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  • Review Article
  • Published:

HDL abnormalities in nephrotic syndrome and chronic kidney disease

Key Points

  • Heavy glomerular proteinuria (nephrotic syndrome) and advanced chronic kidney disease (CKD) can elicit profound changes in the structure and function of HDL

  • HDL abnormalities in nephrotic syndrome impair reverse cholesterol transport and consequently promote foam cell formation, atherosclerosis, and glomerulosclerosis

  • HDL abnormalities in nephrotic syndrome are largely due to lecithin–cholesteryl acyltransferase (LCAT) deficiency caused by urinary losses, elevated plasma cholesterol ester transfer protein levels, hypoalbuminaemia, and/or reduced expression levels of hepatic HDL docking receptor (SRB1)

  • HDL abnormalities in CKD are caused by deficiencies in ApoA-1, ApoA-2, LCAT, paraoxonase-1, glutathione peroxidase, elevated levels of ACAT-1, and increased oxidative and myeloperoxidase modifications to HDL cargo

  • Oxidative and myeloperoxidase modifications to ApoA-1, ApoA-2 and SRB1 impair HDL-mediated reverse cholesterol transport and HDL antioxidant and anti-inflammatory activity

  • HDL abnormalities contribute to endothelial dysfunction, accelerated atherosclerosis, oxidative stress, and systemic inflammation in patients with CKD

Abstract

Normal HDL activity confers cardiovascular and overall protection by mediating reverse cholesterol transport and through its potent anti-inflammatory, antioxidant, and antithrombotic functions. Serum lipid profile, as well as various aspects of HDL metabolism, structure, and function can be profoundly altered in patients with nephrotic range proteinuria or chronic kidney disease (CKD). These abnormalities can, in turn, contribute to the progression of cardiovascular complications and various other comorbidities, such as foam cell formation, atherosclerosis, and/or glomerulosclerosis, in affected patients. The presence and severity of proteinuria and renal insufficiency, as well as dietary and drug regimens, pre-existing genetic disorders of lipid metabolism, and renal replacement therapies (including haemodialysis, peritoneal dialysis, and renal transplantation) determine the natural history of lipid disorders in patients with kidney disease. Despite the adverse effects associated with dysregulated reverse cholesterol transport and advances in our understanding of the underlying mechanisms, safe and effective therapeutic interventions are currently lacking. This Review provides an overview of HDL metabolism under normal conditions, and discusses the features, mechanisms, and consequences of HDL abnormalities in patients with nephrotic syndrome or advanced CKD.

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Figure 1: Production and metabolism of HDL via reverse cholesterol transport.
Figure 2: Protective functions of HDL.
Figure 3: Lipid accumulation in renal cortical tissue of rats with nephrotic syndrome.
Figure 4: Consequences of nephrotic syndrome on lipid metabolism.
Figure 5: Consequences of CKD on lipid metabolism.

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Vaziri, N. HDL abnormalities in nephrotic syndrome and chronic kidney disease. Nat Rev Nephrol 12, 37–47 (2016). https://doi.org/10.1038/nrneph.2015.180

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