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Seminars in Nephrology

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https://read.qxmd.com/read/30827343/emerging-in-vitro-systems-to-screen-and-predict-drug-induced-kidney-toxicity
#1
REVIEW
Tom T G Nieskens, Anna-Karin Sjögren
Drug attrition related to kidney toxicity remains a challenge in drug discovery and development. In vitro models established over the past 2 decades to supplement in vivo studies have improved the throughput capacity of toxicity evaluation, but usually suffer from low predictive value. To achieve a paradigm shift in the prediction of drug-induced kidney toxicity, two aspects are fundamental: increased physiological relevance of the kidney model, and use of appropriate toxicity end points. Recent studies have suggested that increasing the physiological relevance of kidney models can improve their sensitivity to drug-induced damage...
March 2019: Seminars in Nephrology
https://read.qxmd.com/read/30827342/translational-safety-biomarkers-of-kidney-injury
#2
REVIEW
Sean P Troth, Katerina Vlasakova, Shashi Amur, Rupesh P Amin, Warren E Glaab
Acute kidney injury continues to be a common problem and there continues to be a medical need for sensitive translational biomarkers for clinical monitoring. The past decade has yielded unprecedented progress in fundamental research into novel kidney biomarker evaluation and the mechanistic understanding of kidney injury; as such, these novel biomarkers increasingly are being used in preclinical drug development and in early clinical trials of drug candidates on a case-by-case basis, as well as in medical and veterinary practice...
March 2019: Seminars in Nephrology
https://read.qxmd.com/read/30827341/kidney-pathology-and-investigative-nephrotoxicology-strategies-across-species
#3
REVIEW
Kendall S Frazier, Anne M Ryan, Richard A Peterson, Leslie A Obert
Drug-induced kidney toxicity is a significant contributor to acute kidney injury. Nephrotoxic drugs need to be identified during nonclinical testing to highlight potential risk translatable to the intended patient population. When nonclinical kidney toxicity signals arise, scientists and physicians affiliated with clinical trials need to be familiar with commonly encountered drug-induced perturbations in the kidney, terminology, and how these changes relate to clinical risk. Mechanistic and translational toxicologic studies beyond routine histopathology and clinical pathology approaches may be needed to elucidate the pathogenesis and human relevance to inform clinical risk assessment...
March 2019: Seminars in Nephrology
https://read.qxmd.com/read/30827340/modeling-exposure-to-understand-and-predict-kidney-injury
#4
REVIEW
Zhenhong Li, Ciaran Fisher, Iain Gardner, Avijit Ghosh, John Litchfield, Tristan S Maurer
Exposure is a critically important aspect to consider in the study and management of drug-induced kidney injury. Although blood concentrations of kidney toxicants often may provide a valid surrogate measure of kidney exposure, the kidney has several unique physiological and biochemical properties that lend themselves to accumulation or exclusion of some drugs at sites of toxicity. In such cases, an understanding of these pharmacokinetic mechanisms can be as important as understanding the underlying mechanisms of toxicity...
March 2019: Seminars in Nephrology
https://read.qxmd.com/read/30827339/xenobiotic-transporters-in-the-kidney-function-and-role-in-toxicity
#5
REVIEW
Hong Shen, Renato J Scialis, Lois Lehman-McKeeman
The kidney plays a critical role in the elimination of many xenobiotics, and drug-induced kidney injury is a risk factor in drug discovery and development. In addition, accumulation of nephrotoxic compounds, a process often controlled by xenobiotic transporters, is often a prerequisite to kidney injury. Such adverse events are dependent on many transporters, particularly those in the solute carrier and adenosine triphosphate-binding cassette superfamilies. This review details the current understanding of how kidney transporters contribute to toxic outcomes and highlights critical knowledge gaps regarding species differences that account for some lack of predictivity between preclinical animal models and human beings...
March 2019: Seminars in Nephrology
https://read.qxmd.com/read/30827338/epigenetic-regulation-in-kidney-toxicity-insights-from-cisplatin-nephrotoxicity
#6
REVIEW
Xiaohong Xiang, Chunyuan Guo, Chengyuan Tang, Juan Cai, Zheng Dong
Nephrotoxicity, as a result of the exposure of kidney to endogenous and exogenous toxins, is an important factor for acute kidney injury and the development of progressive chronic kidney disease. Cisplatin is among the most widely studied kidney toxicants. In the past decade, epigenetic regulation has emerged as a notable pathogenic mechanism in cisplatin nephrotoxicity, including DNA methylation, histone modification, and noncoding RNAs. In this review, we use cisplatin nephrotoxicity as an example to highlight the epigenetic alteration, function, and underlying mechanism in kidney toxicity...
March 2019: Seminars in Nephrology
https://read.qxmd.com/read/30827337/cellular-and-molecular-mechanisms-of-kidney-toxicity
#7
REVIEW
Lillie Marie A Barnett, Brian S Cummings
Toxicant-induced acute kidney injury is responsible for millions of deaths each year. An underlying cause of toxicant-induced acute kidney injury is renal cell death. As such, understanding the mechanisms by which toxicants cause renal cell death can aid the development of targeted therapies for the prevention and treatment of kidney disease. Accordingly, this article focuses on cellular and molecular mechanisms of nephrotoxicity. This article describes specific factors that make the kidney vulnerable to toxicants...
March 2019: Seminars in Nephrology
https://read.qxmd.com/read/30827336/environmental-and-genetic-factors-influencing-kidney-toxicity
#8
REVIEW
Lawrence H Lash
The kidneys are a frequent target organ for toxicity from exposures to various environmental chemicals and agents. To understand the risk to human health from such exposures, it is important to consider both the underlying chemical and pathologic mechanisms and factors that may modify susceptibility to injury. Choices of exemplary environmental agents to review are based on those with selective effects on the kidneys and for which significant amounts of mechanistic and human data are available. These include the heavy metals cadmium and arsenic, fluoride, the organic solvents trichloroethylene and perchloroethylene, drinking water disinfection by-products haloacids, food and herbal drug contaminants aristolochic acid and melamine, and heat stress...
March 2019: Seminars in Nephrology
https://read.qxmd.com/read/30827335/kidney-safety-assessment-current-practices-in-drug-development
#9
REVIEW
Sean P Troth, Frank Simutis, Gary S Friedman, Susan Todd, Frank D Sistare
The kidney's role as a major route of metabolism and clearance of xenobiotics and its ability to concentrate the glomerular filtrate make it particularly vulnerable to drug-induced toxicity. Improving kidney safety is an active area of research and there is a need in early stages of drug development for strategies and model systems to reliably identify nephrotoxic compounds and sufficiently characterize mechanisms to support drug pipeline decision making. In later stages of drug development the value of sensitive translational biomarkers to monitor kidney toxicity across species in nonclinical and clinical settings is gaining realization...
March 2019: Seminars in Nephrology
https://read.qxmd.com/read/30827334/introduction-kidney-safety-science
#10
EDITORIAL
Vishal S Vaidya
No abstract text is available yet for this article.
March 2019: Seminars in Nephrology
https://read.qxmd.com/read/30606411/kidney-immune-system-crosstalk-in-aki
#11
REVIEW
Kai Singbartl, Cassandra L Formeck, John A Kellum
Acute kidney injury (AKI) now is recognized as a systemic disease. It occurs frequently in critically ill patients and has profound effects on morbidity and mortality. Recent research efforts have shown a bidirectional interplay between AKI and the immune system. Both innate and adaptive immune responses mediate renal injury as well as recovery from AKI. Dendritic cells, monocytes/macrophages, neutrophils, T lymphocytes, and B lymphocytes all play specific roles in the development of AKI. M2 macrophages and regulatory T cells also are pivotal in controlling inflammation, tissue remodeling, and repair after AKI...
January 2019: Seminars in Nephrology
https://read.qxmd.com/read/30606410/aki-and-the-neuroimmune-axis
#12
REVIEW
Shinji Tanaka, Mark D Okusa
Neuroimmune interaction is an emerging concept, wherein the nervous system modulates the immune system and vice versa. This concept is gaining attention as a novel therapeutic target in various inflammatory diseases including acute kidney injury (AKI). Vagus nerve stimulation or treatment with pulsed ultrasound activates the cholinergic anti-inflammatory pathway to prevent AKI in mice. The kidneys are innervated by sympathetic efferent and sensory afferent neurons, and these neurons also may play a role in the modulation of inflammation in AKI...
January 2019: Seminars in Nephrology
https://read.qxmd.com/read/30606409/iron-homeostasis-in-healthy-kidney-and-its-role-in-acute-kidney-injury
#13
REVIEW
Yogesh Scindia PhD, Joseph Leeds Md, Sundararaman Swaminathan Md
Iron is required for key aspects of cellular physiology including mitochondrial function and DNA synthesis and repair. However, free iron is an aberration because of its ability to donate electrons, reduce oxygen, and generate reactive oxygen species. Iron-mediated cell injury or ferroptosis is a central player in the pathogenesis of acute kidney injury. There are several homeostatic proteins and pathways that maintain critical balance in iron homeostasis to allow iron's biologic functions yet avoid ferroptosis...
January 2019: Seminars in Nephrology
https://read.qxmd.com/read/30606408/fibroblast-growth-factor-23-and-klotho-in-aki
#14
REVIEW
Marta Christov, Javier A Neyra, Sanjeev Gupta, David E Leaf
Acute kidney injury (AKI) is associated with many of the same mineral metabolite abnormalities that are observed in chronic kidney disease. These include increased circulating levels of the osteocyte-derived, vitamin D-regulating hormone, fibroblast growth factor 23 (FGF23), and decreased renal expression of klotho, the co-receptor for FGF23. Recent data have indicated that increased FGF23 and decreased klotho levels in the blood and urine could serve as novel predictive biomarkers of incident AKI, or as novel prognostic biomarkers of adverse outcomes in patients with established AKI...
January 2019: Seminars in Nephrology
https://read.qxmd.com/read/30606407/dysregulated-mineral-metabolism-in-aki
#15
REVIEW
David E Leaf, Marta Christov
Dysregulated mineral metabolism is a nearly universal sequalae of acute kidney injury (AKI). Abnormalities in circulating mineral metabolites observed in patients with AKI include hypocalcemia, hyperparathyroidism, hyperphosphatemia, decreased vitamin D metabolite levels, and increased fibroblast growth factor 23 levels. We review the pathophysiology of dysregulated mineral metabolism in AKI with a focus on calcium, phosphate, parathyroid hormone, and vitamin D metabolites. We discuss how mineral metabolite levels can serve as novel prognostic markers for incident AKI and other related outcomes in various clinical settings...
January 2019: Seminars in Nephrology
https://read.qxmd.com/read/30606406/cardiorenal-syndrome-in-acute-kidney-injury
#16
REVIEW
Luca Di Lullo, Patrick Bronson Reeves, Antonio Bellasi, Claudio Ronco
Varying degrees of cardiac and kidney dysfunction commonly are observed in hospitalized patients. As a demonstration of the significant interplay between the heart and kidneys, dysfunction or injury of one organ often contributes to dysfunction or injury of the other. The term cardiorenal syndrome (CRS) was proposed to describe this complex organ cross-talk. Type 3 CRS, also known as acute renocardiac syndrome, is a subtype of CRS that occurs when acute kidney injury contributes to or precipitates the development of acute cardiac dysfunction...
January 2019: Seminars in Nephrology
https://read.qxmd.com/read/30606405/pulmonary-consequences-of-acute-kidney-injury
#17
REVIEW
J Pedro Teixeira, Sophia Ambruso, Benjamin R Griffin, Sarah Faubel
Mortality rates among critically ill patients with acute kidney injury (AKI) requiring renal replacement therapy typically exceed 50%, rates that have not improved significantly despite ongoing advancements in renal replacement therapy. A growing body of animal and human data have accumulated over the past 2 decades that have shown that AKI is associated with a series of distant organ effects that may contribute to the persistently high mortality of AKI. In this review, we describe the pulmonary sequelae of AKI, focusing on mechanisms of pulmonary edema in the context of traditional complications of AKI (eg, volume overload, acidosis) and nontraditional complications of AKI (eg, systemic inflammation)...
January 2019: Seminars in Nephrology
https://read.qxmd.com/read/30606404/epidemiology-pathophysiology-and-management-of-hepatorenal-syndrome
#18
REVIEW
Ahmed Adel Amin, Eman Ibrahim Alabsawy, Rajiv Jalan, Andrew Davenport
Acute kidney injury (AKI) is a common presentation in patients with advanced cirrhosis hospitalized with acute decompensation. A new revised classification now divides AKI in cirrhotic patients into two broad subgroups: hepatorenal syndrome AKI (HRS AKI) and non-hepatorenal syndrome AKI (non-HRS AKI). HRS AKI represents the end-stage complication of decompensated cirrhosis with severe portal hypertension and is characterized by worsening of renal function in the absence of prerenal azotemia, nephrotoxicity, and intrinsic renal disease...
January 2019: Seminars in Nephrology
https://read.qxmd.com/read/30606403/gut-microbiota-kidney-cross-talk-in-acute-kidney-injury
#19
REVIEW
Jing Gong, Sanjeev Noel, Jennifer L Pluznick, Abdel Rahim A Hamad, Hamid Rabb
The recent surge in research on the intestinal microbiota has greatly changed our understanding of human biology. Significant technical advances in DNA sequencing analysis and its application to metagenomics and metatranscriptomics has profoundly enhanced our ability to quantify and track complex microbial communities and to begin understanding their impact on human health and disease. This has led to a better understanding of the relationships between the intestinal microbiome and renal physiology/pathophysiology...
January 2019: Seminars in Nephrology
https://read.qxmd.com/read/30606402/introduction-cross-talk-between-the-kidneys-and-remote-organ-systems-in-aki
#20
EDITORIAL
David E Leaf
No abstract text is available yet for this article.
January 2019: Seminars in Nephrology
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