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Preconditioning strategies to prevent acute kidney injury.

ABSTRACT: Acute kidney injury is a common clinical disorder resulting in significantly increased morbidity and mortality. However, despite extensive research, strategies for prevention or treatment are still lacking in routine clinical practice. Already decades ago, several preconditioning strategies (e. g. ischemic/hypoxic preconditioning and calorie restriction) have been published and their extraordinary effectiveness - especially in rodents - has raised the hope for powerful clinical tools to prevent acute kidney injury. However, the underlying mechanisms are still not completely understood and translation to the clinics has not been successful yet. In this review, the most attractive strategies and the current mechanistic concepts are introduced and discussed. Furthermore, we present clinical trials evaluating the feasibility of preconditioning in the clinical setting.

SUBMITTER: Spath MR

PROVIDER: S-EPMC7135682 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Preconditioning strategies to prevent acute kidney injury.

Späth Martin Richard MR Koehler Felix Carlo FC Hoyer-Allo Karla Johanna Ruth KJR Grundmann Franziska F Burst Volker V Müller Roman-Ulrich RU

F1000Research 20200403

Acute kidney injury is a common clinical disorder resulting in significantly increased morbidity and mortality. However, despite extensive research, strategies for prevention or treatment are still lacking in routine clinical practice. Already decades ago, several preconditioning strategies (e. g. ischemic/hypoxic preconditioning and calorie restriction) have been published and their extraordinary effectiveness - especially in rodents - has raised the hope for powerful clinical tools to prevent ...[more]

PMID: 32269763

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Project description:Sepsis is a common and life-threatening systemic disorder, often leading to acute injury of multiple organs. Here, we show that remote ischemic preconditioning (rIPC), elicited by brief episodes of ischemia and reperfusion in femoral arteries, provides protective effects against sepsis-induced acute kidney injury (AKI). Methods: Limb rIPC was conducted on mice in vivo 24 h before the onset of cecal ligation and puncture (CLP), and serum exosomes derived from rIPC mice were infused into CLP-challenged recipients. In vitro, we extracted and identified exosomes from differentiated C2C12 cells (myotubes) subjected to hypoxia and reoxygenation (H/R) preconditioning, and the exosomes were administered to lipopolysaccharide (LPS)-treated mouse tubular epithelial cells (mTECs) or intravenously injected into CLP-challenged miR-21 knockout mice for rescue experiments. Results: Limb rIPC protected polymicrobial septic mice from multiple organ dysfunction, systemic accumulation of inflammatory cytokines and accelerated parenchymal cell apoptosis through upregulation of miR-21 in a hypoxia-inducible factor 1? (HIF-1?)-dependent manner in the ischemic limbs of mice. However, in miR-21 knockout mice or mice that received HIF-1? siRNA injection into hind limb muscles, the organ protection conferred by limb rIPC was abolished. Mechanistically, we discovered that miR-21 was transported from preischemic limbs to remote organs via serum exosomes. In kidneys, the enhanced exosomal miR-21 derived from cultured myotubes with H/R or the serum of mice treated with rIPC integrated into renal tubular epithelial cells and then targeted the downstream PDCD4/NF-?B and PTEN/AKT pathways, exerting anti-inflammatory and anti-apoptotic effects and consequently attenuating sepsis-induced renal injury both in vivo and in vitro. Conclusion: This study demonstrates a critical role for exosomal miR-21 in renoprotection conferred by limb rIPC against sepsis and suggests that rIPC and exosomes might serve as the possible therapeutic strategies for sepsis-induced kidney injury.

Project description:BackgroundPostoperative acute kidney injury is common after major vascular surgery and is associated with increased morbidity, mortality, and cost. High-performance risk stratification using a machine learning model can inform strategies that mitigate harm and optimize resource use. It is hypothesized that incorporating intraoperative data would improve machine learning model accuracy, discrimination, and precision in predicting acute kidney injury among patients undergoing major vascular surgery.MethodsA single-center retrospective cohort of 1,531 adult patients who underwent nonemergency major vascular surgery, including open aortic, endovascular aortic, and lower extremity bypass procedures, was evaluated. The validated, automated MySurgeryRisk analytics platform used electronic health record data to forecast patient-level probabilistic risk scores for postoperative acute kidney injury using random forest models with preoperative data alone and perioperative data (preoperative plus intraoperative). The MySurgeryRisk predictions were compared with each other as well as with the American Society of Anesthesiologists physical status classification.ResultsMachine learning models using perioperative data had greater accuracy, discrimination, and precision than models using either preoperative data alone or the American Society of Anesthesiologists physical status classification (accuracy: 0.70 vs 0.64 vs 0.62, area under the receiver operating characteristics curve: 0.77 vs 0.68 vs 0.61, area under the precision-recall curve: 0.70 vs 0.58 vs 0.48).ConclusionIn predicting acute kidney injury after major vascular surgery, machine learning approaches that incorporate dynamic intraoperative data had greater accuracy, discrimination, and precision than models using either preoperative data alone or the American Society of Anesthesiologists physical status classification. Machine learning methods have the potential for real-time identification of high-risk patients who may benefit from personalized risk-reduction strategies.

Dataset Information

Preconditioning strategies to prevent acute kidney injury.

Publications

Preconditioning strategies to prevent acute kidney injury.

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