scholarly journals Heme Oxygenase 1: A Defensive Mediator in Kidney Diseases

2021 ◽  
Vol 22 (4) ◽  
pp. 2009
Author(s):  
Anne Grunenwald ◽  
Lubka T. Roumenina ◽  
Marie Frimat

The incidence of kidney disease is rising, constituting a significant burden on the healthcare system and making identification of new therapeutic targets increasingly urgent. The heme oxygenase (HO) system performs an important function in the regulation of oxidative stress and inflammation and, via these mechanisms, is thought to play a role in the prevention of non-specific injuries following acute renal failure or resulting from chronic kidney disease. The expression of HO-1 is strongly inducible by a wide range of stimuli in the kidney, consequent to the kidney’s filtration role which means HO-1 is exposed to a wide range of endogenous and exogenous molecules, and it has been shown to be protective in a variety of nephropathological animal models. Interestingly, the positive effect of HO-1 occurs in both hemolysis- and rhabdomyolysis-dominated diseases, where the kidney is extensively exposed to heme (a major HO-1 inducer), as well as in non-heme-dependent diseases such as hypertension, diabetic nephropathy or progression to end-stage renal disease. This highlights the complexity of HO-1’s functions, which is also illustrated by the fact that, despite the abundance of preclinical data, no drug targeting HO-1 has so far been translated into clinical use. The objective of this review is to assess current knowledge relating HO-1’s role in the kidney and its potential interest as a nephroprotection agent. The potential therapeutic openings will be presented, in particular through the identification of clinical trials targeting this enzyme or its products.

Author(s):  
SHAREEF J. ◽  
SRIDHAR S. B. ◽  
SHARIFF A.

Proton pump inhibitors (PPIs) are most widely used medications for acid related gastrointestinal disorders. Accessible evidence based studies suggest that the increased use of PPI is linked to a greater risk of developing kidney diseases. This review aims to determine the association of kidney disease with the use of proton pump inhibitor with various study designs. PubMed, Scopus and Google Scholar databases as well as a reference list of relevant articles were systematically searched for studies by using the following search terms; ‘proton pump inhibitors’, ‘acute kidney injury’, ‘chronic kidney disease’ and ‘end stage renal disease’. Both observational and randomized controlled trials (RCTs) exploring the association of PPI use with kidney disease were eligible for inclusion. A total of 8 articles, including 9 studies (n = 794,349 participants) were identified and included in the review. Majority of the studies showed a higher risk of kidney outcomes in patients taking PPIs, with effect higher of acute kidney injury (4-to 6-fold) compared with chronic kidney disease and end stage renal disease (1.5-to 2.5-fold). However, the studies suggest that the strength of evidence is weak and could not prove causation. The risk increased considerably with the use of high dose of PPIs and prolonged duration of exposure necessitates the monitoring of renal function. Exercising vigilance in PPI use and cessation of proton pump inhibitor when there is no clear indication may be a reasonable approach to reduce the population burden of kidney diseases.


Author(s):  
I. Dudar ◽  
I. Mykhaloiko

Chronic kidney disease (CKD) has become a global public health problem because of its high prevalence and the accompanying increase in the risk of end-stage renal disease, cardiovascular disease, and premature death. At present there is a number of experimental and clinical data that show that one of the important mechanisms of the pathogenesis of CKD is a violation of the blood coagulation system (hemostasis) both locally in the kidneys and with the capture of the microcirculatory channel of other organs, therefore an important task for specialists in the  nephrology, as well as doctors of other specialties is  understanding  the functioning of the system of hemostasis in normal and in various kidney diseases and the correction of this pathology with drugs. There are several types of haemostasis disorders that may occur in CKD: disseminated intravascular coagulation syndrome (DIC), arterial and venous thrombosis and bleeding. In this review, we tried to determine the place of the DIC in the development and progress of the CKD and to assess the prospects for further research.


2019 ◽  
pp. 373-388
Author(s):  
Fouad T. Chebib ◽  
Vicente E. Torres

Autosomal dominant polycystic kidney disease (ADPKD), the most common monogenic kidney disease, is characterized by relentless development of kidney cysts, hypertension, and eventually end-stage renal disease. The enlargement of the bilateral kidney cysts is gradual throughout the lifetime of the patient until little renal parenchyma is recognizable. At that stage, the average rate of GFR decline is 4.4 to 5.9 mL/min/year. Over the past few years, several advancements in diagnosing, prognosticating, and understanding the pathogenesis of the disease have been made. The natural course of ADPKD makes it an ideal disease to be targeted for renal protection. This chapter discusses various aspects of pathophysiology and molecular pathways and addresses in details the various pharmaceutical and nonpharmaceutical interventions in the journey of prevention of clinical complications of ADPKD.


2020 ◽  
pp. 75-78
Author(s):  
Dimitra Paikopoulou

The world's disease profile is changing, and chronic diseases now account for the majority of global morbidity and mortality. The causes of chronic kidney diseases (CKD) reflect this change. The increase in prevalence of CKD is partly due to a real increase in its frequency (due to the increase in the average age of people surviving), better detection of CKD, but also to the increasing incidence of diabetes and hypertension among people today, not only within the developed world, but also increasingly within the emerging world. Furthermore, hypertension, smoking, hypercholesterolemia, and obesity, currently among the World Health Organization’s (WHO’s) top 10 global health risks, are strongly associated with CKD. The factors, together with increasing diabetes prevalence and an aging population, will result in significant global increases in chronic kidney diseases (CKD) end stage renal disease (ESRD) patients. There are approximately 275000 patients with ESRD in the United States and it is estimated that an additional 8 million US adults have kidney disease (defined as a glomerular filtration rate [GFR] of 60 mL/min per 1.73 m2). Because kidney disease often progresses to ESRD and its attendant complications, the identification of precursors of kidney disease is important, with the belief that interventions will prevent or delay the progression to ESRD.


2021 ◽  
Vol 8 ◽  
Author(s):  
Yunlong Li ◽  
Kuai Ma ◽  
Zhongyu Han ◽  
Mingxuan Chi ◽  
Xiyalatu Sai ◽  
...  

Kidney disease is a general term for heterogeneous damage that affects the function and the structure of the kidneys. The rising incidence of kidney diseases represents a considerable burden on the healthcare system, so the development of new drugs and the identification of novel therapeutic targets are urgently needed. The pathophysiology of kidney diseases is complex and involves multiple processes, including inflammation, autophagy, cell-cycle progression, and oxidative stress. Heme oxygenase-1 (HO-1), an enzyme involved in the process of heme degradation, has attracted widespread attention in recent years due to its cytoprotective properties. As an enzyme with known anti-oxidative functions, HO-1 plays an indispensable role in the regulation of oxidative stress and is involved in the pathogenesis of several kidney diseases. Moreover, current studies have revealed that HO-1 can affect cell proliferation, cell maturation, and other metabolic processes, thereby altering the function of immune cells. Many strategies, such as the administration of HO-1-overexpressing macrophages, use of phytochemicals, and carbon monoxide-based therapies, have been developed to target HO-1 in a variety of nephropathological animal models, indicating that HO-1 is a promising protein for the treatment of kidney diseases. Here, we briefly review the effects of HO-1 induction on specific immune cell populations with the aim of exploring the potential therapeutic roles of HO-1 and designing HO-1-based therapeutic strategies for the treatment of kidney diseases.


2020 ◽  
Vol 3 (2) ◽  
pp. 73-79
Author(s):  
Shanti Khadka ◽  
Rita Adhikari ◽  
Tarun Paudel

Background: Chronic Kidney Disease (CKD) is a progressive irreversible loss of renal function over a period of months or years. When kidney disease progresses, it may eventually lead to kidney failure, which requires dialysis or a kidney transplant to maintains life. Hemodialysis is used for patients who require short term dialysis (days to weeks) and for patients with advanced CKD and End Stage renal Disease (ESRD) who require long term or permanent renal replacement therapy. Hemodialysis significantly and adversely affects the lives of patients, both physically and psychologically. Depression is the most common psychological condition among patients with ESRD. Depression in dialysis patients not only effect mortality, but increased rate of hospitalizations and dialysis withdrawal is also very common. Methods: A descriptive cross sectional research design was carried out to identify the depression level of chronic kidney disease patients receiving Hemodialysis in Western Regional Hospital, Pokhara using Beck Depression Inventory among forty six patients. Results: The study findings revealed that majority of the patients (84.8%) has various degree of depression i.e. mild (21.7%), moderate (30.8%) and severe (32.6%). Only fifteen percent of patient has no depression. There was no statistical association between the level of depression and socio-demographic variables. It can be concluded that the prevalence of depression is high among patients receiving Hemodialysis. Conclusion: The prevalence of depression is high among patients receiving Hemodialysis. It is effective to provide mental health services to the CKD patients receiving Hemodialysis which help them better psychologically adaptation to their disease and improve their quality of life.  


2016 ◽  
Vol 41 (1-3) ◽  
pp. 151-158 ◽  
Author(s):  
James B. Wetmore ◽  
David T. Gilbertson ◽  
Allan J. Collins

Background: While broad-based societal efforts to improve public health have targeted disorders such as cardiovascular disease and cancer for several decades, efforts devoted to kidney disease have developed only more recently. The Peer Kidney Care Initiative, a novel effort designed to address knowledge gaps in the care of patients with kidney disease, examines key disease processes, the roles of geography and seasonality on outcomes, and longitudinal trends in outcomes over time. Summary: Admissions for gastrointestinal bleeds increased approximately 28% between 2004 and 2011 in prevalent patients. Infection with Clostridium difficile increased nearly 70% between 2003 and 2010 in patients within a year of initiation. Admissions for heart failure in prevalent patients decreased approximately 25% between 2004 and 2012, but admissions for volume overload increased a nearly equal amount. Incidence rates varied substantially by geographic region, such that unadjusted rates in the highest region were nearly double than those in the lowest. There was seasonal variation in all-cause mortality of approximately 15-20% in both incident and prevalent patients, suggesting a link between cardiovascular events and seasonally related environmental conditions. New cases of end-stage renal disease fell from 385 per million population in 2003 to 344 in 2012, a decline of approximately 10%. Key Messages: Peer complements existing kidney disease epidemiologic efforts by examining specific actionable disease entities, exploring geographic variation in care, highlighting the role of seasonality on outcomes, and emphasizing the importance of trending outcomes over time as overall societal progress is being made.


Author(s):  
Danielle L Kirkman ◽  
Natalie Bohmke ◽  
Salvatore Carbone ◽  
Ryan S. Garten ◽  
Paula Rodriguez-Miguelez ◽  
...  

Exertional fatigue, defined as the overwhelming and debilitating sense of sustained exhaustion that impacts the ability to perform activities of daily living, is highly prevalent in chronic kidney disease (CKD) and end stage renal disease (ESRD). Subjective reports of exertional fatigue are paralleled by objective measurements of exercise intolerance throughout the spectrum of the disease. The prevalence of exercise intolerance is clinically noteworthy as it leads to increased frailty, worsened quality of life and an increased risk of mortality. The physiological underpinnings of exercise intolerance are multifaceted and still not fully understood. This review aims to provide a comprehensive outline of the potential physiological contributors, both central and peripheral, to kidney disease related exercise intolerance and highlight current and prospective interventions to target this symptom. In this review the kidney disease-related metabolic derangements, cardiac and pulmonary dysfunction, altered physiologic responses to oxygen consumption, vascular derangements and sarcopenia are discussed in the context of exercise intolerance. Lifestyle interventions to improve exertional fatigue, such as aerobic and resistance exercise training, are discussed and the lack of dietary interventions to improve exercise tolerance is highlighted. Current and prospective pharmaceutical and nutraceutical strategies to improve exertional fatigue are also broached. An extensive understanding of the pathophysiological mechanisms of exercise intolerance will allow for the development of more targeted therapeutic approached to improve exertional fatigue and health related quality of life in CKD and ESRD.


2021 ◽  
Vol 12 ◽  
Author(s):  
Ryuichi Nagashima ◽  
Masayuki Iyoda

Innate lymphoid cells (ILCs) are a recently discovered lymphocyte population with high cytokine productive capacity. Type-2 ILCs (ILC2s) are the most studied, and they exert a rapid type-2 immune response to eliminate helminth infections. Massive and sustainable ILC2 activation induces allergic tissue inflammation, so it is important to maintain correct ILC2 activity for immune homeostasis. The ILC2-activating cytokine IL-33 is released from epithelial cells upon tissue damage, and it is upregulated in various kidney disease mouse models and in kidney disease patients. Various kidney diseases eventually lead to renal fibrosis, which is a common pathway leading to end-stage renal disease and is a chronic kidney disease symptom. The progression of renal fibrosis is affected by the innate immune system, including renal-resident ILC2s; however, the roles of ILC2s in renal fibrosis are not well understood. In this review, we summarize renal ILC2 function and characterization in various kidney diseases and highlight the known and potential contributions of ILC2s to kidney fibrosis.


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