Related Experiment Video
Updated: May 18, 2026

Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
Utility of Risk Scores for Predicting Stroke and Intracranial Bleeding Across Levels of Kidney Function in Two Large
Nisha Bansal1, Grace H Tabada2, Yuguang Kang3
1Kidney Research Institute, Division of Nephrology, University of Washington, Seattle, Washington.
Insights
Clinical risk scores for stroke and bleeding in atrial fibrillation (AF) patients with chronic kidney disease (CKD) show modest performance, especially in advanced CKD. New, more accurate risk prediction models are needed for better clinical decision-making.
Area of Science:
- Nephrology and Cardiology
- Clinical Risk Prediction Modeling
- Atrial Fibrillation Management
Background:
- Established clinical risk prediction scores for ischemic stroke and bleeding have not been well validated in patients with chronic kidney disease (CKD) and atrial fibrillation (AF).
- Kidney function significantly impacts cardiovascular risk, yet its influence on the performance of standard risk scores in AF patients is not fully understood.
Purpose of the Study:
- To evaluate the performance of commonly used clinical risk prediction scores for ischemic stroke and intracranial bleeding in patients with AF across a wide spectrum of kidney function.
- To assess how varying levels of estimated glomerular filtration rate (eGFR) affect the discrimination and calibration of these risk scores.
Main Methods:
- Retrospective analysis of two large, community-based cohorts of adult patients with incident AF (Kaiser Permanente and Ontario, Canada).
- Calculation of ischemic stroke risk scores (ATRIA, CHA₂DS₂-VASc, R₂CHADS₂) and a major bleeding risk score (HAS-BLED) stratified by eGFR categories (≥60, 45-59, 30-44, <30 mL/min/1.73 m²).
- Evaluation of model performance using C-statistics for discrimination and calibration plots for accuracy within each eGFR stratum.
Main Results:
- Mean stroke and bleeding risk scores were higher in patients with lower eGFR levels.
- Discrimination (C-statistics) for all evaluated stroke risk scores (ATRIA, CHA₂DS₂-VASc, R₂CHADS₂) and the HAS-BLED bleeding score was significantly lower in patients with eGFR <60 mL/min/1.73 m² compared to those with eGFR ≥60 mL/min/1.73 m².
- The R₂CHADS₂ score demonstrated the lowest discrimination for ischemic stroke (C-statistic 0.57 in eGFR <30 category), and HAS-BLED showed low discrimination for intracranial bleeding (range 0.51-0.56) in lower eGFR groups. Calibration varied across scores and eGFR levels.
Conclusions:
- Current clinical risk prediction scores for stroke and bleeding exhibit modest performance in AF patients with CKD, particularly in those with advanced kidney disease.
- The pathophysiological complexities associated with CKD limit the accuracy of existing risk scores developed for the general AF population.
- There is a critical need for the development of novel, kidney-specific risk models to improve anticoagulation strategies and clinical decision-making in AF patients with CKD.
Rationale & Objective:
The performance of clinical risk prediction scores for ischemic stroke and bleeding are not well established in those with chronic kidney disease (CKD) and atrial fibrillation (AF). We evaluated the performance of 3 risk scores for ischemic stroke and intracranial bleeding in patients across a broad range of kidney function.
Study Design:
Retrospective study.
Setting & Participants:
Two community-based cohorts of adults with incident AF (Kaiser Permanente and Ontario, Canada).
Exposure:
Baseline estimated glomerular filtration rate (eGFR) was calculated using outpatient serum creatinine measures, excluding those with a kidney transplant or receiving dialysis.
Outcome:
Three risk scores for ischemic stroke (ATRIA, CHA2DS2-VASc, and R2CHADS2) and 1 for major bleeding (HAS-BLED) were calculated across eGFR categories (≥60, 45-59, 30-44, and <30 mL/min/1.73 m2). Outcomes included ischemic stroke and intracranial hemorrhage.
Analytical Approach:
C-statistics were calculated and calibration plots generated within eGFR strata.
Results:
There were 101,360 adults with incident AF in the Kaiser Permanente cohort and 33,200 adults with incident AF in the Ontario cohort. The mean risk scores for stroke and bleeding were higher with lower eGFR across all 4 measures. The c-statistics for the stroke prediction scores were lower in those with an eGFR < 60 mL/min/1.73 m2 compared with eGFR ≥ 60 mL/min/1.73 m2 in both cohorts. The lowest discrimination for ischemic stroke was seen with the R2CHADS2 risk score (ranging from 0.53-0.61) with a C statistic of 0.57 for the eGFR < 30 mL/min/1.73 m2 category in both cohorts. The C statistic for ATRIA (range, 0.59-0.64) and CHA2DS2-VASc (range, 0.55-0.61) were also modest across lower eGFR categories compared with eGFR > 60 mL/min/1.73 m2. The discrimination for the HAS-BLED bleeding risk score for intracranial bleeding was also low in those with lower eGFR categories (ranging from 0.51 to 0.56). Calibration varied by risk score and eGFR level.
Limitations:
Observational study.
Conclusions:
Performance of clinically used stroke and bleeding risk prediction scores was modest among those with CKD, particularly at advanced CKD. More accurate risk scores are needed to improve decision making.
Plain-Language Summary:
This retrospective analysis evaluated the predictive accuracy of standard clinical risk scores for ischemic stroke (ATRIA, CHA2DS2-VASc, and R2CHADS2) and intracranial hemorrhage (HAS-BLED) in patients with atrial fibrillation (AF) and varying degrees of kidney function. Using data from 2 large cohorts, Kaiser Permanente and an Ontario-based registry, the study focused on how baseline estimated glomerular filtration rate (eGFR) influenced the discrimination and calibration of these models. The study revealed a significant inverse relationship between kidney function and model reliability. While mean risk scores were higher in patients with lower eGFR, the C statistic and calibration decreased significantly in more advanced stages of kidney disease. The results suggest that the pathophysiological complexities of advanced kidney disease limit the utility of tools to predict stroke and bleeding designed for the general population with AF. Development of kidney-specific risk models is needed to better inform anticoagulation strategies and clinical decision making.
Related Concept Videos
Imaging Studies for Cardiovascular System VI: Calcium -Scoring CT
Drug Dosing in Renal Diseases: Estimation of Glomerular Filtration Rate Based on Serum Creatinine Concentration
Acute Kidney Injury IV: Diagnostic Studies and Prevention
Factors Affecting Renal Clearance: Renal Impairment
One condition associated with renal failure is uremia. Uremia is characterized by impaired glomerular filtration and fluid accumulation in the body. This condition hinders the renal clearance of drugs, resulting in drug accumulation and potential...
Pharmacokinetics in Geriatric Patients: Effect of Age on Drug Excretion
Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches
Non-controlled studies, commonly employed for initial exploration, lack a control group, rendering them susceptible to biases and external influences. In contrast, controlled...