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Updated: Dec 6, 2025
Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
Slope of Kidney Function and Its Association with Longitudinal Mortality and Cardiovascular Disease among Individuals
Paula F Orlandi1,2, Dawei Xie3,2, Wei Yang3,2
1Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania paulaorlandi66@gmail.com.
Insights
Steep declines in estimated glomerular filtration rate (eGFR) increase risks of death and cardiovascular events in CKD patients. However, improving eGFR did not show increased risks, suggesting eGFR slopes are valuable for clinical assessment.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Geriatrics
Background:
- Estimated glomerular filtration rate (eGFR) decline is a known risk factor for adverse outcomes.
- A U-shaped association between eGFR slopes and risks of death and cardiovascular events has been suggested.
- Poor outcomes in individuals with rising eGFR may be linked to clinical deterioration indicators like sarcopenia.
Purpose of the Study:
- To investigate the association between eGFR slopes and risks of death or cardiovascular events.
- To account for multiple confounders in the relationship between eGFR trajectories and clinical outcomes.
- To assess the prognostic value of eGFR changes in patients with moderate to severe chronic kidney disease (CKD).
Main Methods:
- Studied 2738 individuals with moderate to severe CKD from the Chronic Renal Insufficiency Cohort (CRIC) Study.
- Employed linear mixed-effects models to estimate eGFR slopes using up to four annual assessments.
- Utilized Cox proportional hazards models to analyze the association between eGFR slopes and risks of death and cardiovascular events.
Main Results:
- eGFR slopes exhibited a bell-shaped distribution, with an average decline of -1.5 ml/min per 1.73 m² per year.
- Steeper declines in eGFR were progressively associated with increased risks of death (HR, 1.23) and cardiovascular events (HR, 1.19).
- No increased risks of death or cardiovascular events were observed with eGFR rises or declines less steep than average.
Conclusions:
- Steep eGFR declines are linked to increased risks of death and cardiovascular events in moderate to severe CKD.
- eGFR improvement was not associated with increased adverse outcomes.
- eGFR slopes may serve as a valuable tool for clinical risk assessment in adults with CKD.
Background:
Slopes of eGFR have been associated with increased risks of death and cardiovascular events in a U-shaped fashion. Poor outcomes in individuals with rising eGFR are potentially attributable to sarcopenia, hemodilution, and other indicators of clinical deterioration.
Methods:
To investigate the association between eGFR slopes and risks of death or cardiovascular events, accounting for multiple confounders, we studied 2738 individuals with moderate to severe CKD participating in the multicenter Chronic Renal Insufficiency Cohort (CRIC) Study. We used linear, mixed-effects models to estimate slopes with up to four annual eGFR assessments, and Cox proportional hazards models to investigate the association between slopes and the risks of death and cardiovascular events.
Results:
Slopes of eGFR had a bell-shaped distribution (mean [SD], -1.5 [-2] ml/min per 1.73 m2 per year). Declines of eGFR that were steeper than the average decline associated with progressively increasing risks of death (hazard ratio [HR], 1.23; 95% confidence interval [95% CI], 1.09 to 1.39; for a slope 1 SD below the average) and cardiovascular events (HR, 1.19; 95% CI, 1.03 to 1.38). Rises of eGFR or declines lower than the average decline were not associated with the risk of death or cardiovascular events.
Conclusions:
In a cohort of individuals with moderate to severe CKD, we observed steep declines of eGFR were associated with progressively increasing risks of death and cardiovascular events; however, we found no increased risks associated with eGFR improvement. These findings support the potential value of eGFR slopes in clinical assessment of adults with CKD.
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