Recombinant alpha-1 microglobulin to improve outcomes in survivors of AKI.

The underlying pathophysiologic mechanism includes ischemia-reperfusion injury, complement activation, oxidative stress, and heme toxicity.

潜在的病理生理机制包括缺血-再灌注损伤、补体激活、氧化应激和血红素毒性。

Among potential preventive measures, recombinant alpha-1 microglobulin (A1M) emerged as a promising therapeutic candidate to mitigate kidney injury in high-risk clinical settings.

在潜在的预防措施中，重组α-1微球蛋白（A1M）作为一种有前途的治疗候选物出现，以减轻高风险临床环境中的肾损伤。

Preclinical studies have shown its protective effect in different in vitro models such as cellular damage induced by radiation, proteases, and oxidative stress.

临床前研究表明，它在不同的体外模型中具有保护作用，例如由辐射、蛋白酶和氧化应激引起的细胞损伤。

In animal models, pretreatment with A1M significantly attenuated glomerular permeability changes induced by free fetal hemoglobin, reduced markers of oxidative injury in radiation-induced kidney damage, and conferred protection in ischemia-reperfusion injury by stabilizing mitochondrial function.

在动物模型中，A1M的预处理显著减轻了由游离胎儿血红蛋白引起的肾小球通透性变化，减少了辐射诱导的肾脏损伤的氧化损伤标志物，并通过稳定线粒体功能，在缺血再灌注损伤中提供了保护。

These promising results led to the use of A1M in human patients.

这些有希望的结果导致了A1M在人类患者中的使用。

In Phase 1 clinical trials, RMC-035 demonstrated a safety profile with predictable, dose-linear pharmacokinetics.

在I期临床试验中，RMC-035展现出了可预测的剂量线性药代动力学的安全性特征。

Moreover, in a Phase 1 study involving cardiac surgery patients, RMC-035 showed early signals of renal protection as indicated by reductions of renal tubular stress and injury biomarkers.

此外，在涉及心脏手术患者的I期研究中，RMC-035显示出早期的肾脏保护信号，这通过减少肾小管应激和损伤生物标志物得到体现。

Although a Phase 2 trial in cardiac surgery patients did not meet its primary endpoint of reducing the rate of AKI within 72 hours after surgery, a significant decline in major adverse kidney events at 90 days was observed that was mainly driven by a reduced rate of persistent renal dysfunction.

尽管在心脏外科患者中进行的2期试验未能达到其主要终点，即在手术后72小时内降低急性肾损伤（AKI）的发生率，但在90天内主要由持续性肾功能障碍发生率降低所驱动的重大不良肾事件显著下降。

An ongoing Phase 2b study aims to refine dosing strategies and better delineate its long-term renoprotective efficacy.

一项正在进行的2b期研究旨在优化剂量策略并更好地界定其长期肾脏保护效果。

Collectively, these studies seek to answer whether RMC-035 may improve kidney outcomes in settings characterized by oxidative and ischemia-reperfusion injury.

这些研究总体上旨在回答RMC-035是否可能改善在氧化应激和缺血再灌注损伤环境中的肾脏结果。