Among children with end-stage renal disease (ESRD), those who abstract initiated chronic dialysis during the first year of life historically were less likely to survive or receive a kidney transplant ...compared with those who initiated dialysis later in childhood.We hypothesized that recently treated infants have experienced improved outcomes.
We queried the North American Pediatric Renal Trials and Collaborative Studies database, obtaining information on 628 children who initiated maintenance peritoneal dialysis for treatment of ESRD at ,1 year of age. We further subcategorized these children by age(neonates, #31 days and infants, 32–365 days) and date of dialysis initiation (past,1992–1999, and recent, 2000–2012).
Survival while on dialysis and overall survival were significantly better among neonates and infants in the recent cohort. Overall survival at 3 years after dialysis initiation was 78.6%and 84.6% among the recently treated neonates and infants, respectively. Neonates and infants in the recent cohort also were more likely to terminate dialysis for transplantation, and graft survival was improved among recently transplanted infants (3-year graft survival 92.1%).
Among children who initiate chronic peritoneal dialysis for treatment of ESRD in the first year of life, survival has improved in recent years. Graft survival also has improved for the subset of these patients who received a kidney transplant.
Anemia is common and associated with adverse outcomes in children with chronic kidney disease (CKD). Many factors contribute to declining hemoglobin as CKD progresses, but impaired production of ...erythropoietin by failing kidneys is a central cause. Hepcidin-mediated iron restriction also contributes to anemia by downregulating both intestinal iron absorption and release of stored iron for erythropoiesis. The core components of anemia management remain erythropoiesis-stimulating agents (ESA) and iron supplementation, but despite these therapies, a substantial number of children remain anemic. Although escalating ESA dose to target higher hemoglobin has been associated with adverse outcomes in adults, no trials have investigated this association in children, and maintaining hemoglobin levels in a narrow range with conservative ESA dosing is challenging. Judicious use of iron supplementation can enhance the response to ESAs, but the iron storage markers most commonly used in clinical practice have limitations in distinguishing which patients will benefit most from additional iron. Several novel anemia therapies, including hypoxia-inducible factor stabilizers, prolyl hydroxylase inhibitors, and dialysate-delivered iron supplements, have been developed and may offer options for alternative anemia management. However, the safety and efficacy of these agents in children with CKD has yet to be assessed.
New Equations to Estimate GFR in Children with CKD SCHWARTZ, George J; MUNOZ, Alvaro; SCHNEIDER, Michael F ...
Journal of the American Society of Nephrology,
03/2009, Letnik:
20, Številka:
3
Journal Article
Recenzirano
Odprti dostop
The Schwartz formula was devised in the mid-1970s to estimate GFR in children. Recent data suggest that this formula currently overestimates GFR as measured by plasma disappearance of iohexol, likely ...a result of a change in methods used to measure creatinine. Here, we developed equations to estimate GFR using data from the baseline visits of 349 children (aged 1 to 16 yr) in the Chronic Kidney Disease in Children (CKiD) cohort. Median iohexol-GFR (iGFR) was 41.3 ml/min per 1.73 m(2) (interquartile range 32.0 to 51.7), and median serum creatinine was 1.3 mg/dl. We performed linear regression analyses assessing precision, goodness of fit, and accuracy to develop improvements in the GFR estimating formula, which was based on height, serum creatinine, cystatin C, blood urea nitrogen, and gender. The best equation was: GFR(ml/min per 1.73 m(2))=39.1height (m)/Scr (mg/dl)(0.516) x 1.8/cystatin C (mg/L)(0.294)30/BUN (mg/dl)(0.169)1.099(male)height (m)/1.4(0.188). This formula yielded 87.7% of estimated GFR within 30% of the iGFR, and 45.6% within 10%. In a test set of 168 CKiD patients at 1 yr of follow-up, this formula compared favorably with previously published estimating equations for children. Furthermore, with height measured in cm, a bedside calculation of 0.413*(height/serum creatinine), provides a good approximation to the estimated GFR formula. Additional studies of children with higher GFR are needed to validate these formulas for use in screening all children for CKD.
The optimum starting dose of intravenous continuous erythropoietin receptor activator (C.E.R.A.) has been previously determined; this study ascertains the optimum starting dose of subcutaneous ...C.E.R.A. administration in pediatric patients.
Phase 2, open-label, single-arm, multicenter study.
Patients aged 3 months to 17 years with renal anemia and chronic kidney disease (CKD; including those treated with maintenance dialysis and those not treated with dialysis) who were receiving maintenance treatment with erythropoiesis-stimulating agents (ESAs).
Subcutaneous C.E.R.A. administration every 4 weeks (starting dose was based on defined conversion factors).
The primary outcome was the change in hemoglobin concentration between the baseline and evaluation period for each patient. Secondary efficacy measures and safety were also evaluated.
Forty patients aged 0.4-17.7 years were enrolled. The study achieved its primary outcome: the mean change in hemoglobin concentration was an increase of 0.48g/dL; the 95% confidence interval (0.15-0.82) and standard deviation (±1.03) were within the prespecified boundaries (−1 to 1g/dL and<1.5g/dL, respectively). Mean hemoglobin concentrations were maintained within the target 10-12g/dL range in 24 of 38 patients and within±1g/dL of the baseline in 19 of 38 patients, and the median C.E.R.A. subcutaneous dose decreased over time. Efficacy in key subgroups (age group, dialysis type, prior ESA treatment) was consistent with the primary outcome. Thirty-eight patients completed the core period; 25 chose to enter the safety extension period. Safety was consistent with prior studies, with no new signals.
Single-arm and open-label study; small sample size.
Pediatric patients with anemia secondary to CKD who were on, or not on, dialysis could be safely and effectively switched from maintenance ESAs to subcutaneous C.E.R.A. administered every 4 weeks, using defined dose-conversion factors to determine the optimum starting dose.
F. Hoffmann-La Roche Ltd.
The SKIPPER trial registered at ClinicalTrials.gov with study number NCT03552393.
Anemia, a complication of chronic kidney disease, is associated with poor quality of life and an increased risk of hospitalization and mortality. The current treatments for anemia include iron therapy and erythropoiesis-stimulating agents (ESAs); however, the relatively short half-lives of the ESAs epoetin alfa/beta or darbepoetin alfa may require more frequent dosing and hospital visits compared with the ESA known as continuous erythropoietin receptor activator (C.E.R.A.). A previous study demonstrated that children aged 5 years or more with anemia associated with chronic kidney disease who were on hemodialysis could be switched to intravenous C.E.R.A. from their existing epoetin alfa/beta or darbepoetin alfa treatment. This study provides evidence that subcutaneous C.E.R.A. can safely and effectively treat anemia in children, including those aged<5 years and regardless of whether they were on dialysis or the type of dialysis they received (peritoneal dialysis or hemodialysis).
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•Longitudinally measured organophosphate pesticide metabolites and renal function.•Serially measured dialkyl phosphate metabolites were associated with tubular injury.•The association was strongest ...for diethyl metabolites.•Dialkyl phosphate metabolites were associated with higher oxidant stress biomarkers.•Organophosphate pesticides are potentially modifiable risk factors for renal damage.
Growing evidence suggests that exposure to environmental chemicals, such as pesticides, impacts renal function and chronic kidney disease (CKD). However, it is not clear if pesticides may affect CKD progression and no studies exist in children.
The objective of this study was to examine associations between serially measured urinary OP pesticide metabolites and clinical and laboratory measures of kidney function over time among children with CKD.
This study used data on 618 participants enrolled in the CKD in Children study (CKiD), a cohort study of pediatric CKD patients from the US and Canada. Children were followed over an average of 3.0 years (standard deviation (SD) = 1.6) between 2005 and 2015. In serially collected urine samples over time, six nonspecific dialkyl phosphate (DAP) metabolites of OP pesticides were measured. Biomarkers of tubular injury (kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL)) and oxidant stress (8-hydroxy-2′-deoxyguanosine (8-OHdG) and F2-isoprostane) were determined in the same specimens. Estimated glomerular filtration rate (eGFR), proteinuria, and blood pressure were assessed annually.
DAPs were associated with increased KIM-1 and 8-OHdG throughout follow-up. A standard deviation increase in ∑diethyl metabolites was associated with increases of 11.9% (95% Confidence Interval (CI): 4.8%, 19.4%) and 13.2% (95% CI: 9.3%, 17.2%) in KIM-1 and 8-OHdG over time, respectively. DAPs were associated with lower eGFR at baseline and higher eGFR over subsequent years.
These findings provide preliminary evidence suggesting that urinary DAP metabolites are associated with subclinical kidney injury among children with CKD, which may signal the potential for clinical events to manifest in the future. The results from this study are significant from both a clinical and public health perspective, given that OP pesticide exposure is a modifiable risk factor.
Youth with chronic kidney disease are known to have impaired health-related quality of life (HRQOL), particularly as the disorder increases in severity. Few prospective, longitudinal investigations ...of HRQOL within the context of pediatric chronic kidney disease exist. In the current issue, Guha et al. provide a longitudinal assessment of HRQOL for a cohort of youth with chronic kidney disease. Their findings suggest that children may experience meaningful improvement in HRQOL when they transition from dialysis to transplant.
End-stage renal disease requiring renal replacement therapy (RRT) during the neonatal period is a very rare condition, and little information is available regarding long-term RRT and outcomes. To ...gain more information, we performed a collaborative study on patient characteristics and treatment outcomes in children who started RRT as neonates during their first month of life between 2000 and 2011 who were prospectively registered in the ESPN/ERA-EDTA, the IPPN (since 2007), the Japanese registry, or the Australian and New Zealand Dialysis and Transplant (ANZDATA) registry. During the first month of life, 264 patients from 32 countries started RRT and were followed for a median of 29 months (interquartile range 11–60 months). Most neonates (242) started on peritoneal dialysis, 21 started on hemodialysis, and 1 patient with a transplant. The most important causes of renal failure were congenital anomalies of the kidney and urinary tract in 141, cystic kidneys in 35, and cortical necrosis in 30. Within 2 years after the start of RRT, 69 children changed dialysis modality and 53 received a renal transplant. After a median of 7 months, 45 children had died, mainly because of infection, resulting in an estimated 2-year survival of 81%, and 5-year survival of 76%. Growth retardation (63%), anemia (55%), and hypertension (57%) were still major problems after 2 years. Thus, relatively good medium-term patient survival may be achieved with RRT started during the neonatal period, but specific therapeutic challenges continue to exist in this age group.
An increasing number of infants with end-stage kidney disease (ESKD) are surviving and receiving renal replacement therapy (RRT). Unique clinical issues specific to this age group of patients ...influence their short- and long-term outcomes. This review summarizes current epidemiology, clinical characteristics, ethical dilemmas, management concerns, and outcomes of infants requiring chronic dialysis therapy. Optimal care during infancy requires a multidisciplinary team working closely with the patient’s family. Nutritional management, infection prevention, and attention to cardiovascular status are important treatment targets. Although mortality rates remain higher among infants on dialysis compared to older pediatric dialysis patients, outcomes have improved over time. Most importantly, infants who subsequently receive a kidney transplant are now experiencing graft survival rates that are comparable to older pediatric patients.
Background
Comprehensive training of children on peritoneal dialysis (PD) and their caregivers is crucial to minimize peritonitis risk. Few studies have evaluated the impact of training on infection, ...so many published recommendations rely on expert opinion. This study uses data from the SCOPE collaborative to examine the impact of compliance with 4 components of PD training on the risk for peritonitis.
Methods
A retrospective cohort study of children enrolled in the SCOPE collaborative between 2011 and 2021 who received training prior to initiating PD. Compliance with 4 training components were assessed: performance of a home visit, 1:1 training, delaying training ≥ 10 days after PD catheter insertion and average individual training session length ≤ 3 h. Univariate and multivariable generalized linear mixed modeling were used to assess relationships between peritonitis ≤ 90 days after PD training and median days to peritonitis and compliance with each component as well as all-or-none compliance.
Results
Among 1450 trainings, 51.7% had median session length ≤ 3 h, 67.1% delayed training ≥ 10 days after catheter insertion, 74.3% had a home visit and 94.6% had 1:1 training. Only 333 trainings (23%) were compliant with all 4 training components. There was no statistically significant association between compliance with individual components, or all-or-none compliance and either the percentage of catheters with peritonitis ≤ 90 days after training end or median days to peritonitis.
Conclusion
No associations between 4 PD training components and risk for peritonitis were found. SCOPE requires monthly review of PD catheter practices which may have decreased the impact of training non-compliance.
Graphical abstract
A higher resolution version of the Graphical abstract is available as
Supplementary information
Background
Collagen X biomarker (CXM) is a novel biomarker of linear growth velocity. We investigated whether CXM correlated with measured growth velocity in children with impaired kidney function.
...Methods
We used data from children aged 2 through 16 years old enrolled in the Chronic Kidney Disease in Children (CKiD) study. We assessed the association between CXM level and growth velocity based on height measurements obtained at study visits using linear regression models constructed separately by sex, with and without adjustment for CKD covariates. Linear mixed-effects models were used to capture the between-individual and within-individual CXM changes over time associated with concomitant changes in growth velocity from baseline through follow-up.
Results
A total of 967 serum samples from 209 participants were assayed for CXM. CXM correlated more strongly in females compared to male participants. After adjustment for growth velocity and CKD covariates, only proteinuria in male participants affected CXM levels. Finally, we quantified the between- and within-participant associations between CXM level and growth velocity. A between-participant increase of 24% and 15% in CXM level in females and males, respectively, correlated with a 1 cm/year higher growth velocity. Within an individual participant, on average, 28% and 13% increases in CXM values in females and males, respectively, correlated with a 1 cm/year change in measured growth.
Conclusions
CXM measurement is potentially a valuable aid for monitoring growth in pediatric CKD. However, future research, including studies of CXM metabolism, is needed to clarify whether CXM can be a surrogate of growth in children with CKD.
Graphical Abstract
A higher resolution version of the Graphical abstract is available as
Supplementary information
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