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Hyperphosphatemia in CKD

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https://www.readbyqxmd.com/read/29671909/should-phosphate-management-be-limited-to-the-kdigo-kdoqi-guidelines
#1
Sangeet Dhillon-Jhattu, Stuart M Sprague
Hyperphosphatemia is a common complication of CKD. Prior to development of overt hyperphosphatemia, there are several adaptive mechanisms that occur to maintain normal phosphorus equilibrium in patients with CKD. These include an early and progressive rise in fibroblast growth factor 23 (FGF 23), followed by an increase in parathyroid hormone (PTH) with a decrease in 1,25-dihydroxyvitamin D (1,25 Vit D). Over the last 20 years, a large number of studies have shown that hyperphosphatemia is a strong predictor of adverse clinical outcomes including increased incidence of vascular calcification, cardiovascular disease, and all-cause mortality in both individuals with CKD as well as those with normal kidney function...
April 19, 2018: Seminars in Dialysis
https://www.readbyqxmd.com/read/29614098/a-novel-calcimimetic-agent-evocalcet-mt-4580-khk7580-suppresses-the-parathyroid-cell-function-with-little-effect-on-the-gastrointestinal-tract-or-cyp-isozymes-in-vivo-and-in-vitro
#2
Takehisa Kawata, Shin Tokunaga, Miki Murai, Nami Masuda, Waka Haruyama, Youji Shoukei, Yutaka Hisada, Tetsuya Yanagida, Hiroshi Miyazaki, Michihito Wada, Tadao Akizawa, Masafumi Fukagawa
Cinacalcet hydrochloride (cinacalcet), an oral calcimimetic agent has been widely used for the management of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD). In sharp contrast to vitamin D receptor activators, cinacalcet suppresses SHPT without inducing hypercalcemia or hyperphosphatemia. Nevertheless, some patients remain refractory to SHPT with this agent, as the dose cannot be sufficiently increased due to gastrointestinal symptoms. In order to resolve this issue, we have developed a newly synthesized calcimimetic agent, evocalcet (MT-4580/KHK7580)...
2018: PloS One
https://www.readbyqxmd.com/read/29582958/-ckd-mbd-in-peritoneal-dialysis
#3
Anna Rachele Rocca, Tania Gnerre Musto, Sandro Mazzaferro
CKD-MBD is a systemic disorder of the mineral and bone metabolism as a result of CKD. The clinical relevance of this syndrome has led to the identification of the biochemical targets to be achieved in order to improve the outcome of the patient. However, in hemodialysis (HD) and peritoneal dialysis (DP) patients, these targets are not reached. Hyperphosphatemia is a predictor of cardiovascular and all-cause mortality. In DP the removal of phosphorus (P) occurs by diffusion and convection, with a contribution of ultrafiltration of about 11%...
March 2018: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
https://www.readbyqxmd.com/read/29580635/prevention-and-treatment-of-hyperphosphatemia-in-chronic-kidney-disease
#4
REVIEW
Marc G Vervloet, Adriana J van Ballegooijen
Hyperphosphatemia has consistently been shown to be associated with dismal outcome in a wide variety of populations, particularly in chronic kidney disease (CKD). Compelling evidence from basic and animal studies elucidated a range of mechanisms by which phosphate may exert its pathological effects and motivated interventions to treat hyperphosphatemia. These interventions consisted of dietary modifications and phosphate binders. However, the beneficial effects of these treatment methods on hard clinical outcomes have not been convincingly demonstrated in prospective clinical trials...
March 23, 2018: Kidney International
https://www.readbyqxmd.com/read/29566839/cost-effectiveness-of-first-line-sevelamer-and-lanthanum-versus-calcium-based-binders-for-hyperphosphatemia-of-chronic-kidney-disease
#5
Steven Habbous, Sebastian Przech, Janet Martin, Amit X Garg, Sisira Sarma
BACKGROUND: Phosphate binders are used to treat hyperphosphatemia among patients with chronic kidney disease (CKD). OBJECTIVES: To conduct an economic evaluation comparing calcium-free binders sevelamer and lanthanum with calcium-based binders for patients with CKD. METHODS: Effectiveness data were obtained from a recent meta-analysis of randomized trials. Effectiveness was measured as life-years gained and translated to quality-adjusted life-years (QALYs) using utility weights from the literature...
March 2018: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/29533151/comparison-of-renal-function-and-other-predictors-in-lacto-ovo-vegetarians-and-omnivores-with-chronic-kidney-disease
#6
Chou-Yueh Chang, Horng-Rong Chang, Hsing-Chun Lin, Han-Hsin Chang
Objective Vegetarian diets have been shown to increase the risk of certain nutritional deficiencies, such as iron. As a number of patients with chronic kidney disease (CKD) in Taiwan are lacto-ovo vegetarians, the aim of this study was to investigate the effects of different proportions and sources of protein in lacto-ovo vegetarian and omnivorous diets, as well as the influence of adequate dietary protein intake, on renal function and nutritional status of Taiwanese patients with stage 3 to stage 5 CKD. Methods This is a cross-sectional study...
March 13, 2018: Journal of the American College of Nutrition
https://www.readbyqxmd.com/read/29523679/parathyroidectomy-in-the-management-of-secondary-hyperparathyroidism
#7
REVIEW
Wei Ling Lau, Yoshitsugu Obi, Kamyar Kalantar-Zadeh
Secondary hyperparathyroidism develops in CKD due to a combination of vitamin D deficiency, hypocalcemia, and hyperphosphatemia, and it exists in nearly all patients at the time of dialysis initiation. There is insufficient data on whether to prefer vitamin D analogs compared with calcimimetics, but the available evidence suggests advantages with combination therapy. Calcium derangements, patient adherence, side effects, and cost limit the use of these agents. When parathyroid hormone level persists >800 pg/ml for >6 months, despite exhaustive medical interventions, monoclonal proliferation with nodular hyperplasia is likely present along with decreased expression of vitamin D and calcium-sensing receptors...
March 9, 2018: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/29486729/phosphate-stimulates-myotube-atrophy-through-autophagy-activation-evidence-of-hyperphosphatemia-contributing-to-skeletal-muscle-wasting-in-chronic-kidney-disease
#8
Yue-Yue Zhang, Man Yang, Jin-Fang Bao, Li-Jie Gu, Hong-Lei Yu, Wei-Jie Yuan
BACKGROUND: Accelerated muscle atrophy is associated with a three-fold increase in mortality in chronic kidney disease (CKD) patients. It is suggested that hyperphosphatemia might contribute to muscle wasting, but the underlying mechanisms remain unclear. Although evidence indicates that autophagy is involved in the maintenance of muscle homeostasis, it is not known if high phosphate levels can result in activation of autophagy, leading to muscle protein loss. METHODS: Immortalized rat L6 myotubes were exposed to a high concentration of phosphate, with or without autophagy inhibition...
February 27, 2018: BMC Nephrology
https://www.readbyqxmd.com/read/29415929/-pharmacological-pharmaceutical-and-clinical-profiles-of-sucroferric-oxyhydroxide-p-tol%C3%A2-chewable-tab-250%C3%A2-mg-500%C3%A2-mg-a-therapeutic-agent-for-hyperphosphatemia
#9
Satoshi Tatemichi, Fumiaki Nakagaki, Shoichi Yoshioka, Natsuko Shichiri
Sucroferric oxyhydroxide (P-TOL® chewable tablets, 250 and 500 mg) is a phosphate binder for oral use; it is composed of polynuclear iron (III)-oxyhydroxide, sucrose, and starches, and is currently indicated for alleviating hyperphosphatemia in patients with chronic kidney disease (CKD) on dialysis. The results of non-clinical pharmacological studies have suggested that P-TOL consistently decreases serum phosphorus levels in the aqueous environment at pH levels similar to those in the gastrointestinal tract, thereby suppressing the progression of secondary hyperparathyroidism, aberrant calcification, and abnormal bone metabolism associated with hyperphosphatemia...
2018: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
https://www.readbyqxmd.com/read/29409087/-chronic-kidney-disease-update-2018
#10
Markus Ketteler, Christoph Wanner
SGLT2-INHIBITION IN DIABETIC AND NON-DIABETIC KIDNEY DISEASE:  The CANVAS Program Collaborative Group study confirmed nephroprotective actions by canagliflocin comparable to empagliflozin as published in the EMPA-REG Outcome study. Treatment with Liraglutide (LEADER study) also suggests nephroprotection via albuminuria reduction a decreased eGFR decline in subgroups and depending on stages of diabetic nephropathy. KDIGO CKD-MBD GUIDELINE UPDATE 2017:  In July 2017, an update of the KDIGO (Kidney Disease: Improving Global Outcomes) 2009 guideline on diagnostic and treatment chronic kidney disease - mineral and bone disorders (CKD-MBD) was published...
February 2018: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/29372301/effect-of-variations-in-dietary-pi-intake-on-intestinal-pi-transporters-napi-iib-pit-1-and-pit-2-and-phosphate-regulating-factors-pth-fgf-23-and-mepe
#11
Tatiana Martins Aniteli, Flávia Ramos de Siqueira, Luciene Machado Dos Reis, Wagner Vasques Dominguez, Elizabeth Maria Costa de Oliveira, Patrícia Castelucci, Rosa Maria Affonso Moysés, Vanda Jorgetti
Hyperphosphatemia is a common condition in patients with chronic kidney disease (CKD) and can lead to bone disease, vascular calcification, and increased risks of cardiovascular disease and mortality. Inorganic phosphate (Pi ) is absorbed in the intestine, an important step in the maintenance of homeostasis. In CKD, it is not clear to what extent Pi absorption is modulated by dietary Pi . Thus, we investigated 5/6 nephrectomized (Nx) Wistar rats to test whether acute variations in dietary Pi concentration over 2 days would alter hormones involved in Pi metabolism, expression of sodium-phosphate cotransporters, apoptosis, and the expression of matrix extracellular phosphoglycoprotein (MEPE) in different segments of the small intestine...
April 2018: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29357413/defective-interplay-between-mtorc1-activity-and-endoplasmic-reticulum-stress-unfolded-protein-response-in-uremic-vascular-calcification
#12
Dibyendu Panda, Xiuying Bai, Yves Sabbagh, Yan Zhang, Hans-Christian Zaun, Angeliki Karellis, Antonis E Koromilas, Mark Lipman, Andrew C Karaplis
Vascular calcification increases the risk of cardiovascular disease and death in patients with chronic kidney disease (CKD). Increased activity of the mammalian target of rapamycin complex 1 (mTORC1) and endoplasmic reticulum (ER) stress-unfolded protein response (UPR) are reported to partake independently in the pathogenesis of vascular calcification in CKD. However, the association between mTORC1 activity and ER stress-UPR remains unknown. We report here that components of the uremic state (activation of the receptor for advanced glycation end-products (RAGE) or hyperphosphatemia) potentiate vascular smooth muscle cell (VSMC) calcification by inducing persistent and exaggerated activity of mTORC1...
January 10, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29344024/elevated-phosphate-levels-trigger-autophagy-mediated-cellular-apoptosis-in-h9c2-cardiomyoblasts
#13
Yao-Lung Liu, Kuan-Ho Lin, Shanmugam Tamilselvi, Wei-Kung Chen, Chia-Yao Shen, Ray-Jade Chen, Cecilia Hsuan Day, Hsi-Chin Wu, Vijaya Padma Viswanadha, Chih-Yang Huang
BACKGROUND/AIM: In chronic kidney disease (CKD), kidneys fail to maintain phosphorus homeostasis in serum. Elevated phosphorus levels in serum have been associated with cardiovascular diseases in CKD patients and in normal individuals. In this study, we evaluated the level of autophagy- and apoptosis-related markers under different concentrations of hyperphosphate in myocardial cells. METHODS: Modulation inflicted on the levels of various survival-, autophagy-, and apoptosis-related markers were determined by Western blotting analysis using total protein extract...
December 2017: Cardiorenal Medicine
https://www.readbyqxmd.com/read/29340316/npt-iib-inhibition-does-not-improve-hyperphosphatemia-in-ckd
#14
Tobias E Larsson, Chisato Kameoka, Ikumi Nakajo, Yuta Taniuchi, Satoshi Yoshida, Tadao Akizawa, Ronald A Smulders
Introduction: Serum phosphate levels are insufficiently controlled in many patients with end-stage renal disease (ESRD), and novel therapeutic strategies are needed. Blocking intestinal phosphate absorption mediated by sodium-dependent phosphate co-transporter type 2b (NPT-IIb) holds promise; thus, we evaluated the efficacy, safety, tolerability, and pharmacokinetics of the novel and specific small molecule NPT-IIb inhibitor ASP3325 for the first time in humans. Methods: We conducted a randomized, double-blind, placebo-controlled, phase 1a single (n = 88) and multiple (n = 36) ascending dose study in healthy subjects, and a randomized, open-label, uncontrolled, phase 1b study in hyperphosphatemic ESRD patients on hemodialysis (single oral dose, n = 5; multiple oral doses, n = 17)...
January 2018: KI Reports
https://www.readbyqxmd.com/read/29319766/epic-trial-education-programme-impact-on-serum-phosphorous-control-in-ckd-5d-patients-on-hemodialysis
#15
Carmen Tzanno Branco Martins, Bárbara Margareth Menardi Biavo, Clarissa Baia Bargas Uezima, Jacqueline Alves Pereira Dos Santos, Camila Machado de Barros, Elzo Ribeiro Júnior, Paul Clesca Troconis, Cristoforo Scavone, Marcus Vinicius de Souza João Luiz
INTRODUCTION: In stage 5D chronic kidney disease (CKD 5D) patients, the encouragement of treatment adherence by health professionals is a significant clinical challenge. OBJECTIVES: This study evaluates the impact of a nutritional education programme on hyperphosphatemia, utilizing the transtheoretical model of behavior change (TMBC). SUBJECTS AND METHODS: A prospective interventional study comprising 179 CKD 5D patients with hypophosphatemia...
October 2017: Jornal Brasileiro de Nefrologia: ʹorgão Oficial de Sociedades Brasileira e Latino-Americana de Nefrologia
https://www.readbyqxmd.com/read/29240673/urinary-fractional-excretion-of-phosphorus-in-dogs-with-spontaneous-chronic-kidney-disease
#16
Cínthia Ribas Martorelli, Márcia Mery Kogika, Fernanda Chicharo Chacar, Douglas Segalla Caragelasco, Ana Carolina Brandão de Campos Fonseca Pinto, Carla Aparecida Batista Lorigados, Lúcia Conceição Andrade
The increase of urinary fractional excretion of phosphorus (uFEP) may indicate phosphorus retention before the onset of hyperphosphatemia in the early stages of chronic kidney disease (CKD). The hypothesis of this study is whether uFEP may increase during the early stage of CKD as a compensatory mechanism to prevent hyperphosphatemia as well as whether hyperphosphatemia in the late stages is associated with increase or decrease in uFEP in dogs with naturally occurring CKD; therefore, the aim of this study was to determine the uFEP in CKD dogs with different stages...
December 14, 2017: Veterinary Sciences
https://www.readbyqxmd.com/read/29227975/high-phosphate-induced-calcification-of-vascular-smooth-muscle-cells-is-associated-with-the-tlr4-nf-%C3%AE%C2%BAb-signaling-pathway
#17
Daohai Zhang, Xianjin Bi, Yong Liu, Yinghui Huang, Jiachuan Xiong, Xinli Xu, Tangli Xiao, Yanlin Yu, Wei Jiang, Yunjian Huang, Jingbo Zhang, Bo Zhang, Jinghong Zhao
BACKGROUND/AIMS: Hyperphosphatemia is one of the most notable features of chronic kidney disease (CKD). Numerous epidemiological and clinical studies have found that high serum phosphate concentrations are associated with calcification in the coronary arteries. However, the mechanisms underlying the vascular calcification induced by high phosphate have not been understood fully. METHODS: Vascular smooth muscle cells (VSMCs) were cultured in high-phosphate media to induce vascular calcification, which was detected by Alizarin red S staining...
2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/29197521/high-phosphate-induced-downregulation-of-ppar%C3%AE-contributes-to-ckd-associated-vascular-calcification
#18
Liang Liu, Yong Liu, Ying Zhang, Xianjin Bi, Ling Nie, Chi Liu, Jiachuan Xiong, Ting He, Xinlin Xu, Yanlin Yu, Ke Yang, Jun Gu, Yunjian Huang, Jingbo Zhang, Zhiren Zhang, Bo Zhang, Jinghong Zhao
Medial arterial calcification associated with hyperphosphatemia is a main cause of cardiovascular mortality in patients with chronic kidney disease (CKD), but the mechanisms underlying high phosphate-induced vascular calcification remain largely unknown. Here, we observed a significant decrease in the expression of peroxisome proliferator-activated receptor-gamma (PPARγ) in calcified arteries both in CKD patients and in a mouse model of CKD with hyperphosphatemia. In vitro, high phosphate treatment led to a decreased expression of PPARγ in mouse vascular smooth muscle cells (VMSCs), accompanied by apparent osteogenic differentiation and calcification...
January 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29186198/safety-and-efficacy-of-ferric-citrate-in-patients-with-nondialysis-dependent-chronic-kidney-disease
#19
RANDOMIZED CONTROLLED TRIAL
Glenn M Chertow, Geoffrey A Block, John F Neylan, Pablo E Pergola, Katrin Uhlig, Steven Fishbane
Two randomized, placebo-controlled trials conducted in patients with nondialysis-dependent (NDD) chronic kidney disease (CKD), iron deficiency anemia, and normal or elevated serum phosphorus demonstrated that ferric citrate (FC) significantly increased hemoglobin and decreased serum phosphate concentrations. Pooling these trial results could provide a more robust evaluation of the safety and efficacy of FC in this population. We pooled results of a phase 2 (n = 149) and 3 trial (n = 233) of patients randomized and treated for up to 12 and 16 weeks, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/29146611/smooth-muscle-selective-nuclear-factor-%C3%AE%C2%BAb-inhibition-reduces-phosphate-induced-arterial-medial-calcification-in-mice-with-chronic-kidney-disease
#20
Tadashi Yoshida, Maho Yamashita, Chihiro Horimai, Matsuhiko Hayashi
BACKGROUND: Hyperphosphatemia is a major factor promoting the formation of arterial medial calcification in chronic kidney disease (CKD). However, arterial medial calcification begins to occur during the early stages of CKD, when hyperphosphatemia is not yet apparent. It is predicted that other factors also play a role. The aim of the present study was to determine the role of pro-inflammatory nuclear factor-κB (NF-κB) signaling in smooth muscle cells (SMCs) for phosphate-induced arterial medial calcification in CKD mice...
November 16, 2017: Journal of the American Heart Association
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