Postbaseline changes in renal function

• SCr and cystatin C (and corresponding eGFR values) at 12, 24,48 and 72 hours, respectively, and at day 7/discharge, day 30 and day 90.

• Change from baseline, up to day 7/discharge, of peak SCr and cystatin C.

Time-corrected AUC of cystatin C for day 1 to day 4 (72 hours after first dose of IMP).

Need for renal replacement therapy

• Dialysis treatment (for any reason) within 72 hours and within 7 days after end of surgery.

• Dialysis free days from end of surgery to day 30 and day 90, respectively.

MAKE at day 30 and day 90, defined as death, any dialysis or ≥25% reduction of eGFR compared with baseline chronic kidney disease epidemiology collaboration equation (either SCr, cystatin C or both).22–24

AKI characteristics

• AKI within 72 hours after first dose of IMP based on cystatin C and/or UO (AKI of any stage/severity defined as cystatin C ≥1.5 baseline, OR UO <0.5 mL/kg/hour for ≥6 hours).

• AKI within 7 days after first dose of IMP (based on SCr and/or UO criteria, or cystatin C and/or UO criteria).

• AKI persistence, defined as an AKI (KDIGO definition) developing within 72 hours after first dose of IMP and with a duration of ≥72 hours. persistence will also be assessed per AKI severity stage*.

• AKI severity stage* within 72 hours and within 7 days after first dose of IMP

  • *Severity of AKI defined as the following:

    • Stage 1: SCr 1.5–1.9 times baseline within 7 days, or ≥0.3 mg/dL (≥26.5 µmol/L), or urine output <0.5 mL/kg/hour for 6 to <12 hours.

    • Stage 2: SCr 2.0–2.9 times baseline within 7 days or urine output <0.5 mL/kg/hour for ≥12 hours.

    • Stage 3: SCr 3.0 times baseline within 7 days, or increase in SCr 4.0 mg/dL (≥353.6 µmol/L), or initiation of renal replacement therapy or urine output <0.3 mL/kg/hour for ≥24 hours or anuria for ≥12 hours.

Postbaseline changes in urine albumin to creatinine ratio and urine protein to creatinine ratio at day 4, day 30 and day 90.

Pharmacokinetics of RMC-035 in plasma (AUC and Cmax).

Presence and titers of ADA at day 1 (presurgery), day 30 and day 90.

Characteristics of ADA developed at day 30 and day 90 with regards to isotype, neutralising capacity and cross-reactivity with endogenous alpha-1-microglobulin (A1M).

Kidney biomarkers: urine kidney injury molecule 1, neutrophil gelatinase-associated lipocalin, tissue inhibitor of metalloproteinase 2, insulin like growth binding factor protein 7, chemokine ligand 14 (CCL-14), interleukin-18 (IL-18), liver fatty acid binding protein and 8-hydroxy-2'- deoxyguanosine.

Cardiac biomarkers: plasma N-terminal-prohormone of brain natriuretic peptide and cardiac troponin I and T (cTnI, cTnT).

Length of index ICU stay and index hospital stay.

• Index ICU stay (in days) defined as the duration of stay in the ICU.

• Immediately following surgery or recovery room postsurgery until ICU discharge.

• Index hospital stay (in days) is defined as the duration of stay in the hospital from the day of surgery to hospital discharge for the index surgery.

Nature of subject discharge facility (eg, home, skilled nursing facility, rehabilitation centre).

Change from baseline to day 90 in the following patient-reported outcomes:

• MOS 36-Item Short Form Survey Instrument.

• European Quality of Life 5 Domain 5-Level Score.