The relationship between nontraditional risk factors and outcomes in individuals with stage 3 to 4 CKD

Am J Kidney Dis. 2008 Feb;51(2):212-23. doi: 10.1053/j.ajkd.2007.10.035.


Background: Chronic kidney disease is associated with increased risk for cardiovascular disease and mortality. Both traditional and nontraditional cardiovascular disease risk factors may contribute.

Study design: Cohort.

Settings & participants: Community-based adult population of the Atherosclerosis Risk in Communities and Cardiovascular Health Studies with estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m(2).

Predictors: Nontraditional cardiovascular disease risk factors, including body mass index, diastolic blood pressure, and triglyceride, albumin, uric acid, fibrinogen, C-reactive protein, and hemoglobin levels.

Outcomes: Composite of myocardial infarction, stroke, and all-cause mortality. Secondary outcomes included individual components of the composite.

Results: Of 1,678 individuals with decreased eGFR (mean, 51.1 +/- 8.5 mL/min/1.73 m(2)), 891 (53%) reached the composite end point during a median follow-up of 108 months; 23% had a cardiac event, 45% died, and 14% experienced a stroke. Serum albumin level less than 3.9 g/dL (hazard ratio, 0.68 for every 0.3-g/dL decrease; 95% confidence interval, 0.60 to 0.77), increased serum triglyceride level (hazard ratio, 1.07 for every 50-mg/dL increase; 95% confidence interval, 1.02 to 1.12), C-reactive protein level (hazard ratio, 1.15 per log-unit increase; 95% confidence interval, 1.07 to 1.24), and fibrinogen level (hazard ratio, 1.12 per 50-mg/dL increase; 95% confidence interval, 1.07 to 1.18) independently predicted composite events. Both decreased (<14.5 g/dL) and increased (>14.5 g/dL) hemoglobin levels predicted composite events. Serum albumin level less than 3.9 g/dL and increased serum fibrinogen level independently predicted cardiac events. For serum albumin and hemoglobin levels, the relationship with composite and mortality outcomes was nonlinear (P < 0.001).

Limitations: Single assessment of eGFR. No albuminuria data.

Conclusions: Several nontraditional cardiovascular disease risk factors predict adverse outcomes in individuals with stage 3 to 4 chronic kidney disease. The relationship between risk factors and outcomes is often nonlinear.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Biomarkers / blood
  • Blood Pressure
  • Body Mass Index
  • C-Reactive Protein / metabolism
  • Cohort Studies
  • Female
  • Fibrinogen / metabolism
  • Hemoglobins / metabolism
  • Humans
  • Male
  • Middle Aged
  • Odds Ratio
  • Predictive Value of Tests
  • Renal Insufficiency, Chronic / blood
  • Renal Insufficiency, Chronic / etiology*
  • Renal Insufficiency, Chronic / physiopathology*
  • Risk Factors
  • Serum Albumin / metabolism
  • Severity of Illness Index
  • Triglycerides / blood
  • Uric Acid / blood


  • Biomarkers
  • Hemoglobins
  • Serum Albumin
  • Triglycerides
  • Uric Acid
  • Fibrinogen
  • C-Reactive Protein