Dysfunctional High-Density Lipoprotein in Patients on Chronic Hemodialysis

Yamamoto, Shuichi; Yancey, Patricia G.; İkizler, T. Alp; Jerome, W. Gray; Kaseda, Ryohei; Cox, Brian E.; Bian, Aihua; Shintani, Ayumi; Fogo, Agnes B.; Linton, MacRae F.; Fazio, Sergio; Kon, Valentina

doi:10.1016/j.jacc.2012.09.013

Cited by 187 publications

(190 citation statements)

References 43 publications

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“…In addition, high HDL concentrations are associated with decreased endothelial adhesion molecule expression, increased endothelial nitric oxide production, and decreased endothelial damage 14, 16, 17. Decreased HDL anti‐inflammatory, antioxidant, and endothelial protective capacities are associated with an increased risk of chronic kidney disease 32, 33, 34, 35. Each of these processes (systemic inflammation, oxidative stress, and endothelial dysfunction and damage) plays a key role in the pathogenesis of AKI 9, 11, 35, 36, 37.…”

Section: Discussionmentioning

confidence: 99%

“…Decreased HDL anti‐inflammatory, antioxidant, and endothelial protective capacities are associated with an increased risk of chronic kidney disease 32, 33, 34, 35. Each of these processes (systemic inflammation, oxidative stress, and endothelial dysfunction and damage) plays a key role in the pathogenesis of AKI 9, 11, 35, 36, 37. Therefore, in an analogous manner to their role in chronic kidney dysfunction, these HDL functional capacities could contribute to postoperative renal function and AKI.…”

Section: Discussionmentioning

confidence: 99%

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High‐Density Lipoprotein Cholesterol Concentration and Acute Kidney Injury After Cardiac Surgery

Smith

Blume

Linton

et al. 2017

JAHA

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BackgroundAcute kidney injury (AKI) after cardiac surgery is associated with increased short‐ and long‐term mortality. Inflammation, oxidative stress, and endothelial dysfunction and damage play important roles in the development of AKI. High‐density lipoproteins (HDLs) have anti‐inflammatory and antioxidant properties and improve endothelial function and repair. Statins enhance HDL's anti‐inflammatory and antioxidant capacities. We hypothesized that a higher preoperative HDL cholesterol concentration is associated with decreased AKI after cardiac surgery and that perioperative statin exposure potentiates this association.Methods and ResultsWe tested our hypothesis in 391 subjects from a randomized clinical trial of perioperative atorvastatin to reduce AKI after cardiac surgery. A 2‐component latent variable mixture model was used to assess the association between preoperative HDL cholesterol concentration and postoperative change in serum creatinine, adjusted for known AKI risk factors and suspected confounders. Interaction terms were used to examine the effects of preoperative statin use, preoperative statin dose, and perioperative atorvastatin treatment on the association between preoperative HDL and AKI. A higher preoperative HDL cholesterol concentration was independently associated with a decreased postoperative serum creatinine change (P=0.02). The association between a high HDL concentration and an attenuated increase in serum creatinine was strongest in long‐term statin‐using patients (P=0.008) and was further enhanced with perioperative atorvastatin treatment (P=0.004) and increasing long‐term statin dose (P=0.003).ConclusionsA higher preoperative HDL cholesterol concentration was associated with decreased AKI after cardiac surgery. Preoperative and perioperative statin treatment enhanced this association, demonstrating that pharmacological potentiation is possible during the perioperative period.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00791648.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

High‐Density Lipoprotein Cholesterol Concentration and Acute Kidney Injury After Cardiac Surgery

Smith

Blume

Linton

et al. 2017

JAHA

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“…The ability of HDL to remove cholesterol from lipid-laden macrophages via ABCA-1 is markedly reduced in patients undergoing haemodialysis compared to that of healthy controls 83 . A series of studies have demonstrated an accumulation of neutral lipids in the artery wall and kidneys of rat models of CKD, despite upregulation of ABCA-1 and ABCG1 84,85 .…”

Section: Upregulation Of Acatmentioning

confidence: 92%

HDL abnormalities in nephrotic syndrome and chronic kidney disease

2015

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| 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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“…These abnormalities work in concert to lower HDL levels and impair HDL maturation as well as its antioxidant, anti-inflammatory and reverse cholesterol transport capacities. In patients on haemodialysis, the ability of HDL to remove cholesterol from lipid-laden macro phages, 8 reverse LDL oxidation and prevent monocyte attachment to, and infiltration of, the vascular endothelium 7 is greatly reduced. HDL from patients with ESRD can trigger the release of inflammatory cytokines by macrophages, 7,8 a phenomenon that is partly attributable to the presence of SAA.…”

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confidence: 99%

“…In patients on haemodialysis, the ability of HDL to remove cholesterol from lipid-laden macro phages, 8 reverse LDL oxidation and prevent monocyte attachment to, and infiltration of, the vascular endothelium 7 is greatly reduced. HDL from patients with ESRD can trigger the release of inflammatory cytokines by macrophages, 7,8 a phenomenon that is partly attributable to the presence of SAA. 7 The mechanism that underlies the elevated serum HDL cholesterol levels in a subgroup of patients with ESRD in the study by Silbernagel et al, 1 and in other studies, 9,10 is unclear.…”

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confidence: 99%