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Background: Children with chronic kidney disease (CKD) are at risk for cognitive dysfunction. The aim of this study was to investigate associations between executive functions (EF), anemia, and iron deficiency. Methods: A total of 688 children > 6 years of age enrolled in the Chronic Kidney Disease in Children (CKiD) study who underwent evaluation for EF were included. Hemoglobin (Hgb) was characterized as low (1st–5th percentile) or very low (< 1st percentile) compared to normative values for age, sex, and race irrespective of erythropoiesis-stimulating agent (ESA) usage. Longitudinal analysis was conducted using consecutive visit pairs, with anemia status defined as new onset, resolved, or persistent. Linear mixed models with random intercept were used and adjusted for key covariates. Results: Anemia was present in 41% of children, and median Hgb was 11.8 gm/dl. New onset anemia was associated with lower digit span total score (− 0.75, 95% CI − 1.36, − 0.15, p = 0.01). Persistent anemia was associated with lower scores on color-word inhibition/switching (β = − 0.98; 95% CI − 1.78, − 0.18, p = 0.02). Errors of omission were significantly higher (worse) in those with persistent anemia (β = 2.67, 95% CI 0.18, 5.17, p = 0.04). Very low Hgb levels were significantly associated with lower color-word inhibition/switching scores (β = − 1.33, 95% CI − 2.16, − 0.51; p = 0.002). Anemia and low GFR were associated with lower category fluency scores compared to non-anemic subjects with higher GFR (β = − 1.09, 95% CI − 2.09, − 0.10, p = 0.03). Conclusions: The presence of anemia, in addition to its severity and duration in children with CKD, is associated with poorer scores on select measures of EF. A higher resolution version of the Graphical abstract is available as Supplementary information [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The purpose of the study was to explore associations between neurocognitive function and chronic kidney disease (CKD)-related clinical characteristics. Twenty-nine children, ages 7 to 19 years, with an estimated creatinine clearance (eCrCl) of 4–89 ml/min per 1.73 m2 body surface area were enrolled. Intellectual function (IQ), memory, and attention were measured and expressed as age-based standard scores. Clinical data were obtained by physical examination, laboratory testing, parental questionnaires and medical chart review. Pearson correlations and standard Student’s t-tests were used to identify significant ( P < 0.05) relationships between targeted clinical variables and neurocognitive scores. Increased CKD severity correlated with lower IQ ( P = 0.001) and memory function ( P = 0.02). Memory function was lower in children with longer duration of disease ( P = 0.03). Similarly, IQ scores were lowest when kidney disease had started at a younger age ( P = 0.03) and with a greater percent of life with CKD ( P = 0.04). Our findings provide preliminary evidence that increased disease severity, longer duration of disease, and younger age of onset of kidney disease potentially place children with CKD at increased risk of neurocognitive deficits. Additional investigation is required to better quantify these risk factors, particularly regarding how much variability is accounted for by these specific risk factors. [ABSTRACT FROM AUTHOR]

Darbepoetin alfa, an erythropoiesis-stimulating glycoprotein, has proved efficacious in the treatment of anemia of chronic kidney disease (CKD) in adult subjects. However, little information is available from pediatric populations. We conducted an open-label, non-inferiority, 28-week study comparing the efficacy of darbepoetin alfa with that of recombinant human erythropoietin (rHuEpo) in pediatric subjects with CKD. Subjects, aged 1–18, who were receiving stable rHuEpo treatment ( n=124) were randomized (1:2) to either continue receiving rHuEpo or convert to darbepoetin alfa, with doses titrated to achieve and maintain hemoglobin (Hb) levels between 10.0 and 12.5 g/dl. Darbepoetin alfa was considered to be non-inferior to rHuEpo if the lower limit of the two-sided 95% confidence interval (CI) for the difference in the mean change in Hb between the two treatment groups was above −1.0 g/dl. The adjusted mean change in Hb between the baseline and the evaluation period for the rHuEpo and darbepoetin alfa groups was −0.16 g/dl and 0.15 g/dl, respectively, with a difference of 0.31 g/dl (95% CI: −0.45, 1.07) between the means. These results, and the comparable safety profiles, demonstrate that darbepoetin alfa is non-inferior to rHuEpo in the treatment of anemia in pediatric patients with CKD. [ABSTRACT FROM AUTHOR]

Studies in adult dialysis patients have identified anemia as a risk factor for patient morbidity and mortality. Limited comparable outcome data are available from children. We used the database from the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) to identify patients <18 years of age who initiated dialysis (hemodialysis and peritoneal dialysis) between 1992 and 2001 with no prior history of dialysis or transplantation. A Cox proportional hazards model was used to evaluate the association between anemia (hematocrit <33%) at 30 days post initiation of dialysis and patient mortality. The association between anemia and prolonged hospitalization was also evaluated. Of the 1,942 patients (male 56%), 68% were anemic on day 30. One hundred and seventy-one patient deaths were reported over the 9-year observation period. The multivariate analysis demonstrated anemia to be associated with a 52% higher risk of death (adjusted relative risk 1.52, 95% confidence interval 1.03–2.26, P=0.037). Cardiopulmonary disease was the primary reported cause of death associated with anemia, accounting for 22% of cases. The presence of anemia was also associated with an increased risk for prolonged hospitalization, irrespective of dialysis modality. In conclusion, the presence of anemia 1 month after initiation of dialysis iis associated with an increased risk of prolonged hospitalization and death in pediatric patients. Further studies should ascertain whether anemia per se increases the risk of death or whether it is a marker for other conditions that shorten patient survival, such as chronic inflammation or recurrent infection. [ABSTRACT FROM AUTHOR]

Chronic renal failure in young children is associated with impaired cognitive development, but recent studies present a more optimistic perspective. An important question is whether the earlier initiation of renal replacement therapy (RRT) might prevent the reported developmental retardation. The cognitive development of 31 patients (age <5 years with a serum creatinine clearance of <20% of normal) undergoing different treatment modalities was monitored by repeated measurements during a prospective 3-year study. Fifteen patients received conservative treatment and 16 patients were on dialysis treatment at the start of the project. We were able to evaluate the effect of the onset of RRT on 12 patients who were transferred from conservative treatment to dialysis. At the beginning of the study, the cognitive development of the total group was significantly delayed (mean developmental index=78.5, SD=19.5) compared with a normal population. Patients undergoing conservative treatment scored significantly higher ( P<0.01) than those on dialysis. The effect of starting dialysis treatment appeared to be positive, but only a significant short-term improvement was observed. Follow-up evaluation of 7 patients on conservative treatment and of 9 dialysis patients over a 2-year period did not show any significant change in a positive or negative direction. The present study revealed that pre-school dialysis patients are at risk with respect to their cognitive development. This is particularly true for the group with concomitant disorders. Less severe disease in the group on conservative treatment may be assumed to be a positive contributing factor to the more normal performance of these patients. No evidence was found to support the hypothesis that the earlier initiation of dialysis treatment will have a beneficial effect on development. [ABSTRACT FROM AUTHOR]

Children with chronic renal failure (CRF) show developmental, intellectual and motor disturbances. It is questionable if an early start of renal replacement therapy may prevent or delay these disturbances. We studied the neurological and intellectual development of children <5 years suffering from CRF (creatinine clearance <20% of normal) prospectively, over a period of 3 years. As part of the neurological study, brainstem auditory evoked potentials (BAEP) and somatosensory evoked potentials (SSEP) were recorded. Measurements were performed in a group of 22 children every 6 months. In 18 of these children CRF was present from birth. Sufficient data were available for analysis in 19 (BAEP) and 22 (SSEP), respectively. A delay of peak I of BAEP gave indications for peripheral conduction disturbances, possibly due to cochlear dysfunction. Brainstem conduction was normal. There were no differences between the children treated conservatively ( n = 9) and those treated with continuous ambulatory peritoneal dialysis (CAPD) ( n = 10). In children <2.5 years SSEP showed a delayed thalamocortical conduction, which was not observed in older children. This might indicate a delayed myelination in young children with CRF. No differences were found between the children treated conservatively ( n = 10) and those treated with CAPD ( n = 12). [ABSTRACT FROM AUTHOR]

The incidence of sensorineural hearing loss (SNHL) was investigated in 68 patients who reached chronic renal failure (CRF) in childhood with the aim of identifying possible risk factors. Tests were carried out by means of pure-tone and impedance audiometry. SNHL was found in 29% of patients on conservative treatment, 28% of patients on hemodialysis, and 47% after renal transplantation. Differences among groups were not significant. A significant correlation was found with the administration of ototoxic drugs (aminoglycosides and furosemide). We hypothesize that SNHL may be reduced in patients with CRF or on renal replacement therapy by strictly monitoring ototoxic therapy. [ABSTRACT FROM AUTHOR]

Background The national average for achieving the KDOQI-recommended hemoglobin (Hgb) target level of 11-12 g/dL is low with the current anemia management protocol of measuring Hgb levels every 2-4 weeks to guide intervention. The objective of this study was to correlate initial Hgb readings from the CRIT-LINE monitor with actual serum Hgb levels in pediatric patients on hemodialysis (HD). Methods Data were collected from pediatric HD patients who had Hgb tests ordered for routine and/or clinical reasons. Hgb concentrations were read with the CRIT-LINE after 0.5 or 1 L of blood had been processed by HD in patients with a body weight of ≤20 or >20 kg, respectively. Ultrafiltration was kept at a minimum until the CRIT-LINE Hgb was read. Results In total, 217 Hgb readings from 23 HD patients were analyzed. Results showed a statistically significant correlation between CRIT-LINE readings and laboratory Hgb measurements (r = 0.94, p < 0.0001) using Pearson correlation coefficients for well-distributed data. The mean Hgb levels measured by CRIT-LINE and the laboratory were 11.12 ± 1.63 and 11.31 ± 1.69 g/dL, respectively. Conclusions The CRIT-LINE monitor is an accurate instrument for monitoring Hgb levels in HD patients. Further studies will be needed to evaluate whether using CRIT-LINE Hgb levels to guide anemia management will improve the percentage of children with Hgb levels within target., Author(s): Rouba Garro[sup.1] , Scott Sutherland[sup.2] , Liz Bayes[sup.2] [sup.3] , Steven Alexander[sup.2] , Cynthia Wong[sup.2] Author Affiliations: (1) Department of Pediatrics, Division of Nephrology, Emory University, 2015 Uppergate Drive [...]

This is a summary of the Task Force on Chronic Kidney Disease in Children convened April 24, 2002, by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [...]