Dyslipidemia and cardiovascular health in childhood nephrotic syndrome
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Published on: May 6, 2018
Pankaj Hari1, Priyanka Khandelwal2, William E Smoyer3,4
1Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India. pankajhari@hotmail.com.
Insights
Children with steroid-resistant nephrotic syndrome (SRNS) face accelerated atherosclerosis due to dyslipidemia. Managing high lipid levels in these children may require lifestyle changes and medications, with new therapies showing promise.
Area of Science:
- Pediatric Nephrology
- Cardiovascular Risk in Chronic Kidney Disease
- Lipid Metabolism Disorders
Background:
- Children with steroid-resistant nephrotic syndrome (SRNS) exhibit increased cardiovascular risk factors, potentially leading to accelerated atherosclerosis.
- This cardiovascular risk is significantly higher in SRNS compared to steroid-sensitive nephrotic syndrome, especially with progression to chronic kidney disease.
- Dyslipidemia is a known cardiovascular risk factor in adults with nephrotic syndrome (NS), but its extent and impact in pediatric SRNS are less understood.
Purpose of the Study:
- To evaluate the extent of cardiovascular risk associated with dyslipidemia in children with SRNS.
- To explore the mechanisms of lipid metabolism abnormalities in pediatric SRNS.
- To discuss current and potential therapeutic strategies for managing dyslipidemia in this vulnerable population.
Main Methods:
- Review of existing literature on lipid metabolism and cardiovascular risk in pediatric SRNS.
- Analysis of lipid abnormalities including hypertriglyceridemia, hypercholesterolemia, and altered lipoprotein lipase activity.
- Examination of potential therapeutic interventions, including lifestyle modifications and pharmacological agents.
Main Results:
- Children with SRNS demonstrate significant lipid metabolism abnormalities, including elevated apolipoprotein B-containing lipoproteins and increased PCSK9 levels.
- Evidence suggests accelerated atherosclerosis in pediatric SRNS patients with persistent high lipid levels.
- Current management guidelines may need adaptation, and various lipid-lowering therapies are being considered, despite limited trial data.
Conclusions:
- Dyslipidemia represents a significant and potentially modifiable cardiovascular risk in children with SRNS.
- While established and novel therapies show promise, careful consideration of side effects and long-term impacts is crucial.
- Further research, including randomized controlled trials, is needed to establish optimal lipid-lowering strategies for pediatric SRNS.
Abstract:
Children with steroid-resistant nephrotic syndrome (SRNS) are exposed to multiple cardiovascular risk factors predisposing them to accelerated atherosclerosis. This risk is negligible in steroid-sensitive nephrotic syndrome, but a substantial proportion of children with SRNS progress to chronic kidney disease, exacerbating the already existing cardiovascular risk. While dyslipidemia is an established modifiable risk factor for cardiovascular disease in adults with NS, it is uncertain to what extent analogous risks exist for children. There is increasing evidence of accelerated atherosclerosis in children with persistently high lipid levels, especially in refractory NS. Abnormalities of lipid metabolism in NS include hypertriglyceridemia and hypercholesterolemia due to elevated apolipoprotein B-containing lipoproteins, decreased lipoprotein lipase and hepatic lipase activity, increased hepatic PCSK9 levels, and reduced hepatic uptake of high-density lipoprotein. Existing guidelines for the management of dyslipidemia in children may be adapted to target lower lipid levels in children with NS, but they will most likely require both lifestyle modifications and pharmacological therapy. While there is a lack of data from randomized controlled trials in children with NS demonstrating the benefit of lipid-lowering drugs, therapies including statins, bile acid sequestrants, fibrates, ezetimibe, and LDL apheresis have all been suggested and/or utilized. However, concerns with the use of lipid-lowering drugs in children include unclear side effect profiles and unknown long-term impacts on neurological development and puberty. The recent introduction of anti-PCSK9 monoclonal antibodies and other therapies targeted to the molecular mechanisms of lipid transport disrupted in NS holds promise for the future treatment of dyslipidemia in NS.
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