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Kidney Week

Abstract: FR-PO0094

Efficacy of RMC-035 in Reducing MAKE90 in Patients with and Without AKI After Cardiac Surgery: Post Hoc Analysis of the AKITA Study

Session Information

Category: Acute Kidney Injury

  • 102 AKI: Clinical, Outcomes, and Trials

Authors

  • Reusch, Michael, Guard Therapeutics International AB, Stockholm, Sweden
  • Zarbock, Alexander, Universitatsklinikum Munster Klinik fur Anasthesiologie Operative Intensivmedizin und Schmerztherapie, Münster, NRW, Germany
  • Agervald, Tobias, Guard Therapeutics International AB, Stockholm, Sweden

Group or Team Name

  • AKITA Study Group.
Background

RMC-035, a therapeutic variant of alpha-1-microglobulin, demonstrated kidney-protective properties in the Phase 2a AKITA study of patients undergoing open-chest cardiac surgery who were at elevated risk for acute kidney injury (AKI) [eClinicalMedicine 2024;76: 102830].

Methods

This post-hoc analysis evaluated changes in estimated glomerular filtration rate (eGFR) through day 90 and the incidence of major adverse kidney events (MAKE90) - a composite of death, renal replacement therapy, or ≥25% decline in eGFR - and modified MAKE90 (mMAKE90 = MAKE90 excluding death) by/at 90 days post-surgery, in 177 patients (RMC-035: n=89; placebo: n=88). Analyses were stratified by the presence or absence of AKI within 72h defined by KDIGO criteria. eGFR was calculated using serum creatinine (SCr), cystatin C (CysC), or a combination of both. Data on patient counts, proportions, relative risks (RR), 90% confidence intervals (CI90), and p-values are reported.

Results

Patients with AKI experienced greater declines in eGFR compared to those without AKI. RMC-035 was associated with improved eGFR outcomes by day 90 compared to placebo, regardless of AKI status. Similarly, RMC-035 reduced the incidence of MAKE90 in both AKI and non-AKI subgroups. The treatment effect was more pronounced in patients with AKI when eGFR was assessed using cystatin C (CysC) or the combined CysC/SCr method (Figure 1). Findings for modified MAKE90 (mMAKE90) were consistent with those for MAKE90.

Conclusion

Post-operative AKI is a known risk factor for adverse renal outcomes by day 90. However, unlike in the placebo group, this association was not observed in patients treated with RMC-035, suggesting that pharmacological intervention targeting AKI could mitigate long-term renal impairment.

Figure 1: MAKE90 Overall and by AKI

Funding

  • Commercial Support – Guard Therapeutics International AB

Digital Object Identifier (DOI)