PMID- 37180511
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230920
IS  - 2468-0249 (Electronic)
IS  - 2468-0249 (Linking)
VI  - 8
IP  - 5
DP  - 2023 May
TI  - Recombinant Alpha-1-Microglobulin (RMC-035) to Prevent Acute Kidney Injury in 
      Cardiac Surgery Patients: Phase 1b Evaluation of Safety and Pharmacokinetics.
PG  - 980-988
LID - 10.1016/j.ekir.2023.02.1071 [doi]
AB  - INTRODUCTION: Acute kidney injury (AKI) is a common complication in cardiac 
      surgery patients and prevention is needed to improve clinical outcomes. 
      Alpha-1-microglobulin (A1M) is a physiological antioxidant with strong 
      tissue-protective and cell-protective properties that has demonstrated 
      renoprotective effects. RMC-035, a recombinant variant of endogenous human A1M, 
      is being developed for the prevention of AKI in cardiac surgery patients. 
      METHODS: In this phase 1b, randomized, double-blind, and parallel group clinical 
      study, 12 cardiac surgery patients undergoing elective, open-chest, on-pump 
      coronary artery bypass graft and/or valve surgery with additional predisposing 
      AKI risk factors were enrolled to receive in total 5 intravenous doses of either 
      RMC-035 or placebo. The primary objective was to evaluate the safety and 
      tolerability of RMC-035. The secondary objective was to evaluate its 
      pharmacokinetic properties. RESULTS: RMC-035 was well tolerated. The nature and 
      frequency of adverse events (AEs) were consistent with the expected background 
      rates in the underlying patient population with no AEs reported as related to 
      study drug. No clinically relevant changes were observed for vital signs or 
      laboratory parameters except for renal biomarkers. Several established AKI urine 
      biomarkers were reduced at 4 hours after first dose administration in the 
      treatment group, indicating a reduced perioperative tubular cell injury following 
      RMC-035 treatment. CONCLUSION: Multiple intravenous doses of RMC-035 were well 
      tolerated in patients undergoing cardiac surgery. Observed RMC-035 plasma 
      exposures were safe and in the range of expected pharmacological activity. 
      Furthermore, urine biomarkers suggest reduced perioperative kidney cell injury, 
      warranting further investigation of RMC-035 as a potential renoprotective 
      treatment.
CI  - (c) 2023 Published by Elsevier Inc. on behalf of the International Society of 
      Nephrology.
FAU - Weiss, Raphael
AU  - Weiss R
AD  - Department of Anesthesiology, Intensive Care and Pain Medicine, University 
      Hospital Munster, Munster, Germany.
FAU - Meersch, Melanie
AU  - Meersch M
AD  - Department of Anesthesiology, Intensive Care and Pain Medicine, University 
      Hospital Munster, Munster, Germany.
FAU - Wempe, Carola
AU  - Wempe C
AD  - Department of Anesthesiology, Intensive Care and Pain Medicine, University 
      Hospital Munster, Munster, Germany.
FAU - von Groote, Thilo
AU  - von Groote T
AD  - Department of Anesthesiology, Intensive Care and Pain Medicine, University 
      Hospital Munster, Munster, Germany.
FAU - Agervald, Tobias
AU  - Agervald T
AD  - Guard Therapeutics International AB, Stockholm, Sweden.
AD  - Renal Division, Department of Clinical Science, Intervention and Technology, 
      Karolinska Institutet, Stockholm, Sweden.
FAU - Zarbock, Alexander
AU  - Zarbock A
AD  - Department of Anesthesiology, Intensive Care and Pain Medicine, University 
      Hospital Munster, Munster, Germany.
LA  - eng
PT  - Journal Article
DEP - 20230211
PL  - United States
TA  - Kidney Int Rep
JT  - Kidney international reports
JID - 101684752
PMC - PMC10166741
OTO - NOTNLM
OT  - acute kidney injury
OT  - alpha-1-microglobulin
OT  - cardiac surgery
OT  - inflammation
OT  - perioperative medicine
OT  - prevention
EDAT- 2023/05/14 19:13
MHDA- 2023/05/14 19:14
PMCR- 2023/02/11
CRDT- 2023/05/14 12:07
PHST- 2022/10/24 00:00 [received]
PHST- 2023/01/24 00:00 [revised]
PHST- 2023/02/06 00:00 [accepted]
PHST- 2023/05/14 19:13 [pubmed]
PHST- 2023/05/14 19:14 [medline]
PHST- 2023/05/14 12:07 [entrez]
PHST- 2023/02/11 00:00 [pmc-release]
AID - S2468-0249(23)01168-3 [pii]
AID - 10.1016/j.ekir.2023.02.1071 [doi]
PST - epublish
SO  - Kidney Int Rep. 2023 Feb 11;8(5):980-988. doi: 10.1016/j.ekir.2023.02.1071. 
      eCollection 2023 May.