Elsevier

Seminars in Nephrology

Volume 29, Issue 6, November 2009, Pages 610-620
Seminars in Nephrology

Disorders of Lipid Metabolism and Chronic Kidney Disease in the Elderly

https://doi.org/10.1016/j.semnephrol.2009.07.006Get rights and content

Summary

The growing population of elderly with chronic kidney disease (CKD) is at greater risk for cardiovascular disease given an independent risk of CKD, as well as from added dyslipidemia of aging and renal dysfunction. Changes in lipid metabolism with more isodense and high-dense, triglyceride-rich particles, low high-density lipoprotein cholesterol, and increased triglyceride levels occur with CKD and aging, which are noted to have significant atherogenic potential. In addition, lipid abnormalities may lead to the progression of CKD. Cardiovascular mortality in the end-stage renal disease population is more than 10 times higher than the general population. Treatment of dyslipidemia in the general population suggests important benefits both in reducing cardiovascular risk and in the prevention of cardiovascular disease. Secondary analyses of elderly subgroups of various large prospective studies with statins suggest treatment benefit with statin use in the elderly. Similarly limited data from secondary analyses of CKD subgroups of larger prospective trials using statins also suggest a possible benefit in cardiovascular outcomes and the progression of kidney disease. However, randomized trials have yet to confirm similar benefits and targets of treatment for dyslipidemia in the elderly with CKD and end-stage renal disease. Treatment in the elderly with CKD should be individualized and outweigh risks of side effects and drug–drug interactions. There is a need for further specific investigation of dyslipidemia of CKD in the aging population in relation to renal disease progression and cardiovascular outcome.

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

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