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Kidney Week

Abstract: FR-PO0093

Kidney Function Following Open-Chest 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

Cardiac surgery with cardiopulmonary bypass may induce significant renal stress and damage, which can lead to adverse outcomes such as acute kidney injury and the development or progression of chronic kidney disease (CKD). The AKITA study evaluated the efficacy and safety of RMC-035 - a novel analogue of alpha-1-microglobulin - in preserving postoperative renal function in this vulnerable population [eClinicalMedicine 2024;76: 102830].

Methods

The trajectory of estimated glomerular filtration rate (eGFR), changes from baseline and categorical declines in eGFR were evaluated through day 90. The relative risk (RR) and 90% confidence interval (CI90) for modified major adverse kidney events at/by day 90 (mMAKE90) - a composite of renal replacement therapy or a significant decline in eGFR - were analyzed by comparing RMC-035 (n=89) to placebo (n=88), using various eGFR thresholds. eGFR was calculated using centrally collected measurements of serum creatinine (SCr), cystatin C (CysC), and a combined approach.

Results

By day 90, between 67% and 76% of placebo-treated patients experienced a decline in eGFR, with 14% to 16% showing a reduction of ≥30%. In the overall population, point estimates for the RR of mMAKE90 consistently and progressively favored RMC-035 up to a 40% decline in eGFR. The lowest RR, 0.29, was observed at the 30% threshold when using eGFR-SCr. For eGFR-CysC and eGFR-SCr/CysC, the lowest RRs were observed at the 40% threshold, at 0.48 and 0.39, respectively.

Conclusion

Approximately 15% of cardiac surgery patients experience a decline of ≥30% in renal function by day 90. Traditional eGFR decline thresholds commonly applied in long-term CKD trials (e.g., >50%) are infeasible in the cardiac surgery context due to low event rates. This post-hoc analysis suggests that eGFR decline thresholds of 30% to 40% may offer the most appropriate balance of sensitivity and specificity for evaluating the efficacy of interventions such as RMC-035 in this setting.

Summary overview of modified MAKE90 by degree of eGFR loss using different eGFR calculation methods [RR (CI90) RMC-035 vs Placebo]
 ≥10% eGFR loss
or RRT
≥20% eGFR loss
or RRT
≥30% eGFR loss
or RRT
≥40% eGFR loss
or RRT
≥50% eGFR loss
or RRT
SCr0.76
(0.48-1.20)
0.66
(0.36-1.22)
0.29
(0.11-0.76)
0.64
(0.23-1.80)
0.78
(0.26-2.32)
CysC0.99
(0.72-1.36)
0.79
(0.52-1.21)
0.79
(0.45-1.41)
0.48
(0.21-1.07)
0.76
(0.27-2.15)
SCR&CysC0.89
(0.62-1.29)
0.66
(0.38-1.14)
0.79
(0.45-1.41)
0.39
(0.14-1.06)
0.95
(0.31-2.97)

Funding

  • Commercial Support – Guard Therapeutics International AB

Digital Object Identifier (DOI)