98) days, 27 (52.9%) patients experienced a total of 39 AKI episodes, translating into one AKI episode per 100 patient days. Multiple AKIs occurred in 11 (21.6%) patients and 18 (35.3%) progressed to AKD. Four patients died, all with ongoing or previous AKI. Patients with AKD were, on average, older (10 vs. 6 years; = 0.03) and had higher baseline body mass index (BMI) [standard deviation score (SDS) 0.83 vs. 0.04, = 0.05], whereas patients with recurrent AKI had higher baseline estimated glomerular filtration rate (eGFR) (244.1 vs. 193.9 ml/min/1.73 m, = 0.02). In the adjusted Cox models (HR; 95% CI), older age (1.10; 1.01-1.20) was associated with higher risk of overall AKI and higher eGFR (1.02; 1.01-1.04) was associated with higher risk of recurrent AKI, while older age (1.17; 1.04-1.31), higher eGFR (HR 1.01; 1.0-1.02), and higher BMI SDS (1.66; 1.01-2.72) were associated with higher risk of AKD. AKI is a frequent early complication of allo-HSCT in children, and approximately one fifth experience AKI recurrence and one third develop AKD. Older age, higher BMI, and higher eGFR at the day of transplant may have an effect on the risk of AKI development and its course.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fped.2020.00499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7481355PMC
August 2020

Pathophysiology and consequences of arterial stiffness in children with chronic kidney disease.

Pediatr Nephrol 2020 Sep 7. Epub 2020 Sep 7.

Great Ormond Street Hospital for Children NHS Foundation Trust, University College London, Institute of Child Health, London, UK.

Changes in arterial structure and function are seen early in the course of chronic kidney disease (CKD) and have been causally associated with cardiovascular (CV) morbidity. Numerous potential injuries encompassing both traditional and uremia-specific CV risk factors can induce structural arterial changes and accelerate arterial stiffening. When the buffering capacity of the normally elastic arteries is reduced, damage to vulnerable microcirculatory beds can occur. Moreover, the resultant increase to cardiac afterload contributes to the development of left ventricular hypertrophy and cardiac dysfunction. Adult studies have linked arterial stiffness with increased risk of mortality, CV events, cognitive decline, and CKD progression. Pulse wave velocity (PWV) is currently the gold standard of arterial stiffness assessment but its measurement in children is challenging due to technical difficulties and physiologic aspects related to growth and poor standardization between algorithms for calculating PWV. Nevertheless, studies in pediatric CKD have reported increased arterial stiffness in children with advanced CKD, on dialysis, and after kidney transplantation. Development of arterial stiffness in children with CKD is closely related to mineral-bone disease and hypertension, but other factors may also play a significant role. The clinical relevance of accelerated arterial stiffness in childhood on cardiovascular outcomes in adult life remains unclear, and prospective studies are needed. In this review we discuss mechanisms leading to arterial stiffness in CKD and its clinical implications, along with issues surrounding the technical aspects of arterial stiffness assessment in children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00467-020-04732-yDOI Listing
September 2020

Patient- and parent proxy-reported outcome measures for life participation in children with chronic kidney disease: a systematic review.

Nephrol Dial Transplant 2020 11;35(11):1924-1937

Sydney School of Public Health, University of Sydney, Sydney, NSW, Australia.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ndt/gfaa132DOI Listing
November 2020

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

Kidney Int 2020 08 26;98(2):464-475. Epub 2020 Apr 26.

ESPN/ERA-EDTA Registry, Amsterdam UMC, University of Amsterdam, Department of Medical Informatics, Amsterdam Public Health Research Institute, Meibergdreef 9, Amsterdam, The Netherlands.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.kint.2020.03.029DOI Listing
August 2020

Prevalence of arterial hypertension, hemodynamic phenotypes, and left ventricular hypertrophy in children after coarctation repair: a multicenter cross-sectional study.

Pediatr Nephrol 2020 11 11;35(11):2147-2155. Epub 2020 Jun 11.

Department of Nephrology and Arterial Hypertension, The Children's Memorial Health Institute, Warsaw, Poland.

Background: This study aimed to evaluate hemodynamic phenotypes and prevalence of left ventricular hypertrophy in children after coarctation repair with right arm and leg blood pressure difference < 20 mmHg. Secondary objectives were analysis of effects of age at intervention, residual gradient across the descending aorta, and type of correction.

Methods: Blood pressure status and left ventricular hypertrophy were diagnosed according to European Society of Hypertension 2016 guidelines.

Results: Of 90 patients with a median age 12.5 (8.9-15.8) years, 8.5 (6.0-11.8) years after coarctation repair who were included, 42 (46.7%) were hypertensive. Isolated systolic hypertension dominated among 29 hypertensive patients with uncontrolled or masked hypertension (25 of 29; 86.2%). Of the 48 patients with office normotension, 14.6% (7) had masked hypertension, 8.3% (4) had ambulatory prehypertension, and 54.2% (26) were truly normotensive. Left ventricular hypertrophy was diagnosed in 29 patients (32.2%), including 14 of 42 (33.3%) hypertensive and 15 of 48 (31.3%) normotensive patients. The peak systolic gradient across the descending aorta was greater in hypertensive subjects (33.3 ± 12.7 mmHg) compared with normotensive subjects (25 ± 8.2 mmHg, p = 0.0008). Surgical correction was performed earlier than percutaneous intervention (p < 0.0001) and dominated in 40 of 48 (83.3%) normotensive versus 24 of 42 (57.1%) hypertensive patients (p = 0.006).

Conclusions: Arterial hypertension with isolated systolic hypertension as the dominant phenotype and left ventricular hypertrophy are prevalent even after successful coarctation repair. Coarctation correction from the age of 9 years and older was associated with a higher prevalence of hypertension.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00467-020-04645-wDOI Listing
November 2020

Rapid response in the COVID-19 pandemic: a Delphi study from the European Pediatric Dialysis Working Group.

Pediatr Nephrol 2020 09 17;35(9):1669-1678. Epub 2020 May 17.

Division of Pediatric Nephrology and Gastroenterology, Comprehensive Center for Pediatrics, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Background: COVID-19 was declared a global health emergency. Since children are less than 1% of reported cases, there is limited information to develop evidence-based practice recommendations. The objective of this study was to rapidly gather expert knowledge and experience to guide the care of children with chronic kidney disease during the COVID-19 pandemic.

Methods: A four-round multi-center Delphi exercise was conducted among 13 centers in 11 European countries of the European Pediatric Dialysis Working Group (EPDWG) between March, 16th and 20th 2020. Results were analyzed using a mixed methods qualitative approach and descriptive statistics.

Results: Thirteen COVID-19 specific topics of particular need for guidance were identified. Main themes encompassed testing strategies and results (n = 4), changes in use of current therapeutics (n = 3), preventive measurements of transmission and management of COVID-19 (n = 3), and changes in standard clinical care (n = 3). Patterns of center-specific responses varied according to regulations and to availability of guidelines.

Conclusions: As limited quantitative evidence is available in real time during the rapid spread of the COVID-19 pandemic, qualitative expert knowledge and experience represent the best evidence available. This Delphi exercise demonstrates that use of mixed methodologies embedded in an established network of experts allowed prompt analysis of pediatric nephrologists' response to COVID-19 during this fast-emerging public health crisis. Such rapid sharing of knowledge and local practices is essential to timely and optimal guidance for medical management of specific patient groups in multi-country health care systems such as those of Europe and the US.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00467-020-04584-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230035PMC
September 2020

Colostomy in children on chronic peritoneal dialysis.

Pediatr Nephrol 2020 01 30;35(1):119-126. Epub 2019 Oct 30.

Children's Mercy Kansas City, Kansas City, MO, USA.

Background: This study aimed to evaluate outcome of children on chronic peritoneal dialysis (PD) with a concurrent colostomy.

Methods: Patients were identified through the International Pediatric Peritoneal Dialysis Network (IPPN) registry. Matched controls were randomly selected from the registry. Data were collected through the IPPN database and a survey disseminated to all participating sites.

Results: Fifteen centers reported 20 children who received chronic PD with a co-existing colostomy. The most common cause of end stage kidney disease was congenital anomalies of the kidney and urinary tract (n = 16, 80%). The main reason for colostomy placement was anorectal malformation (n = 13, 65%). The median age at colostomy creation and PD catheter (PDC) insertion were 0.1 (IQR, 0-2.2) and 2.8 (IQR 0.2-18.8) months, respectively. The colostomies and PDCs were present together for a median 18 (IQR, 4.9-35.8) months. The median age at PDC placement in 46 controls was 3.4 (IQR, 0.2-7.4) months of age. Fourteen patients (70%) developed 39 episodes of peritonitis. The annualized peritonitis rate was significantly higher in the colostomy group (1.13 vs. 0.70 episodes per patient year; p = 0.02). Predominant causative microorganisms were Staphylococcus aureus (15%) and Pseudomonas aeruginosa (13%). There were 12 exit site infection (ESI) episodes reported exclusively in colostomy patients. Seven colostomy children (35%) died during their course of PD, in two cases due to peritonitis.

Conclusion: Although feasible in children with a colostomy, chronic PD is associated with an increased risk of peritonitis and mortality. Continued efforts to reduce infection risk for this complex patient population are essential.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00467-019-04372-xDOI Listing
January 2020

Isolated nocturnal and isolated daytime hypertension associate with altered cardiovascular morphology and function in children with chronic kidney disease: findings from the Cardiovascular Comorbidity in Children with Chronic Kidney Disease study.

J Hypertens 2019 11;37(11):2247-2255

Center for Pediatrics and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany.

Introduction: Prevalence of isolated nocturnal hypertension (INH) and isolated daytime hypertension (IDH) is around 10% in adults. Data in children, especially in chronic kidney disease (CKD), are lacking. The aim of this cross-sectional multicenter cohort study was to define the prevalence of INH and IDH and its association with cardiovascular morphology and function, that is, pulse wave velocity (PWV), carotid intima-media thickness (cIMT), or left ventricular mass index (LVMI) in children with CKD.

Methods: Ambulatory blood pressure (BP) monitoring profiles were analyzed in 456 children with CKD stages III-V participating in the Cardiovascular Comorbidity in Children with Chronic Kidney Disease Study (64.3% males, 71.3% congenital anomaly of the kidney and urinary tract, age 12.5 ± 3.2 years, estimated glomerular filtration rate 29 ± 12 ml/min per 1.73 m). Baseline PWV, cIMT, and LVMI were compared in normotension, INH, IDH, or sustained 24-h hypertension.

Results: Prevalence of sustained hypertension was 18.4%, of INH 13.4%, and of IDH 3.7%. PWV SDS (SD score) and cIMT SDS were significantly higher in sustained hypertension and INH, and PWV SDS was significantly higher in IDH, compared with normotension. LVMI was significantly increased in sustained hypertension, but not in INH or IDH. Determinants of INH were smallness for gestational age, older age, higher height SDS and parathyroid hormone, and shorter duration of CKD. In logistic regression analysis, day/night-time hypertension or ambulatory BP monitoring pattern (normal, INH, IDH, sustained hypertension) were independently associated with cardiovascular outcome measures: elevated night-time BP was associated with increased cIMT, PWV, and left ventricular hypertrophy; INH was associated with cIMT.

Conclusion: INH is present in almost one out of seven children with predialysis CKD; INH and nocturnal hypertension in general are associated with alterations of arterial morphology and function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/HJH.0000000000002160DOI Listing
November 2019

Acute dialysis in children: results of a European survey.

J Nephrol 2019 Jun 4;32(3):445-451. Epub 2019 Apr 4.

Nephrology and Dialysis Unit, Pediatric Subspecialties Department, Institute for Scientific Research, Bambino Gesù Children's Hospital, Piazza S. Onofrio 4, 00165, Rome, Italy.

The number of children with acute kidney injury (AKI) requiring dialysis is increasing. To date, systematic analysis has been largely limited to critically ill children treated with continuous renal replacement therapy (CRRT). We conducted a survey among 35 European Pediatric Nephrology Centers to investigate dialysis practices in European children with AKI. Altogether, the centers perform dialysis in more than 900 pediatric patients with AKI per year. PD and CRRT are the most frequently used dialysis modalities, accounting for 39.4% and 38.2% of treatments, followed by intermittent HD (22.4%). In units treating more than 25 cases per year and in those with cardiothoracic surgery programs, PD is the most commonly chosen dialysis modality. Also, nearly one quarter of centers, in countries with a gross domestic product below $35,000/year, do not utilize CRRT at all. Dialysis nurses are exclusively in charge of CRRT management in 45% of the cases and pediatric intensive care nurses in 25%, while shared management is practiced in 30%. In conclusion, this survey indicates that the choice of treatment modalities for dialysis in children with AKI in Europe is affected by the underlying ethiology of the disease, organization/set-up of centers and socioeconomic conditions. PD is utilized as often as CRRT, and also intermittent HD is a commonly applied treatment option. A prospective European AKI registry is planned to provide further insights on the epidemiology, management and outcomes of dialysis in pediatric AKI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40620-019-00606-1DOI Listing
June 2019

Iron deficiency anemia-related gut microbiota dysbiosis in infants and young children: A pilot study.

Acta Microbiol Immunol Hung 2018 Dec 12;65(4):551-564. Epub 2018 Nov 12.

1 Clinic of Children's Diseases, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University , Vilnius, Lithuania.

Nutritional iron deficiency (ID) causes not only anemia but also malfunction of the entire human organism. Recently, a role of the gut microbiota has been hypothesized, but limited data are available especially in infants. Here, we performed a pilot study to explore the gut microbiota in 10 patients with iron deficiency anemia (IDA) and 10 healthy controls aged 6-34 months. Fresh stool samples were collected from diapers, and the fecal microbiota was profiled by next-generation sequencing of the V3-V4 hypervariable region of the 16S rRNA gene. Except for diet diversity, the breastfeeding status at the enrollment, the exclusive breastfeeding duration, and the introduction of complementary foods did not differ between groups. Distinct microbial signatures were found in IDA patients, with increased relative abundance of Enterobacteriaceae (mean relative abundance, patients vs. controls, 4.4% vs. 3.0%) and Veillonellaceae (13.7% vs. 3.6%), and reduced abundance of Coriobacteriaceae (3.5% vs. 8.8%) compared to healthy controls. A decreased Bifidobacteriaceae/Enterobacteriaceae ratio was observed in IDA patients. Notwithstanding the low sample size, our data highlight microbiota dysbalance in IDA worth for further investigations, aimed at unraveling the ID impact on the microbiome trajectory in early life, and the possible long-term consequences.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1556/030.65.2018.045DOI Listing
December 2018

Renal Replacement Therapy in Children in Lithuania: Challenges, Trends, and Outcomes.

Medicina (Kaunas) 2018 Nov 2;54(5). Epub 2018 Nov 2.

Institute of Clinical Medicine, Vilnius University, LT-08406 Vilnius, Lithuania.

Pediatric renal replacement therapy (RRT) in Lithuania resumed in 1994 after a 12-year pause in renal transplantation. Management of end stage renal disease (ESRD) has changed, and outcomes have improved over decades. Our aim was to evaluate the dynamics of RRT in Lithuania in the period 1994⁻2015, describe its distinctive features, and compare our results with other countries. Data between 1994 and 2015 were collected from patients under the age of 18 years with ESRD receiving RRT. The data included: Hemodialysis (HD), peritoneal dialysis (PD), transplantation incidence and prevalence, transplant waiting time, dialysis modalities before transplantation, causes of ESRD and gender distribution in transplanted patients, and patient and graft survival. RRT incidence and prevalence maintained an increase up until 2009. Sixty-four transplantations were performed. Juvenile nephronophthisis (25.9%) was the primary cause of ESRD in transplanted children. The transplant waiting time median was 8.0 months. The male to female ratio post-transplantation was 1.02. Patient survival after transplantation at 10 years was 90.0%, while graft survival for living (related) was 77.0% and 51.1% for deceased. Twelve patients died while on RRT. RRT numbers are increasing in Lithuania. HD is the primary treatment of choice before transplantation, with continued low numbers of preemptive transplantation. Patient survival post-transplantation is favorable, though graft survival is less satisfactory.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/medicina54050078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262335PMC
November 2018

Infants with congenital nephrotic syndrome have comparable outcomes to infants with other renal diseases.

Pediatr Nephrol 2019 04 29;34(4):649-655. Epub 2018 Oct 29.

Great Ormond Street Hospital for Children NHS Foundation Trust, London, WC1N 3JH, UK.

Background: Children with congenital nephrotic syndrome (CNS) commonly develop end stage renal failure in infancy and require dialysis, but little is known about the complications and outcomes of dialysis in these children.

Methods: We conducted a retrospective case note review across members of the European Society for Pediatric Nephrology Dialysis Working Group to evaluate dialysis management, complications of dialysis, and outcomes in children with CNS.

Results: Eighty children (50% male) with CNS were identified form 17 centers over a 6-year period. Chronic dialysis was started in 44 (55%) children at a median age of 8 (interquartile range 4-14) months. Of these, 17 (39%) were on dialysis by the age of 6 months, 30 (68%) by 1 year, and 40 (91%) by 2 years. Peritoneal dialysis (PD) was the modality of choice in 93%, but 34% switched to hemodialysis (HD), largely due to catheter malfunction (n = 5) or peritonitis (n = 4). The peritonitis rate was 0.77 per patient-year. Weight and height SDS remained static after 6 months on dialysis. In the overall cohort, at final follow-up, 29 children were transplanted, 18 were still on dialysis (15 PD, 3 HD), 19 were in pre-dialysis chronic kidney disease (CKD), and there were 14 deaths (8 on dialysis). Median time on chronic dialysis until transplantation was 9 (6-18) months, and the median age at transplantation was 22 (14-28) months.

Conclusions: Infants with CNS on dialysis have a comparable mortality, peritonitis rate, growth, and time to transplantation as infants with other primary renal diseases reported in international registry data.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00467-018-4122-0DOI Listing
April 2019

Management of children with congenital nephrotic syndrome: challenging treatment paradigms.

Nephrol Dial Transplant 2019 08;34(8):1369-1377

Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.

Background: Management of children with congenital nephrotic syndrome (CNS) is challenging. Bilateral nephrectomies followed by dialysis and transplantation are practiced in most centres, but conservative treatment may also be effective.

Methods: We conducted a 6-year review across members of the European Society for Paediatric Nephrology Dialysis Working Group to compare management strategies and their outcomes in children with CNS.

Results: Eighty children (50% male) across 17 tertiary nephrology units in Europe were included (mutations in NPHS1, n = 55; NPHS2, n = 1; WT1, n = 9; others, n = 15). Excluding patients with mutations in WT1, antiproteinuric treatment was given in 42 (59%) with an increase in S-albumin in 70% by median 6 (interquartile range: 3-8) g/L (P < 0.001). Following unilateral nephrectomy, S-albumin increased by 4 (1-8) g/L (P = 0.03) with a reduction in albumin infusion dose by 5 (2-9) g/kg/week (P = 0.02). Median age at bilateral nephrectomies (n = 29) was 9 (7-16) months. Outcomes were compared between two groups of NPHS1 patients: those who underwent bilateral nephrectomies (n = 25) versus those on conservative management (n = 17). The number of septic or thrombotic episodes and growth were comparable between the groups. The response to antiproteinuric treatment, as well as renal and patient survival, was independent of NPHS1 mutation type. At final follow-up (median age 34 months) 20 (80%) children in the nephrectomy group were transplanted and 1 died. In the conservative group, 9 (53%) remained without dialysis, 4 (24%; P < 0.001) were transplanted and 2 died.

Conclusion: An individualized, stepwise approach with prolonged conservative management may be a reasonable alternative to early bilateral nephrectomies and dialysis in children with CNS and NPHS1 mutations. Further prospective studies are needed to define indications for unilateral nephrectomy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ndt/gfy165DOI Listing
August 2019

Assessment of Risk Factors for Iron Deficiency Anemia in Infants and Young Children: A Case-Control Study.

Breastfeed Med 2018 09 10;13(7):493-499. Epub 2018 Aug 10.

1 Clinic of Children's Diseases, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University , Vilnius, Lithuania .

Introduction: Iron deficiency anemia (IDA) is common in children aged 0-35 months in Lithuania. Nevertheless, there are no studies investigating IDA in this age group. We aimed to identify the major risk factors for disease development focusing on medical history and dietary habits.

Methods: A prospective case-control study was conducted in a university hospital. The enrolled cohort was divided into three groups: IDA infants (IDA-In; n = 36, aged 3-11 months), IDA children (IDA-Ch; n = 23, aged 12-32 months), and healthy controls (HCs; n = 32, aged 6-34 months).

Results: There was a higher number of premature, low birth weight (LBW), and faster gaining weight infants in the IDA-In group. Their diet diversity was lower than IDA-Ch and HC. In contrast, the IDA-Ch group had no signs of impaired iron stores at birth or higher iron need for fast growth; their diet diversity was similar to that of HC, but meat was introduced later as compared with those in the IDA-In and HC groups. Consumption of cow's milk was rather low among all study participants, but consumption of sugar-added products was found to be a new emerging problem. Exclusive breastfeeding did not differ in duration and prevalence; the age for introduction of complementary foods was similar in all groups.

Conclusions: Low compliance with World Health Organization (WHO) recommendations on breastfeeding and complementary feeding suggests an urgent need for nutritional counseling in early childhood, especially in premature, LBW, and fast gaining weight infants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/bfm.2018.0083DOI Listing
September 2018

Risk Factors for Early Dialysis Dependency in Autosomal Recessive Polycystic Kidney Disease.

J Pediatr 2018 08 9;199:22-28.e6. Epub 2018 May 9.

Department of Pediatrics, University Hospital of Cologne, Cologne, Germany; Center for Molecular Medicine, University Hospital of Cologne, Cologne, Germany.

Objective: To identify prenatal, perinatal, and postnatal risk factors for dialysis within the first year of life in children with autosomal recessive polycystic kidney disease (ARPKD) as a basis for parental counseling after prenatal and perinatal diagnosis.

Study Design: A dataset comprising 385 patients from the ARegPKD international registry study was analyzed for potential risk markers for dialysis during the first year of life.

Results: Thirty-six out of 385 children (9.4%) commenced dialysis in the first year of life. According to multivariable Cox regression analysis, the presence of oligohydramnios or anhydramnios, prenatal kidney enlargement, a low Apgar score, and the need for postnatal breathing support were independently associated with an increased hazard ratio for requiring dialysis within the first year of life. The increased risk associated with Apgar score and perinatal assisted breathing was time-dependent and vanished after 5 and 8 months of life, respectively. The predicted probabilities for early dialysis varied from 1.5% (95% CI, 0.5%-4.1%) for patients with ARPKD with no prenatal sonographic abnormalities to 32.3% (95% CI, 22.2%-44.5%) in cases of documented oligohydramnios or anhydramnios, renal cysts, and enlarged kidneys.

Conclusions: This study, which identified risk factors associated with onset of dialysis in ARPKD in the first year of life, may be helpful in prenatal parental counseling in cases of suspected ARPKD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2018.03.052DOI Listing
August 2018

Prevalence of Hypertension in Children with Early-Stage ADPKD.

Clin J Am Soc Nephrol 2018 06 19;13(6):874-883. Epub 2018 Apr 19.

Division of Nephrology, Department of Pediatric Subspecialties, and

Background And Objectives: Autosomal dominant polycystic kidney disease is the most common inheritable kidney disease, frequently thought to become symptomatic in adulthood. However, patients with autosomal dominant polycystic kidney disease may develop signs or symptoms during childhood, in particular hypertension. Although ambulatory BP monitoring is the preferred method to diagnose hypertension in pediatrics, data in children with autosomal dominant polycystic kidney disease are limited.

Design, Setting, Participants, & Measurements: Our retrospective multicenter study was conducted to collect ambulatory BP monitoring recordings from patients with autosomal dominant polycystic kidney disease age <18 years old. Basic anthropometric parameters as well as data on kidney function, BP treatment, and kidney ultrasound were also collected.

Results: Data from 310 children with autosomal dominant polycystic kidney disease with a mean age of 11.5±4.1 years old were collected at 22 European centers. At the time when ambulatory BP monitoring was performed, 95% of children had normal kidney function. Reference data for ambulatory BP monitoring were available for 292 patients. The prevalence rates of children with hypertension and/or those who were treated with antihypertensive drugs were 31%, 42%, and 35% during daytime, nighttime, or the entire 24-hour cycle, respectively. In addition, 52% of participants lacked a physiologic nocturnal BP dipping, and 18% had isolated nocturnal hypertension. Logistic regression analysis showed a significant association between a categorical cyst score that was calculated on the basis of the number of cysts >1 cm per kidney and daytime hypertension (odds ratio, 1.70; 95% confidence interval, 1.21 to 2.4; =0.002), nighttime hypertension (odds ratio, 1.31; 95% confidence interval, 1.05 to 1.63; =0.02), or 24-hour hypertension (odds ratio, 1.39; 95% confidence interval, 1.08 to 1.81; =0.01). Kidney length, expressed as SD score, was also significantly associated with nighttime hypertension (odds ratio, 1.23; 95% confidence interval, 1.06 to 1.42; =0.10).

Conclusions: These data indicate high prevalence of hypertension in children with autosomal dominant polycystic kidney disease starting at young ages.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2215/CJN.11401017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989684PMC
June 2018

Vaccination Practices in Pediatric Dialysis Patients Across Europe. A European Pediatric Dialysis Working Group and European Society for Pediatric Nephrology Dialysis Working Group Study.

Nephron 2018 12;138(4):280-286. Epub 2017 Dec 12.

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Background: Data on the immunization practices in pediatric chronic kidney disease (CKD) patients are scarce. The purpose of this study was to evaluate current vaccination practices for children on dialysis across European pediatric nephrology centers.

Methods: A total of 18 tertiary pediatric nephrology centers from 12 European countries were included in the study. The data on universal national immunization programs and immunization practices for children with chronic disease or risk were recorded from European Center for Disease Prevention and Control and the World Health Organization. The immunization practices and center protocols for monitoring antibody titers after vaccination in dialysis patients were obtained through a questionnaire.

Results: All centers included in the study recommended immunization against hepatitis B virus (HBV), diphtheria, tetanus, pertussis, Hemophilus influenzae type b (Hib), poliomyelitis, measles, mumps, rubella (MMR), and streptococcus pneumonia in dialysis patients. In 16 centers, dialysis patients were vaccinated against influenza virus annually. HBV protective antibody titers were measured in 17 centers (during dialysis period in 14 centers, during pre-renal transplantation preparations in 14 centers or in both times in 11 centers). Hepatitis A virus (HAV) was reported to be followed in 13 centers, in 8 centers during dialysis period, and in 11 centers during pre-RTx preparations. MMR and varicella-zoster virus (VZV) protective antibody titers were measured during the dialysis period or before renal transplantation (RTx) in 12 and 15 centers, respectively, and in 6 centers both titers were checked both times.

Conclusion: There are variations in vaccination practice across Europe. Children with CKD, those undergoing dialysis, and transplant candidates should receive age-appropriate vaccinations before RTx as well as before the transition to adult nephrology clinics and antibody levels should be monitored to evaluate the immunization status before and after RTx.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000485398DOI Listing
September 2019

Association of Serum Soluble Urokinase Receptor Levels With Progression of Kidney Disease in Children.

JAMA Pediatr 2017 11 6;171(11):e172914. Epub 2017 Nov 6.

Department of Medicine, Rush University Medical Center, Chicago, Illinois.

Importance: Conventional methods to diagnose and monitor chronic kidney disease (CKD) in children, such as creatinine level and cystatin C-derived estimated glomerular filtration rate (eGFR) and assessment of proteinuria in spot or timed urine samples, are of limited value in identifying patients at risk of progressive kidney function loss. Serum soluble urokinase receptor (suPAR) levels strongly predict incident CKD stage 3 in adults.

Objective: To determine whether elevated suPAR levels are associated with renal disease progression in children with CKD.

Design, Setting, And Participants: Post hoc analysis of 2 prospectively followed up pediatric CKD cohorts, ie, the ESCAPE Trial (1999-2007) and the 4C Study (2010-2016), with serum suPAR level measured at enrollment and longitudinal eGFR measured prospectively. In the 2 trials, a total of 898 children were observed at 30 (ESCAPE Trial; n = 256) and 55 (4C Study; n = 642) tertiary care hospitals in 13 European countries. Renal diagnoses included congenital anomalies of the kidneys and urinary tract (n = 637 [70.9%]), tubulointerstitial nephropathies (n = 92 [10.2%]), glomerulopathies (n = 69 [7.7%]), postischemic CKD (n = 42 [4.7%]), and other CKD (n = 58 [6.5%]). Total follow-up duration was up to 7.9 years, and median follow-up was 3.1 years. Analyses were conducted from October 2016 to December 2016.

Exposures: Serum suPAR level was measured at enrollment, and eGFR was measured every 2 months in the ESCAPE Trial and every 6 months in the 4C Study. The primary end point of CKD progression was a composite of 50% eGFR loss, eGFR less than 10 mL/min/1.73 m2, or initiation of renal replacement therapy.

Main Outcomes And Measures: The primary end point in this study was renal survival, defined as a composite of 50% loss of GFR that persisted for at least 1 month, the start of renal replacement therapy, or an eGFR less than 10 mL/min/1.73 m2.

Results: Of the 898 included children, 560 (62.4%) were male, and the mean (SD) patient age at enrollment was 11.9 (3.5) years. The mean (SD) eGFR was 34 (16) mL/min/1.73 m2. The 5-year end point-free renal survival was 64.5% (95% CI, 57.4-71.7) in children with suPAR levels in the lowest quartile compared with 35.9% (95% CI, 28.7-43.0) in those in the highest quartile (P < .001). By multivariable analysis, the risk of attaining the end point was higher in children with glomerulopathies and increased with age, blood pressure, proteinuria, and lower eGFR at baseline. In patients with baseline eGFR greater than 40 mL/min/1.73 m2, higher log-transformed suPAR levels were associated with a higher risk of CKD progression after adjustment for traditional risk factors (hazard ratio, 5.12; 95% CI, 1.56-16.7; P = .007).

Conclusions And Relevance: Patients with high suPAR levels were more likely to have progression of their kidney disease. Further studies should determine whether suPAR levels can identify children at risk for future CKD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamapediatrics.2017.2914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6121753PMC
November 2017

De novo weekly and biweekly darbepoetin alfa dosing in pediatric patients with chronic kidney disease.

Pediatr Nephrol 2018 Jan 17;33(1):125-137. Epub 2017 Aug 17.

Amgen Inc., Thousand Oaks, CA, USA.

Background: Darbepoetin alfa is a commonly prescribed erythropoiesis-stimulating agent (ESA) for correcting anemia in pediatric chronic kidney disease (CKD) patients. However, little information exists on its use in ESA-naïve patients. This study evaluated the efficacy and safety of darbepoetin alfa in pediatric patients initiating ESA therapy.

Methods: One-hundred sixteen pediatric ESA-naïve subjects (aged 1-18 years) with CKD stages 3-5D and hemoglobin (Hb) <10 g/dl from 43 centers in the US, Europe, and Mexico were randomized by age (three groups) and dialysis status (yes vs. no) to receive darbepoetin alfa once weekly (QW) or every 2 weeks (Q2W) subcutaneously (not on dialysis and peritoneal dialysis subjects) and intravenously (hemodialysis subjects). The drug was titrated to achieve Hb levels of 10.0-12.0 g/dl over 25 weeks. Patient- and parent-reported health-related outcomes were measured by the Pediatric Quality of Life Inventory (PedsQL™) in children ≥2 years.

Results: In both groups, mean Hb concentrations increased to ≥11.0 g/dl over the first 3 months of treatment and remained stable within the 10.0-12.0 g/dl target range. The median time to achieve hemoglobin ≥10 g/dl was slightly longer for subjects <12 years (QW and Q2W, both 28 days) vs. those ≥12 years (23 and 22 days, respectively). Adverse event profiles were similar between groups, with QW, four (7%) and Q2W, five (9%). PedsQL™ scores showed modest increases.

Conclusions: Darbepoetin alfa can be safely administered either QW or Q2W to ESA-naïve pediatric patients with CKD-related anemia to achieve Hb targets of 10.0-12.0 g/dl.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00467-017-3758-5DOI Listing
January 2018

The impact of IgM deposits on the outcome of Nephrotic syndrome in children.

BMC Nephrol 2017 Aug 3;18(1):260. Epub 2017 Aug 3.

Institute of Clinical Medicine, Faculty of medicine, Vilnius University, M.K.Ciurlionio srt. 21, 03101, Vilnius, Lithuania.

Background: The significance of IgM deposits in glomerular mesangium has been controversial since they were first described due to the variations in the both the definitions used and described impact on clinical outcome. The aim of our study was to evaluate the significance of the IgM deposits in the glomerular mesangium for outcomes of nephrotic syndrome (NS) in children.

Methods: Forty-five children with NS who underwent renal biopsy at tertiary pediatric hospital from January 1st, 2000 to December 31st, 2015 and the pathology diagnosis of minimal change disease, focal segmental glomerulosclerosis and mesangial hypercellularity (MH) were retrospectively analyzed. IgM positivity was defined as ≥1+ imunofluorescence with predominantly mesangial distribution. The patients were stratified into IgM-positive (n = 18) and IgM-negative (n = 27).

Results: At the end of the median follow-up 4.5 years (range 0.17-13.14), the IgM-positive group was represented by 11 patients (61.1%) in remission, 3 patients (16.7%) with active disease and normal kidney function, 2 (11.1%) patients with active disease and impaired kidney function, 2 (11.1%) patients on renal replacement therapy. Accordingly, the IgM-negative group included 13 patients (48.1%) in remission, 12 (44.4%) with active disease and normal kidney function, 1 (3.7%) with active disease and impaired kidney function, 1 (3.7%) on renal replacement therapy, with no statistical significance between groups (p = 0.186).

Conclusions: This study did not reveal significant differences of the disease outcomes between IgM-positive and IgM-negative groups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12882-017-0674-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5543753PMC
August 2017

Metabolic acidosis is common and associates with disease progression in children with chronic kidney disease.

Kidney Int 2017 12 18;92(6):1507-1514. Epub 2017 Jul 18.

Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, Heidelberg University Hospital, Heidelberg, Germany. Electronic address:

Recent studies in adult chronic kidney disease (CKD) suggest that metabolic acidosis is associated with faster decline in estimated glomerular filtration rate (eGFR). Alkali therapies improve the course of kidney disease. Here we investigated the prevalence and determinants of abnormal serum bicarbonate values and whether metabolic acidosis may be deleterious to children with CKD. Associations between follow-up serum bicarbonate levels categorized as under 18, 18 to under 22, and 22 or more mmol/l and CKD outcomes in 704 children in the Cardiovascular Comorbidity in Children with CKD Study, a prospective cohort of pediatric patients with CKD stages 3-5, were studied. The eGFR and serum bicarbonate were measured every six months. At baseline, the median eGFR was 27 ml/min/1.73m and median serum bicarbonate level 21 mmol/l. During a median follow-up of 3.3 years, the prevalence of metabolic acidosis (serum bicarbonate under 22 mmol/l) was 43%, 60%, and 45% in CKD stages 3, 4, and 5, respectively. In multivariable analysis, the presence of metabolic acidosis as a time-varying covariate was significantly associated with log serum parathyroid hormone through the entire follow-up, but no association with longitudinal growth was found. A total of 211 patients reached the composite endpoint (ESRD or 50% decline in eGFR). In a multivariable Cox model, children with time-varying serum bicarbonate under 18 mmol/l had a significantly higher risk of CKD progression compared to those with a serum bicarbonate of 22 or more mmol/l (adjusted hazard ratio 2.44; 95% confidence interval 1.43-4.15). Thus, metabolic acidosis is a common complication in pediatric patients with CKD and may be a risk factor for secondary hyperparathyroidism and kidney disease progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.kint.2017.05.006DOI Listing
December 2017

Long-Term Outcome of Steroid-Resistant Nephrotic Syndrome in Children.

J Am Soc Nephrol 2017 Oct 31;28(10):3055-3065. Epub 2017 May 31.

Division of Pediatric Nephrology, University Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany;

We investigated the value of genetic, histopathologic, and early treatment response information in prognosing long-term renal outcome in children with primary steroid-resistant nephrotic syndrome. From the PodoNet Registry, we obtained longitudinal clinical information for 1354 patients (disease onset at >3 months and <20 years of age): 612 had documented responsiveness to intensified immunosuppression (IIS), 1155 had kidney biopsy results, and 212 had an established genetic diagnosis. We assessed risk factors for ESRD using multivariate Cox regression models. Complete and partial remission of proteinuria within 12 months of disease onset occurred in 24.5% and 16.5% of children, respectively, with the highest remission rates achieved with calcineurin inhibitor-based protocols. Ten-year ESRD-free survival rates were 43%, 94%, and 72% in children with IIS resistance, complete remission, and partial remission, respectively; 27% in children with a genetic diagnosis; and 79% and 52% in children with histopathologic findings of minimal change glomerulopathy and FSGS, respectively. Five-year ESRD-free survival rate was 21% for diffuse mesangial sclerosis. IIS responsiveness, presence of a genetic diagnosis, and FSGS or diffuse mesangial sclerosis on initial biopsy as well as age, serum albumin concentration, and CKD stage at onset affected ESRD risk. Our findings suggest that responsiveness to initial IIS and detection of a hereditary podocytopathy are prognostic indicators of favorable and poor long-term outcome, respectively, in children with steroid-resistant nephrotic syndrome. Children with multidrug-resistant sporadic disease show better renal survival than those with genetic disease. Furthermore, histopathologic findings may retain prognostic relevance when a genetic diagnosis is established.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1681/ASN.2016101121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5619960PMC
October 2017

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

Am J Kidney Dis 2017 May 10;69(5):617-625. Epub 2016 Dec 10.

Dialysis Unit, IRCCS Giannina Gaslini, Genoa, Italy.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.ajkd.2016.09.024DOI Listing
May 2017

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.

Am J Kidney Dis 2016 Nov 21;68(5):782-788. Epub 2016 Aug 21.

Department of Pediatric, Academic Medical Center, Amsterdam, the Netherlands.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.ajkd.2016.06.019DOI Listing
November 2016