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klotho factor in diabetic nephropathy

Alfonso Farías-Basulto, Héctor Ramón Martínez-Ramírez, Erika Fabiola Gómez-García, Alfonso Martín Cueto-Manzano, Laura Cortés-Sanabria, Luis Eduardo Hernández-Ramos, Guadalupe Ramírez-López, Francisco Mendoza-Carrera
INTRODUCTION: Diabetic nephropathy is a leading cause of chronic kidney disease (CKD). In diabetes, changes in serum levels of both soluble alpha Klotho (sKL) and fibroblast growth factor 23 (FGF-23) have been associated with CKD progression. OBJECTIVE: To evaluate the associations of circulating levels of sKL and FGF-23 with the presence of early nephropathy (EN) in diabetic patients. METHODS: A cross-sectional study in 136 Mexicans with type 2 diabetes mellitus (T2DM)...
February 1, 2019: Archives of Medical Research
Eda Dokumacioglu, Hatice Iskender, Ahmet Musmul
Objective Non-alcoholic fatty liver disease, steatohepatitis and nephropathy are considered among the most important complications of diabetes mellitus (DM), which recently increased due to increased frequency of DM and the prolonged life span of diabetic patients The aim of the present study was to reveal the possible effect of hesperidin (HP) on alpha-klotho (α-KL)/ fibroblast growth factor-23 (FGF-23) pathway in rats with diabetes induced by streptozotocin (STZ). Materials and methods Thirty six male Sprague-Dawley rats were randomly divided into three groups...
January 2019: Biomedicine & Pharmacotherapy
Eiichiro Kanda, Masumi Ai, Mitsuyo Okazaki, Masayuki Yoshida, Yoshitaka Maeda
BACKGROUND: Atherosclerosis is often a complication of chronic kidney disease (CKD) because of dyslipidemia and CKD-mineral and bone disorder. High-density lipoproteins (HDLs) are grouped into various subclasses composed of multiple proteins and lipids, and their transformation is altered in CKD. We investigated the roles of lipoprotein subclasses in CKD progression, and atherosclerosis, and the relationships with Klotho and fibroblast growth factor (FGF) 23. METHODS: Seventy-one CKD patients were enrolled in this prospective cohort study in Japan...
2016: PloS One
Xiao-Qin Wang, Xin-Rong Zou, Yuan Clare Zhang
Although traditional Chinese medicine (TCM) and Western medicine have evolved on distinct philosophical foundations and reasoning methods, an increasing body of scientific data has begun to reveal commonalities. Emerging scientific evidence has confirmed the validity and identified the molecular mechanisms of many ancient TCM theories. One example is the concept of "Kidneys Govern Bones." Here we discuss the molecular mechanisms supporting this theory and its potential significance in treating complications of chronic kidney disease (CKD) and diabetes mellitus...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
Ayca Inci, Funda Sari, Melahat Coban, Refik Olmaz, Suleyman Dolu, Metin Sarıkaya, Necat Yılmaz
The relationship between soluble Klotho (s-Klotho) levels, fibroblast growth factor 23 (FGF23) levels, and albuminuria in patients with diabetic chronic kidney disease (CKD) remains unclear. A total of 109 patients with type 2 diabetes (mean age 61.63±9.77 years), at the outpatient clinic of the Antalya Research and Training Hospital Nephrology Unit between January and June 2014, as well as 32 healthy controls (mean age 49.53±7.32 years) were enrolled for this cross-sectional study. Patients were classified into three groups according to their urinary albumin creatinine ratio (UACR), normoalbuminuria (UACR<30 mg/g), microalbuminuria (UACR 30-300 mg/g), and macroalbuminuria (UACR>300 mg/g)...
August 2016: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
Burcu Dogan, Izzet Hakki Arikan, Derya Guler, Nursen Keles, Banu Isbilen, Ferruh Isman, Aytekin Oguz
PURPOSE: To investigate the soluble Klotho (sKlotho) and fibroblast growth factor-23 (FGF-23) levels and echocardiographic findings in type 1 diabetic patients with no or early diabetic nephropathy. METHODS: A total of 147 subjects (mean age 34.1 ± 9.2 years, 55.8 % were females) including type 1 diabetic patients with glomerular filtration rate (GFR) >60 ml/min (n = 71, mean age 34.3 ± 9.5 years, 54.9 % were females) and healthy controls (n = 76, mean age 33...
March 2016: International Urology and Nephrology
Can Wu, Qiuyue Wang, Chuan Lv, Ningning Qin, Sha Lei, Qin Yuan, Guan Wang
OBJECTIVE: To investigate the changes of serum anti-aging protein Klotho and neutrophil gelatinase-associated lipocalin (NGAL) levels and their correlation in type 2 diabetes mellitus (T2DM) patients at different stages of diabetic kidney disease (DKD) determined by urinary albuminuria. METHODS: 462 cases with T2DM were divided into three groups: normoalbuminuric [N-UAlb; urinary albumin to creatinine ratio (UACR) < 30 mg/g, n=180], microalbuminuric [M-UAlb; UACR 30-300 mg/g, n = 158], macroalbuminuric [L-UAlb; UACR > 300 mg/g, n = 124]...
November 2014: Diabetes Research and Clinical Practice
Eun Young Lee, Sang Soo Kim, Ji-Sung Lee, In Joo Kim, Sang Heon Song, Seung-Kuy Cha, Kyu-Sang Park, Jeong Suk Kang, Choon Hee Chung
OBJECTIVE: Although α-klotho is known as an anti-aging, antioxidant, and cardio-renal protective protein, the clinical implications of soluble α-klotho levels in patients with diabetes have not been evaluated. Therefore, this study evaluated whether plasma and urinary α-klotho levels are associated with albuminuria in kidney disease in diabetes. RESEARCH DESIGN AND METHODS: A total of 147 patients with type 2 diabetes and 25 healthy control subjects were enrolled...
2014: PloS One
Jau-Shyang Huang, Chao-Tang Chuang, Mei-Hsin Liu, Sheng-Hsuan Lin, Jinn-Yuh Guh, Lea-Yea Chuang
Although exogenous klotho attenuates renal fibrosis, it is not known if exogenous klotho attenuates diabetic nephropathy (DN). Thus, we studied the anti-fibrotic mechanisms of klotho in terms of transforming growth factor-β (TGF-β) and signaling pathways in high glucose (HG, 30 mM)-cultured renal interstitial fibroblast (NRK-49F) cells. We found that HG increased klotho mRNA and protein expression. HG also activated TGF-β Smad2/3 signaling and activated extracellular signal-regulated kinase (ERK1/2) and p38 kinase signaling...
June 5, 2014: Molecular and Cellular Endocrinology
K-C Huang, Y-G Cherng, L-J Chen, C-T Hsu, J-T Cheng
A marked decrease of klotho expression was observed in the kidney of streptozotocin-induced diabetic rats (STZ rats) showing diabetic nephropathy. It has been documented that klotho is the target gene of PPARγ. However, the effect of PPARγ agonist on klotho expression in kidney of STZ rats remains obscure. Thus, we used rosiglitazone (TZD) as PPARγ agonist to investigate the effect on renal dysfunction in STZ rats. Treatment of TZD reversed the lower levels of PPARγ, klotho, and FGFR1 expressions in kidneys of STZ rats without the correction of hyperglycemia...
April 2014: Hormone and Metabolic Research
Cristina Zanchi, Monica Locatelli, Ariela Benigni, Daniela Corna, Susanna Tomasoni, Daniela Rottoli, Flavio Gaspari, Giuseppe Remuzzi, Carlamaria Zoja
Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone mainly produced by bone that acts in the kidney through FGF receptors and Klotho. Here we investigated whether the kidney was an additional source of FGF23 during renal disease using a model of type 2 diabetic nephropathy. Renal expression of FGF23 and Klotho was assessed in Zucker diabetic fatty (ZDF) and control lean rats at 2, 4, 6, 8 months of age. To evaluate whether the renoprotective effect of angiotensin converting enzyme (ACE) inhibitor in this model was associated with changes in FGF23 and Klotho, ZDF rats received ramipril from 4, when proteinuric, to 8 months of age...
2013: PloS One
Joris van Ark, Hans-Peter Hammes, Marcory C R F van Dijk, Chris P H Lexis, Iwan C C van der Horst, Clark J Zeebregts, Marc G Vervloet, Bruce H R Wolffenbuttel, Harry van Goor, Jan-Luuk Hillebrands
BACKGROUND: Diabetes is associated with a high incidence of macrovascular disease (MVD), including peripheral and coronary artery disease. Circulating soluble-Klotho (sKlotho) is produced in the kidney and is a putative anti-aging and vasculoprotective hormone. Reduced Klotho levels may therefore increase cardiovascular risk in diabetes. We investigated if sKlotho levels are decreased in type 2 diabetes and associate with MVD in the absence of diabetic nephropathy, and whether hyperglycemia affects renal Klotho production in vitro and in vivo...
2013: Cardiovascular Diabetology
Janaka Karalliedde, Giuseppe Maltese, Benjamin Hill, Giancarlo Viberti, Luigi Gnudi
BACKGROUND AND OBJECTIVES: Soluble Klotho is an anti-aging phosphaturic protein associated with vascular-renal protection. In vitro and in vivo studies have demonstrated that renin-angiotensin system (RAS) blockade increases soluble Klotho levels. The effect of RAS blockers on soluble Klotho in patients with diabetic kidney disease (DKD) is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Plasma-soluble Klotho was measured in a secondary analysis of a randomized controlled clinical trial performed at a single university hospital center (ClinicalTrials...
November 2013: Clinical Journal of the American Society of Nephrology: CJASN
Yi Lin, Makoto Kuro-o, Zhongjie Sun
Klotho is a recently discovered anti-aging gene and is primarily expressed in kidneys. In humans, the klotho level decreases with age whereas the prevalence of chronic kidney disease (CKD) increases with age. Diabetic nephropathy is the most common form of CKD, which leads to end-stage renal disease. A decrease in klotho has been found in kidneys of patients with diabetic nephropathy. The purpose of this study is to assess whether klotho gene deficiency affects early diabetic nephropathy in a mouse of model of type 1 diabetes induced by streptozotocin (STZ)...
October 2013: Endocrinology
M F Cheng, L J Chen, M C Wang, C T Hsu, J T Cheng
Fibrosis is the final disorder of end-stage renal disease. Activation of fibroblast growth factor (FGF) 23-klotho axis could suppress renal fibrosis in mice. Also, a marked decrease of klotho expression was observed in the kidney of streptozotocin-induced diabetic rats (STZ rats). However, relation of FGF in renal fibrosis remained unclear. This study was aimed to screen the effect of hyperglycemia on FGF receptor (FGFR) and fibrosis in kidney of rats with diabetic nephropathy and investigate this potential mechanism in cultured Madin-Darby Canine Kidney (MDCK) epithelial cells...
January 2014: Hormone and Metabolic Research
Ina Maria Kacso, Cosmina Ioana Bondor, Gabriel Kacso
OBJECTIVES: Both kidney expression and soluble serum Klotho are influenced by chronic kidney disease (CKD) and diabetes. Serum Klotho is a yet poorly explored biomarker. We describe, for the first time to our knowledge, serum Klotho in diabetic patients with CKD and its relationship to vascular endothelial growth factor A (VEGF-A). DESIGN AND METHODS: We included 43 controls and 146 diabetic patients with different stages of CKD. Laboratory evaluation, urinary albumin/creatinine ratio (UACR), Klotho (ELISA), VEGF-A (ELISA) were performed...
November 2012: Clinical Biochemistry
Pedro Iglesias, Rafael Selgas, Sara Romero, Juan J Díez
Fibroblast growth factor 21 (FGF21), a 181 amino acid circulating protein, is a member of the FGF superfamily, with relevant metabolic actions. It acts through the interaction with specific FGF receptors and a cofactor called β-Klotho, whose expression is predominantly detected in metabolically active organs. FGF21 stimulates glucose uptake in adipocytes via the induction of glucose transporter-1. This action is additive and independent of insulin. β-Cell function and survival are preserved, and glucagon secretion is reduced by this protein, thus decreasing hepatic glucose production and improving insulin sensitivity...
September 2012: European Journal of Endocrinology
Osamu Asai, Kimihiko Nakatani, Tomohiro Tanaka, Hirokazu Sakan, Akihiro Imura, Shuhei Yoshimoto, Ken-ichi Samejima, Yukinari Yamaguchi, Masaru Matsui, Yasuhiro Akai, Noboru Konishi, Masayuki Iwano, Yoichi Nabeshima, Yoshihiko Saito
Hypercalciuria is one of the early manifestations of diabetic nephropathy. We explored here the role of α-Klotho, a protein expressed predominantly in distal convoluted tubules that has a role in calcium reabsorption. We studied 31 patients with early diabetic nephropathy and compared them with 31 patients with IgA nephropathy and 7 with minimal change disease. Renal α-Klotho expression was significantly lower and urinary calcium excretion (UCa/UCr) significantly higher in diabetic nephropathy than in IgA nephropathy or minimal change disease...
March 2012: Kidney International
Yanhua Zhao, Srijita Banerjee, Nilay Dey, Wanda S LeJeune, Partha S Sarkar, Reynolds Brobey, Kevin P Rosenblatt, Ronald G Tilton, Sanjeev Choudhary
OBJECTIVE: Klotho is an antiaging hormone present in the kidney that extends the lifespan, regulates kidney function, and modulates cellular responses to oxidative stress. We investigated whether Klotho levels and signaling modulate inflammation in diabetic kidneys. RESEARCH DESIGN AND METHODS: Renal Klotho expression was determined by quantitative real-time PCR and immunoblot analysis. Primary mouse tubular epithelial cells were treated with methylglyoxalated albumin, and Klotho expression and inflammatory cytokines were measured...
July 2011: Diabetes
Elena M V de Cavanagh, Felipe Inserra, León Ferder
Protein and lipid oxidation-mainly by mitochondrial reactive oxygen species (mtROS)-was proposed as a crucial determinant of health and lifespan. Angiotensin II (Ang II) enhances ROS production by activating NAD(P)H oxidase and uncoupling endothelial nitric oxide synthase (NOS). Ang II also stimulates mtROS production, which depresses mitochondrial energy metabolism. In rodents, renin-angiotensin system blockade (RAS blockade) increases survival and prevents age-associated changes. RAS blockade reduces mtROS and enhances mitochondrial content and function...
January 1, 2011: Cardiovascular Research
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