The Pivotal Role of Oxidative Stress in the Pathophysiology of Cardiovascular-Renal Remodeling in Kidney Disease

The excessive activation of the renin-angiotensin system in kidney disease leads to alteration of intracellular pathways which concur altogether to the induction of cardiovascular and renal remodeling, exposing these patients since the very beginning of the renal injury to chronic kidney disease and progression to end stage renal disease, a very harmful and life threatening clinical condition. Oxidative stress plays a pivotal role in the pathophysiology of renal injury and cardiovascular-renal remodeling, the long-term consequence of its effect. This review will examine the role of oxidative stress in the most significant pathways involved in cardiovascular and renal remodeling with a focus on the detrimental effects of oxidative stress-mediated renal abnormalities on the progression of the disease and of its complications. Food for thoughts on possible therapeutic target are proposed on the basis of experimental evidences.

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AT1 antagonism and renin inhibition in mice: pivotal role of targeting angiotensin II in chronic kidney disease

AJP Renal Physiology ◽

10.1152/ajprenal.00672.2011 ◽

2012 ◽

Vol 303 (7) ◽

pp. F1037-F1048 ◽

Cited By ~ 20

Author(s):

Christoph Fraune ◽

Sascha Lange ◽

Christian Krebs ◽

Alexandra Hölzel ◽

Jana Baucke ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Renal Injury ◽

Plasma Concentrations ◽

Renin Angiotensin System ◽

Pivotal Role ◽

Angiotensin System ◽

Renin Angiotensin ◽

Renin Inhibition

The role of the renin-angiotensin system in chronic kidney disease involves multiple peptides and receptors. Exerting antipodal pathophysiological mechanisms, renin inhibition and AT1 antagonism ameliorate renal damage. However, it is unclear which mechanism exerts better nephroprotection. We compared the renin inhibitor aliskiren with the AT1 antagonist losartan in mice with chronic kidney disease due to renal ablation. Doses were adjusted to equipotent inhibition of the renin-angiotensin system, determined via a dose-response quantifying plasma and renal renin expression. Six-week treatment with either 500 mg/l drinking water losartan or 50 mg·kg−1·day−1 aliskiren significantly decreased albuminuria, glomerular damage, and transcription rates of renal injury markers to a similar extent. An array analysis comparing renal gene expression of losartan- and aliskiren-treated mice evaluating >34,000 transcripts demonstrated regulation for 14 genes only, with small differences. No superior nephroprotection was found by combining losartan and aliskiren. Compared with plasma concentrations, aliskiren accumulated ∼7- to 29-fold in the heart, liver, lung, and spleen and ∼156-fold in the kidney. After withdrawal, plasma concentrations dropped to zero within 24 h, whereas renal tissue concentrations declined slowly over days. Withdrawal of aliskiren in mice with chronic kidney disease revealed a significantly delayed re-increase in albuminuria compared with withdrawal of losartan. This study demonstrates equieffective nephroprotection of renin inhibition and AT1 antagonism in mice with chronic kidney disease without additional benefit of combination therapy. These observations underscore the pivotal role of targeting ANG II to reduce renal injury.

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Emerging Therapy-Related Kidney Disease

Archives of Pathology & Laboratory Medicine ◽

10.5858/133.2.268 ◽

2009 ◽

Vol 133 (2) ◽

pp. 268-278

Author(s):

Lois J. Arend ◽

Tibor Nadasdy

Keyword(s):

Kidney Disease ◽

Renal Injury ◽

Recent Literature ◽

Renal Toxicity ◽

Kidney Injury ◽

Clinical History ◽

Drug Induced ◽

Stage Renal Disease ◽

End Stage

Abstract Context.—Many new therapies have emerged within the last 5 to 10 years to treat a variety of conditions. Several of these have direct or indirect renal toxicities that may go undiagnosed without careful attention of the pathologist to a patient's clinical history, particularly the addition of new medications or treatments. Objective.—To discuss patterns of renal injury resulting from medications or therapeutic regimens that have been introduced within the last 10 years. Recognition of these patterns may allow the pathologist to alert the attending clinician to a possible drug-induced renal injury and prevent further deterioration of renal function and possible chronic kidney disease. Data Sources.—A review of recent literature and unpublished observations of case-derived material. Conclusions.—A number of newer therapies have emerged as agents of renal toxicity, producing a variety of pathologic changes in the kidney. The outcome can be acute or chronic glomerular, tubular, interstitial, and/or vascular injury. Some drugs will result in irreversible changes and end-stage renal disease, whereas many of the alterations can be reversed with removal of the offending agent, avoiding potential long-term kidney injury.

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Role of Myeloperoxidase in Patients with Chronic Kidney Disease

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/1069743 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 30

Author(s):

Bojana Kisic ◽

Dijana Miric ◽

Ilija Dragojevic ◽

Julijana Rasic ◽

Ljiljana Popovic

Keyword(s):

Oxidative Stress ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Public Health Problem ◽

Cardiovascular Complications ◽

The Body ◽

Stage Renal Disease ◽

End Stage

Chronic kidney disease (CKD) is a worldwide public health problem. Patients with CKD have a number of disorders in the organism, and the presence of oxidative stress and systemic inflammation in these patients is the subject of numerous studies. Chronic inflammation joined with oxidative stress contributes to the development of numerous complications: accelerated atherosclerosis process and cardiovascular disease, emergence of Type 2 diabetes mellitus, development of malnutrition, anaemia, hyperparathyroidism, and so forth, affecting the prognosis and quality of life of patients with CKD. In this review we presented the potential role of the myeloperoxidase enzyme in the production of reactive/chlorinating intermediates and their role in oxidative damage to biomolecules in the body of patients with chronic kidney disease and end-stage renal disease. In addition, we discussed the role of modified lipoprotein particles under the influence of prooxidant MPO intermediates in the development of endothelial changes and cardiovascular complications in renal failure.

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Chronic Kidney Disease—Effect of Oxidative Stress

Chinese Journal of Biology ◽

10.1155/2014/216210 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6 ◽

Cited By ~ 15

Author(s):

Subha Palaneeswari Meenakshi Sundaram ◽

Sivakumar Nagarajan ◽

Arcot Jagdeeshwaran Manjula Devi

Keyword(s):

Oxidative Stress ◽

Risk Factors ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Disease Effect ◽

Cv Disease ◽

Stage Renal Disease ◽

End Stage ◽

Annual Mortality

Chronic kidney disease (CKD) is a growing health problem with increasing incidence. The annual mortality of end-stage renal disease patients is about 9%, which is 10–20 fold higher than the general population, approximately 50% of these deaths are due to cardiovascular (CV) disease. CV risk factors, such as diabetes, hypertension, and hyperlipidemia, are strongly associated with poor outcome. Many other nontraditional risk factors such as inflammation, infection, oxidative stress, anemia, and malnutrition are also present. In this review we will focus on the role of oxidative stress in chronic kidney disease.

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The Pathogenesis of End-Stage Renal Disease from the Standpoint of the Theory of General Pathological Processes of Inflammation

International Journal of Molecular Sciences ◽

10.3390/ijms222111453 ◽

2021 ◽

Vol 22 (21) ◽

pp. 11453

Author(s):

Evgenii Gusev ◽

Liliya Solomatina ◽

Yulia Zhuravleva ◽

Alexey Sarapultsev

Keyword(s):

Kidney Disease ◽

Renal Disease ◽

Chronic Renal Disease ◽

Classical Type ◽

Low Grade ◽

Systemic Complications ◽

Life Threatening ◽

Microcirculatory Disorders ◽

Stage Renal Disease ◽

End Stage

Chronic kidney disease can progress to end-stage chronic renal disease (ESRD), which requires the use of replacement therapy (dialysis or kidney transplant) in life-threatening conditions. In ESRD, irreversible changes in the kidneys are associated with systemic changes of proinflammatory nature and dysfunctions of internal organs, skeletal muscles, and integumentary tissues. The common components of ESRD pathogenesis, regardless of the initial nosology, are (1) local (in the kidneys) and systemic chronic low-grade inflammation (ChLGI) as a risk factor for diabetic kidney disease and its progression to ESRD, (2) inflammation of the classical type characteristic of primary and secondary autoimmune glomerulonephritis and infectious recurrent pyelonephritis, as well as immune reactions in kidney allograft rejection, and (3) chronic systemic inflammation (ChSI), pathogenetically characterized by latent microcirculatory disorders and manifestations of paracoagulation. The development of ChSI is closely associated with programmed hemodialysis in ESRD, as well as with the systemic autoimmune process. Consideration of ESRD pathogenesis from the standpoint of the theory of general pathological processes opens up the scope not only for particular but also for universal approaches to conducting pathogenetic therapies and diagnosing and predicting systemic complications in severe nephropathies.

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The Potential Role of Catheter-Based Renal Sympathetic Denervation in Chronic and End-Stage Kidney Disease

Journal of Cardiovascular Pharmacology and Therapeutics ◽

10.1177/1074248415624156 ◽

2016 ◽

Vol 21 (4) ◽

pp. 344-352 ◽

Cited By ~ 9

Author(s):

Yusuke Sata ◽

Markus P. Schlaich

Keyword(s):

Blood Pressure ◽

Renal Function ◽

Kidney Disease ◽

End Stage Renal Disease ◽

Renal Denervation ◽

Potential Role ◽

Stage Renal Disease ◽

End Stage ◽

Renal Sympathetic

Sympathetic activation is a hallmark of chronic and end-stage renal disease and adversely affects cardiovascular prognosis. Hypertension is present in the vast majority of these patients and plays a key role in the progressive deterioration of renal function and the high rate of cardiovascular events in this patient cohort. Augmentation of renin release, tubular sodium reabsorption, and renal vascular resistance are direct consequences of efferent renal sympathetic nerve stimulation and the major components of neural regulation of renal function. Renal afferent nerve activity directly influences sympathetic outflow to the kidneys and other highly innervated organs involved in blood pressure control via hypothalamic integration. Renal denervation of the kidney has been shown to reduce blood pressure in many experimental models of hypertension. Targeting the renal nerves directly may therefore be specifically useful in patients with chronic and end-stage renal disease. In this review, we will discuss the potential role of catheter-based renal denervation in patients with impaired kidney function and also reflect on the potential impact on other cardiovascular conditions commonly associated with chronic kidney disease such as heart failure and arrhythmias.

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Role of vitamin D in oxidative stress modulation in end‐stage renal disease patients: A double‐blind randomized clinical trial

Hemodialysis International ◽

10.1111/hdi.12849 ◽

2020 ◽

Vol 24 (3) ◽

pp. 367-373

Author(s):

Leila Malekmakan ◽

Zeinab Karimi ◽

Afshin Mansourian ◽

Maryam Pakfetrat ◽

Jamshid Roozbeh ◽

...

Keyword(s):

Oxidative Stress ◽

Clinical Trial ◽

Vitamin D ◽

Renal Disease ◽

Randomized Clinical Trial ◽

End Stage Renal Disease ◽

Double Blind ◽

Stage Renal Disease ◽

End Stage

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Dietary Antioxidant Supplements and Uric Acid in Chronic Kidney Disease: A Review

Nutrients ◽

10.3390/nu11081911 ◽

2019 ◽

Vol 11 (8) ◽

pp. 1911 ◽

Cited By ~ 18

Author(s):

Stefanos Roumeliotis ◽

Athanasios Roumeliotis ◽

Evangelia Dounousi ◽

Theodoros Eleftheriadis ◽

Vassilios Liakopoulos

Keyword(s):

Oxidative Stress ◽

Chronic Kidney Disease ◽

Uric Acid ◽

Kidney Disease ◽

Serum Levels ◽

Maintenance Hemodialysis ◽

Antioxidant Supplements ◽

Stage Renal Disease ◽

End Stage ◽

And Oxidative Stress

Increased serum levels of uric acid have been associated with the onset and development of chronic kidney disease (CKD), cardiovascular disease, and mortality, through several molecular pathogenetic mechanisms, such as inflammation and oxidative stress. Oxidative stress is present even in the early stages of CKD, progresses parallelly with the deterioration of kidney function, and is even more exacerbated in end-stage renal disease patients undergoing maintenance hemodialysis. Although acting in the plasma as an antioxidant, once uric acid enters the intracellular environment; it behaves as a powerful pro-oxidant. Exogenous intake of antioxidants has been repeatedly shown to prevent inflammation, atherosclerosis and oxidative stress in CKD patients. Moreover, certain antioxidants have been proposed to exert uric acid-lowering properties. This review aims to present the available data regarding the effects of antioxidant supplements on both oxidative stress and uric acid serum levels, in a population particularly susceptible to oxidative damage such as CKD patients.

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The Key Role of Epithelial to Mesenchymal Transition (EMT) in Hypertensive Kidney Disease

International Journal of Molecular Sciences ◽

10.3390/ijms20143567 ◽

2019 ◽

Vol 20 (14) ◽

pp. 3567 ◽

Cited By ~ 3

Author(s):

Teresa Seccia ◽

Brasilina Caroccia ◽

Maria Piazza ◽

Gian Paolo Rossi

Keyword(s):

Kidney Disease ◽

Molecular Mechanisms ◽

Epithelial To Mesenchymal Transition ◽

Renal Diseases ◽

Hypertensive Nephropathy ◽

Mesenchymal Transition ◽

Afferent Arterioles ◽

Stage Renal Disease ◽

End Stage

Accumulating evidence indicates that epithelial-to-mesenchymal transition (EMT), originally described as a key process for organ development and metastasis budding in cancer, plays a key role in the development of renal fibrosis in several diseases, including hypertensive nephroangiosclerosis. We herein reviewed the concept of EMT and its role in renal diseases, with particular focus on hypertensive kidney disease, the second leading cause of end-stage renal disease after diabetes mellitus. After discussing the pathophysiology of hypertensive nephropathy, the ‘classic’ view of hypertensive nephrosclerosis entailing hyalinization, and sclerosis of interlobular and afferent arterioles, we examined the changes occurring in the glomerulus and tubulo-interstitium and the studies that investigated the role of EMT and its molecular mechanisms in hypertensive kidney disease. Finally, we examined the reasons why some studies failed to provide solid evidence for renal EMT in hypertension.

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