Cystatin C vs Creatinine eGFR in Advanced CKD: an analysis of the STOP-ACEi Trial

Background and hypothesis 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. Methods Cystatin C eGFR were calculated at baseline, 12-, 24- and 36-months using CKD-EPI Cystatin 2012, EKFC 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 eGFR (CKD-EPI 2012) at baseline were 17.8 mg/L [SD: 6.3] and 17.9 ml/min/1.73m2 [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% CI: -2.39 to -0.52, p=0.002). The estimated least squares mean difference at 24 months was -2.27 (95% CI: -3.48 to -1.06, p<0.001). The estimated least squares mean difference at 36 months was -1.72 (95% CI: -3.48 to 0.03, p=0.05). 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 whom creatinine is likely to be less accurate.