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Cystatin C vs creatinine eGFR in advanced CKD: an analysis of the STOP-ACEi trial
Sebastian Spencer1,2,3, Robert Desborough2,3, Samir Mehta4
1University of Hull.
Insights
Discontinuing renin-angiotensin system inhibitor therapy in advanced chronic kidney disease (CKD) did not significantly alter cystatin C estimated glomerular filtration rate (eGFR) over 36 months. Cystatin C eGFR is a reliable alternative to creatinine eGFR in advanced CKD.
Area of Science:
- Nephrology
- Pharmacology
- Biomarkers
Background:
- Secondary analysis of the STOP-ACEi trial.
- Focus on advanced chronic kidney disease (CKD).
- Investigated renin-angiotensin system inhibitor (RASi) therapy impact on cystatin C estimated glomerular filtration rate (eGFR).
Purpose of the Study:
- To evaluate the effect of discontinuing or continuing RASi therapy on cystatin C eGFR in advanced CKD patients.
- To compare cystatin C eGFR with traditional creatinine-based eGFR in this population.
Main Methods:
- Calculated cystatin C eGFRs using CKD-EPI 2012, EKFC, and CKD-EPI Combined 2021 equations at multiple time points.
- Employed complete case analysis, mixed-effects linear regression, pattern mixture models, and joint models.
- Excluded samples post-kidney replacement therapy initiation.
Main Results:
- No significant difference in mean cystatin C eGFR between STOP and CONTINUE arms at 12, 24, and 36 months.
- Estimated least squares mean differences ranged from -1.46 to -2.27 mL/min/1.73 m².
- Sensitivity and joint models supported primary findings.
Conclusions:
- Discontinuing RASi therapy has a similar impact on cystatin C eGFR compared to continuing it in advanced CKD.
- Cystatin C eGFR is a reliable alternative to creatinine eGFR, especially when creatinine accuracy is compromised in advanced CKD.
Background:
In this secondary analysis of the STOP-ACEi trial, we explored the impact of discontinuing or continuing renin-angiotensin system inhibitor therapy in people with advanced chronic kidney disease on cystatin C estimated glomerular filtration rate (eGFR).
Methods:
Cystatin C eGFRs were calculated at baseline, 12, 24 and 36 months using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) cystatin 2012, European Kidney Function Consortium and CKD-EPI Combined 2021 equations. We excluded samples obtained after the initiation of kidney replacement therapy. Primary analysis used complete case analysis and mixed-effects linear regression model, adjusting for minimization variables, baseline value, time-point and treatment by time interaction. Sensitivity analysis was conducted using a pattern mixture model to account for missing data that was not at random. To model the longitudinal cystatin C data with time-to-event data, a joint model was utilized which incorporated the cystatin C measurements at various time points and accounted for the occurrence of kidney replacement therapy.
Results:
The mean cystatin C eGFRs (CKD-EPI 2012) at baseline were 17.8 mg/L [standard deviation (SD 6.3)] and 17.9 mL/min/1.73 m2 (SD 6.3) in the STOP and CONTINUE arms, respectively. The estimated least squares mean difference at 12 months between STOP and CONTINUE arm was -1.46 [95% confidence interval (CI) -2.39 to -0.52, P = .002]. The estimated least squares mean difference at 24 months was -2.27 (95% CI -3.48 to -1.06, P < .001). The estimated least squares mean difference at 36 months was -1.72 (95% CI -3.48 to 0.03, P = .05).
Conclusion:
Our results are consistent with the primary study's analysis and sensitivity analyses support these findings and provide additional insights. Our findings demonstrate the similarity of creatinine and cystatin eGFR results and therefore support the use of cystatin C as an alternative marker of eGFR in advanced CKD, particularly in those in whom creatinine is likely to be less accurate.
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