"Obesity and Chronic Kidney Disease"


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"Obesity and Chronic Kidney Disease"

  1. 1. Obesity and Chronic Kidney Disease <ul><li>Over 60 million US adults are obese </li></ul><ul><ul><li>Obesity is associated with cardiovascular disease risk factors and kidney disease risk factors including diabetes and hypertension </li></ul></ul><ul><ul><li>Most epidemiologic studies in the US assess obesity using the body mass index (BMI) </li></ul></ul><ul><ul><li>Waist-to-Hip Ratio (WHR) is an alternate measure of obesity that is less influenced by muscle mass and may be a better marker of obesity in some populations </li></ul></ul>
  2. 2. Obesity and Chronic Kidney Disease <ul><li>Chronic Kidney Disease (CKD) is associated with decreased muscle mass </li></ul><ul><ul><li>In a patient with CKD, BMI is affected by fat or muscle mass and fluid status </li></ul></ul><ul><ul><li>Therefore in a patient with CKD, lower BMI may reflect decreased fat (mostly subcutaneous) or decreased muscle mass, and the ultimate effect of BMI on outcomes will depend on the relative contributions of each as well as the amount of visceral fat </li></ul></ul><ul><ul><li>Therefore, BMI might not be the ideal anthropometric measurement for assessing obesity in patients with CKD </li></ul></ul>
  3. 3. What is Chronic Kidney Disease <ul><li>1) Kidney damage for 3 or more months </li></ul><ul><ul><li>Most commonly manifest with albuminuria/proteinuria </li></ul></ul><ul><ul><li>and/or </li></ul></ul><ul><li>2) Decreased kidney function for 3 or more months </li></ul><ul><ul><li>Glomerular filtration rate (GFR) <60 mL/min/1.73m 2 with or without other damage </li></ul></ul>National Kidney Foundation. Am J Kidney Dis . 2002;39(2 suppl 1):S1-266.
  4. 4. USRDS 2008, JAMA 2007; Am J Kidney Dis. 2002;39(2 suppl 1):S1-266. CLASSIFICATION OF AND ACTION PLAN FOR CKD Stage Description GFR Prevalence, n (%) Action Plan -- Increased risk > 60 with risk factors -- Screening, risk reduction 1 Kidney damage, normal GFR > 90 3,600,000 (1.8) Diagnosis, treat comorbidities, slow progression 2 Kidney damage, GFR reduced 60-89 6,500,000 (3.2) Assess progression 3 Moderate CKD 30-59 15,500,000 (7.7) Evaluate and treat complications 4 Severe CKD 15-29 700,000 (0.4) Prepare for kidney replacement therapy 5 Kidney Failure <15 or dialysis 500,000 (0.2) Kidney replacement therapy
  5. 5. Obesity in the US Prevalence of BMI > 30 kg/m 2
  6. 6. Incidence of ESRD in the US (per million people) USRDS 2007 Annual Data Report Am J Kidney Dis 51 (1 Suppl 1), 2008
  7. 7. Complications of CKD <ul><li>Progression to kidney failure/ESRD </li></ul><ul><li>Complications associated with low GFR </li></ul><ul><ul><li>Anemia </li></ul></ul><ul><ul><li>Bone and Mineral Disorder </li></ul></ul><ul><ul><li>Cardiovascular disease </li></ul></ul>
  8. 8. Incidence of Cardiovascular Disease Events by Level of Kidney Function Go AS, et al. N Engl J Med . 2004;351(13):1296-1305.
  9. 9. Assessing Obesity <ul><li>BMI highly correlated with subcutaneous fat area but poor correlation with visceral fat area in CKD </li></ul><ul><ul><li>(0.76 in women and 0.68 in men)* </li></ul></ul><ul><li>Increased WHR may reflect both an increase in visceral fat and a relative lack of gluteal muscle </li></ul><ul><li>WHR differentiates between android (abdominal) and gynoid (buttock) obesity </li></ul>*Sanches et al. Am J Kidney Dis 52: 66-73, 2008
  10. 10. WHR and BMI as Risk Factors for Cardiovascular Events in CKD <ul><li>Data pooled from two community-based, longitudinal studies evaluating cardiovascular risk: </li></ul><ul><ul><li>Atherosclerosis Risk in Communities (ARIC) </li></ul></ul><ul><ul><li>Cardiovascular Health Study (CHS) </li></ul></ul><ul><li>Study Outcomes: </li></ul><ul><ul><li>Primary outcome: cardiac events (composite of myocardial infarction and fatal coronary disease) </li></ul></ul><ul><ul><li>Secondary outcomes: composite of stroke, cardiac events and death </li></ul></ul>Elsayed et al. Am J Kidney Dis 52: 49-57, 2008
  11. 11. Study Sample ARIC n=15,792 CHS n=5,888 Initial Population N=21,680 Eligible Population n=21,246 Missing baseline eGFR n=329 Baseline eGFR <15 n=27 Baseline eGFR >=60 n=19,577 Final Population eGFR 15-60 n=1,669 - - -
  12. 12. Methods <ul><li>Predictor Variables: </li></ul><ul><ul><li>Waist-to-Hip Ratio </li></ul></ul><ul><ul><li>Body Mass Index </li></ul></ul><ul><li>Statistical Methods: </li></ul><ul><ul><li>WHR and BMI were examined as continuous variables and as categorical variables: </li></ul></ul><ul><ul><ul><li>WHR in three sex-specific tertiles to match distribution frequency of BMI </li></ul></ul></ul><ul><ul><ul><li>BMI in a priori groups (<25, 25-30, > 30 kg/m 2 ) </li></ul></ul></ul><ul><li>Cox regression models used for analyses </li></ul><ul><ul><li>Adjusting for age, sex, race, education, smoking, alcohol, prior CVD, diabetes, hypertension, baseline GFR, cholesterol, albumin and study of origin </li></ul></ul>
  13. 13. Results <ul><li>Baseline characteristics: </li></ul><ul><ul><li>Mean age of 70.3 years and 33.5% had baseline CVD </li></ul></ul><ul><ul><li>Mean WHR was 0.97 in men and 0.90 in women </li></ul></ul><ul><ul><li>Mean BMI was 27.2 +/- 4.6 in both men and women </li></ul></ul><ul><li>Pearson correlation between WHR and BMI was 0.31 </li></ul><ul><ul><li>49% of participants were in the same classification group </li></ul></ul>
  14. 14. Baseline Characteristics
  15. 15. Results <ul><li>334 (20.6%) cardiac events and 775 (46.5%) composite events occurred over 9.3 years </li></ul><ul><li>Univariate results for WHR: </li></ul><ul><ul><li>HR = 1.53 (1.33-1.76) per 0.1 increase for cardiac events </li></ul></ul><ul><ul><li>HR = 1.32 (1.21-1.45) per 0.1 increase for composite events </li></ul></ul><ul><li>Univariate results for BMI </li></ul><ul><ul><li>HR = 0.99 (0.97-1.01) per 1 kg/m 2 increase for cardiac events </li></ul></ul><ul><ul><li>HR = 0.92 (0.88-0.97) per 1 kg/m 2 increase for composite events </li></ul></ul>
  16. 16. Results of Continuous Models <ul><li>In multivariable models, WHR showed a trend toward increased risk of cardiac events but no relationship with composite outcomes in continuous models </li></ul><ul><ul><li>HR = 1.16 (0.99-1.35) per 0.1 increase for cardiac events </li></ul></ul><ul><li>Higher BMI was not associated with outcomes </li></ul>Table. Hazard ratios associated with measures for cardiac outcomes 0.97-1.02 1.00 Multivariate 0.97-1.01 0.99 Univariate B M I 0.99- 1.35 1.16 Multivariate 1.33-1.76 1.53 Univariate W H R CI Hazard Ratio Model
  17. 17. Graphical presentation of the relationship between obesity measures and cardiac events Graphical presentation of restricted cubic splines of BMI and WHR on the log hazard of cardiac events in unadjusted models. P <0.0001 for the association between WHR and cardiac events and p=0.15 for the association between BMI and cardiac events
  18. 19. Survival Plots for the Cardiac Outcome
  19. 20. Sensitivity Analyses <ul><li>If hypertension, cholesterol level, and diabetes were removed from the multivariable model; WHR remained a significant risk for MI/Fatal CHD [HR 1.26 (95% CI: 1.08-1.47), p-value 0.004], while BMI remained a non-significant risk factor for MI/Fatal CHD [HR = 1.01 (95% CI: 0.99-1.04), p-value 0.3] </li></ul><ul><li>No significant interaction between WHR and CKD </li></ul>
  20. 21. Conclusions <ul><li>WHR, but not BMI, is associated with cardiac events in persons with CKD </li></ul><ul><li>Relying exclusively on BMI may underestimate the importance of obesity as a cardiovascular disease risk factor in persons with CKD </li></ul><ul><li>WHR is relatively easy to obtain and appears to impart clinically useful information regarding risk of CVD in patients with CKD </li></ul>