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Metabolic causes of progression renal diseases

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https://www.readbyqxmd.com/read/28437467/mutant-uromodulin-expression-leads-to-altered-homeostasis-of-the-endoplasmic-reticulum-and-activates-the-unfolded-protein-response
#1
Céline Schaeffer, Stefania Merella, Elena Pasqualetto, Dejan Lazarevic, Luca Rampoldi
Uromodulin is the most abundant urinary protein in physiological conditions. It is exclusively produced by renal epithelial cells lining the thick ascending limb of Henle's loop (TAL) and it plays key roles in kidney function and disease. Mutations in UMOD, the gene encoding uromodulin, cause autosomal dominant tubulointerstitial kidney disease uromodulin-related (ADTKD-UMOD), characterised by hyperuricemia, gout and progressive loss of renal function. While the primary effect of UMOD mutations, retention in the endoplasmic reticulum (ER), is well established, its downstream effects are still largely unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28436957/pyruvate-kinase-m2-activation-may-protect-against-the-progression-of-diabetic-glomerular-pathology-and-mitochondrial-dysfunction
#2
Weier Qi, Hillary A Keenan, Qian Li, Atsushi Ishikado, Aimo Kannt, Thorsten Sadowski, Mark A Yorek, I-Hsien Wu, Samuel Lockhart, Lawrence J Coppey, Anja Pfenninger, Chong Wee Liew, Guifen Qiang, Alison M Burkart, Stephanie Hastings, David Pober, Christopher Cahill, Monika A Niewczas, William J Israelsen, Liane Tinsley, Isaac E Stillman, Peter S Amenta, Edward P Feener, Matthew G Vander Heiden, Robert C Stanton, George L King
Diabetic nephropathy (DN) is a major cause of end-stage renal disease, and therapeutic options for preventing its progression are limited. To identify novel therapeutic strategies, we studied protective factors for DN using proteomics on glomeruli from individuals with extreme duration of diabetes (ł50 years) without DN and those with histologic signs of DN. Enzymes in the glycolytic, sorbitol, methylglyoxal and mitochondrial pathways were elevated in individuals without DN. In particular, pyruvate kinase M2 (PKM2) expression and activity were upregulated...
April 24, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28403850/rationale-and-design-of-a-multicenter-placebo-controlled-double-blind-randomized-trial-to-evaluate-the-effect-of-empagliflozin-on-endothelial-function-the-emblem-trial
#3
RANDOMIZED CONTROLLED TRIAL
Atsushi Tanaka, Michio Shimabukuro, Yosuke Okada, Isao Taguchi, Minako Yamaoka-Tojo, Hirofumi Tomiyama, Hiroki Teragawa, Seigo Sugiyama, Hisako Yoshida, Yasunori Sato, Atsushi Kawaguchi, Yumi Ikehara, Noritaka Machii, Tatsuya Maruhashi, Kosuke R Shima, Toshinari Takamura, Yasushi Matsuzawa, Kazuo Kimura, Masashi Sakuma, Jun-Ichi Oyama, Teruo Inoue, Yukihito Higashi, Shinichiro Ueda, Koichi Node
BACKGROUND: Type 2 diabetes mellitus (T2DM) is characterized by systemic metabolic abnormalities and the development of micro- and macrovascular complications, resulting in a shortened life expectancy. A recent cardiovascular (CV) safety trial, the EMPA-REG OUTCOME trial, showed that empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, markedly reduced CV death and all-cause mortality and hospitalization for heart failure in patients with T2DM and established CV disease (CVD)...
April 12, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28397867/oxidative-stress-causes-hypertension-and-activation-of-nuclear-factor-%C3%AE%C2%BAb-after-high-fructose-and-salt-treatments
#4
Waleska C Dornas, Leonardo M Cardoso, Maísa Silva, Natália L S Machado, Deoclécio A Chianca-Jr, Andréia C Alzamora, Wanderson G Lima, Vincent Lagente, Marcelo E Silva
There is evidence that diets rich in salt or simple sugars as fructose are associated with abnormalities in blood pressure regulation. However, the mechanisms underlying pathogenesis of salt- and fructose-induced kidney damage and/or consequent hypertension yet remain largely unexplored. Here, we tested the role of oxidative state as an essential factor along with high salt and fructose treatment in causing hypertension. Fischer male rats were supplemented with a high-fructose diet (20% in water) for 20 weeks and maintained on high-salt diet (8%) associate in the last 10 weeks...
April 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28390001/defective-glycolysis-and-the-use-of-2-deoxy-d-glucose-in-polycystic-kidney-disease-from-animal-models-to-humans
#5
REVIEW
Riccardo Magistroni, Alessandra Boletta
Autosomal dominant polycystic kidney disease (ADPKD) is an inherited renal disease characterized by bilateral renal cyst formation. ADPKD is one of the most common rare disorders, accounting for ~10% of all patients with end-stage renal disease (ESRD). ADPKD is a chronic disorder in which the gradual expansion of cysts that form in a minority of nephrons eventually causes loss of renal function due to the compression and degeneration of the surrounding normal parenchyma. Numerous deranged pathways have been identified in the cyst-lining epithelia, prompting the design of potential therapies...
April 7, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28277831/dapagliflozin-potential-beneficial-effects-in-the-prevention-and-treatment-of-renal-and-cardiovascular-complications-in-patients-with-type-2-diabetes
#6
REVIEW
Paola Fioretto, Angelo Avogaro
Diabetic kidney disease is the leading cause of end-stage renal disease, a significant contributor to cardiovascular (CV) disease, responsible for much of the morbidity and mortality in patients with type 2 diabetes (T2DM). Strategies to slow or prevent the onset and progression of diabetic kidney disease are critical for effectively managing T2DM and reducing CV risk. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are effective antidiabetic agents, which may provide nephroprotective and CV protective effects...
April 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28258533/current-therapeutic-approaches-in-the-management-of-hyperglycemia-in-chronic-renal-disease
#7
REVIEW
Vishnu Garla, Licy Yanes-Cardozo, Lillian F Lien
Diabetes mellitus (DM) and chronic kidney disease (CKD) are intricately intertwined. DM is the most common cause of CKD. Adequate control of DM is necessary for prevention of progression of CKD, while careful management of the metabolic abnormalities in CKD will assist in achieving better control of DM. Two of the key organs involved in glucose production are the kidney and the liver. Furthermore, the kidney also plays a role in glucose filtration and reabsorption. In CKD, monitoring of glycemic control using traditional methods such as Hemoglobin A1c (Hba1c) must be done with caution secondary to associated hematological abnormalities in CKD...
March 2017: Reviews in Endocrine & Metabolic Disorders
https://www.readbyqxmd.com/read/28210839/thrombotic-microangiopathy-caused-by-methionine-synthase-deficiency-diagnosis-and-treatment-pitfalls
#8
Maria Helena Vaisbich, Andressa Braga, Maria Gabrielle, Clarissa Bueno, Flávia Piazzon, Fernando Kok
BACKGROUND: Inborn errors of cobalamin (Cbl) metabolism form a large group of rare diseases. One of these, Cbl deficiency type C (CblC), is a well-known cause of thrombotic microangiopathy (TMA), especially in infants. However, there has only been a single published case of TMA associated to Cbl deficiency type G (CblG), also known as methionine synthase deficiency (MSD). CASE DIAGNOSIS/TREATMENT: A 21-month-old boy presented with pallor and oral ulcers during episodes of upper respiratory infection (URI)...
February 16, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28205547/microrna-17-family-promotes-polycystic-kidney-disease-progression-through-modulation-of-mitochondrial-metabolism
#9
Sachin Hajarnis, Ronak Lakhia, Matanel Yheskel, Darren Williams, Mehran Sorourian, Xueqing Liu, Karam Aboudehen, Shanrong Zhang, Kara Kersjes, Ryan Galasso, Jian Li, Vivek Kaimal, Steven Lockton, Scott Davis, Andrea Flaten, Joshua A Johnson, William L Holland, Christine M Kusminski, Philipp E Scherer, Peter C Harris, Marie Trudel, Darren P Wallace, Peter Igarashi, Edmund C Lee, John R Androsavich, Vishal Patel
Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent genetic cause of renal failure. Here we identify miR-17 as a target for the treatment of ADPKD. We report that miR-17 is induced in kidney cysts of mouse and human ADPKD. Genetic deletion of the miR-17∼92 cluster inhibits cyst proliferation and PKD progression in four orthologous, including two long-lived, mouse models of ADPKD. Anti-miR-17 treatment attenuates cyst growth in short-term and long-term PKD mouse models. miR-17 inhibition also suppresses proliferation and cyst growth of primary ADPKD cysts cultures derived from multiple human donors...
February 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28203327/a-rapid-screening-test-on-dried-blood-for-the-neonatal-diagnosis-of-tyrosinemia-type-i
#10
Farahnaz Bodaghkhan, Bita Geramizadeh, Abbas Abdollah Rajeh, Mahmoud Haghighat, Mohsen Dehghani, Naser Honar, Mojgan Zahmatkeshan, Mohammad-Hadi Imanieh
BACKGROUND: Tyrosinemia is an inherited metabolic disorder characterized by elevated levels of tyrosine and its metabolites in plasma. Without treatment, the disease will progress to hepatic and renal failure, so that without liver transplantation will cause death in less than 10 years of age. So, early diagnosis and treatment can be life saving and crucial. It means that with early treatment starting in the neonatal period, the patient can have normal life with very few restrictions in diets containing tyrosine and phenylalanine...
October 2016: Iranian Journal of Pediatrics
https://www.readbyqxmd.com/read/28196866/sglt2-protein-expression-is-increased-in-human-diabetic-nephropathy-sglt2-protein-inhibition-decreases-renal-lipid-accumulation-inflammation-and-the-development-of-nephropathy-in-diabetic-mice
#11
Xiaoxin X Wang, Jonathan Levi, Yuhuan Luo, Komuraiah Myakala, Michal Herman-Edelstein, Liru Qiu, Dong Wang, Yingqiong Peng, Almut Grenz, Scott Lucia, Evgenia Dobrinskikh, Vivette D D'Agati, Hermann Koepsell, Jeffrey B Kopp, Avi Z Rosenberg, Moshe Levi
There is very limited human renal sodium gradient-dependent glucose transporter protein (SGLT2) mRNA and protein expression data reported in the literature. The first aim of this study was to determine SGLT2 mRNA and protein levels in human and animal models of diabetic nephropathy. We have found that the expression of SGLT2 mRNA and protein is increased in renal biopsies from human subjects with diabetic nephropathy. This is in contrast to db-db mice that had no changes in renal SGLT2 protein expression. Furthermore, the effect of SGLT2 inhibition on renal lipid content and inflammation is not known...
March 31, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28160246/hypogonadotropic-hypogonadism-in-males-with-glycogen-storage-disease-type-1
#12
Evelyn M Wong, Anna Lehman, Philip Acott, Jane Gillis, Daniel L Metzger, Sandra Sirrs
BACKGROUND: Glycogen storage disease type 1 is an autosomal recessive disorder with an incidence of 1 in 100,000. Long-term complications include chronic blood glucose lability, lactic academia, short stature, osteoporosis, delayed puberty, gout, progressive renal insufficiency, systemic or pulmonary hypertension, hepatic adenomas at risk for malignant transformation, anemia, vitamin D deficiency, hyperuricemic nephrocalcinosis, inflammatory bowel syndrome (type 1b), hypertriglyceridemia, and irregular menstrual cycles...
February 4, 2017: JIMD Reports
https://www.readbyqxmd.com/read/28097824/mechanisms-of-metabolic-memory-and-renal-hypoxia-as-a-therapeutic-target-in-diabetic-kidney-disease
#13
REVIEW
Yosuke Hirakawa, Tetsuhiro Tanaka, Masaomi Nangaku
Diabetic kidney disease (DKD) is a worldwide public health problem. The definition of DKD is under discussion. Although the term DKD was originally defined as 'kidney disease specific to diabetes,' DKD frequently means chronic kidney disease with diabetes mellitus and includes not only classical diabetic nephropathy, but also kidney dysfunction as a result of nephrosclerosis and other causes. Metabolic memory plays a crucial role in the progression of various complications of diabetes, including DKD. The mechanisms of metabolic memory in DKD are supposed to include advanced glycation end-products, deoxyribonucleic acid methylation, histone modifications and non-coding ribonucleic acid including micro ribonucleic acid...
May 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28088910/sodium-glucose-cotransporter-2-inhibitors-sglt2i-their-role-in-cardiometabolic-risk-management
#14
Niki Katsiki, Dimitri P Mikhailidis, Michael J Theodorakis
BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a novel category of oral antidiabetic drugs that inhibit renal glucose reabsorption and increase renal glucose excretion, thus lowering plasma glucose levels. This unique mechanism of SGLT2i action is insulin independent, thus improving glycemic control without promoting hypoglycemia in the absence of exogenously administered insulin. METHODS: The present narrative review addresses the putative associations between SGLT2i and several cardiovascular (CV) and microvascular risk factors, as well as their effects on cardiac and renal function...
January 13, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28052632/impact-of-hepatitis-c-virus-therapy-on-metabolism-and-public-health
#15
REVIEW
Mitchell L Shiffman, Nadege T Gunn
Chronic hepatitis C virus (HCV) is associated with insulin resistance (IR) and leads to type 2 diabetes mellitus (T2DM) and hepatic steatosis in many patients. These metabolic complications of HCV have been shown to accelerate the progression of fibrosis to cirrhosis and increase the risk of hepatocellular carcinoma. The metabolic syndrome is a common disorder that also includes IR, T2DM and hepatic steatosis. Approximately 20%-30% of patients with chronic HCV also have co-existent metabolic syndrome. The cause of steatosis in patients with the features of both the metabolic syndrome and chronic HCV is sometime difficult to determine...
January 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28036114/does-statins-promote-vascular-calcification-in-chronic-kidney-disease
#16
Zhimin Chen, Abdul Rashid Qureshi, Paolo Parini, Eva Hurt-Camejo, Jonaz Ripsweden, Torkel B Brismar, Peter Barany, Armand Jaminon, Leon J Schurgers, Olof Heimburger, Bengt Lindholm, Peter Stenvinkel
BACKGROUND: In end-stage renal disease (ESRD), coronary artery calcification (CAC) and inflammation contribute to cardiovascular disease (CVD). Statins do not improve survival in ESRD patients and their effect on vascular calcification is unclear. We explored associations between CAC, inflammatory biomarkers, statins and mortality in ESRD. MATERIAL AND METHODS: In 240 ESRD patients (63% males; median age 56 years) from cohorts including 86 recipients of living donor kidney transplant (LD-Rtx), 96 incident dialysis patients and 58 prevalent peritoneal dialysis patients, associations of CAC score (Agatston Units, AUs), interleukin-6 (IL-6) with high-sensitivity C-reactive protein (hsCRP), tumour necrosis factor (TNF), use of statins and all-cause mortality were analysed...
December 30, 2016: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27990015/the-renal-fanconi-syndrome-in-cystinosis-pathogenic-insights-and-therapeutic-perspectives
#17
REVIEW
Stephanie Cherqui, Pierre J Courtoy
Cystinosis is an autosomal recessive metabolic disease that belongs to the family of lysosomal storage disorders. It is caused by a defect in the lysosomal cystine transporter, cystinosin, which results in an accumulation of cystine in all organs. Despite the ubiquitous expression of cystinosin, a renal Fanconi syndrome is often the first manifestation of cystinosis, usually presenting within the first year of life and characterized by the early and severe dysfunction of proximal tubule cells, highlighting the unique vulnerability of this cell type...
February 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/27903991/role-of-oxidative-stress-and-inflammatory-factors-in-diabetic-kidney-disease
#18
Esmat Aghadavod, Samaneh Khodadadi, Azar Baradaran, Parto Nasri, Mahmood Bahmani, Mahmoud Rafieian-Kopaei
Diabetic nephropathy (DN) is a serious complication of diabetes mellitus, and its prevalence has been increasing in developed countries. Diabetic nephropathy has become the most common single cause of end-stage renal disease worldwide. Oxidative stress and inflammation factors are hypothesized to play a role in the development of late diabetes complications. Chronic hyperglycemia increases oxidative stress, significantly modifies the structure and function of proteins and lipids, and induces glycoxidation and peroxidation...
November 2016: Iranian Journal of Kidney Diseases
https://www.readbyqxmd.com/read/27878313/targeting-renal-glucose-reabsorption-to-treat-hyperglycaemia-the-pleiotropic-effects-of-sglt2-inhibition
#19
REVIEW
Volker Vallon, Scott C Thomson
Healthy kidneys filter ∼160 g/day of glucose (∼30% of daily energy intake) under euglycaemic conditions. To prevent valuable energy from being lost in the urine, the proximal tubule avidly reabsorbs filtered glucose up to a limit of ∼450 g/day. When blood glucose levels increase to the point that the filtered load exceeds this limit, the surplus is excreted in the urine. Thus, the kidney provides a safety valve that can prevent extreme hyperglycaemia as long as glomerular filtration is maintained. Most of the capacity for renal glucose reabsorption is provided by sodium glucose cotransporter (SGLT) 2 in the early proximal tubule...
February 2017: Diabetologia
https://www.readbyqxmd.com/read/27873229/subclinical-kidney-damage-in-hypertensive-patients-a-renal-window-opened-on-the-cardiovascular-system-focus-on-microalbuminuria
#20
Giuseppe Mulè, Antonella Castiglia, Claudia Cusumano, Emilia Scaduto, Giulio Geraci, Dario Altieri, Epifanio Di Natale, Onofrio Cacciatore, Giovanni Cerasola, Santina Cottone
The kidney is one of the major target organs of hypertension.Kidney damage represents a frequent event in the course of hypertension and arterial hypertension is one of the leading causes of end-stage renal disease (ESRD).ESRD has long been recognized as a strong predictor of cardiovascular (CV) morbidity and mortality. However, over the past 20 years a large and consistent body of evidence has been produced suggesting that CV risk progressively increases as the estimated glomerular filtration rate (eGFR) declines and is already significantly elevated even in the earliest stages of renal damage...
2017: Advances in Experimental Medicine and Biology
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