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Modification of Association of Cystatin C With Kidney and Cardiovascular Outcomes by Obesity
Debbie C Chen1, Rebecca Scherzer2, Joachim H Ix3
1Division of Nephrology, Department of Medicine, University of California at San Francisco, San Francisco; Kidney Health Research Collaborative, San Francisco VA Medical Center & University of California, San Francisco; Genentech, Inc., South San Francisco.
Insights
Obesity does not alter the association between cystatin C-based estimated glomerular filtration rate (eGFRcys) and adverse outcomes like mortality or kidney failure. Cystatin C can help predict risks in individuals with obesity.
Area of Science:
- Nephrology
- Cardiology
- Obesity Medicine
Background:
- Cystatin C-based estimated glomerular filtration rate (eGFRcys) is increasingly used for risk assessment, potentially offering stronger associations with adverse outcomes than creatinine-based eGFR (eGFRcr).
- Obesity may independently influence cystatin C levels, raising questions about its impact on the predictive power of eGFRcys for clinical outcomes.
Purpose of the Study:
- To investigate whether obesity, measured by body mass index (BMI) and waist circumference, modifies the association between eGFRcys and risks of all-cause mortality, kidney failure, atherosclerotic cardiovascular disease (ASCVD), and heart failure (HF).
Main Methods:
- A cohort study of 27,249 US adults from the Reasons for Geographic and Racial Differences in Stroke Study.
- Utilized multivariable Cox and Fine-Gray models with interaction terms to assess the influence of BMI categories and waist circumference quartiles on eGFRcys-outcome associations.
Main Results:
- Each 15 mL/min/1.73 m2 decrease in eGFRcys was associated with increased mortality risk across all waist circumference quartiles and BMI categories.
- No significant modification of the association between eGFRcys and mortality, kidney failure, incident ASCVD, or incident HF was observed based on obesity status (all Pinteraction > 0.05).
Conclusions:
- Obesity does not modify the prognostic value of eGFRcys for adverse kidney and cardiovascular outcomes.
- Cystatin C can be reliably used for risk prognostication in individuals with obesity, irrespective of their weight status.
Rationale & Objective:
Cystatin C-based estimated glomerular filtration rate (eGFRcys) has stronger associations with adverse clinical outcomes than creatinine-based eGFR (eGFRcr). Obesity may be associated with higher cystatin C levels, independent of kidney function, but it is unknown whether obesity modifies associations of eGFRcys with kidney and cardiovascular outcomes.
Study Design:
Cohort study.
Setting & Participants:
27,249 US adults in the Reasons for Geographic and Racial Differences in Stroke Study.
Predictors:
eGFRcys, eGFRcr, waist circumference, and body mass index (BMI).
Outcome:
All-cause mortality, kidney failure, incident atherosclerotic cardiovascular disease (ASCVD), and incident heart failure (HF).
Analytical Approach:
Multivariable Cox and Fine-Gray models with multiplicative interaction terms were constructed to investigate whether waist circumference quartiles or BMI categories modified associations of eGFRcys with risks of 4 clinical outcomes.
Results:
Participants had a mean age of 65 years; 54% were women, 41% were Black, and 21% had an eGFRcys<60mL/min/1.73m2. The baseline prevalence of abdominal obesity (waist circumference≥88cm for women or≥102cm for men) was 48% and obesity was 38%. In multivariable adjusted analyses, each 15mL/min/1.73m2 lower eGFRcys was associated with higher HR and 95% CI of mortality in each waist circumference quartile (first quartile, 1.19 [1.15-1.24]; second quartile, 1.22 [1.18-1.26]; third quartile, 1.20 [1.16-1.24]; fourth quartile, 1.19 [1.15-1.23]) as well as within each BMI category (BMI<24.9: 1.21 [1.17-1.25]; BMI 25.0-29.9: 1.21 [1.18-1.25]; BMI 30.0-34.9: 1.20 [1.16-1.25]; BMI≥35: 1.17, [1.12-1.22]). Neither waist circumference nor BMI modified the association of eGFRcys with mortality, kidney failure, incident ASCVD, or incident HF (all Pinteraction>0.05).
Limitations:
Included only Black and White persons in the United States.
Conclusion:
Obesity did not modify the association of eGFRcys with all-cause mortality, kidney failure, incident ASCVD, or incident HF. Among individuals with obesity, cystatin C may be used to provide eGFR-based risk prognostication for adverse outcomes.
Plain-Language Summary:
Cystatin C is increasingly used in clinical practice to estimate kidney function, and cystatin C-based eGFR (eGFRcys) may be used to determine risk for adverse clinical outcomes. Adiposity may increase serum levels of cystatin C, independent of kidney function. This cohort study investigated whether associations of eGFRcys with adverse kidney and cardiovascular outcomes are modified by measures of obesity, waist circumference, and body mass index. We found that obesity does not modify associations of eGFRcys with 4 clinical outcomes and conclude that among individuals with obesity, cystatin C may be used to provide eGFR-based risk prognostication for adverse outcomes.
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