ARTEMIS: Ravulizumab to Protect Patients With CKD From CSA-AKI and MAKE

CSA-AKI without recovery was defined as experiencing CSA-AKI based on highest observed serum creatinine (sCr) from randomization to Day 7 post CPB and had occurrence of non-recovered (complete [sCr < 1.1*baseline] or partial [sCr ≥ 1.1 to < 1.5*baseline]) CSA-AKI at Day 90.

The occurrence of post-operative CSA-AKI was defined as the presence of one of the following two observations during the 7 days after surgery with CPB, based on the modified Kidney Disease: Improving Global Outcomes (nonprofit foundation, KDIGO) criteria:

• An increase in sCr by ≥ 0.3 milligrams per deciliter (mg/dL) in a 48-hour period, or
• An increase in sCr to ≥ 1.5*baseline within the 7 days following CPB.

Estimated percentages were calculated using imputation of missing data. Missing values were imputed as non-events.

Occurrence of severe CSA-AKI from randomization to Day 7 and Day 30 post-CPB was defined as meeting KDIGO stage 2 or 3 based on the highest observed sCr from randomization to Day 7 and Day 30 post-CPB. Estimated percentages were calculated using imputation of missing data. Missing values were imputed as non-events.

CSA-AKI Staging by Modified KDIGO Criteria:

• AKI Stage 1 - An increase in sCr by ≥ 0.3 mg/dL in a 48-hour period, or an increase in sCr to ≥ 1.5 to < 2.0*baseline.
• AKI Stage 2 - An increase in sCr to ≥ 2.0 to < 3.0*baseline.
• AKI Stage 3 - An increase in sCr to ≥ 3.0*baseline, or an increase in sCr to ≥ 4.0 mg/dL in participants meeting AKI criteria, or initiation of KRT.

Estimated percentages were calculated using imputation of missing data. Missing data for the death component were addressed using a multiple imputation approach under the assumption of MAR. Missing values for the KRT component were imputed as non-events.

Estimated all-cause mortality data (estimated percentage of participants who died) from randomization to Day 90 post-CPB is reported in this outcome measure.

Estimated percentages were calculated using imputation of missing data. Missing data for death were addressed using a multiple imputation approach under the assumption of MAR. A summary of all-cause mortality through to the end of the study, without imputation for missing data, is located in the 'Reported Adverse Events' Section.

The length of post-operative ICU stay was calculated based on the date/time of post-operative ICU discharge - the date/time of post-operative ICU admission for a participant who was admitted to ICU post-surgery and was alive at ICU discharge.

Estimated medians were calculated using imputation of missing data. Missing length of post-operative ICU stay was imputed by the worst value due to death and median of all participants due to other reasons.

MAKE30 and MAKE60 were defined as meeting at least one of the following criteria:

• Decrease from baseline in eGFR (CKD-EPI formula using sCysC) of ≥ 25% at Day 30 or 60 post CPB,
• Initiation of KRT through Days 30 or 60 post CPB, or
• Death from any cause through Days 30 or 60 post CPB.

Estimated percentages were calculated using imputation of missing data. Missing data for KRT initiation or death were imputed as non-events. Missing eGFR values were addressed using a two-step multiple imputation approach under the assumption of MAR.

MAKE30, MAKE60 and MAKE90 were defined as meeting at least one of the following three criteria:

• Decrease from baseline in eGFR (CKD-EPI formula using sCr) of ≥ 25% at Days 30, 60, or 90 post CPB,
• Initiation of KRT through Days 30, 60, or 90 post CPB, or
• Death from any cause through Days 30, 60, or 90 post CPB.

Estimated percentages were calculated using imputation of missing data. Missing data for KRT initiation or death were imputed as non-events. Missing eGFR values were addressed using a two-step multiple imputation approach under the assumption of MAR.

The estimated percentage of participants who died from any cause from randomization through Days 30, 60, or 90 are reported. Note that data imputation for this outcome measure is different than the imputation for the 'All-cause Mortality' outcome measure. Missing data for this outcome measure were imputed as non-events. A summary of all-cause mortality through to the end of the study, without imputation for missing data, is located in the 'Reported Adverse Events' Section.

Estimated percentage of participants with initiation of KRT through Days 30, 60, or 90 post-CPB are reported.

Estimated percentages were calculated using imputation of missing data. Missing data were imputed as non-events.

Estimated percentage of participants with a decrease from baseline in eGFR (CKD-EPI formula using sCysC) of ≥ 25% at Days 30 or 60 post-CPB is reported.

Estimated percentages were calculated using imputation of missing data. Missing eGFR values were addressed using a two-step multiple imputation approach under the assumption of MAR.

Estimated percentage of participants with a decrease from baseline in eGFR (CKD-EPI formula using sCr) of ≥ 25% at Days 30, 60, or 90 post-CPB is reported.

Estimated percentages were calculated using imputation of missing data. Missing eGFR values were addressed using a two-step multiple imputation approach under the assumption of MAR.

Estimated percentages were calculated using imputation of missing data. Missing data for KRT initiation or death were imputed as non-events.

Post-operative renal failure was a Society of Thoracic Surgeons (STS) metric based on modified Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (RIFLE) failure creatinine criteria and was defined as:

• An increase in sCr to ≥ 3.0*baseline,
• An increase in sCr to ≥ 4.0 mg/dL with an increase of at least 0.5 mg/dL from baseline, or
• Initiation of KRT.

Estimated percentages were calculated using imputation of missing data. Missing values were imputed as non-events.

The occurrence of post-operative CSA-AKI was defined as the presence of one of the following two observations during the 3 or 7 days after surgery with CPB, based on the modified KDIGO criteria:

• An increase in sCr by ≥ 0.3 mg/dL in a 48-hour period, or
• An increase in sCr to ≥ 1.5*baseline within the 7 days following CPB.

CSA-AKI Staging by Modified KDIGO Criteria:

• AKI Stage 1 - An increase in sCr by ≥ 0.3 mg/dL in a 48-hour period, or an increase in sCr to ≥ 1.5 to < 2.0*baseline.
• AKI Stage 2 - An increase in sCr to ≥ 2.0 to < 3.0*baseline.
• AKI Stage 3 - An increase in sCr to ≥ 3.0*baseline, or an increase in sCr to ≥ 4.0 mg/dL in participants meeting AKI criteria, or initiation of KRT.

CSA-AKI without recovery was defined as experiencing CSA-AKI based on highest observed sCr from randomization to Day 7 post CPB and had occurrence of non-recovered (complete [sCr < 1.1*baseline] or partial [sCr ≥ 1.1 to < 1.5*baseline]) CSA-AKI at Days 15, 30, or 60.

The occurrence of post-operative CSA-AKI was defined as the presence of one of the following two observations during the 7 days after surgery with CPB, based on the KDIGO criteria:

• An increase in sCr by ≥ 0.3 milligrams per deciliter (mg/dL) in a 48-hour period, or
• An increase in sCr to ≥ 1.5*baseline within the 7 days following CPB.

Estimated percentages were calculated using imputation of missing data. Missing values were imputed as non-events.

AKI was defined as sCr > 1.5*baseline at Days 3, 7, 15, 30, 60, and 90 post-CPB.

Estimated percentages were calculated using imputation of missing data. Missing values were imputed as non-events.

Occurrence of post-operative CSA-AKI was using modified KDIGO criteria within 7 days after CPB: An increase in sCr by ≥0.3 mg/dL in a 48-hour period or ≥1.5*baseline within the 7 days following CPB.

Stages of post-CSA-AKI kidney function to determine AKI progression:

• Post-AKI stage 0 - Complete recovery: sCr <1.1*baseline or partial recovery: sCr ≥1.1 to <1.5 × baseline;
• Post-AKI Stage 1 - sCr ≥1.5 to <2.0*baseline;
• Post-AKI Stage 2 - sCr ≥2.0 - <3.0*baseline;
• Post-AKI Stage 3 - sCr ≥3.0*baseline, or sCr ≥4.0 mg/dL in participants meeting CSA-AKI criteria or KRT.

AKI progression:

• AKI recovery - Complete: sCr <1.1*baseline or Partial: sCr ≥1.1 - <1.5*baseline
• AKI improvement - Move down 1 or more stages from the highest CSA-AKI stage, or remained in stage 3 but discontinued KRT;
• Stable AKI - Unchanged AKI or KRT status;
• Worsening AKI - Moved up 1 or more stages from the highest CSA-AKI stage, or Remained in Stage 3 but initiated KRT.