Precision Medicine in Acute Kidney Injury: A Promising Future?
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ABSTRACT:
SUBMITTER: Schaub JA
PROVIDER: S-EPMC6444650 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Acute kidney injury (AKI) remains a complex challenge with diverse underlying pathological mechanisms and etiologies. Current detection methods predominantly rely on serum creatinine, which exhibits substantial limitations in specificity and poses the issue of late-stage detection of kidney injury. In this review, we propose an up-to-date and comprehensive summary of advancements that identified novel biomarker candidates in blood and urine and ideal criteria for AKI biomarkers such as renal injury specificity, mechanistic insight, prognostic capacity, and affordability. Recently identified biomarkers not only indicate injury location but also offer valuable insights into a range of pathological processes, encompassing reduced glomerular filtration rate, tubular function, inflammation, and adaptive response to injury. The clinical applications of AKI biomarkers are becoming extensive and serving as relevant tools in distinguishing acute tubular necrosis from other acute renal conditions. Also, these biomarkers can offer significant insights into the risk of progression to chronic kidney disease CKD and in the context of kidney transplantation. Integration of these biomarkers into clinical practice has the potential to improve early diagnosis of AKI and revolutionize the design of clinical trials, offering valuable endpoints for therapeutic interventions and enhancing patient care and outcomes.
| S-EPMC10813773 | biostudies-literature
Project description:Acute kidney injury (AKI) currently is diagnosed by a temporal trend of a single blood analyte: serum creatinine. This measurement is neither sensitive nor specific to kidney injury or its protean forms. Newer biomarkers, neutrophil gelatinase-associated lipocalin (NGAL, Lipocalin 2, Siderocalin), or kidney injury molecule-1 (KIM-1, Hepatitis A Virus Cellular Receptor 1), accelerate the diagnosis of AKI as well as prospectively distinguish rapidly reversible from prolonged causes of serum creatinine increase. Nonetheless, these biomarkers lack the capacity to subfractionate AKI further (eg, sepsis versus ischemia versus nephrotoxicity from medications, enzymes, or metals) or inform us about the primary and secondary sites of injury. It also is unknown whether all nephrons are injured in AKI, whether all cells in a nephron are affected, and whether injury responses can be stimulus-specific or cell type-specific or both. In this review, we summarize fully agnostic tissue interrogation approaches that may help to redefine AKI in cellular and molecular terms, including single-cell and single-nuclei RNA sequencing technology. These approaches will empower a shift in the current paradigm of AKI diagnosis, classification, and staging, and provide the renal community with a significant advance toward precision medicine in the analysis AKI.
| S-EPMC5753434 | biostudies-literature
Project description:Sepsis is a leading cause of morbidity and mortality in critically ill children, and acute kidney injury (AKI) is a frequent complication that confers an increased risk for poor outcomes. Despite the documented consequences of sepsis-associated AKI (SA-AKI), no effective disease-modifying therapies have been identified to date. As such, the only treatment options for these patients remain prevention and supportive care, both of which rely on the ability to promptly and accurately identify at risk and affected individuals. To achieve these goals, a variety of biomarkers have been investigated to help augment our currently limited predictive and diagnostic strategies for SA-AKI, however, these have had variable success in pediatric sepsis. In this mini-review, we will briefly outline the current use of biomarkers for SA-AKI, and propose a new framework for biomarker discovery and utilization that considers the individual patient's sepsis inflammatory response. Now recognized to be a key driver in the complex pathophysiology of SA-AKI, understanding the dysregulated host immune response to sepsis is a growing area of research that can and should be leveraged to improve the prediction and diagnosis of SA-AKI, while also potentially identifying novel therapeutic targets. Reframing SA-AKI in this manner - as a direct consequence of the individual patient's sepsis inflammatory response - will facilitate a precision medicine approach to its management, something that is required to move the care of this consequential disorder forward.
| S-EPMC8079650 | biostudies-literature
Project description:Acute kidney injury (AKI) is common in hospitalized patients of all ages and is associated with significant morbidity and mortality. Accurate prediction and early identification of AKI is of utmost importance because no therapy exists to mitigate AKI once it has occurred. Yet, serum creatinine lacks adequate sensitivity and specificity, and quantification of urine output is challenging in incontinent children without indwelling bladder catheters. Integration of clinically available biomarkers have the potential to delineate unique AKI phenotypes that could have important prognostic and therapeutic implications. Plasma Cystatin C, urine neutrophil gelatinase associated lipocalin (NGAL) and the urinary product of tissue inhibitor metalloproteinase (TIMP-2) and insulin growth factor binding protein-7 (IGFBP7) are clinically available. These biomarkers have been studied in heterogenous populations across the age spectrum and in a variety of clinical settings for prediction of AKI. The purpose of this review is to describe and discuss the clinically available AKI biomarkers including how they have been used to delineate AKI phenotypes.
| S-EPMC9046880 | biostudies-literature
Project description:Precision medicine has captured the imagination of the medical community with visions of therapies precisely targeted to the specific individual's genetic, biological, social, and environmental profile. However, in practice it has become synonymous with genomic medicine. As such its successes have been limited, with poor predictive or clinical value for the majority of people. It adds little to lifestyle medicine, other than in establishing why a healthy lifestyle is effective in combatting chronic disease. The challenge of lifestyle medicine remains getting people to actually adopt, sustain, and naturalize a healthy lifestyle, and this will require an approach that treats the patient as a person with individual needs and providing them with suitable types of support. The future of lifestyle medicine is holistic and person-centered rather than technological.
| S-EPMC7092395 | biostudies-literature
Project description:Objective. Spinal cord injury (SCI) is a devastating neurological disorder caused by trauma. Pathophysiological events occurring after SCI include acute, subacute, and chronic phases, while complex mechanisms are comprised. As an abundant source of natural drugs, Traditional Chinese Medicine (TCM) attracts much attention in SCI treatment recently. Hence, this review provides an overview of pathophysiology of SCI and TCM application in its therapy. Methods. Information was collected from articles published in peer-reviewed journals via electronic search (PubMed, SciFinder, Google Scholar, Web of Science, and CNKI), as well as from master's dissertations, doctoral dissertations, and Chinese Pharmacopoeia. Results. Both active ingredients and herbs could exert prevention and treatment against SCI, which is linked to antioxidant, anti-inflammatory, neuroprotective, or antiapoptosis effects. The detailed information of six active natural ingredients (i.e., curcumin, resveratrol, epigallocatechin gallate, ligustrazine, quercitrin, and puerarin) and five commonly used herbs (i.e., Danshen, Ginkgo, Ginseng, Notoginseng, and Astragali Radix) was elucidated and summarized. Conclusions. As an important supplementary treatment, TCM may provide benefits in repair of injured spinal cord. With a general consensus that future clinical approaches will be diversified and a combination of multiple strategies, TCM is likely to attract greater attention in SCI treatment.
| S-EPMC4826935 | biostudies-literature
Project description:Acute kidney injury (AKI) complicates recovery from cardiac surgery in up to 30 % of patients, injures and impairs the function of the brain, lungs, and gut, and places patients at a 5-fold increased risk of death during hospitalization. Renal ischemia, reperfusion, inflammation, hemolysis, oxidative stress, cholesterol emboli, and toxins contribute to the development and progression of AKI. Preventive strategies are limited, but current evidence supports maintenance of renal perfusion and intravascular volume while avoiding venous congestion, administration of balanced salt as opposed to high-chloride intravenous fluids, and the avoidance or limitation of cardiopulmonary bypass exposure. AKI that requires renal replacement therapy occurs in 2-5 % of patients following cardiac surgery and is associated with 50 % mortality. For those who recover from renal replacement therapy or even mild AKI, progression to chronic kidney disease in the ensuing months and years is more likely than for those who do not develop AKI. Cardiac surgery continues to be a popular clinical model to evaluate novel therapeutics, off-label use of existing medications, and nonpharmacologic treatments for AKI, since cardiac surgery is fairly common, typically elective, provides a relatively standardized insult, and patients remain hospitalized and monitored following surgery. More efficient and time-sensitive methods to diagnose AKI are imperative to reduce this negative outcome. The discovery and validation of renal damage biomarkers should in time supplant creatinine-based criteria for the clinical diagnosis of AKI.
| S-EPMC4931708 | biostudies-literature
Project description:The cure rate of childhood acute lymphoblastic leukemia (ALL) has exceeded 90% in some contemporary clinical trials. However, the dose intensity of conventional chemotherapy has been pushed to its limit. Further improvement in outcome will need to rely more heavily on molecular therapeutic as well as immuno-and cellular-therapy approaches together with precise risk stratification. Children with ETV6-RUNX1 or hyperdiploid > 50 ALL who achieve negative minimal residual disease during early remission induction are suitable candidates for reduction in treatment. Patients with Philadelphia chromosome (Ph)-positive or Ph-like ALL with ABL-class fusion should be treated with dasatinib. BH3 profiling and other preclinical methods have identified several high-risk subtypes, such as hypodiplod, early T-cell precursor, immature T-cell, KMT2A-rearranged, Ph-positive and TCF-HLF-positive ALL, that may respond to BCL-2 inhibitor venetoclax. There are other fusions or mutations that may serve as putative targets, but effective targeted therapy has yet to be established. For other high-risk patients or poor early treatment responders who do not have targetable genetic lesions, current approaches that offer hope include blinatumomab, inotuzumab and CAR-T cell therapy for B-ALL, and daratumumab and nelarabine for T-ALL. With the expanding therapeutic armamentarium, we should start focus on rational combinations of targeted therapy with non-overlapping toxicities.
| S-EPMC9671279 | biostudies-literature
Project description:Precision medicine is increasingly recognized as a promising approach to improve disease treatment, taking into consideration the individual clinical and biological characteristics shared by specific subgroups of patients. In specific fields such as oncology and hematology, precision medicine has already started to be implemented in the clinical setting and molecular testing is routinely used to select treatments with higher efficacy and reduced adverse effects. The application of precision medicine in psychiatry is still in its early phases. However, there are already examples of predictive models based on clinical data or combinations of clinical, neuroimaging and biological data. While the power of single clinical predictors would remain inadequate if analyzed only with traditional statistical approaches, these predictors are now increasingly used to impute machine learning models that can have adequate accuracy even in the presence of relatively small sample size. These models have started to be applied to disentangle relevant clinical questions that could lead to a more effective management of psychiatric disorders, such as prediction of response to the mood stabilizer lithium, resistance to antidepressants in major depressive disorder or stratification of the risk and outcome prediction in schizophrenia. In this narrative review, we summarized the most important findings in precision medicine in psychiatry based on studies that constructed machine learning models using clinical, neuroimaging and/or biological data. Limitations and barriers to the implementation of precision psychiatry in the clinical setting, as well as possible solutions and future perspectives, will be presented.
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Project description: Not available
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