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Assessment of Kidney Function in Mouse Models of Glomerular Disease
Published on: June 30, 2018
Outcomes and Risk Factors of Widened Difference in Estimated Glomerular Filtration Rate Based on Creatinine or
Min W Kang1, Jae-Ik Oh2, Jinsun Lee2
1Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea.
Insights
Discrepancies between cystatin C-based and creatinine-based estimated glomerular filtration rates (eGFRdiff) indicate higher risks for death, myocardial infarction, and stroke. An adjusted model using eGFRcr improved clinical outcome prediction.
Area of Science:
- Nephrology
- Cardiology
- Epidemiology
Background:
- Discrepancies between cystatin C-based (eGFRcys) and creatinine-based (eGFRcr) estimated glomerular filtration rates (eGFR) are clinically significant.
- Understanding the implications of these differences (eGFRdiff) is crucial for patient outcomes.
Purpose of the Study:
- To explore the clinical outcomes associated with eGFRdiff.
- To develop and validate an adjustment model using eGFRcr and clinical variables to approximate eGFRcys.
Main Methods:
- Retrospective cohort study of 343,854 UK Biobank participants.
- Analysis of risks for death, myocardial infarction (MI), and ischemic stroke based on eGFRdiff categories (< -15, -15 to 15, > 15).
- Development and validation of a regression model using eGFRcr and associated clinical variables to approximate eGFRcys.
Main Results:
- Individuals with eGFRdiff < -15 showed increased risks of death (HR, 1.37), MI (HR, 1.23), and ischemic stroke (HR, 1.19).
- Factors associated with eGFRdiff < -15 included obesity, high intake of fats/carbohydrates, low protein intake, diabetes, and smaller kidney volumes.
- A simplified regression model using eGFRcr, sex, age, height, weight, and BMI significantly improved correlation with eGFRcys and enhanced clinical outcome prediction.
Conclusions:
- eGFRdiff < -15 is linked to elevated risks of adverse clinical outcomes.
- Diverse clinical and lifestyle factors are associated with significant eGFRdiff.
- An adjusted model approximating eGFRcys using eGFRcr and basic clinical data offers superior prediction of clinical outcomes.
Rationale & Objective:
Recent studies have highlighted the clinical significance of the discrepancies between cystatin C--based CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) estimated glomerular filtration rate (eGFR) (eGFRcys) and creatinine-based CKD-EPI eGFR (eGFRcr). This study explores the implications of the differences between eGFRcys and eGFRcr (eGFRdiff) on clinical outcomes and aims to develop an adjustment model using eGFRcr and associated clinical variables.
Study Design:
Retrospective cohort study.
Setting & Participants:
A total of 343,854 UK Biobank participants.
Exposure:
eGFRdiff (mL/min/1.73 m2): lower (eGFRcys - eGFRcr < -15), middle (-15 ≤ eGFRcys - eGFRcr ≤ 15), and upper (eGFRcys - eGFRcr > 15).
Outcome:
Death, myocardial infarction (MI), and ischemic stroke.
Analytical Approach:
We analyzed the risks of death, MI, and ischemic stroke in groups with eGFRdiff < -15 and eGFRdiff > 15 using Cox proportional hazards models. Logistic regression analysis was used to identify variables associated with eGFRdiff. In addition, we developed and validated a regression model using eGFRcr and variables associated with eGFRdiff to approximate eGFR with optimal performance.
Results:
Individuals with eGFRdiff < -15 were associated with increased risks of death (HR, 1.37 [1.30-1.44]), MI (HR, 1.23 [1.15-1.33]), and ischemic stroke (HR, 1.19 [1.08-1.31]). Variables associated with eGFRdiff < -15 included high waist/hip circumference, high body weight, low fat-free mass, high fat/carbohydrate intake, low protein intake, diabetes, and smaller kidney volumes. A simplified regression model approximating eGFRcys was developed, using only eGFRcr, sex, age, height, weight, and body mass index. In the validation, applying the simplified linear model to eGFRcr significantly enhanced its correlation with eGFRcys and improved clinical outcome prediction, as demonstrated by favorable net reclassification indices for death, MI, and ischemic stroke.
Limitations:
The absence of true GFR data.
Conclusions:
This study confirmed that eGFRdiff < -15 is associated with increased risks of clinical outcomes and identified diverse factors associated with eGFRdiff. We developed an adjusted model to approximate eGFRcr to eGFRcys, demonstrating superior clinical outcome association using the adjusted values.
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