Seminars in nephrology
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Seminars in nephrology · Jan 2018
ReviewTranslating Knowledge Into Therapy for Acute Kidney Injury.
No therapies have been shown to improve outcomes in patients with acute kidney injury (AKI). Given the high morbidity and mortality associated with AKI this represents an important unmet medical need. A common feature of all of the therapeutic development efforts for AKI is that none were driven by target selection or preclinical modeling that was based primarily on human data. ⋯ The National Institutes of Health precision medicine initiative offers an opportunity to address this. By creating a molecular tissue atlas of AKI, defining patient subgroups, and identifying critical cells and pathways involved in human AKI, this initiative has the potential to transform our current approach to therapeutic discovery. In this review, we discuss the opportunities and challenges that this initiative presents, with a specific focus on AKI, what additional efforts will be needed to apply these discoveries to therapeutic development, and how we believe this effort might lead to the development of new therapeutics for subsets of patients with AKI.
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Seminars in nephrology · Jan 2018
ReviewPrecision Medicine for Acute Kidney Injury (AKI): Redefining AKI by Agnostic Kidney Tissue Interrogation and Genetics.
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. ⋯ 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.
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Pregnancy-related acute kidney injury (AKI) has declined in incidence in the last three decades, although it remains an important cause of maternal and fetal morbidity and mortality. Pregnancy-related causes of AKI such as preeclampsia, acute fatty liver of pregnancy, HELLP (Hemolysis, Elevated Liver function tests, Low Platelets) syndrome, and the thrombotic microangiopathies (thrombotic thrombocytopenic purpura, atypical hemolytic-uremic syndrome [HUS]) exhibit overlapping features and often present as diagnostic dilemmas. Differentiating among these conditions may be difficult or impossible based on clinical criteria only. ⋯ Non-pregnancy related causes such as volume depletion and pyelonephritis require early and aggressive resuscitative as well as antibiotic measures respectively. We will discuss in this review the various etiologies of AKI in pregnancy, current diagnostic approaches, and the latest treatment strategies. Given the recent trends of increasing maternal age at the time of pregnancy, and the availability of modern reproductive methods increase the risks of AKI in pregnancy in the coming years.
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Seminars in nephrology · May 2017
ReviewNephrology Education and Continuing Education in Resource-Limited Settings.
Nephrology training programs in high-income countries have transitioned from an apprenticeship model to a well-structured, resource-driven model that supports continual professional development. In contrast, in low- and middle-income countries, medical training and in particular nephrology training has lagged behind owing to resource limitations. ⋯ The nephrology training curriculum for low- and middle-income countries ideally should focus on local and regional needs, implementation of preventive measures for risk modification, education of a multidisciplinary health care workforce, raising general awareness of kidney disease, and optimizing the use of available resources. The ultimate goal being overall better recognition and care for patients with kidney disease.
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Seminars in nephrology · Jan 2016
ReviewQuantifying Glomerular Filtration Rates in Acute Kidney Injury: A Requirement for Translational Success.
Acute kidney injury (AKI) remains a vexing clinical problem that results in unacceptably high patient mortality, development of chronic kidney disease, and accelerated progression to end-stage kidney disease. Although clinical risks factors for developing AKI have been identified, there is no reasonable surveillance technique to definitively and rapidly diagnose and determine the extent of severity of AKI in any patient. ⋯ The use of both one- and two-compartment models, as well as continuous monitoring, are being developed. This review documents the need for glomerular filtration rate measurement in AKI patients and discusses the approaches being taken to deliver this overdue technique that is necessary to help propel nephrology to individualization of care and therapeutic success.