Beyond the Threshold: Continuous Creatinine Change and Outcomes After Endovascular Thrombectomy for Acute Ischemic Stroke

BACKGROUND: Contrast-associated acute kidney injury (CA-AKI) after endovascular thrombectomy (EVT) worsens outcomes in acute ischemic stroke, but threshold-based definitions do not capture prognostic information from subthreshold changes. We tested whether early creatinine change within 48 hours of EVT conveys graded prognostic information beyond dichotomous CA-AKI. METHODS: We performed a secondary analysis of the CAN-REST (Contrast-Associated Nephropathy After Endovascular Stroke Treatment; REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT06596603) registry, a retrospective multicenter observational cohort study of 6638 EVT-treated adults with acute ischemic stroke enrolled at 73 centers in 16 countries between January 1 and December 31, 2023. Early creatinine change was quantified as the natural logarithm ratio of 48-hour creatinine to baseline creatinine (ln[48-hour/baseline creatinine]), with CA-AKI defined per Kidney Disease: Improving Global Outcomes criteria (≥0.3 mg/dL or ≥1.5× baseline rise within 48 hours). Multivariable logistic regression adjusted for prespecified baseline and periprocedural covariates examined associations with 90-day modified Rankin Scale shift and in-hospital mortality; linear versus restricted cubic spline specification was selected by likelihood ratio testing, and contrasts were estimated at ±10%, ±25%, and ±50%. RESULTS: Greater creatinine worsening within 48 hours of EVT was independently associated with an unfavorable 90-day modified Rankin Scale shift (adjusted common odds ratio per 1-unit log-ratio increase, 1.48 [95% CI, 1.07-2.04]; linear) and in-hospital mortality (nonlinear dose-response, of larger magnitude). A 10% increase in creatinine at 48 hours-well below Kidney Disease: Improving Global Outcomes threshold-was associated with worse functional outcome (adjusted common odds ratio, 1.04 [95% CI, 1.01-1.07]) and death (adjusted odds ratio, 1.22 [95% CI, 1.13-1.32]); a 10% decrease in creatinine at 48 hours was associated with lower odds of both outcomes (adjusted common odds ratio, 0.96 [95% CI, 0.93-0.99] and 0.74 [95% CI, 0.65-0.86]). The functional-outcome association concentrated at upper modified Rankin Scale cut-points (severe disability, death); effect modification by baseline renal function was not significant. CONCLUSIONS: Early creatinine change after EVT conveys graded, outcome-specific prognostic information extending below formal CA-AKI thresholds, with a dose-response detectable at changes as modest as ±10%, complementing binary CA-AKI as a framework for post-EVT renal risk assessment. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT06596603.