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Background: Few studies describe acute kidney injury (AKI) burden during paediatric cisplatin therapy and post-cisplatin kidney outcomes. We determined risk factors for and rate of (1) AKI during cisplatin therapy, (2) chronic kidney disease (CKD) and hypertension 2–6 months post-cisplatin, and (3) whether AKI is associated with 2–6-month outcomes. Methods: This prospective cohort study enrolled children (aged < 18 years at cancer diagnosis) treated with cisplatin from twelve Canadian hospitals. AKI during cisplatin therapy (primary exposure) was defined based on Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine criteria (≥ stage one). Severe electrolyte abnormalities (secondary exposure) included ≥ grade three hypophosphatemia, hypokalemia, or hypomagnesemia (National Cancer Institute Common Terminology Criteria for Adverse Events v4.0). CKD was albuminuria or decreased kidney function for age (KDIGO guidelines). Hypertension was defined based on the 2017 American Academy of Pediatrics guidelines. Results: Of 159 children (median [interquartile range [IQR]] age: 6 [2–12] years), 73/159 (46%) participants developed AKI and 55/159 (35%) experienced severe electrolyte abnormalities during cisplatin therapy. At median [IQR] 90 [76–110] days post-cisplatin, 53/119 (45%) had CKD and 18/128 (14%) developed hypertension. In multivariable analyses, AKI was not associated with 2–6-month CKD or hypertension. Severe electrolyte abnormalities during cisplatin were associated with having 2–6-month CKD or hypertension (adjusted odds ratio (AdjOR) [95% CI]: 2.65 [1.04–6.74]). Having both AKI and severe electrolyte abnormalities was associated with 2–6-month hypertension (AdjOR [95% CI]: 3.64 [1.05–12.62]). Conclusions: Severe electrolyte abnormalities were associated with kidney outcomes. Cisplatin dose optimization to reduce toxicity and clear post-cisplatin kidney follow-up guidelines are needed. [ABSTRACT FROM AUTHOR]

Background: Children with chronic kidney disease (CKD) generally have worse educational and psychosocial outcomes compared with their healthy peers. This can impair their ability to manage their treatment, which in turn can have long-term health consequences through to adulthood. We attempted to capture the experiences of children with CKD and to describe the perspectives of their parents and caregivers on access to educational and psychosocial support. Methods: Children with CKD (n = 34) and their caregivers (n = 62) were sampled via focus groups from pediatric hospitals in Australia, Canada, and the USA. Sixteen focus groups were convened and the transcripts were analyzed thematically. Results: We identified four themes: disruption to self-esteem and identity (emotional turmoil of adolescence, wrestling with the sick self, powerlessness to alleviate child's suffering, balancing normality and protection); disadvantaged by lack of empathy and acceptance (alienated by ignorance, bearing the burden alone); a hidden and inaccessible support system (excluded from formal psychological support, falling behind due to being denied special considerations); and building resilience (finding partners in the journey, moving towards acceptance of the illness, re-establishing childhood). Conclusions: Children with CKD and their caregivers encountered many barriers in accessing psychosocial and educational support and felt extremely disempowered and isolated as a consequence. Improved availability and access to psychosocial and educational interventions are needed to improve the wellbeing and educational advancement of children with CKD. A higher resolution version of the Graphical abstract is available as Supplementary information. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) and kidney failure in childhood are associated with significant and life-altering morbidities and lower quality of life. Emerging evidence suggests that management should be guided in part by symptom burden; however, there is currently no standardized assessment tool for quantifying symptom burden in this pediatric population. This study aimed to develop and refine a patient-reported symptom assessment tool for children with CKD/kidney failure (PRO-Kid), to evaluate the frequency and impact of symptoms. Methods: This was a prospective observational study of children and caregivers of children with CKD/kidney failure at two Canadian pediatric care centers. Building on previously published patient-reported outcome measures (PROs) for the assessment of symptom burden in other populations, we drafted a 13-item questionnaire. Cognitive interviews were performed with children and caregivers of children with CKD/kidney failure to iteratively refine the questionnaire. Results: Twenty-four participants completed cognitive interviewing (11 children, 13 caregivers). The most common symptoms endorsed were feeling left out, feeling sad/depressed, inability to focus, tiredness, nausea, vomiting, not wanting to eat, and changes in the taste of food. Feeling left out was added to the questionnaire as almost all participants voiced this as a frequent and impactful symptom, resulting in a 14-item questionnaire. Conclusions: PRO-Kid is the first pediatric CKD/kidney failure-specific PRO tool to assess symptom burden. Future work should validate this tool in a larger cohort so that it may be used to improve the care of children living with CKD/kidney failure. A higher resolution version of the Graphical abstract is available as Supplementary information [ABSTRACT FROM AUTHOR]

Background: Children and adolescents with mild to moderate chronic kidney disease (CKD) are at high risk for mild but persistent impairment in executive functions, which have been associated with low health‐related quality of life (HRQOL) among children and adolescents with chronic health conditions. However, no similar link has been established among children and adolescents with mild to moderate CKD. Given the essential role executive functions play in the development of adequate cognitive, emotional and social skills, it is essential to gain a clearer understating of the magnitude and attributes of executive functions and its link to HRQOL in order to inform appropriate medical and educational interventions for this patient population. Objective: The aim of this study is to examine the relationship between executive functions, socio‐emotional functioning and HRQOL in children and adolescents with mild to moderate CKD. Methods: A cross‐sectional design was used for this secondary data analysis of 199 children and adolescents (ages 6–17) with mild to moderate CKD from the United States and Canada who receive care at hospitals associated with the Chronic Kidney Disease in Children Study (CKiD). Results: The presence of impairment in executive functions and socio‐emotional functioning (internalizing problems) significantly predicted lower HRQOL after controlling for key covariates (i.e., maternal education, anaemia and hypertension). Further, internalizing problems partially mediated the relationship between executive functions and HRQOL such that impairment in executive functions predicted lower HRQOL directly and indirectly by contributing to higher internalizing problems, which further contributed to low HRQOL. Conclusion: This study underscores the importance of executive functions and socio‐emotional functioning in the manifestation of HRQOL. Given that HRQOL is potentially compromised for many children and adolescents with mild to moderate CKD, it will be important for both clinicians and researchers to examine a range of factors, including executive functions and socio‐emotional functioning, in order to optimize HRQOL. [ABSTRACT FROM AUTHOR]

Background: With advances in care, neonates undergoing cardiac repairs are surviving more frequently. Our objectives were to 1) estimate the prevalence of chronic kidney disease (CKD) and hypertension 6 years after neonatal congenital heart surgery and 2) determine if cardiac surgery-associated acute kidney injury (CS-AKI) is associated with these outcomes. Methods: Two-center prospective, longitudinal single-visit cohort study including children with congenital heart disease surgery as neonates between January 2005 and December 2012. CKD (estimated glomerular filtration rate < 90 mL/min/1.73m2 or albumin/creatinine ≥3 mg/mmol) and hypertension (systolic or diastolic blood pressure ≥ 95th percentile for age, sex, and height) prevalence 6 years after surgery was estimated. The association of CS-AKI (Kidney Disease: Improving Global Outcomes definition) with CKD and hypertension was determined using multiple regression. Results: Fifty-eight children with median follow-up of 6 years were evaluated. CS-AKI occurred in 58%. CKD and hypertension prevalence were 17% and 30%, respectively; an additional 15% were classified as having elevated blood pressure. CS-AKI was not associated with CKD or hypertension. Classification as cyanotic postoperatively was the only independent predictor of CKD. Postoperative days in hospital predicted hypertension at follow-up. Conclusions: The prevalence of CKD and hypertension is high in children having neonatal congenital heart surgery. This is important; early identification of CKD and hypertension can improve outcomes. These children should be systematically followed for the evolution of these negative outcomes. CS-AKI defined by current standards may not be a useful clinical tool to decide who needs follow-up and who does not. [ABSTRACT FROM AUTHOR]

Background: The role of environmental exposure to lead as a risk factor for chronic kidney disease (CKD) and its progression remains controversial, and most studies have been limited by a lack of direct glomerular filtration rate (GFR) measurement. Objective: We evaluated the association between lead exposure and GFR in children with CKD. Methods: In this cross-sectional study, we examined the association between blood lead levels (BLLs) and GFR measured by the plasma disappearance of iohexol among 391 participants in the Chronic Kidney Disease in Children (CKiD) prospective cohort study. Results: Median BLL and GFR were 1.2 µg/dL and 44.4 mL/min per 1.73 m2, respectively. The average percent change in GFR for each 1-µg/dL increase in BLL was −2.1 (95% CI: −6.0, 1.8). In analyses stratified by CKD diagnosis, the association between BLL and GFR was stronger among children with glomerular disease underlying CKD; in this group, each 1-µg/dL increase in BLL was associated with a −12.1 (95% CI: −22.2, −1.9) percent change in GFR. In analyses stratified by anemia status, each 1-µg/dL increase in BLL among those with and without anemia was associated with a −0.3 (95% CI: −7.2, 6.6) and −4.6 (95% CI: −8.9, −0.3) percent change in GFR, respectively. Conclusions: There was no significant association between BLL and directly measured GFR in this relatively large cohort of children with CKD, although associations were observed in some subgroups. Longitudinal analyses are needed to examine the temporal relationship between lead and GFR decline, and to further examine the impact of underlying cause of CKD and anemia/hemoglobin status among patients with CKD. [ABSTRACT FROM AUTHOR]

Malformations of the kidney and lower urinary tract are the most frequent cause of end-stage renal disease in children. Mutations in HNF1Β and PAX2 commonly cause syndromic urinary tract malformation. We searched for mutations in HNF1Β and PAX2 in North American children with renal aplasia and hypodysplasia (RHD) enrolled in the Chronic Kidney Disease in Children Cohort Study (CKiD). We identified seven mutations in this multiethnic cohort (10% of patients). In HNF1Β, we identified a nonsense (p.R181X), a missense (p.S148L), and a frameshift (Y352fsX352) mutation, and one whole gene deletion. In PAX2, we identified one splice site (IVS4-1G>T), one missense (p.G24E), and one frameshift (G24fsX28) mutation. All mutations occurred in Caucasians, accounting for 14% of disease in this subgroup. The absence of mutations in other ethnicities is likely due to the limited sample size. There were no differences in clinical parameters (age, baseline eGFR, blood pressure, body mass index, progression) between patients with or without HNF1B and PAX2 mutations. A significant proportion of North American Caucasian patients with RHD carry mutations in HNF1Β or PAX2 genes. These patients should be evaluated for complications (e.g., diabetes for HNF1Β mutations, colobomas for PAX2) and referred for genetic counseling. [ABSTRACT FROM AUTHOR]

Outcome body size of gastrostomy tube (g-tube)-fed children with chronic kidney disease (CKD) was investigated. CKD patients, stages 2–5, who had a g-tube inserted and removed between 1985 and 2007 were retrospectively reviewed ( n = 20) for anthropometrics, lab values, and steroid use from insertion to latest date. CKD patients never having had a g-tube placed ( n = 82) acted as the comparison population with similar data collection at start and end of the latest 5-year period. Body mass index (BMI)-for-age, weight (Wt)-for-age, and height (Ht)-for-age z scores were calculated and compared between groups. Median age at insertion and duration of g-tube treatment was 1.7 years (range 0.9–15.6), and 2.9 years (range 0.9–11.8), respectively. There was a significant increase in Wt- ( p < 0.01), and BMI-for-age ( p < 0.03) z score, but not for Ht-for-age between insertion and removal for subjects. There were no significant differences in Ht-, Wt-, or BMI-for-age z scores, from removal to 5 years post-removal. In the comparison population, there were no significant differences in Ht-, Wt-, or BMI-for-age z scores over the 5-year period. Approximately 36% of the non-tube-fed comparison population and 50% of the tube-fed subjects were overweight or obese at the most recent evaluation. In both subjects and the comparison group, overweight and obesity is associated with transplant status and steroid use. G-tube feeding is an effective method for achieving catch-up weight and moderate height gain in pediatric CKD patients, and does not apparently predispose patients to obesity after removal; however, overweight and obesity may pose problems to children with CKD whether or not they are tube fed. [ABSTRACT FROM AUTHOR]

• 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 F 2 -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. [ABSTRACT FROM AUTHOR]