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Discordance in Creatinine- and Cystatin C-Based eGFR and Clinical Outcomes: A Meta-Analysis
Michelle M Estrella1, Shoshana H Ballew2, Yingying Sang2
1Kidney Health Research Collaborative, University of California San Francisco and San Francisco Veterans Affairs Health Care System, San Francisco.
Insights
A significant percentage of patients show a large difference in estimated glomerular filtration rate (eGFR) when calculated using cystatin C versus creatinine. This eGFR discordance is linked to increased risks of mortality and kidney failure.
Area of Science:
- Nephrology
- Clinical Epidemiology
- Biomarker Research
Background:
- Estimated glomerular filtration rates (eGFRs) are crucial for assessing kidney function.
- Discrepancies exist between eGFR calculated using creatinine (eGFRcr) and cystatin C (eGFRcys).
- The clinical significance and prevalence of these eGFR differences are not well understood.
Purpose of the Study:
- To determine the prevalence of discordance between eGFRcys and eGFRcr.
- To identify patient characteristics associated with significant eGFR differences.
- To assess the association of eGFR discordance with adverse health outcomes.
Main Methods:
- Individual-level meta-analysis of data from the Chronic Kidney Disease Prognosis Consortium (CKD-PC).
- Inclusion of participants with concurrent cystatin C and creatinine measurements and outcome data.
- Definition of a large negative eGFR difference (eGFRdiff) as eGFRcys being at least 30% lower than eGFRcr.
Main Results:
- 11% of outpatients and 35% of inpatients exhibited a large negative eGFRdiff.
- In outpatients, a large negative eGFRdiff was associated with significantly higher rates of all-cause mortality (HR 1.69), cardiovascular mortality (HR 1.61), atherosclerotic cardiovascular disease (HR 1.35), heart failure (HR 1.54), and kidney failure (HR 1.29).
Conclusions:
- A substantial proportion of patients, particularly inpatients, demonstrate significant discordance between eGFRcys and eGFRcr.
- This eGFR discordance, specifically lower eGFRcys, is a significant predictor of adverse outcomes including mortality and kidney failure.
- The findings highlight the clinical importance of evaluating eGFR differences in patient risk stratification.
Importance:
Estimated glomerular filtration rates (eGFRs) can differ according to whether creatinine or cystatin C is used for the eGFR calculation, but the prevalence and importance of these differences remain unclear.
Objectives:
To evaluate the prevalence of a discordance between cystatin C-based eGFR (eGFRcys) and creatinine-based eGFR (eGFRcr), identify characteristics associated with greater discordance, and evaluate associations of discordance with adverse outcomes.
Data Sources:
Participants in the Chronic Kidney Disease Prognosis Consortium (CKD-PC).
Study Selection:
Participants with concurrent cystatin C and creatinine measurements and clinical outcome measurement.
Data Extraction And Synthesis:
Between April 2024 and August 2025, data were synthesized using individual-level meta-analysis.
Main Outcomes And Measures:
The primary independent measurement was a large negative eGFR difference (eGFRdiff), defined as an eGFRcys that was at least 30% lower than eGFRcr. Secondary (dependent) outcomes included all-cause and cardiovascular mortality, atherosclerotic cardiovascular disease, heart failure, and kidney failure with replacement therapy.
Results:
A total of 821 327 individuals from 23 outpatient cohorts (mean [SD] age, 59 [12] years; 48% female; 13.5% with diabetes; 40% with hypertension) and 39 639 individuals from 2 inpatient cohorts (mean [SD] age, 67 [16] years; 31% female; 30% with diabetes; 72% with hypertension) were included. Among outpatient participants, 11% had a large negative eGFRdiff (range, 3%-50%). Among inpatients, 35% had a large negative eGFRdiff. Among outpatient participants, at a mean (SD) follow-up of 11 (4) years, a large negative eGFRdiff, compared with an eGFRdiff between -30% and 30%, was associated with higher rates of all-cause mortality (28.4 vs 16.8 per 1000 person-years [PY]; hazard ratio [HR], 1.69 [95% CI, 1.57-1.82]), cardiovascular mortality (6.1 vs 3.8 per 1000 PY; HR, 1.61 [95% CI, 1.48-1.76]), atherosclerotic cardiovascular disease (13.3 vs 9.8 per 1000 PY; HR, 1.35 [95% CI, 1.27-1.44]), heart failure (13.2 vs 8.6 per 1000 PY; HR, 1.54 [95% CI, 1.40-1.68]), and kidney failure with replacement therapy (2.7 vs 2.1 per 1000 PY; HR, 1.29 [95% CI, 1.13-1.47]).
Conclusions And Relevance:
In the CKD-PC, 11% of outpatient participants and 35% of hospitalized patients had an eGFRcys that was at least 30% lower than their eGFRcr. In the outpatient setting, presence of eGFRcys at least 30% lower than eGFRcr was associated with significantly higher rates of all-cause mortality, cardiovascular events, and kidney failure.
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