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https://www.readbyqxmd.com/read/30257247/the-future-experimental-therapies-for-renal-disease-in-diabetes
#1
REVIEW
Georgia E Fouli, Luigi Gnudi
Diabetic nephropathy is the commonest cause of end-stage renal disease and affects between 30 and 45% of patients with diabetes mellitus. There is no cure for diabetic nephropathy and the current management of this condition includes glycaemic control, blockade of the renin-angiotensin aldosterone system and lifestyle changes. However, many patients eventually progress to end-stage renal disease. The exact pathogenesis of diabetic nephropathy is still being researched, and recent advances have led to the development of several novel potential therapeutic targets...
September 26, 2018: Nephron
https://www.readbyqxmd.com/read/29503620/oxidative-stress-and-renal-fibrosis-recent-insights-for-the-development-of-novel-therapeutic-strategies
#2
REVIEW
Wenshan Lv, George W Booz, Fan Fan, Yangang Wang, Richard J Roman
Chronic kidney disease (CKD) is a significant worldwide healthcare problem. Regardless of the initial injury, renal fibrosis is the common final pathway leading to end stage renal disease. Although the underlying mechanisms are not fully defined, evidence indicates that besides inflammation, oxidative stress plays a crucial role in the etiology of renal fibrosis. Oxidative stress results from an imbalance between the production of free radicals that are often increased by inflammation and mitochondrial dysfunction, and reduced anti-oxidant defenses...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29374293/effects-of-the-sglt2-inhibitor-ipragliflozin-on-various-diabetic-symptoms-and-progression-of-overt-nephropathy-in-type-2-diabetic-mice
#3
Atsuo Tahara, Toshiyuki Takasu
Diabetic nephropathy is the leading cause of end-stage renal disease and is associated with high-cardiovascular risk and significant morbidity and mortality. The recent development of sodium-glucose cotransporter (SGLT) 2 inhibitors offers a new antidiabetic therapy via enhanced glucose excretion; however, the beneficial effect of these drugs on the development of type 2 diabetic overt nephropathy is still largely unclear. We examined the therapeutic effects of the SGLT2 inhibitor ipragliflozin on various diabetic symptoms and the progression of nephropathy in uninephrectomized type 2 diabetic mice, which exhibit not only typical diabetic symptoms, such as impaired insulin secretion, glucose intolerance, hyperglycemia, and obesity, but also overt nephropathy with decline in renal function...
April 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28911396/myrciaria-cauliflora-extracts-attenuate-diabetic-nephropathy-involving-the-ras-signaling-pathway-in-streptozotocin-nicotinamide-mice-on-a-high-fat-diet
#4
Chia-Chun Wu, Chi-Nan Hung, Yi-Chen Shin, Chau-Jong Wang, Hui-Pei Huang
Diabetic nephropathy (DN) is a major cause of end-stage renal disease and its mortality is continuously increasing worldwide. Previous studies indicate that reactive oxygen species play an important role in high glucose-induced renal injury. Myrciaria cauliflora has been reported as a functional food rich in anthocyanins possessing anti-oxidative and anti-inflammatory properties. This study examined whether M. cauliflora extracts (MCE) can attenuate diabetic nephropathy progression in type 2 diabetes mellitus mice...
January 2016: Journal of Food and Drug Analysis
https://www.readbyqxmd.com/read/27854278/n-methyl-2-pyridone-5-carboxamide-2py-major-metabolite-of-nicotinamide-an-update-on-an-old-uremic-toxin
#5
REVIEW
Aurélie Lenglet, Sophie Liabeuf, Sandra Bodeau, Loïc Louvet, Aurélien Mary, Agnès Boullier, Anne Sophie Lemaire-Hurtel, Alexia Jonet, Pascal Sonnet, Said Kamel, Ziad A Massy
N-methyl-2-pyridone-5-carboxamide (2PY, a major metabolite of nicotinamide, NAM) was recently identified as a uremic toxin. Recent interventional trials using NAM to treat high levels of phosphorus in end-stage renal disease have highlighted new potential uremic toxicities of 2PY. In the context of uremia, the accumulation of 2PY could be harmful-perhaps by inhibiting poly (ADP-ribose) polymerase-1 activity. Here, we review recently published data on 2PY's metabolism and toxicological profile.
November 15, 2016: Toxins
https://www.readbyqxmd.com/read/26627442/polymorphisms-in-nadph-oxidase-cyba-gene-modify-the-risk-of-esrd-in-patients-with-chronic-glomerulonephritis
#6
Hui Zhou, Min Chen, Ying Zhu, Bing Wang, Xiao-ning Liu, Zhi Zuo, Feng-Ying Tang
End-stage renal disease (ESRD) was defined as start of renal replacement therapy or death due to kidney disease. However, death due to acute kidney injury was not included. It typically occurs when chronic renal failure progresses to a point where the kidneys are permanently functioning at less than 10% of their capacity. Oxidative stress (OS) plays a crucial role in ESRD. Nicotinamide adenine dinucleotide phosphate (NADPH) is one of the most important enzymes during oxidative stress. Cytochrome b light chain (CYBA), encoded by a polymorphic gene, which is a critical component of the nicotinamide adenine dinucleotide (NADH)/NADPH oxidase system and plays an important role in electron transport and superoxide anion production, is located on chromosome band 16q24 and has six exons spanning almost 7...
2016: Renal Failure
https://www.readbyqxmd.com/read/26598845/niacin-and-chronic-kidney-disease
#7
Yutaka Taketani, Masashi Masuda, Hisami Yamanaka-Okumura, Sawako Tatsumi, Hiroko Segawa, Ken-ichi Miyamoto, Eiji Takeda, Hironori Yamamoto
Chronic kidney disease (CKD) is an increasing problem worldwide. The number of end-stage renal disease patients requiring treatment by dialysis is estimated to be increasing by 10,000 patients per year in Japan. Furthermore, an estimated 13 million people are living with CKD in Japan. Various complications are associated with CKD, including cardiovascular disease (CVD). More than one-third of CKD patients die from CVD. Thus, prevention of CVD is a primary concern for the treatment of CKD patients. CKD-mineral and bone disorder (CKD-MBD) is a serious complication that typically leads to CVD...
2015: Journal of Nutritional Science and Vitaminology
https://www.readbyqxmd.com/read/26588494/the-emerging-role-of-sirtuin-1-in-cellular-metabolism-diabetes-mellitus-diabetic-kidney-disease-and-hypertension
#8
REVIEW
A Guclu, F M Erdur, K Turkmen
Despite diagnostic and therapeutic approaches, diabetic kidney disease (DKD) is the most common cause of end-stage renal disease worldwide. Sirtuins, a group of nicotinamid adenine dinucleotide (NAD) dependent enzymes, can deacetylase target enzymes that regulate a wide variety of cellular processes regarding protein, carbohydrate and lipid metabolism, mitochondrial homeostasis and programmed cell death mechanisms including autophagy and apoptosis. Among sirtuins, sirtuin 1 (SIRT1) has been the most studied one in the pathogenesis and progression of DKD...
March 2016: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/26420678/efficacy-and-safety-of-nicotinamide-in-the-management-of-hyperphosphatemia-in-pediatric-patients-on-regular-hemodialysis
#9
RANDOMIZED CONTROLLED TRIAL
Radwa El Borolossy, Lamia Mohamed El Wakeel, Ihab El Hakim, Nagwa Sabri
BACKGROUND: Hyperphosphatemia is a common problem in patients with end-stage renal disease (ESRD) who are on maintenance hemodialysis (HD) and contributes to the development of secondary hyperparathyroidism and cardiovascular complications. Nicotinamide (NAM) has been shown in some studies to inhibit intestinal and renal sodium/phosphorus co-transporters and reduce serum phosphorus levels. We have therefore evaluated the efficacy and safety of NAM as adjunctive therapy to calcium-based phosphate binders to control hyperphosphatemia in hemodialysis patients...
February 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/25967123/rationale-and-approaches-to-phosphate-and-fibroblast-growth-factor-23-reduction-in-ckd
#10
REVIEW
Tamara Isakova, Joachim H Ix, Stuart M Sprague, Kalani L Raphael, Linda Fried, Jennifer J Gassman, Dominic Raj, Alfred K Cheung, John W Kusek, Michael F Flessner, Myles Wolf, Geoffrey A Block
Patients with CKD often progress to ESRD and develop cardiovascular disease (CVD), yet available therapies only modestly improve clinical outcomes. Observational studies report independent associations between elevated serum phosphate and fibroblast growth factor 23 (FGF23) levels and risks of ESRD, CVD, and death. Phosphate excess induces arterial calcification, and although elevated FGF23 helps maintain serum phosphate levels in the normal range in CKD, it may contribute mechanistically to left ventricular hypertrophy (LVH)...
October 2015: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/25862415/allelic-variations-in-the-cyba-gene-of-nadph-oxidase-and-risk-of-kidney-complications-in-patients-with-type-1-diabetes
#11
Thiago A Patente, Kamel Mohammedi, Naïma Bellili-Muñoz, Fathi Driss, Manuel Sanchez, Frédéric Fumeron, Ronan Roussel, Samy Hadjadj, Maria Lúcia Corrêa-Giannella, Michel Marre, Gilberto Velho
Oxidative stress plays a pivotal role in the pathophysiology of diabetic nephropathy, and the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system is an important source of reactive oxygen species in hyperglycemic conditions in the kidney. Plasma concentration of advanced oxidation protein products (AOPP), a marker of oxidative stress, is increased in patients with diabetic nephropathy. We investigated associations of variants in the CYBA gene, encoding the regulatory subunit p22(phox) of NADPH oxidase, with diabetic nephropathy and plasma AOPP and myeloperoxidase (MPO) concentrations in type 1 diabetic patients...
September 2015: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/25567503/plasma-renalase-in-chronic-kidney-disease-differences-and-similarities-between-humans-and-rats
#12
REVIEW
Janete Quelhas-Santos, Manuel Pestana
Renalase was described in 2005 as a new flavoprotein expressed mainly in the kidney that functions as a flavin adenine dinucleotide (FAD)- and nicotinamide adenine dinucleotide (NADH)-dependent amine oxidase. In contrast to other monoamine oxidases, renalase can be secreted into both plasma and urine where it has been suggested to metabolise catecholamines and contribute to blood pressure control. Renalase was first reported to be undetectable in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD), suggesting a causal link between the reduced plasma renalase levels, increased plasma catecholamine, and heightened cardiovascular risk that are well documented in this population...
2014: Current Hypertension Reviews
https://www.readbyqxmd.com/read/25342908/niacin-as-a-drug-repositioning-candidate-for-hyperphosphatemia-management-in-dialysis-patients
#13
REVIEW
Sooyoung Shin, Sukhyang Lee
Nearly all patients with end-stage renal disease develop hyperphosphatemia. These patients typically require oral phosphate binders for life-long phosphorus management, in addition to dietary restrictions and maintenance dialysis. Recently, niacin, a traditional antilipemic agent, drew attention as an experimental treatment for hyperphosphatemia. The purpose of this article was to report on new findings regarding niacin's novel effects and to review the possibility of repurposing niacin for hyperphosphatemia treatment in dialysis patients by elucidating its safety and efficacy profiles along with its synergistic clinical benefits...
2014: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/25176603/therapeutic-targets-for-treating-fibrotic-kidney-diseases
#14
REVIEW
So-Young Lee, Sung I Kim, Mary E Choi
Renal fibrosis is the hallmark of virtually all progressive kidney diseases and strongly correlates with the deterioration of kidney function. The renin-angiotensin-aldosterone system blockade is central to the current treatment of patients with chronic kidney disease (CKD) for the renoprotective effects aimed to prevent or slow progression to end-stage renal disease (ESRD). However, the incidence of CKD is still increasing, and there is a critical need for new therapeutics. Here, we review novel strategies targeting various components implicated in the fibrogenic pathway to inhibit or retard the loss of kidney function...
April 2015: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/24409659/visfatin-is-not-associated-with-inflammatory-markers-in-patients-on-hemodialysis
#15
Ivana Celap, Ana-Maria Simundic, Nora Nikolac, Marijana Miler, Ivana Zec, Karmela Altabas, Sinisa Sefer
BACKGROUND: Cardiovascular events are a major cause of death in patients with end-stage renal disease. Endothelial dysfunction represents a key event in atherosclerosis development and has been implicated in the pathophysiology of different forms of cardiovascular disease, including chronic kidney disease. In recent years, visfatin, a ubiquitous adipokine, has been described as a potent marker of endothelial inflammation and dysfunction. The aim of the study was to investigate the association of visfatin with well-known markers of inflammation and endothelial dysfunction...
2013: Clinical Laboratory
https://www.readbyqxmd.com/read/24287278/endogenous-nampt-dampens-chemokine-expression-and-apoptotic-responses-in-stressed-tubular-cells
#16
Alberto Benito-Martin, Alvaro C Ucero, María Concepción Izquierdo, Beatriz Santamaria, Belén Picatoste, Susana Carrasco, Oscar Lorenzo, Marta Ruiz-Ortega, Jesus Egido, Alberto Ortiz
Diabetic nephropathy (DN) is the most common cause of end-stage renal disease and identification of new therapeutic targets is needed. Nicotinamide phosphoribosyltransferase (NAMPT) is both an extracellular and intracellular protein. Circulating NAMPT is increased in diabetics and in chronic kidney disease patients. The role of NAMPT in renal cell biology is poorly understood. NAMPT mRNA and protein were increased in the kidneys of rats with streptozotocin-induced diabetes. Immunohistochemistry localized NAMPT to glomerular and tubular cells in diabetic rats...
February 2014: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/24140862/contribution-of-endogenously-produced-reactive-oxygen-species-to-the-activation-of-podocyte-nlrp3-inflammasomes-in-hyperhomocysteinemia
#17
Justine M Abais, Min Xia, Guangbi Li, Todd W B Gehr, Krishna M Boini, Pin-Lan Li
Hyperhomocysteinemia (hHcys) is an important pathogenic factor contributing to the progression of end-stage renal disease. Recent studies have demonstrated the implication of nicotinamide adenine dinucleotide phosphate oxidase-mediated NLRP3 inflammasome activation in the development of podocyte injury and glomerular sclerosis during hHcys. However, it remains unknown which reactive oxygen species (ROS) are responsible for this activation of NLRP3 inflammasomes and how such action of ROS is controlled. This study tested the contribution of common endogenous ROS including superoxide (O2(-)), hydrogen peroxide (H2O2), peroxynitrite (ONOO(-)), and hydroxyl radical (OH) to the activation of NLRP3 inflammasomes in mouse podocytes and glomeruli...
February 2014: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/24000048/use-of-nicotinamide-to-treat-hyperphosphatemia-in-dialysis-patients
#18
REVIEW
Aurélie Lenglet, Sophie Liabeuf, Pauline Guffroy, Albert Fournier, Michel Brazier, Ziad A Massy
Hyperphosphatemia in chronic kidney disease (CKD) has been associated with elevated cardiovascular morbidity and mortality. Serum phosphate control remains a cornerstone of the clinical management of patients with CKD, in order to both attenuate the progression of secondary hyperparathyroidism or bone disease and (possibly) reduce the risk of vascular calcification. Despite technical improvements in dialysis and the use of dietary restrictions, drug therapy is often required to control phosphate levels in patients with end-stage renal disease (ESRD)...
September 2013: Drugs in R&D
https://www.readbyqxmd.com/read/23526664/nicotinic-acid-and-nicotinamide-a-review-of-their-use-for-hyperphosphatemia-in-dialysis-patients
#19
REVIEW
Amanda Rennick, Rabih Kalakeche, Lindsey Seel, Brian Shepler
Phosphate binders have traditionally been used to treat hyperphosphatemia, a common complication in patients with end stage renal disease (ESRD). New evidence suggests that nicotinic acid and its metabolites may effectively decrease phosphorus absorption in the gastrointestinal tract, thereby reducing serum phosphorus concentrations. We conducted a literature search to identify studies of patients with ESRD on dialysis that evaluated the role of niacin and related compounds in decreasing serum phosphorus levels...
June 2013: Pharmacotherapy
https://www.readbyqxmd.com/read/23485535/effect-of-silymarin-on-streptozotocin-nicotinamide-induced-type-2-diabetic-nephropathy-in-rats
#20
Nagarajan Sheela, Manonmani Alvin Jose, Duraiswami Sathyamurthy, Balasubramanian Nandha Kumar
INTRODUCTION: Diabetic nephropathy is the major cause of end-stage renal disease worldwide. Silymarin is a flavonoid mixture obtained from Silybum marianum. Various preclinical and clinical studies have revealed that it has antidiabetic activity. The objective of this study was to evaluate the effect of silymarin on type 2 diabetic nephropathy in rats. MATERIALS AND METHODS: Non-insulin-dependent diabetes mellitus was induced in overnight-fasted male albino Wistar rats by an intramuscular injection of streptozotocin and nicotinamide...
March 2013: Iranian Journal of Kidney Diseases
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