ABSTRACT
Ischemia-reperfusion injury is a major cause of acute kidney injury. Many cytokines are involved in the pathogenesis of renal ischemia-reperfusion injury. IL24 is a member of the IL10 family and has gained importance because of its apoptosis-inducing effects in tumor disease besides its immunoregulative function. Littles is known about the role of IL24 in kidney disease. Using a mouse model, we found that IL24 is upregulated in the kidney after renal ischemia-reperfusion injury and that tubular epithelial cells and infiltrating inflammatory cells are the source of IL24. Mice lacking IL24 are protected from renal injury and inflammation. Cell culture studies showed that IL24 induces apoptosis in renal tubular epithelial cells, which is accompanied by an increased endoplasmatic reticulum stress response. Moreover, IL24 induces robust expression of endogenous IL24 in tubular cells, fostering ER-stress and apoptosis. In kidney transplant recipients with delayed graft function and patients at high risk to develop acute kidney injury after cardiac surgery IL24 is upregulated in the kidney and serum. Taken together, IL24 can serve as a biomarker, plays an important mechanistic role involving both extracellular and intracellular targets, and is a promising therapeutic target in patients at risk of or with ischemia-induced acute kidney injury.
Subject(s)
Acute Kidney Injury , Reperfusion Injury , Animals , Mice , Mice, Inbred C57BL , Acute Kidney Injury/etiology , Reperfusion Injury/metabolism , Kidney/pathology , Apoptosis , Interleukins/metabolism , Epithelial Cells/metabolismABSTRACT
BACKGROUND: Individualized medicine uses data on biological characteristics of individual patients in order to tailor treatment planning to their unique constitution. With respect to the practice of anesthesiology and intensive care medicine, it bears the potential to systematize the often complex medical care of critically ill patients and to improve outcomes. OBJECTIVE: The aim of this narrative review is to provide an overview of the possible applications of the principles of individualized medicine in anesthesiology and intensive care medicine. MATERIAL AND METHODS: Based on a search in MEDLINE, CENTRAL and Google Scholar, the results of previous studies and systematic reviews are narratively synthesized and the implications for the scientific and clinical practice are presented. RESULTS AND DISCUSSION: There are possibilities for individualization and an increase in precision of patient care in most if not all problems in anesthesiology and symptoms in intensive medical care. Even now, all practicing physicians can initiate measures to individualize treatment at different timepoints throughout the course of treatment. Individualized medicine can supplement and be integrated into protocols. Plans for future applications of individualized medicine interventions should consider the feasibility in a real-world setting. Clinical studies should contain process evaluations in order to create ideal preconditions for a successful implementation. Quality management, audits and feedback should become a standard procedure to ensure sustainability. In the long run, individualization of care, especially in the critically ill, should be enshrined in guidelines and become an integral part of clinical practice.
Subject(s)
Anesthesiology , Humans , Critical Illness/therapy , Critical Care , Delivery of Health Care , Precision MedicineABSTRACT
Sepsis and septic shock are a major public health concern and are still associated with high rates of morbidity and mortality. Whilst there is growing understanding of different phenotypes and endotypes of sepsis, all too often treatment strategies still only employ a "one-size-fits-all" approach. Biomarkers offer a unique opportunity to close this gap to more precise treatment approaches by providing insight into clinically hidden, yet complex, pathophysiology, or by individualizing treatment pathways. Predicting and evaluating systemic inflammation, sepsis or septic shock are essential to improve outcomes for these patients. Besides opportunities to improve patient care, employing biomarkers offers a unique opportunity to improve clinical research in patients with sepsis. The high rate of negative clinical trials in this field may partly be explained by a high degree of heterogeneity in patient cohorts and a lack of understanding of specific endotypes or phenotypes. Moving forward, biomarkers can support the selection of more homogeneous cohorts, thereby potentially improving study conditions of clinical trials. This may finally pave the way to a precision medicine approach to sepsis, septic shock and complication of sepsis in the future.
ABSTRACT
Renal replacement therapy is after mechanical ventilation one of the most important and frequently used organ replacement therapies in daily routine intensive care practice. In contrast to mechanical ventilation, quality standards for renal replacement therapy are less well known and defined. In this position paper of the German Interdisciplinary Association for Intensive Care and Emergency Medicine, we describe quality standards of renal replacement procedures in order to improve therapy of patients with severe acute kidney injury.