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

Peter Stenvinkel, Olof Heimbürger, Furcy Paultre, Ulf Diczfalusy, Tao Wang, Lars Berglund, Tomas Jogestrand

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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- α (TNF-α 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 ≥ 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.

Original languageEnglish (US)
Pages (from-to)1899-1911
Number of pages13
JournalKidney International
Volume55
Issue number5
DOIs
StatePublished - 1999
Externally publishedYes

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Keywords

  • Apo(a) isoforms
  • Atherosclerosis
  • Cardiovascular disease
  • Inflammation
  • Nutrition
  • Oxidative stress
  • Uremia

ASJC Scopus subject areas

  • Nephrology

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