Anorexia and malnutrition are associated with poor outcomes in children with chronic kidney disease (CKD).
Observational cohort study.
We assessed changes in body mass index (BMI) as kidney function ...declines and its association with risk for end-stage renal disease (ESRD) among 854 participants followed between 2005 to 2013 in the CKD in Children (CKiD) Study.
Repeated measurements of estimated glomerular filtration rate (eGFR) by serum creatinine concentration in our trajectory analysis using mixed models; change in BMI z score (per year) after eGFR decreased to <35mL/min/1.73m2 in logistic regression models.
Repeated measurements of BMI z score (as a reflection of weight status) in our trajectory analysis; ESRD in logistic regression models.
During a mean longitudinal follow-up of 3.4 years, BMI z scores remained stable until eGFR decreased to <35mL/min/1.73m2. When eGFR decreased to <35mL/min/1.73m2, a mean decline in BMI z score of 0.13 (95% CI, 0.09-0.17) was noted with each 10–mL/min/1.73m2 further decline in eGFR. This was statistically significantly different from the weight trajectory when eGFR was ≥35mL/min/1.73 m2 (P<0.001). Among children and adolescents with significant weight loss (defined as decline in BMI z score > 0.2 per year) after eGFR decreased to <35mL/min/1.73m2, the odds of ESRD was 3.28 (95% CI, 1.53-7.05) times greater compared with participants with stable BMI z scores (BMI z score change per year of 0-0.1).
Observational nature of our study, lack of longitudinal assessments of inflammatory markers.
In children and adolescents with CKD, weight loss mostly occurs when eGFR decreases to <35mL/min/1.73m2, and this weight loss was associated with higher risk for ESRD. Further studies are needed to define the reasons for the association between weight loss and more rapid progression to ESRD in children and adolescents.
IMPORTANCE: The kidney failure risk equation (KFRE) has been shown to accurately estimate progression to kidney failure in adults with chronic kidney disease (CKD). Use of the KFRE in children with ...CKD, if accurate, would help to optimize planning for end-stage renal disease (ESRD) care. OBJECTIVE: To determine whether the KFRE adequately discriminates the risk of ESRD in children with CKD. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included 603 children with an estimated glomerular filtration rate of less than 60 mL/min/1.73 m2 in the Chronic Kidney Disease in Children study, a national multicenter observational study. Data were collected from January 1, 2005, through July 31, 2013, and analyzed from September 30, 2016, through September 8, 2017. EXPOSURES: The primary predictive factors were the 4-variable (age, sex, bedside Schwartz estimated glomerular filtration rate, and ratio of albumin to creatinine levels) and 8-variable (4 variables plus serum calcium, phosphate, bicarbonate, and albumin levels) KFREs, which provide 1-, 2-, and 5-year estimates of the risk of progression to ESRD. MAIN OUTCOMES AND MEASURES: Time to ESRD. The Cox proportional hazards model was used to examine the association between the KFRE score and time to ESRD. C statistics were used to discriminate ESRD risk by the KFRE, with a value of greater than 0.80 indicating strong discrimination. RESULTS: Of the 603 children included in the study, 378 were boys (62.7%) and 225 were girls (37.3%); median age at study entry was 12 years (interquartile range, 8-15 years). Median estimated glomerular filtration rate was 44 mL/min/1.73 m2. Four hundred fifty-seven participants (75.8%) had a nonglomerular cause of CKD. Median observation time was 3.8 years (interquartile range, 1.7-6.2 years); 144 (23.9%) developed ESRD within 5 years of enrollment. The 4-variable KFRE scores discriminated risk of ESRD, with C statistics of 0.90, 0.86, and 0.81 for the 1-, 2-, and 5-year risk scores, respectively. Results were similar using the 8-variable equation. CONCLUSIONS AND RELEVANCE: The KFRE is a simple tool that provides excellent discrimination of the risk of ESRD. Results suggest that the KFRE could be incorporated into the clinical care of children with CKD to aid in anticipatory guidance, timing of referral for transplant evaluation, and planning for dialysis access.
Ambulatory blood pressure (BP) monitoring (ABPM) is the best method of detecting abnormal BP in patients with chronic kidney disease (CKD), whose hypertension may be missed with casual BP ...measurements. We report ABPM findings in 332 children 1 year after entry in the Chronic Kidney Disease in Children cohort study. All of the subjects underwent casual and ambulatory BP measurement. BP was categorized based on casual and ABPM results into normal (42%), white-coat (4%), masked (35%), and ambulatory (14%) hypertension. Only half of the subjects had a normal ABPM. BP load was elevated (>25%) in 52% (n=172), whereas mean BP was elevated in 32% (n=105). In multivariate analysis, those using an angiotensin-converting enzyme inhibitor were 89% more likely to have a normal ABPM than those who did not report using an angiotensin-converting enzyme inhibitor (odds ratio, 1.89 95% CI, 1.17–3.04). For every 20% faster decline in annualized glomerular filtration rate change, the odds of an abnormal ABPM increased 26% (odds ratio, 1.26 95% CI, 0.97–1.64). A 2.25-fold increase in urine protein:creatinine ratio annualized change was associated with a 39% higher odds of an abnormal ABPM (odds ratio, 1.39 95% CI, 1.06–1.82). Abnormalities on ABPM are common in children with chronic kidney disease and are strongly associated with known risk factors for end-stage renal disease. Individuals on angiotensin-converting enzyme inhibitors were less likely to have abnormal ABPM, suggesting a possible therapeutic intervention. ABPM should be used to monitor risk and guide therapy in children with chronic kidney disease.
Traditional and nontraditional cardiovascular disease risk factors are highly prevalent in children with chronic kidney disease (CKD). We examined the longitudinal association of adiposity with ...cardiac damage among children with CKD and explored whether this association was modified by sex.
Prospective cohort study.
Children with mild-to-moderate CKD enrolled in the Chronic Kidney Disease in Children (CKiD) Study at 49 pediatric nephrology centers across North America.
Age- and sex-specific body mass index (BMI) z score.
Age- and sex-specific left ventricular mass index (LVMI) z score and left ventricular hypertrophy (LVH).
Longitudinal analyses using mixed-effects models to estimate sex-specific associations of BMI z scores with LVMI z score and with LVH, accounting for repeated measurements over time.
Among 725 children with 2,829 person-years of follow-up, median age was 11.0 years and median estimated glomerular filtration rate was 52.6mL/min/1.73m2. Nearly one-third of both boys and girls were overweight or obese, median LVMI z score was 0.18 (IQR: −0.67, 1.08), and 11% had LVH. Greater BMI z scores were independently associated with greater LVMI z scores and greater odds of LVH. For each 1-unit higher BMI z score, LVMI z score was 0.24 (95% CI, 0.17-0.31) higher in boys and 0.38 (95% CI, 0.29-0.47) higher in girls (Pinteraction = 0.01). For each 1-unit higher BMI z score, the odds of LVH was 1.5-fold (95% CI, 1.1-2.1) higher in boys and 3.1-fold (95% CI, 1.8-4.4) higher in girls (Pinteraction = 0.005).
Not all children had repeated measurements. LVH is a surrogate and not a hard cardiac outcome. The observational design limits causal inference.
In children, adiposity is independently associated with the markers of cardiac damage, LVMI z score and LVH. This association is stronger among girls than boys. Pediatric overweight and obesity may therefore have a substantial impact on cardiovascular risk among children with CKD.
The Standardizing Care to Improve Outcomes in Pediatric ESRD Collaborative is a quality improvement initiative that aims to reduce peritoneal dialysis-associated infections in pediatric patients on ...chronic peritoneal dialysis. Our objectives were to determine whether provider compliance with peritoneal dialysis catheter care bundles was associated with lower risk for infection at the individual patient level and describe the epidemiology, risk factors, and outcomes for peritonitis in the Standardizing Care to Improve Outcomes in Pediatric ESRD Collaborative.
We collected peritoneal dialysis characteristics, causative organisms, compliance with care bundles, and outcomes in children with peritonitis between October of 2011 and September of 2014. Chi-squared tests, t tests, and generalized linear mixed models were used to assess risk factors for peritonitis.
Of 734 children enrolled (54% boys; median age =9 years old; interquartile range, 1-15) from 29 centers, 391 peritonitis episodes occurred among 245 individuals over 10,130 catheter-months. The aggregate annualized peritonitis rate was 0.46 episodes per patient-year. Rates were highest among children ≤2 years old (0.62 episodes per patient-year). Gram-positive peritonitis predominated (37.8%) followed by culture-negative (24.7%), gram-negative (19.5%), and polymicrobial (10.3%) infections; fungal only peritonitis accounted for 7.7% of episodes. Compliance with the follow-up bundle was associated with a lower rate of peritonitis (rate ratio, 0.49; 95% confidence interval, 0.30 to 0.80) in the multivariable model. Upward orientation of the catheter exit site (rate ratio, 4.2; 95% confidence interval, 1.49 to 11.89) and touch contamination (rate ratio, 2.22; 95% confidence interval, 1.44 to 3.34) were also associated with a higher risk of peritonitis. Infection outcomes included resolution with antimicrobial treatment alone in 76.6%, permanent catheter removal in 12.2%, and catheter removal with return to peritoneal dialysis in 6% of episodes.
Lower compliance with standardized practices for follow-up peritoneal dialysis catheter care in the Standardizing Care to Improve Outcomes in Pediatric ESRD Collaborative was associated with higher risk of peritonitis. Quality improvement and prevention strategies have the potential to reduce peritoneal dialysis-associated peritonitis.
Studies of adults have demonstrated an association between metabolic acidosis, as measured by low serum bicarbonate levels, and CKD progression. We evaluated this relationship in children using data ...from the Chronic Kidney Disease in Children study.
The relationship between serum bicarbonate and a composite end point, defined as 50% decline in eGFR or KRT, was described using parametric and semiparametric survival methods. Analyses were stratified by underlying nonglomerular and glomerular diagnoses, and adjusted for demographic characteristics, eGFR, proteinuria, anemia, phosphate, hypertension, and alkali therapy.
Six hundred and three participants with nonglomerular disease contributed 2673 person-years of follow-up, and 255 with a glomerular diagnosis contributed 808 person-years of follow-up. At baseline, 39% (237 of 603) of participants with nonglomerular disease had a bicarbonate level of ≤22 meq/L and 36% (85 of 237) of those participants reported alkali therapy treatment. In participants with glomerular disease, 31% (79 of 255) had a bicarbonate of ≤22 meq/L, 18% (14 of 79) of those participants reported alkali therapy treatment. In adjusted longitudinal analyses, compared with participants with a bicarbonate level >22 meq/L, hazard ratios associated with a bicarbonate level of <18 meq/L and 19-22 meq/L were 1.28 95% confidence interval (95% CI), 0.84 to 1.94 and 0.91 (95% CI, 0.65 to 1.26), respectively, in children with nonglomerular disease. In children with glomerular disease, adjusted hazard ratios associated with bicarbonate level ≤18 meq/L and bicarbonate 19-22 meq/L were 2.16 (95% CI, 1.05 to 4.44) and 1.74 (95% CI, 1.07 to 2.85), respectively. Resolution of low bicarbonate was associated with a lower risk of CKD progression compared with persistently low bicarbonate (≤22 meq/L).
In children with glomerular disease, low bicarbonate was linked to a higher risk of CKD progression. Resolution of low bicarbonate was associated with a lower risk of CKD progression. Fewer than one half of all children with low bicarbonate reported treatment with alkali therapy. Long-term studies of alkali therapy's effect in patients with pediatric CKD are needed.
Congenital anomalies of the kidney and urinary tract and genetic disorders cause most cases of CKD in children. This study evaluated the relationships between baseline proteinuria and BP and ...longitudinal changes in GFR in children with these nonglomerular causes of CKD.
Urine protein-to-creatinine ratio, casual systolic and diastolic BP (normalized for age, sex, and height), and GFR decline were assessed in the prospective CKD in Children cohort study.
A total of 522 children, median age 10 years (interquartile range, 7, 14 years) with nonglomerular CKD were followed for a median of 4.4 years. The mean baseline GFR in the cohort was 52 ml/min per 1.73 m(2) (95% confidence interval 95% CI, 50 to 54) and declined 1.3 ml/min per 1.73 m(2) per year on average (95%CI, 1.6 to 1.1). A 2-fold higher baseline urine protein-to-creatinine ratio was associated with an accelerated GFR decline of 0.3 ml/min per 1.73 m(2) per year (95% CI, 0.4 to 0.1). A 1-unit higher baseline systolic BP z-score was associated with an additional GFR decline of 0.4 ml/min per 1.73 m(2) per year (95% CI, 0.7 to 0.1). Among normotensive children, larger GFR declines were associated with larger baseline urine protein-to-creatinine ratios; eGFR declines of 0.8 and 1.8 ml/min per 1.73 m(2) per year were associated with urine protein-to-creatinine ratio <0.5 and ≥0.5 mg/mg, respectively. Among children with elevated BP, average GFR declines were evident but were not larger in children with higher levels of proteinuria.
Baseline proteinuria and systolic BP levels are independently associated with CKD progression in children with nonglomerular CKD.
Summary
Renal disease is a common complication experienced by patients with sickle cell disease (SCD), though the epidemiology of acute kidney injury (AKI) in paediatric patients and its impact on ...long‐term renal outcomes is unclear. We utilized the Pediatric Health Information System (PHIS) to identify inpatient encounters of paediatric patients with SCD admitted for vaso‐occlusive pain crisis (VOC). Overall, 1·4% of patients experienced at least one episode of AKI and 2·5% of admissions were complicated by AKI. Patients with at least one episode of AKI were more likely to be adolescents or young adults at the time of their initial admission, had increased rates of admission to the ICU, longer lengths of stay, increased costs of hospitalization, increased risk of readmission and increased rates of SCD‐related comorbidities. Generalized estimating equation modelling demonstrated that increasing age, history of hypertension, history of haematuria and history of chronic kidney disease were associated with increased odds of developing AKI, though hydroxycarbamide use (OR 0·64, 95% CI 0·44–0·94) was protective. Episodes of AKI during hospitalization in children with SCD are associated with increased morbidity and utilization of hospital resources. Increasing the use of hydroxycarbamide may decrease the likelihood of this complication.
Objectives To compare the health-related quality of life (HRQoL) of children with chronic kidney disease (CKD) and short stature (SS) with that of children with CKD and normal height (NH), to ...evaluate the impact of catch-up growth and growth hormone (GH) use on HRQoL, and to describe the concordance of perceptions of HRQoL between children with SS and NH and their parents. Study design Four hundred eighty-three children and/or parents enrolled in the multicenter Chronic Kidney Disease in Children study who had completed the Pediatric Quality of Life Inventory (Version 4.0) on at least 2 Chronic Kidney Disease in Children study visits composed this substudy population. Participants were dichotomized into NH or SS groups. The demographic characteristics that varied at baseline (sex, glomerular filtration rate, and parent education) were controlled for in the main analysis evaluating the impact of catch-up growth and use of GH on HRQoL. Results Multivariate modeling (controlling for confounding variables) revealed a significant association between both catch-up growth and GH use on parent–proxy reports of child physical functioning ( P < .05) and social functioning ( P < .05). Older children with CKD (15-17 years old) had significantly higher ratings than their parents on the Pediatric Quality of Life Inventory Physical, Emotional, Social, and School Functioning scales compared with younger children (8-14 years old). Conclusion The finding that height gains and GH use are associated with increases in physical and social functioning by parent report provides additional support for interventions to improve height in children with CKD. The importance of evaluating both the parent and child perceptions of HRQoL is supported by our results.
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