Chapter 3: Assessment of lipid status in children with CKD

RATIONALE Young adults with eGFR o15 ml/min/1.73 m have at least 10-fold higher risk for CVD mortality compared to the general population. Many recent studies document the prevalence of CVD risk factors in children with CKD. However, due to limited follow-up, few studies demonstrate the association of dyslipidemia with clinical CVD events in adolescents or young adults, especially in the setting of CKD. In the general pediatric population, lipid levels in childhood are predictive of future lipid levels and subsequent cardiovascular events. The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study shows that initial fatty streaks seen in adolescents with normal kidney function develop into atheromatous plaques in young adults. Over 50% of children 10-14 years old had early fatty streaks, and 8% had fibrous plaques, thus confirming that atherosclerosis begins in childhood. Additional longitudinal studies demonstrate an association between childhood lipid levels and adult onset coronary artery disease. Moreover, this atherosclerotic process is likely accelerated in nephrotic syndrome, proteinuric states and chronic kidney disease due to abnormal lipid metabolism and other atherogenic risk factors, thus putting children and adolescents at risk for developing CVD as they age into adulthood. In the Bogalusa Heart Study, body mass index, LDL-C, and systolic blood pressure were associated with atherosclerotic disease of the aorta and coronary vessels of children. Recent studies of subclinical atherosclerotic CVD in children with familial hypercholesterolemia found an increase in intimal medial thickness of the aorta and carotid arteries compared to that of healthy young children. Thus, atherosclerotic disease appears to begin in childhood, and dyslipidemia in children may play an important role in the early pathogenesis of atherosclerosis. In children with CKD, the relationship between dyslipidemias and subsequent atherosclerotic clinical events is not known due to short follow-up in observational studies or clinical trials. Recently, the Cardiovascular Risk Reduction in High-Risk Pediatric Patients: A Scientific Statement from the American Heart Association Expert Panel on Population and Prevention Science stated that CVD prevention in many chronic pediatric conditions was warranted given the high risk of developing disease as adults. The recent National Institutes of Health Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents in 2011 addressed specific questions of screening for dyslipidemias in children and adolescents and also treatment of dyslipidemias. Cholesterol and its metabolism are important in children as cholesterol is the basis of cell membranes, myelin formation, subcellular organelles and steroid hormones which are all key for natural growth and development. Based on growth and development, lipid levels vary depending on age, puberty, and gender. Lipid levels are very low at birth and increase during the first year of life [mean TC of 3.9 mmol/ l (150 mg/dl), LDL-C 2.6 mmol/l (100 mg/dl), and HDL-C 1.4 mmol/l (55 mg/dl)] where they remain fairly constant till age 12 and are slightly lower in girls than boys. During puberty, there is a decrease in TC, LDL-C, and a slight decrease in HDL-C in boys. After puberty, TC and LDL-C increase to adult levels in boys and girls. Boys continue to have a slightly lower HDL-C than girls. Due to these variations in levels, former guidelines used the 95th percentile for age and gender to determine the upper limit of acceptable values. More recently, ageand genderspecific curves for lipoproteins linked to CVD risk over 15-20 years have been used instead. A simplified and more practical approach has been to define acceptable, borderline high and high lipid concentration for children and adolescents based on these curves (see Table 5). Many studies document the prevalence of dyslipidemias among children with CKD and ESRD. As in adults, the pattern of dyslipidemias in children with CKD is greatly influenced by the underlying pathogenesis and duration of CKD, severity of proteinuria, and treatment. Due to this variability, the prevalence of hypercholesterolemia ranges from 39% to 65% in children with CKD. Among 391 children from the North American observational cohort study, CKiD (Chronic Kidney Disease in Children), TG and non-HDL-C levels increased as the measured GFR declined in this cross sectional study population. Conversely, HDL-C was lower for those with a lower GFR. Factors that impacted TG, HDLC and non-HDL-C levels were primarily GFR, significant proteinuria and obesity by multivariate analyses. Over half the population had no evidence of dyslipidemias and of the remainder, 25% had a single abnormal lipid level, and the other 25% had at least 2 abnormal lipid levels. The most c h a p t e r 3 http://www.kidney-international.org