Chronic kidney disease (CKD) is a life-long condition associated with substantial morbidity and premature death due to complications from a progressive decrease in kidney function. The incidence and ...prevalence of all stages of CKD in children continues to increase worldwide. Between 2000 and 2008, the kidney replacement therapy incidence rate in those aged 0-19 years increased 5.9% to 15 per million population, highlighting the importance of CKD research in children. Many comorbid conditions seen in adults with CKD, including cardiovascular disease and cognitive impairment, also are highly prevalent in children, implicitly demonstrating the crucial need for initiating therapy early to improve health outcomes in children with CKD. The CKiD (Chronic Kidney Disease in Children) Study is a prospective cohort study of 586 children aged 1-16 years with an estimated glomerular filtration rate of 30-90 mL/min/1.73 m2 . Since its inception, CKiD has identified risk factors for CKD progression and cardiovascular disease in children with CKD and highlighted the effects of CKD on outcomes unique to children, including neurocognitive development and growth. This review summarizes the findings to date, illustrating the spectrum of CKD-associated complications in children and emphasizing areas requiring further investigation. Taken in sum, these elements stress that initiating treatment at an early age is essential for reducing long-term morbidity and mortality in children with CKD.
Background Few studies have prospectively evaluated the progression of chronic kidney disease (CKD) in children and adolescents, as well as factors associated with progression. Study Design ...Prospective multicenter observational cohort study. Setting & Participants 496 children and adolescents with CKD enrolled in the Chronic Kidney Disease in Children (CKiD) Study. Predictors Proteinuria, hypoalbuminemia, blood pressure, dyslipidemia, and anemia. Outcomes Parametric failure-time models were used to characterize adjusted associations between baseline levels and changes in predictors and time to a composite event of renal replacement therapy or 50% decline in glomerular filtration rate (GFR). Results 398 patients had nonglomerular disease and 98 had glomerular disease; of these, 29% and 41%, respectively, progressed to the composite event after median follow-ups of 5.2 and 3.7 years, respectively. Demographic and clinical characteristics and outcomes differed substantially according to the underlying diagnosis; hence, risk factors for progression were assessed in stratified analyses, and formal interactions by diagnosis were performed. Among patients with nonglomerular disease and after adjusting for baseline GFR, times to the composite event were significantly shorter with urinary protein-creatinine ratio > 2 mg/mg, hypoalbuminemia, elevated blood pressure, dyslipidemia, male sex, and anemia, by 79%, 69%, 38%, 40%, 38%, and 45%, respectively. Among patients with glomerular disease, urinary protein-creatinine ratio >2 mg/mg, hypoalbuminemia, and elevated blood pressure were associated with significantly reduced times to the composite event by 94%, 71%, and 67%, respectively. Variables expressing change in patient clinical status over the initial year of the study contributed significantly to the model, which was cross-validated internally. Limitations Small number of events in glomerular patients and use of internal cross-validation. Conclusions Characterization and modeling of risk factors for CKD progression can be used to predict the extent to which these factors, either alone or in combination, would shorten the time to renal replacement therapy or 50% decline in GFR in children with CKD.
In contrast to the increasing availability of information pertaining to the care of children with chronic kidney disease (CKD) from large-scale observational and interventional studies, ...epidemiological information on the incidence and prevalence of pediatric CKD is currently limited, imprecise, and flawed by methodological differences between the various data sources. There are distinct geographic differences in the reported causes of CKD in children, in part due to environmental, racial, genetic, and cultural (consanguinity) differences. However, a substantial percentage of children develop CKD early in life, with congenital renal disorders such as obstructive uropathy and aplasia/hypoplasia/dysplasia being responsible for almost one half of all cases. The most favored end-stage renal disease (ESRD) treatment modality in children is renal transplantation, but a lack of health care resources and high patient mortality in the developing world limits the global provision of renal replacement therapy (RRT) and influences patient prevalence. Additional efforts to define the epidemiology of pediatric CKD worldwide are necessary if a better understanding of the full extent of the problem, areas for study, and the potential impact of intervention is desired.
Using data (2655 observations from 928 participants) from the Chronic Kidney Disease in Children Study, we developed and internally validated new glomerular filtration rate estimating equations for ...clinical use in children and young adults: two forms of K × heigh(ht) / serum creatinine(sCr) and two forms of K × 1 / cystatin C(cysC). For each marker, one equation used a sex-dependent K; in the other, K is sex-and age-dependent. Glomerular filtration rate (GFR) was measured directly by plasma iohexol disappearance. The equations using ht⁄sCr had sex-specific constants of 41.8 for males and 37.6 for females. In the age- dependent models, K increased monotonically for children 1-18 years old and was constant for young adults 18-25 years. For males, K ranged from 35.7 for one-year-olds to 50.8 for those 18 and older. For females, the values of K ranged from 33.1 to 41.4. Constant K values for cystatin-C equations were 81.9 for males and 74.9 for females. With age-dependency, K varied non-monotonically with the highest values at age 15 for males (K of 87.2) and 12 years for females (K of 79.9). Use of an age-dependent K with ht/sCr models reduced average bias, notably in young children and young adults; age-dependent cystatin-C models produced similar agreement to using a constant K in children under 18 years, but reduced bias in young adults. These age-dependent proposed equations were evaluated alongside estimated GFRs from 11 other published equations for pediatrics and young adults. Only our proposed equations yielded non- significant bias and within 30% accuracy values greater than 85% in both the pediatric and young adult subpopulations.
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Exposure to environmental chemicals may be a modifiable risk factor for progression of chronic kidney disease (CKD). The purpose of this study was to examine the impact of serially assessed exposure ...to bisphenol A (BPA) and phthalates on measures of kidney function, tubular injury, and oxidative stress over time in a cohort of children with CKD.
Samples were collected between 2005 and 2015 from 618 children and adolescents enrolled in the Chronic Kidney Disease in Children study, an observational cohort study of pediatric CKD patients from the US and Canada. Most study participants were male (63.8%) and white (58.3%), and participants had a median age of 11.0 years (interquartile range 7.6 to 14.6) at the baseline visit. In urine samples collected serially over an average of 3.0 years (standard deviation SD 1.6), concentrations of BPA, phthalic acid (PA), and phthalate metabolites were measured as well as biomarkers of tubular injury (kidney injury molecule-1 KIM-1 and neutrophil gelatinase-associated lipocalin NGAL) and oxidative stress (8-hydroxy-2'-deoxyguanosine 8-OHdG and F2-isoprostane). Clinical renal function measures included estimated glomerular filtration rate (eGFR), proteinuria, and blood pressure. Linear mixed models were fit to estimate the associations between urinary concentrations of 6 chemical exposure measures (i.e., BPA, PA, and 4 phthalate metabolite groups) and clinical renal outcomes and urinary concentrations of KIM-1, NGAL, 8-OHdG, and F2-isoprostane controlling for sex, age, race/ethnicity, glomerular status, birth weight, premature birth, angiotensin-converting enzyme inhibitor use, angiotensin receptor blocker use, BMI z-score for age and sex, and urinary creatinine. Urinary concentrations of BPA, PA, and phthalate metabolites were positively associated with urinary KIM-1, NGAL, 8-OHdG, and F2-isoprostane levels over time. For example, a 1-SD increase in ∑di-n-octyl phthalate metabolites was associated with increases in NGAL (β = 0.13 95% CI: 0.05, 0.21, p = 0.001), KIM-1 (β = 0.30 95% CI: 0.21, 0.40, p < 0.001), 8-OHdG (β = 0.10 95% CI: 0.06, 0.13, p < 0.001), and F2-isoprostane (β = 0.13 95% CI: 0.01, 0.25, p = 0.04) over time. BPA and phthalate metabolites were not associated with eGFR, proteinuria, or blood pressure, but PA was associated with lower eGFR over time. For a 1-SD increase in ln-transformed PA, there was an average decrease in eGFR of 0.38 ml/min/1.73 m2 (95% CI: -0.75, -0.01; p = 0.04). Limitations of this study included utilization of spot urine samples for exposure assessment of non-persistent compounds and lack of specific information on potential sources of exposure.
Although BPA and phthalate metabolites were not associated with clinical renal endpoints such as eGFR or proteinuria, there was a consistent pattern of increased tubular injury and oxidative stress over time, which have been shown to affect renal function in the long term. This raises concerns about the potential for clinically significant changes in renal function in relation to exposure to common environmental toxicants at current levels.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The coronavirus disease 2019 (COVID-19) pandemic, technological advancements, regulatory waivers, and user acceptance have converged to boost telehealth activities. Due to the state of emergency, ...regulatory waivers in the United States have made it possible for providers to deliver and bill for services across state lines for new and established patients through Health Insurance Portability and Accountability Act (HIPAA)- and non–HIPAA-compliant platforms with home as the originating site and without geographic restrictions. Platforms have been developed or purchased to perform videoconferencing, and interdisciplinary dialysis teams have adapted to perform virtual visits. Telehealth experiences and challenges encountered by dialysis providers, clinicians, nurses, and patients have exposed health care disparities in areas such as access to care, bandwidth connectivity, availability of devices to perform telehealth, and socioeconomic and language barriers. Future directions in telehealth use, quality measures, and research in telehealth use need to be explored. Telehealth during the public health emergency has changed the practice of health care, with the post–COVID-19 world unlikely to resemble the prior era. The future impact of telehealth in patient care in the United States remains to be seen, especially in the context of the Advancing American Kidney Health Initiative.
When affected by coronavirus disease 2019 (COVID-19), most children have milder disease than what is experienced by adults. However, a subset of these children develops a multisystem inflammatory ...syndrome that can lead to shock and multiorgan failure. In the current issue, Basalely et al. characterize acute kidney injury in pediatric patients with acute COVID-19 and multisystem inflammatory syndrome. Despite the associated morbidity, this cohort provides evidence of kidney recovery in most affected children.
The Chronic Kidney Disease in Children study is a cohort of about 600 children with chronic kidney disease (CKD) in the United States and Canada. The independent variable for our observations was a ...measurement of glomerular filtration rate (GFR) by iohexol disappearance (iGFR) at the first two visits 1 year apart and during alternate years thereafter. In a previous report, we had developed GFR estimating equations utilizing serum creatinine, blood urea nitrogen, height, gender, and cystatin C measured by an immunoturbidimetric method; however, the correlation coefficient of cystatin C and GFR (-0.69) was less robust than expected. Therefore, 495 samples were re-assayed using immunonephelometry. The reciprocal of immunonephelometric cystatin C was as well correlated with iGFR as was height/serum creatinine (both 0.88). We developed a new GFR estimating equation using a random 2/3 of 965 person-visits and applied it to the remaining 1/3 as a validation data set. In the validation data set, the correlation of the estimated GFR with iGFR was 0.92 with high precision and no bias; 91 and 45% of eGFR values were within 30 and 10% of iGFR, respectively. This equation works well in children with CKD in a range of GFR from 15 to 75ml/min per 1.73m2. Further studies are needed to establish the applicability to children of normal stature and muscle mass, and higher GFR.
Chronic Kidney Disease in Children VanSickle, Judith Sebestyen; Warady, Bradley A
The Pediatric clinics of North America,
12/2022, Letnik:
69, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Chronic kidney disease (CKD) in children occurs mostly due to congenital anomalies of kidney and urinary tract and hereditary diseases. For advanced cases, a multidisciplinary team is needed to ...manage nutritional requirements and complications such as hypertension, hyperphosphatemia, proteinuria, and anemia. Neurocognitive assessment and psychosocial support are essential. Maintenance dialysis in children with end-stage renal failure has become the standard of care in many parts of the world. Children younger than 12 years have 95% survival after 3 years of dialysis initiation, whereas the survival rate for children aged 4 years or younger is about 82% at one year."
Background Hyperuricemia is associated with essential hypertension in children. No previous studies have evaluated the effect of hyperuricemia on progression of chronic kidney disease (CKD) in ...children. Study Design Prospective observational cohort study. Setting & Participants Children and adolescents (n = 678 cross-sectional; n = 627 longitudinal) with a median age of 12.3 (IQR, 8.6-15.6) years enrolled at 52 North American sites of the CKiD (CKD in Children) Study. Predictor Serum uric acid level (<5.5, 5.5-7.5, and >7.5 mg/dL). Outcomes Composite end point of either >30% decline in glomerular filtration rate (GFR) or initiation of renal replacement therapy. Measurements Age, sex, race, blood pressure status, GFR, CKD cause, urine protein-creatinine ratio (<0.5, 0.5-<2.0, and ≥2.0 mg/mg), age- and sex-specific body mass index > 95th percentile, use of diuretics, and serum uric acid level. Results Older age, male sex, lower GFR, and body mass index > 95th percentile were associated with higher uric acid levels. 162, 294, and 171 participants had initial uric acid levels < 5.5, 5.5 to 7.5, or >7.5 mg/dL, respectively. We observed 225 instances of the composite end point over 5 years. In a multivariable parametric time-to-event analysis, compared with participants with initial uric acid levels < 5.5 mg/dL, those with uric acid levels of 5.5 to 7.5 or >7.5 mg/dL had 17% shorter (relative time, 0.83; 95% CI, 0.62-1.11) or 38% shorter (relative time, 0.62; 95% CI, 0.45-0.85) times to event, respectively. Hypertension, lower GFR, glomerular CKD cause, and elevated urine protein-creatinine ratio were also associated with faster times to the composite end point. Limitations The study lacked sufficient data to examine how use of specific medications might influence serum uric acid levels and CKD progression. Conclusions Hyperuricemia is a previously undescribed independent risk factor for faster progression of CKD in children and adolescents. It is possible that treatment of children and adolescents with CKD with urate-lowering therapy could slow disease progression.
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