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 one 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 75 ml/min per 1.73 m2. Further studies are needed to establish the applicability to children of normal stature and muscle mass, and higher GFR.
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An estimated 650,000 Americans will have ESRD by 2010. Young adults with kidney failure often develop progressive chronic kidney disease (CKD) in childhood and adolescence. The Chronic Kidney Disease in Children (CKiD) prospective cohort study of 540 children aged 1 to 16 yr and have estimated GFR between 30 and 75 ml/min per 1.73 m 2 was established to identify novel risk factors for CKD progression; the impact of kidney function decline on growth, cognition, and behavior; and the evolution of cardiovascular disease risk factors. Annually, a physical examination documenting height, weight, Tanner stage, and standardized BP is conducted, and cognitive function, quality of life, nutritional, and behavioral questionnaires are completed by the parent or the child. Samples of serum, plasma, urine, hair, and fingernail clippings are stored in biosamples and genetics repositories. GFR is measured annually for 2 yr, then every other year using iohexol, HPLC creatinine, and cystatin C. Using age, gender, and serial measurements of Tanner stage, height, and creatinine, compared with iohexol GFR, a formula to estimate GFR that will improve on traditional pediatric GFR estimating equations when applied longitudinally is expected to be developed. Every other year, echocardiography and ambulatory BP monitoring will assess risk for cardiovascular disease. The primary outcome is the rate of decline of GFR. The CKiD study will be the largest North American multicenter study of pediatric CKD.
SummaryBackground and objectives Autosomal dominant polycystic kidney disease (ADPKD) is characterized by increased total kidney volume (TKV) and renal failure. This study aimed to determine if height-adjusted TKV (htTKV) predicts the onset of renal insufficiency.Design, setting, participants, & measurements This prospective, observational, longitudinal, multicenter study included 241 adults with ADPKD and preserved renal function. Magnetic resonance imaging and iothalamate clearance were used to measure htTKV and GFR, respectively. The association between baseline htTKV and the attainment of stage 3 CKD (GFR ,60 ml/min per 1.73 m 2 ) during follow-up was determined.Results After a mean follow-up of 7.9 years, stage 3 CKD was attained in 30.7% of the enrollees. Using baseline htTKV, negative correlations with GFR increased from 20.22 at baseline to 20.65 at year 8. In multivariable analysis, a baseline htTKV increase of 100 cc/m significantly predicted the development of CKD within 8 years with an odds ratio of 1.48 (95% confidence interval: 1.29, 1.70). In receiver operator characteristic curve analysis, baseline htTKV of 600 cc/m most accurately defined the risk of developing stage 3 CKD within 8 years with an area under the curve of 0.84 (95% confidence interval: 0.79, 0.90). htTKV was a better predictor than baseline age, serum creatinine, BUN, urinary albumin, or monocyte chemotactic protein-1 excretion (P,0.05).Conclusions Baseline htTKV $600 cc/m predicted the risk of developing renal insufficiency in ADPKD patients at high risk for renal disease progression within 8 years of follow-up, qualifying htTKV as a prognostic biomarker in ADPKD.
H3Africa is developing capacity for health-related genomics research in Africa
Significant disparities in CKD rates and outcomes exist between black and white Americans. Health disparities are defined as health differences that adversely affect disadvantaged populations, on the basis of one or more health outcomes. CKD is the complex result of genetic and environmental factors, reflecting the balance of nature and nurture. Social determinants of health have an important role as environmental components, especially for black populations, who are disproportionately disadvantaged. Understanding the social determinants of health and appreciating the underlying differences associated with meaningful clinical outcomes may help nephrologists treat all their patients with CKD in an optimal manner. Altering the social determinants of health, although difficult, may embody important policy and research efforts, with the ultimate goal of improving outcomes for patients with kidney diseases, and minimizing the disparities between groups.
Background Few studies have prospectively evaluated the progression of chronic kidney disease (CKD) in children and factors associated with progression. Study Design Prospective assessment of risk factors for the composite event of renal replacement therapy (RRT) or 50% glomerular filtration rate (GFR) decline. Setting and Participants 496 children with CKD enrolled in the Chronic Kidney Disease in Children (CKiD) study. Outcomes Parametric failure time models were used to characterize adjusted associations between baseline levels and changes of predictors and the time to composite event. Results The cohort consisted of 398 children with non-glomerular and 98 children with glomerular disease, of whom 29% and 41%, respectively progressed to the composite event after a median follow-up of 5.2 and 3.7 years. Demographic, clinical characteristics and outcomes differed substantially according to underlying diagnosis, hence risk factors for progression were assessed in stratified analyses and formal interactions by diagnosis were performed. Among non-glomerular patients and after adjusting for baseline GFR, times to the composite event were significantly reduced with Up/c > 2 mg/mg, hypoalbuminemia, elevated blood pressure, dyslipidemia, male gender and anemia by 79%, 69%, 38%, 40%, 38% and 45%, respectively. Among patients with glomerular disease, Up/c > 0.5 mg/mg, hypoalbuminemia and elevated blood pressure 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 RRT/50% decline of GFR in children with CKD.
In this review of 126 publications, we report that an overwhelming majority of adults born at preterm gestations remain healthy and well. However, a small, but a significant fraction of them remain at higher risk for neurological, personality and behavioural abnormalities, cardio-pulmonary functional limitations, systemic hypertension and metabolic syndrome compared to their term-born counterparts. The magnitude of increased risk differed across organ systems and varied across reports. The risks were proportional to the degree of prematurity at birth and seemed to occur more frequently among preterm infants born in the final two decades of the 20th century and later. These findings have considerable public health and clinical practice relevance.
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