"Obesity and Chronic Kidney Disease"

Copyright © 2008 Society for Heart Attack Prevention and Eradication. All Rights Reserved.

Obesity and Chronic Kidney Disease

• Over 60 million US adults are obese Obesity is associated with cardiovascular disease risk

factors and kidney disease risk factors including diabetes and hypertension

Most epidemiologic studies in the US assess obesity using the body mass index (BMI)

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


Obesity and Chronic Kidney Disease

• Chronic Kidney Disease (CKD) is associated with decreased muscle mass In a patient with CKD, BMI is affected by fat or muscle

mass and fluid status 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

Therefore, BMI might not be the ideal anthropometric measurement for assessing obesity in patients with CKD


What is Chronic Kidney Disease

1) Kidney damage for 3 or more months Most commonly manifest with albuminuria/proteinuria

and/or

2) Decreased kidney function for 3 or more months Glomerular filtration rate (GFR) <60 mL/min/1.73m2 with or

without other damage

National Kidney Foundation. Am J Kidney Dis. 2002;39(2 suppl 1):S1-266.


Stage Description GFR Prevalence, n (%) Action Plan

-- Increased risk>60 with risk

factors-- Screening, risk reduction

1Kidney damage,

normal GFR>90 3,600,000 (1.8)

Diagnosis, treat comorbidities, slow

progression

2Kidney damage,

GFR reduced60-89 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

USRDS 2008, JAMA 2007; Am J Kidney Dis. 2002;39(2 suppl 1):S1-266.

CLASSIFICATION OF AND ACTION PLAN FOR CKD


Obesity in the US

Prevalence of BMI >30 kg/m2


Incidence of ESRD in the US (per million people)

USRDS 2007 Annual Data Report Am J Kidney Dis 51 (1 Suppl 1), 2008


Complications of CKD

• Progression to kidney failure/ESRD• Complications associated with low GFR

Anemia Bone and Mineral Disorder Cardiovascular disease


Incidence of Cardiovascular Disease Events by Level of Kidney Function

0

1

2

3

4

5

6

7

>60 45-59 30-44 15-29 <15

eGFR (mL/min/1.73m2)

Ad

just

ed H

azar

d R

atio

Mortality

CVD Event

Hospitalization

Go AS, et al. N Engl J Med. 2004;351(13):1296-1305.


Assessing Obesity

• BMI highly correlated with subcutaneous fat area but poor correlation with visceral fat area in CKD (0.76 in women and 0.68 in men)*

• Increased WHR may reflect both an increase in visceral fat and a relative lack of gluteal muscle

• WHR differentiates between android (abdominal) and gynoid (buttock) obesity

*Sanches et al. Am J Kidney Dis 52: 66-73, 2008


WHR and BMI as Risk Factors for Cardiovascular Events in CKD

• Data pooled from two community-based, longitudinal studies evaluating cardiovascular risk: Atherosclerosis Risk in Communities (ARIC) Cardiovascular Health Study (CHS)

• Study Outcomes: Primary outcome: cardiac events (composite of

myocardial infarction and fatal coronary disease) Secondary outcomes: composite of stroke, cardiac

events and death

Elsayed et al. Am J Kidney Dis 52: 49-57, 2008


Study Sample

ARICn=15,792

CHSn=5,888

Initial PopulationN=21,680

Eligible Populationn=21,246

Missing baseline eGFRn=329

Baseline eGFR <15n=27

Baseline eGFR >=60n=19,577

Final PopulationeGFR 15-60

n=1,669

-

- -


Methods

• Predictor Variables: Waist-to-Hip Ratio Body Mass Index

• Statistical Methods: WHR and BMI were examined as continuous variables

and as categorical variables:• WHR in three sex-specific tertiles to match distribution

frequency of BMI• BMI in a priori groups (<25, 25-30,>30 kg/m2)

• Cox regression models used for analyses Adjusting for age, sex, race, education, smoking,

alcohol, prior CVD, diabetes, hypertension, baseline GFR, cholesterol, albumin and study of origin


Results

• Baseline characteristics: Mean age of 70.3 years and 33.5% had baseline CVD Mean WHR was 0.97 in men and 0.90 in women Mean BMI was 27.2 +/- 4.6 in both men and women

• Pearson correlation between WHR and BMI was 0.31 49% of participants were in the same classification

group


Baseline Characteristics


Results

• 334 (20.6%) cardiac events and 775 (46.5%) composite events occurred over 9.3 years

• Univariate results for WHR: HR = 1.53 (1.33-1.76) per 0.1 increase for cardiac

events HR = 1.32 (1.21-1.45) per 0.1 increase for composite

events

• Univariate results for BMI HR = 0.99 (0.97-1.01) per 1 kg/m2 increase for

cardiac events HR = 0.92 (0.88-0.97) per 1 kg/m2 increase for

composite events


Results of Continuous Models

• In multivariable models, WHR showed a trend toward increased risk of cardiac events but no relationship with composite outcomes in continuous models HR = 1.16 (0.99-1.35) per 0.1 increase for cardiac

events

• Higher BMI was not associated with outcomesModel

HazardRatio

CI

WHR

Univariate 1.53 1.33-1.76

Multivariate 1.16 0.99- 1.35

BMI

Univariate 0.99 0.97-1.01

Multivariate 1.00 0.97-1.02

Table. Hazard ratios associated with measures for cardiac outcomes


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



Survival Plots for the Cardiac Outcome


Sensitivity Analyses

1) 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]

2) No significant interaction between WHR and CKD


Conclusions

• WHR, but not BMI, is associated with cardiac events in persons with CKD

• Relying exclusively on BMI may underestimate the importance of obesity as a cardiovascular disease risk factor in persons with CKD

• WHR is relatively easy to obtain and appears to impart clinically useful information regarding risk of CVD in patients with CKD

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"Obesity and Chronic Kidney Disease"