Disorders of Lipid Metabolism and Chronic Kidney Disease in the Elderly
Section snippets
Characteristics of CKD Dyslipidemia
With the progression of renal disease, there is notable change in lipoprotein metabolism and serum lipid levels.12, 13 Increased triglyceride levels and low HDLc levels with only mild increase or normal or low LDLc levels are noted in patients with CKD and ESRD. Low levels of apolipoprotein (apo) A-I, apo A-II, and apo-E as well as increases in apoB and apoC-III concentrations often precede abnormalities in serum lipids13, 14, 15 (Fig 1). Increases in apoC-III, increased very low-density lipids
Perspectives from Animal Studies
Animal studies have indicated that the abnormal lipid metabolism in CKD and aging are mediated by altered expression of a number of transcriptional factors and nuclear hormone receptors. In animal models of CKD there is evidence for increased expression of the sterol regulatory element binding protein-1 (SREBP-1) and SREBP-2 in the liver and in the adipose tissue. SREBP-1 and SREBP-2 are master regulators of fatty acid, triglyceride, and cholesterol synthesis and therefore mediate increased
CKD in the Elderly
With increasing age, there is also an increase in the prevalence of CKD. The US National Health and Nutrition Examination Survey from 1999 to 2004 estimated that more than a third of adults older than 70 years age have moderate CKD.47 A cross-sectional evaluation of 9,806 older adults in Germany between ages 50 and 74 years who presented for a general health check-up found that 17.4% of subjects had CKD. The prevalence of stages 1 and 2 was 4.6% and 4.7%, respectively, whereas 17.4% of subjects
Dyslipidemia with Increasing Age
Approximately 33% of elderly men and 50% of elderly women have a total cholesterol level greater than 240.56 A greater prevalence of metabolic syndrome including central obesity with insulin resistance, increased blood pressure, and dyslipidemia characterized by increased triglyceride levels, small high dense LDL, and a low concentration of HDL is being noted in older adults.57, 58 With a higher prevalence of cardiovascular events in older individuals, dyslipidemia poses a greater attributable
Dyslipidemia and Progression of CKD
Although experimental data support a role for dyslipidemia in the progression of renal disease,62, 63 the data in human beings extends primarily from observational studies. High triglyceride levels and low HDL as seen in CKD predicted an increase in the risk of renal dysfunction when participants of the Atherosclerosis Risk in Communities were followed up for approximately 3 years.64 Similarly, a low HDL and high LDL/HDL cholesterol ratio suggested a greater risk for an increase in serum
Lipid Lowering and Cardiovascular Outcomes in the Elderly
Secondary prevention trials using LDLc-lowering therapies have shown a benefit of lipid lowering on both cardiac events and all-cause mortality, with limited data available in older subjects. However, evidence from subgroup analysis of older patients from lipid- lowering trials suggests a similar benefit in cardiovascular outcomes in the elderly compared with that seen in younger subjects (Table 1).
Lipid Lowering in CKD and ESRD
Although changes in lipoprotein metabolism and serum lipids occur with increasing renal dysfunction, data suggesting a benefit of lipid-lowering agents, principally statins, among patients with CKD, remain limited (Table 2). A subgroup analysis of 1,329 CKD patients in the Heart Protection Study, including patients with a creatinine level from 1.3 to 2.3 mg/dL over 5 years' duration, showed a relative risk reduction of 28% (95% CI, 0.75-0.85; P = .05) with simvastatin use of 40 mg/d.81 The
Summary
Metabolic changes that occur with progressive renal failure and aging predispose patients to lipid abnormalities with increased atherogenic potential. Changes in expression of transcriptional and nuclear hormone receptors may be contributing. Suggestions of further CKD progression and increased cardiovascular risk from abnormal lipid metabolism causes concern for preventive treatment. At present, secondary analysis of large treatment trials with various statin agents suggest cardiovascular risk
References (90)
- et al.
Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey
Am J Kidney Dis
(2003) - et al.
Outcome and risk factors of ischemic heart disease in chronic uremia
Kidney Int
(1996) - et al.
Dyslipidemia and the progression of renal disease in chronic renal failure patients
Kidney Int Suppl
(2005) - et al.
Effect of lipid reduction on the progression of renal disease: a meta-analysis
Kidney Int
(2001) - et al.
Managing dyslipidemia in chronic kidney disease
J Am Coll Cardiol
(2008) Lipid and lipoprotein metabolism in chronic kidney disease
J Ren Nutr
(2009)- et al.
Abnormalities in lipoprotein metabolism in hemodialysis patients
Kidney Int Suppl
(1999) - et al.
Lipoprotein alterations in hemodialysis: differences between diabetic and nondiabetic patients
Metabolism
(2003) - et al.
Lipoperoxidation and hemodialysis
Metabolism
(2008) - et al.
Lipid peroxidation in hemodialysis patients: effect of vitamin C supplementation
Clin Biochem
(2008)
Enhanced LDL oxidation in uremic patients: an additional mechanism for accelerated atherosclerosis?
Kidney Int
Upregulation of lipogenic enzymes genes expression in white adipose tissue of rats with chronic renal failure is associated with higher level of sterol regulatory element binding protein-1
Metabolism
Increased gene expression of liver SREBP-2 in experimental chronic renal failure
Atherosclerosis
Decreased peroxisome proliferator-activated receptor alpha gene expression is associated with dyslipidemia in a rat model of chronic renal failure
Metabolism
Hepatic tissue sterol regulatory element binding protein 2 and low-density lipoprotein receptor in nephrotic syndrome
Metabolism
Role of altered renal lipid metabolism and the sterol regulatory element binding proteins in the pathogenesis of age-related renal disease
Kidney Int
Leptin decreases lipogenic enzyme gene expression through modification of SREBP-1c gene expression in white adipose tissue of aging rats
Metabolism
Diet and aging
Cell Metab
Circulating adiponectin levels increase in rats on caloric restriction: the potential for insulin sensitization
Exp Gerontol
Specific SIRT1 activation mimics low energy levels and protects against diet-induced metabolic disorders by enhancing fat oxidation
Cell Metab
SirT1 gain of function increases energy efficiency and prevents diabetes in mice
Cell Metab
Epidemiology of chronic kidney disease: results from a population of older adults in Germany
Prev Med
The case for chronic kidney disease, diabetes mellitus, and myocardial infarction being equivalent risk factors for cardiovascular mortality in patients older than 65 years
Am J Cardiol
Plasma lipids and risk of developing renal dysfunction: the atherosclerosis risk in communities study
Kidney Int
Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial
Lancet
Clinically relevant differences between the statins: implications for therapeutic selection
Am J Med
Fluvastatin prevents cardiac death and myocardial infarction in renal transplant recipients: post-hoc subgroup analyses of the ALERT study
Am J Transplant
Clofibrate-induced muscle damage in patients with chronic renal failure
Lancet
Death risk in hemodialysis patients: the predictive value of commonly measured variables and an evaluation of death rate differences between facilities
Am J Kidney Dis
Hypocholesterolemia is a significant predictor of death in a cohort of chronic hemodialysis patients
Kidney Int
Study of Heart and Renal Protection (SHARP)
Kidney Int Suppl
Chronic kidney disease and the risk for cardiovascular disease, renal replacement, and death in the United States Medicare population, 1998 to 1999
J Am Soc Nephrol
Annual Data Report
Cardiovascular disease risk factors in chronic kidney disease: overall burden and rates of treatment and control
Arch Intern Med
Predictors of the progression of renal disease in the Modification of Diet in Renal Disease Study
Kidney Int
Lipoprotein abnormalities are associated with increased rate of progression of human chronic renal insufficiency
Nephrol Dial Transplant
Effect of pravastatin on rate of kidney function loss in people with or at risk for coronary disease
Circulation
Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis
N Engl J Med
Dyslipidemia in chronic kidney disease: an approach to pathogenesis and treatment
Am J Nephrol
Dyslipidemia of chronic renal failure: the nature, mechanisms, and potential consequences
Am J Physiol Renal Physiol
Selective deficiency of hepatic triglyceride lipase in uremic patients
N Engl J Med
Are uremia, diabetes, and atherosclerosis linked with impaired antioxidant mechanisms?
J Investig Med
Oxidative stress markers in pre-uremic patients
Clin Nephrol
Alteration in plasma antioxidant capacity in various degrees of chronic renal failure
Clin Nephrol
Contribution of increased HMG-CoA reductase gene expression to hypercholesterolemia in experimental chronic renal failure
Mol Cell Biochem
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Impact of elderly gastrointestinal alterations on in vitro digestion of salmon, sardine, sea bass and hake: Proteolysis, lipolysisand bioaccesibilityt of calcium and vitamins
2020, Food ChemistryCitation Excerpt :Since fat digestion seems not to be affected by elderly gastrointestinal conditions, health problems like dyslipidemia could be associated to an imbalance between the recruitment of lipid substrates and the capacity of their subsequent oxidation by lipid metabolism (Toth & Tchernof, 2000). This condition is well common in older individuals and is characterized by increased triglyceride levels, small high dense LDL, and a low concentration of HDL is being noted in older adults (Choudhury, Tuncel, & Levi, 2009). Moreover, the lower pancreatic enzymes and bile concentration, and alterations in the oral and gastric phase, may not be sufficient to cause an alteration over the extent of lipolysis.
Chaperone-mediated autophagy in the kidney: The road more traveled
2014, Seminars in NephrologyCitation Excerpt :However, the lipid profile of lysosomes from the fat-fed mice was similar to that seen in lysosomes from aging animals, in which reduced LAMP-2A also arose from increased instability of this receptor at the lysosomal membrane.2 Because lipid changes in the kidney are hallmarks of kidney dysfunction in diabetes and aging,62 these mechanisms may influence renal disease in these settings. Another major factor regulating CMA activity is the activity of other proteolytic pathways.
Association of remnant cholesterol with decreased kidney function or albuminuria: a population-based study in the U.S.
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