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Reasons for the lack of salutary effects of cholesterol-lowering interventions in end-stage renal disease populations.

ABSTRACT: Cardiovascular disease (CVD) is the main cause of premature death in patients with chronic kidney disease (CKD). The underlying mechanisms of CVD in patients with mild to moderate CKD are different from those with end-stage renal disease (ESRD). While serum cholesterol is frequently elevated and contributes to atherosclerosis in many CKD patients, particularly those with nephrotic proteinuria, it is usually normal, even subnormal, in most ESRD patients receiving hemodialysis. CVD in the ESRD population is primarily driven by oxidative stress, inflammation, accumulation of the oxidation-prone intermediate-density lipoproteins, chylomicron remnants and small dense low-density lipoprotein particles as well as high-density lipoprotein deficiency and dysfunction, hypertension, vascular calcification, and arrhythmias. Only a minority of hemodialysis patients have hypercholesterolemia which is most likely due to genetic or unrelated factors. In addition, due to peritoneal losses of proteins which simulate nephrotic syndrome, peritoneal dialysis patients often exhibit hypercholesterolemia. Clearly when present, hypercholesterolemia contributes to CVD in the CKD and ESRD population and justifies cholesterol-lowering therapy. However, the majority of ESRD patients and a subpopulation of CKD patients with minimal proteinuria have normal or subnormal serum cholesterol levels and do not benefit from and can be potentially harmed by statin therapy. In fact the lack of efficacy of statins in hemodialysis patients has been demonstrated in several randomized clinical trials. This review is intended to provide an overview of the mechanisms responsible for the failure of statins to reduce cardiovascular morbidity and mortality in most ESRD patients and to advocate the adoption of individualized care principles in the management of dyslipidemia in this population.

SUBMITTER: Vaziri ND

PROVIDER: S-EPMC3595172 | biostudies-other | 2013

REPOSITORIES: biostudies-other

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Reasons for the lack of salutary effects of cholesterol-lowering interventions in end-stage renal disease populations.

Vaziri Nosratola D ND Norris Keith C KC

Blood purification 20130122 1-3

Cardiovascular disease (CVD) is the main cause of premature death in patients with chronic kidney disease (CKD). The underlying mechanisms of CVD in patients with mild to moderate CKD are different from those with end-stage renal disease (ESRD). While serum cholesterol is frequently elevated and contributes to atherosclerosis in many CKD patients, particularly those with nephrotic proteinuria, it is usually normal, even subnormal, in most ESRD patients receiving hemodialysis. CVD in the ESRD pop ...[more]

PMID: 23343544

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Project description:OBJECTIVE:Serum albumin is a marker of malnutrition and inflammation and has been demonstrated as a strong predictor of mortality in chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. Yet, whether serum albumin levels in late-stage CKD are associated with adverse outcomes after the transition to ESRD is unknown. We hypothesize that lower levels and a decline in serum albumin in late-stage CKD are associated with higher risk of mortality and hospitalization rates 1 year after transition to ESRD. DESIGN AND METHODS:This retrospective cohort study included 29,124 US veterans with advanced CKD transitioning to ESRD between 2007 and 2015. We evaluated the association of pre-ESRD (91 days before transition) serum albumin with 12-month post-ESRD all-cause, cardiovascular, and infection-related mortalities and hospitalization rates as well as the association of 1-year pre-ESRD albumin slope and 12-month post-ESRD mortality using hierarchical multivariable adjustments. RESULTS:There was a negative linear association between serum albumin and all-cause mortality, such that risk doubled (hazard ratio [HR]: 2.07, 95% confidence interval [CI]: 1.87, 2.28) for patients with the lowest serum albumin <2.8 g/dL (ref: ?4.0 g/dL) after full adjustment. A consistent relationship was observed between serum albumin and cardiovascular and infection-related mortality, and hospitalization outcomes. An increase in serum albumin of >0.25 g/dL/year was associated with reduced mortality risk (HR: 0.76, 95% CI: 0.63, 0.91) compared with a slight decline in albumin (ref: >-0.25 to 0 g/dL/year), whereas a decline more than 0.5 g/dL/year was associated with a 55% higher risk in mortality (HR: 1.55, 95% CI: 1.43, 1.68) in fully adjusted models. CONCLUSIONS:Lower pre-ESRD serum albumin was associated with higher post-ESRD all-cause, cardiovascular, and infection-related mortalities and hospitalization rates. Declining serum albumin levels in the pre-ESRD period were also associated with worse 12-month post-ESRD mortality.

Project description:BackgroundPrevious studies have demonstrated that early pre-end-stage renal disease (ESRD) nephrology care could improve postdialysis prognosis. However, less is known about the specific types of interventions responsible for the improved outcomes. We hypothesized that more frequent predialysis laboratory testing is associated with better postdialysis outcomes in incident ESRD patients.MethodsIn all, 23?089 patients with available outpatient laboratory tests performed during the 2-year predialysis (i.e. prelude) period were identified from a total of 52?172 American veterans with chronic kidney disease (CKD) transitioning to dialysis between October 2007 and September 2011. The associations between the frequency of combined laboratory tests, including serum creatinine, serum potassium and hemoglobin (test trio), with postdialysis mortality and hospitalization were examined in multivariable adjusted Cox and logistic regression models.ResultsWhen entering the 2-year prelude period, the mean age (Standard Deviation) of the patients was 66.2 (SD 11.3)?years and the mean estimated glomerular filtration rate was 46.8 (SD 23.9)?mL/min/1.73 m2. In all, 14% of patients had the test trio performed less than twice in 24?months and 8.9% had the trio measured more often than every other month. Over a 2.5-year median postdialysis follow-up period, 15?303 (66.3%) patients died (mortality rate 260/1000 patient-years). The adjusted hazard ratio of all-cause mortality and adjusted odds ratio of the composite of hospitalization or death associated with lab testing done >12/24?months compared with 2-?4/24 months were 0.68 [95% confidence interval (CI) 0.65-0.73] and 0.70 (95% CI 0.62-0.79), respectively.ConclusionsMore frequent laboratory testing in patients with advanced CKD is associated with better clinical outcomes after dialysis. Further examination in clinical trials is needed before the implementation of more frequent laboratory testing in clinical practice.

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Reasons for the lack of salutary effects of cholesterol-lowering interventions in end-stage renal disease populations.

Publications

Reasons for the lack of salutary effects of cholesterol-lowering interventions in end-stage renal disease populations.

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