Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure

Kidney Int. 1999 May;55(5):1899-911. doi: 10.1046/j.1523-1755.1999.00422.x.

Abstract

Background: Atherosclerotic cardiovascular disease and malnutrition are widely recognized as leading causes of the increased morbidity and mortality observed in uremic patients. C-reactive protein (CRP), an acute-phase protein, is a predictor of cardiovascular mortality in nonrenal patient populations. In chronic renal failure (CRF), the prevalence of an acute-phase response has been associated with an increased mortality.

Methods: One hundred and nine predialysis patients (age 52 +/- 1 years) with terminal CRF (glomerular filtration rate 7 +/- 1 ml/min) were studied. By using noninvasive B-mode ultrasonography, the cross-sectional carotid intima-media area was calculated, and the presence or absence of carotid plaques was determined. Nutritional status was assessed by subjective global assessment (SGA), dual-energy x-ray absorptiometry (DXA), serum albumin, serum creatinine, serum urea, and 24-hour urine urea excretion. The presence of an inflammatory reaction was assessed by CRP, fibrinogen (N = 46), and tumor necrosis factor-alpha (TNF-alpha; N = 87). Lipid parameters, including Lp(a) and apo(a)-isoforms, as well as markers of oxidative stress (autoantibodies against oxidized low-density lipoprotein and vitamin E), were also determined.

Results: Compared with healthy controls, CRF patients had an increased mean carotid intima-media area (18.3 +/- 0.6 vs. 13.2 +/- 0.7 mm2, P < 0.0001) and a higher prevalence of carotid plaques (72 vs. 32%, P = 0.001). The prevalence of malnutrition (SGA 2 to 4) was 44%, and 32% of all patients had an acute-phase response (CRP > or = 10 mg/liter). Malnourished patients had higher CRP levels (23 +/- 3 vs. 13 +/- 2 mg/liter, P < 0.01), elevated calculated intima-media area (20.2 +/- 0.8 vs. 16.9 +/- 0.7 mm2, P < 0.01) and a higher prevalence of carotid plaques (90 vs. 60%, P < 0.0001) compared with well-nourished patients. During stepwise multivariate analysis adjusting for age and gender, vitamin E (P < 0.05) and CRP (P < 0.05) remained associated with an increased intima-media area. The presence of carotid plaques was significantly associated with age (P < 0.001), log oxidized low-density lipoprotein (oxLDL; P < 0.01), and small apo(a) isoform size (P < 0.05) in a multivariate logistic regression model.

Conclusion: These results indicate that the rapidly developing atherosclerosis in advanced CRF appears to be caused by a synergism of different mechanisms, such as malnutrition, inflammation, oxidative stress, and genetic components. Apart from classic risk factors, low vitamin E levels and elevated CRP levels are associated with an increased intima-media area, whereas small molecular weight apo(a) isoforms and increased levels of oxLDL are associated with the presence of carotid plaques.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorptiometry, Photon
  • Aged
  • Apolipoproteins A / blood
  • Arteriosclerosis / diagnostic imaging
  • Arteriosclerosis / epidemiology*
  • Arteriosclerosis / immunology
  • Autoantibodies / blood
  • Biomarkers
  • C-Reactive Protein / analysis
  • Carotid Arteries / diagnostic imaging
  • Carotid Arteries / pathology
  • Cross-Sectional Studies
  • Female
  • Fibrinogen / analysis
  • Humans
  • Hyperlipidemias / epidemiology
  • Hyperlipidemias / immunology
  • Inflammation / epidemiology*
  • Inflammation / immunology
  • Kidney Failure, Chronic / epidemiology*
  • Kidney Failure, Chronic / immunology
  • Lipoprotein(a) / blood
  • Lipoproteins, LDL / blood
  • Male
  • Middle Aged
  • Nutrition Assessment
  • Oxidative Stress
  • Prevalence
  • Protein-Energy Malnutrition / epidemiology*
  • Protein-Energy Malnutrition / immunology
  • Regression Analysis
  • Risk Factors
  • Tumor Necrosis Factor-alpha / analysis
  • Tunica Intima / pathology
  • Ultrasonography
  • Vitamin E / blood

Substances

  • Apolipoproteins A
  • Autoantibodies
  • Biomarkers
  • Lipoprotein(a)
  • Lipoproteins, LDL
  • Tumor Necrosis Factor-alpha
  • oxidized low density lipoprotein
  • Vitamin E
  • Fibrinogen
  • C-Reactive Protein