HDL abnormalities in nephrotic syndrome and chronic kidney disease

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.

Kidney function is associated with an altered protein composition of high-density lipoprotein

“…Notably, no significant associations were observed between HDL protein abundance and albuminuria, a finding potentially in contrast with prior descriptions of extensive HDL protein remodeling in the setting of nephrotic syndrome. 56, 57 It is possible, therefore, that changes in HDL protein composition only become evident with nephrotic range proteinuria. Alternatively, HDL remodeling in nephrotic syndrome may not solely be due to albuminuria but also may result from hypoalbuminemia or other components of this syndrome, as has been previously suggested.…”

Disorders of Lipid Metabolism in Chronic Kidney Disease

“…One of the noteworthy examples of the HDL cholesterol metabolism dysregulation is the one observed in patients with nephrotic syndrome [22]. In patients with nephrotic syndrome, serum HDL cholesterol levels may be normal or below the normal limits, but the ratio of HDL cholesterol to total serum cholesterol is significantly decreased.…”

“…This also results in an increased level of HDL 3 to HDL 2 ratio, which can possibly be linked to the formation of the atherosclerotic plaques. Increased cholesterol ester transfer protein levels and reduced hepatic HDL cholesterol docking receptors (SRB1) are additional considerable factors causing HDL cholesterol dysfunction in patients with nephrotic syndrome [22]. As a result, HDL cholesterol deficiency and HDL cholesterol dysfunction may play a crucial role in the development of atherosclerosis.…”

Metabolomic Signatures of Chronic Kidney Disease of Diverse Etiologies in the Rats and Humans

“…CKD is associated with accumulation of lipids in the renal tissue which is primarily due to tubular reabsorption of filtered lipid-bound proteins 36,37 and impaired fatty acid oxidation and contributes to the pathogenesis of renal fibrosis. 31 Our CKD patients exhibited significant reduction of plasma stearic acid and 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 13 ricinoleic acid levels.…”