Environmental and Occupational Exposures in Kidney Disease
Summary: More than 8 million deaths each year are attributed to noncommunicable environmental hazards where people live, work, and play. Physical or chemical hazards may be inhaled, ingested, or absorbed through the skin, affecting all organ systems, including the kidney. Heavy metals, pesticides, and infections are some of the environmental hazards associated with kidney dysfunction and chronic kidney disease. The severity of the effects of these exposures likely is modulated by the timing and duration of exposure, genetic susceptibility, and other conditions, and may lead to the development of acute and/or chronic kidney...
Source: Seminars in Nephrology - May 1, 2019 Category: Urology & Nephrology Authors: Madeleine K. Scammell, Caryn M. Sennett, Zoe E. Petropoulos, Jeanne Kamal, James S. Kaufman Source Type: research

Genetic and Developmental Factors in Chronic Kidney Disease Hotspots
Summary: Chronic kidney disease increasingly is being recognized as an important global public health problem. Interindividual susceptibility to kidney disease is high and likely is dependent on risk modulation through genetics, fetal and early childhood development, environmental circumstances, and comorbidities. Traditionally, the chronic kidney disease burden has been ascribed largely to hypertension and diabetes. Increasingly, evidence is accumulating that nontraditional risk factors may predominate in some regions and populations, contributing to epidemics of kidney disease. (Source: Seminars in Nephrology)
Source: Seminars in Nephrology - May 1, 2019 Category: Urology & Nephrology Authors: David Friedman, Valerie A. Luyckx Source Type: research

Social Determinants of CKD Hotspots
Summary: Chronic kidney disease (CKD) hotspots are defined as countries, regions, communities, or ethnicities with a higher than average incidence of CKD when compared with the worldwide, country, or regional rates. Here, we describe what is known about socially determined CKD hotspots, that is, the burden of CKD among socially defined communities that often collocate geographically. We focus on the poor, the homeless, and the food insecure, and their intersection with other social determinants of health, including race/ethnicity. (Source: Seminars in Nephrology)
Source: Seminars in Nephrology - May 1, 2019 Category: Urology & Nephrology Authors: Deidra C. Crews, Tessa K. Novick Source Type: research

Mesoamerican Nephropathy
Summary: Mesoamerican endemic nephropathy is a type of chronic kidney disease of unknown origin, present in pockets of high prevalence along the Pacific Ocean coast of the Mesoamerican region, from southwest Mexico to Costa Rica. The disease is common in young adult men, most often yet not exclusively from agricultural communities, and with a high mortality rate. Kidney biopsy specimens show primarily tubular atrophy and interstitial fibrosis with some glomerular changes attributed to ischemia. Exposure to agrochemicals, heavy metals or metalloids, intense physical activity under heat stress with dehydration, infections, a...
Source: Seminars in Nephrology - May 1, 2019 Category: Urology & Nephrology Authors: Ricardo Correa-Rotter, Ram ón García-Trabanino Source Type: research

Chronic Kidney Disease of Unknown Etiology: Hotspots in India and Other Asian Countries
Summary: There has been increased reporting of chronic kidney disease of unknown etiology (CKDu) in certain agricultural communities in the world. In India, an increased prevalence of CKDu has been observed in the states of Andhra Pradesh, Odisha, Goa, and Maharashtra. Although no single causative factor has been proved, several have been proposed: water-borne agrochemicals, silica, chemical flavors in betel nuts, and pesticides. The renal biopsy findings have been similar to those seen in Sri Lanka and Mesoamerican nephropathy in that the predominant findings have been tubular atrophy and interstitial fibrosis with little...
Source: Seminars in Nephrology - May 1, 2019 Category: Urology & Nephrology Authors: Georgi Abraham, Sanjay K. Agarwal, Swarnalatha Gowrishankar, Madhusudan Vijayan Source Type: research

Chronic Interstitial Nephritis in Agricultural Communities (CINAC) in Sri Lanka
Summary: A significant increase in cases of chronic kidney disease has been observed in the dry zone of Sri Lanka. This unusual chronic kidney disease was first reported in the early 1990s among middle-aged paddy farmers. Considering epidemiologic and histopathologic findings, the disease recently was named chronic interstitial nephritis in agricultural communities (CINAC). Twenty-five years after the first report, CINAC is the most significant public health issue in the paddy farming areas with more than 70,000 estimated patients and many deaths. (Source: Seminars in Nephrology)
Source: Seminars in Nephrology - May 1, 2019 Category: Urology & Nephrology Authors: Channa Jayasumana Source Type: research

Balkan Endemic Nephropathy and the Causative Role of Aristolochic Acid
Summary: Balkan endemic nephropathy is a chronic tubulointerstitial disease with insidious onset, slowly progressing to end-stage renal disease and frequently associated with urothelial carcinoma of the upper urinary tract (UTUC). It was described in South-East Europe at the Balkan peninsula in rural areas around tributaries of the Danube River. After decades of intensive investigation, the causative factor was identified as the environmental phytotoxin aristolochic acid (AA) contained in Aristolochia clematitis, a common plant growing in wheat fields that was ingested through home-baked bread. (Source: Seminars in Nephrology)
Source: Seminars in Nephrology - May 1, 2019 Category: Urology & Nephrology Authors: Bojan Jelakovi ć, Živka Dika, Volker M. Arlt, Marie Stiborova, Nikola M. Pavlović, Jovan Nikolić, Jean-Marie Colet, Jean-Louis Vanherweghem, Joëlle L. Nortier Source Type: research

Other Potential CKD Hotspots in the World: The Cases of Mexico and the United States
Summary: Hotspots of chronic kidney disease of unknown etiology (CKDu) have been identified throughout the globe, of which the Mesoamerican nephropathy in Central America is the most conspicuous example. It affects mainly agricultural workers, heat exposure during extenuating shifts leading to sudden dehydration and subsequent acute kidney injury (AKI) episodes is the main hypothesis, with other factors such as environmental and social determinants playing an underlying role. Recent reports have suggested that Mexico and the United States may have newly identified CKDu hotspots. (Source: Seminars in Nephrology)
Source: Seminars in Nephrology - May 1, 2019 Category: Urology & Nephrology Authors: Diego J. Aguilar, Magdalena Madero Source Type: research

CKD Hotspots: Challenges and Areas of Opportunity
This article summarizes the main gaps and areas of opportunity related to CKD hotspots that were discussed in a recent CKD Global Summit sponsored by the International Society of Nephrology. (Source: Seminars in Nephrology)
Source: Seminars in Nephrology - May 1, 2019 Category: Urology & Nephrology Authors: Gregorio T. Obrador, Adeera Levin Source Type: research

Introduction: CKD Hotspots
CKD hotspots refer to countries, regions, communities, or ethnicities with a higher than average incidence of CKD.1 Although noncommunicable diseases, such as diabetes and hypertension, are the leading causes of CKD in developed and in most developing countries, infections and CKD of unknown etiology (CKDu) are the most frequent causes in the majority of CKD hotspots.2,3 The term CKDu has been used to describe CKD that is not attributable to any traditional risk factor, such as diabetes, hypertension, or human immunodeficiency virus. (Source: Seminars in Nephrology)
Source: Seminars in Nephrology - May 1, 2019 Category: Urology & Nephrology Authors: Gregorio T. Obrador, Adeera Levin Source Type: research

Chronic Kidney Disease in New Zealand M āori and Pacific People
Summary: Chronic kidney disease (CKD) disproportionately affects M āori (the indigenous people of New Zealand [NZ]) as well as Pacific people, particularly from Samoa, Tonga, and Fiji. As New Zealand is home to the largest population of Pacific people, New Zealand and the Pacific Islands fulfil the definition of a CKD ‘hotspot’. Although diabetic nephropathy i s the major cause of CKD, with disproportionately higher rates in NZ Māori and Pacific people, there is increasing evidence that there is a familial predisposition to CKD that is not due to diabetes. (Source: Seminars in Nephrology)
Source: Seminars in Nephrology - May 1, 2019 Category: Urology & Nephrology Authors: Robert J. Walker, Malama Tafunai, Amrish Krishnan Source Type: research

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Table of Contents
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Source: Seminars in Nephrology - May 1, 2019 Category: Urology & Nephrology Source Type: research

Introduction: Kidney Safety Science
The three tenets of kidney safety science are as follows: (1) to predict compounds that are potentially toxic to the human kidney before they reach human beings; (2) to show kidney damage can be monitored and reversed for therapeutic candidates with a low therapeutic index for kidney safety; and (3) to counteract kidney damage by developing safe and effective targeted therapeutics (Fig. 1). (Source: Seminars in Nephrology)
Source: Seminars in Nephrology - February 28, 2019 Category: Urology & Nephrology Authors: Vishal S. Vaidya Source Type: research

Kidney Safety Assessment: Current Practices in Drug Development
Summary: 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 setting...
Source: Seminars in Nephrology - February 28, 2019 Category: Urology & Nephrology Authors: Sean P. Troth, Frank Simutis, Gary S. Friedman, Susan Todd, Frank D. Sistare Source Type: research

Environmental and Genetic Factors Influencing Kidney Toxicity
Summary: 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. (Source: Seminars in Nephrology)
Source: Seminars in Nephrology - February 28, 2019 Category: Urology & Nephrology Authors: Lawrence H. Lash Source Type: research

Cellular and Molecular Mechanisms of Kidney Toxicity
This article describes specific factors that make the kidney vulnerable to toxicants. (Source: Seminars in Nephrology)
Source: Seminars in Nephrology - February 28, 2019 Category: Urology & Nephrology Authors: Lillie Marie A. Barnett, Brian S. Cummings Source Type: research

Epigenetic Regulation in Kidney Toxicity: Insights From Cisplatin Nephrotoxicity
Summary: 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. (Source: Seminars in Nephrology)
Source: Seminars in Nephrology - February 28, 2019 Category: Urology & Nephrology Authors: Xiaohong Xiang, Chunyuan Guo, Chengyuan Tang, Juan Cai, Zheng Dong Source Type: research

Modeling Exposure to Understand and Predict Kidney Injury
Summary: 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. (Source: Seminars in Nephrology)
Source: Seminars in Nephrology - February 28, 2019 Category: Urology & Nephrology Authors: Zhenhong Li, Ciaran Fisher, Iain Gardner, Avijit Ghosh, John Litchfield, Tristan S. Maurer Source Type: research

Kidney Pathology and Investigative Nephrotoxicology Strategies Across Species
Summary: 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 ...
Source: Seminars in Nephrology - February 28, 2019 Category: Urology & Nephrology Authors: Kendall S. Frazier, Anne M. Ryan, Richard A. Peterson, Leslie A. Obert Source Type: research

Translational Safety Biomarkers of Kidney Injury
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. (Source: Seminars in Nephrology)
Source: Seminars in Nephrology - February 28, 2019 Category: Urology & Nephrology Authors: Sean P. Troth, Katerina Vlasakova, Shashi Amur, Rupesh P. Amin, Warren E. Glaab Source Type: research

Emerging In Vitro Systems to Screen and Predict Drug-Induced Kidney Toxicity
Summary: 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. (Source: Seminars in Nephrology)
Source: Seminars in Nephrology - February 28, 2019 Category: Urology & Nephrology Authors: Tom T.G. Nieskens, Anna-Karin Sj ögren Source Type: research

Xenobiotic Transporters in the Kidney: Function and Role in Toxicity
Summary: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 spe...
Source: Seminars in Nephrology - February 28, 2019 Category: Urology & Nephrology Authors: Hong Shen, Renato J. Scialis, Lois Lehman-McKeeman Source Type: research

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Source: Seminars in Nephrology - February 28, 2019 Category: Urology & Nephrology Source Type: research

Pulmonary Consequences of Acute Kidney Injury
Summary: 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, volum...
Source: Seminars in Nephrology - December 31, 2018 Category: Urology & Nephrology Authors: J. Pedro Teixeira, Sophia Ambruso, Benjamin R. Griffin, Sarah Faubel Source Type: research

Epidemiology, Pathophysiology, and Management of Hepatorenal Syndrome
Summary: 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. (Source: Seminars in Nephrology)
Source: Seminars in Nephrology - December 31, 2018 Category: Urology & Nephrology Authors: Ahmed Adel Amin, Eman Ibrahim Alabsawy, Rajiv Jalan, Andrew Davenport Source Type: research

Cardiorenal Syndrome in Acute Kidney Injury
Summary: 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. (Source: Seminars in Nephrology)
Source: Seminars in Nephrology - December 31, 2018 Category: Urology & Nephrology Authors: Luca Di Lullo, Patrick Bronson Reeves, Antonio Bellasi, Claudio Ronco Source Type: research

Dysregulated Mineral Metabolism in AKI
Summary: 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...
Source: Seminars in Nephrology - December 31, 2018 Category: Urology & Nephrology Authors: David E. Leaf, Marta Christov Source Type: research

Fibroblast Growth Factor 23 and Klotho in AKI
Summary: 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. (Source: Seminars in Nephrology)
Source: Seminars in Nephrology - December 31, 2018 Category: Urology & Nephrology Authors: Marta Christov, Javier A. Neyra, Sanjeev Gupta, David E. Leaf Source Type: research

Iron Homeostasis in Healthy Kidney and its Role in Acute Kidney Injury
Summary: 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. (Source: Seminars in Nephrology)
Source: Seminars in Nephrology - December 31, 2018 Category: Urology & Nephrology Authors: Yogesh Scindia, PhD, Joseph Leeds, MD, Sundararaman Swaminathan, MD Source Type: research

Kidney-Immune System Crosstalk in AKI
Summary: 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. (Source: Seminars in Nephrology)
Source: Seminars in Nephrology - December 31, 2018 Category: Urology & Nephrology Authors: Kai Singbartl, Cassandra L. Formeck, John A. Kellum Source Type: research

AKI and the Neuroimmune Axis
Summary: 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. (Source: Seminars in Nephrology)
Source: Seminars in Nephrology - December 31, 2018 Category: Urology & Nephrology Authors: Shinji Tanaka, Mark D. Okusa Source Type: research

Gut Microbiota-Kidney Cross-Talk in Acute Kidney Injury
Summary: 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. (Source: Seminars in Nephrology)
Source: Seminars in Nephrology - December 31, 2018 Category: Urology & Nephrology Authors: Jing Gong, Sanjeev Noel, Jennifer L. Pluznick, Abdel Rahim A. Hamad, Hamid Rabb Source Type: research

Introduction: Cross-Talk Between the Kidneys and Remote Organ Systems in AKI
Cross-talk between the kidneys and the heart has long been appreciated. The kidneys are referred to in the Talmud —the central text of Judaism, written during approximately the 4th century AD—as the organs that “give the heart advice and counsel.”1 During the Middle Ages, the Italian physician Gentile da Foligno referred to heart disease as one of the major conditions that affected the color and output of urine.2 In the 19th century the English physician, Richard Bright, observed that cardiac hypertrophy was a common disorder in patients suffering from chronic kidney disease (CKD). (Source: Seminars in Nephrology)
Source: Seminars in Nephrology - December 31, 2018 Category: Urology & Nephrology Authors: David E. Leaf Source Type: research

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Source: Seminars in Nephrology - December 31, 2018 Category: Urology & Nephrology Source Type: research

Update on Chronic Kidney Disease Mineral and Bone Disorder in Cardiovascular Disease
Summary: Chronic kidney disease mineral and bone disorder (MBD) encompasses changes in mineral ion and vitamin D metabolism that are widespread in the setting of chronic kidney disease and end-stage renal disease. MBD components associate with cardiovascular disease in many epidemiologic studies. Through impacts on hypertension, activation of the renin-angiotensin-aldosterone system, vascular calcification, endothelial function, and cardiac remodeling and conduction, MBD may be a direct and targetable cause of cardiovascular disease. (Source: Seminars in Nephrology)
Source: Seminars in Nephrology - November 1, 2018 Category: Urology & Nephrology Authors: Joseph Lunyera, Julia J. Scialla Source Type: research

Cardiovascular Disease in Children and Adolescents With Chronic Kidney Disease
Summary: The lifespan of children with advanced chronic kidney disease (CKD), although improved over the past 2 decades, remains low compared with the general pediatric population. Similar to adults with CKD, cardiovascular disease accounts for a majority of deaths in children with CKD because these patients have a high prevalence of traditional and uremia-related risk factors for cardiovascular disease. The cardiovascular alterations that cause these terminal events begin early in pediatric CKD. (Source: Seminars in Nephrology)
Source: Seminars in Nephrology - November 1, 2018 Category: Urology & Nephrology Authors: Donald J. Weaver, Mark Mitsnefes Source Type: research

Dialysis Prescription and Sudden Death
Summary: In the United States, end-stage renal disease patients receiving hemodialysis have an exceedingly high risk of sudden cardiac death (SCD), accounting for 29% of death events, likely relating to their uremic milieu, recurring exposure to fluid and electrolyte fluxes, and underlying cardiovascular pathology. Furthermore, epidemiologic studies have shown that SCD events, as well as mortality and hospitalizations, occur most frequently on the first dialysis day after the long interdialytic gap, suggesting that abrupt fluctuations in the accumulation and removal of electrolytes, fluid, and uremic toxins over the dialys...
Source: Seminars in Nephrology - November 1, 2018 Category: Urology & Nephrology Authors: Connie M. Rhee, Jason A. Chou, Kamyar Kalantar-Zadeh Source Type: research

Risk Stratification and Treatment of Coronary Disease in Chronic Kidney Disease and End-Stage Kidney Disease
Summary: Patients with advanced chronic kidney disease have an enormous burden of cardiovascular morbidity and mortality, but, paradoxically, their representation in randomized trials for the evaluation and management of coronary artery disease has been limited. Clinicians therefore are faced with the conundrum of synergizing evidence from observational studies, expert opinion, and extrapolation from the general population to provide care to this complex and clinically distinct patient population. (Source: Seminars in Nephrology)
Source: Seminars in Nephrology - November 1, 2018 Category: Urology & Nephrology Authors: Gautam R. Shroff, Tara I. Chang Source Type: research

Heart Failure in End-Stage Kidney Disease: Pathophysiology, Diagnosis, and Therapeutic Strategies
Summary: Heart failure (HF) is a major comorbidity in patients with end-stage kidney disease (ESKD). The pathogenesis of HF in patients on renal replacement therapy represents the confluence of several traditional and nontraditional vascular risk factors, unique to the milieu of chronic kidney disease and the dialysis modality. The diagnosis of HF with ESKD is complicated by the background of frequent inevitable fluid shifts superimposed on underlying myocardial pump abnormalities and dialysis-induced myocardial stunning. (Source: Seminars in Nephrology)
Source: Seminars in Nephrology - November 1, 2018 Category: Urology & Nephrology Authors: Janani Rangaswami, Peter A. McCullough Source Type: research

Oral Anticoagulation in Patients With End-Stage Kidney Disease on Dialysis and Atrial Fibrillation
Summary: Patients with end-stage kidney disease (ESKD) have an elevated incidence of atrial fibrillation (AF) and are at increased risk for thromboembolic events. However, these patients are also at increased risk for bleeding and it is unclear whether they benefit from an oral anticoagulant. Point prevalent on July 1, 2015, only ~28% of dialysis patients with AF were on oral anticoagulation. Warfarin was the most commonly used oral anticoagulant, followed by apixaban, while dabigatran and rivaroxaban were rarely used. (Source: Seminars in Nephrology)
Source: Seminars in Nephrology - November 1, 2018 Category: Urology & Nephrology Authors: Austin Hu, Jingbo Niu, Wolfgang C. Winkelmayer Source Type: research

Causal Connections From Chronic Kidney Disease to Cardiac Fibrosis
Summary: Cardiovascular disease and heart failure are the primary cause of morbidity and mortality in patients with chronic kidney disease. Because impairment of kidney function correlates with heart failure and cardiac fibrosis, a kidney –heart axis is suspected. Although our understanding of the underlying mechanisms still is evolving, the possibility that kidney–heart messengers could be intercepted offers ample reason to focus on this clinically highly relevant problem. Here, we review the current knowledge of how kidney inju ry causes heart failure and fibrosis. (Source: Seminars in Nephrology)
Source: Seminars in Nephrology - November 1, 2018 Category: Urology & Nephrology Authors: Melanie S. Hulshoff, Sandip K. Rath, Xingbo Xu, Michael Zeisberg, Elisabeth M. Zeisberg Source Type: research

Introduction: Cardiovascular Disease in Chronic Kidney Disease
Since Linder's seminal observation of an apparent acceleration of atherosclerosis in hemodialysis patients,1 it has become increasingly clear that individuals with chronic kidney disease (CKD) suffer from an extraordinarily high risk of cardiovascular morbidity and a rate of cardiovascular mortality that increases as kidney function declines and is many-fold higher in individuals with end-stage kidney disease (ESKD) than in those with preserved kidney function. More than 40 years have passed since Lindner's initial report, however, despite the high prevalence of CKD and outsized proportion of Medicare spending dedicated to...
Source: Seminars in Nephrology - November 1, 2018 Category: Urology & Nephrology Authors: David M. Charytan Source Type: research

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