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Benjamin Wu, Murad Melhem, Raju Subramanian, Ping Chen, Bethlyn Jaramilla Sloey, Bruno Fouqueray, M Benjamin Hock, Gary L Skiles, Andrew T Chow, Edward Lee
Etelcalcetide, a d-amino acid peptide, is an intravenous calcimimetic approved for the treatment of secondary hyperparathyroidism. Etelcalcetide binds the calcium-sensing receptor and increases its sensitivity to extracellular calcium, thereby decreasing secretion of parathyroid hormone (PTH) by chief cells. Etelcalcetide and its low-molecular-weight transformation products are rapidly cleared by renal excretion in healthy subjects, but clearance is substantially reduced and dependent on hemodialysis in end-stage renal disease...
March 13, 2018: Journal of Clinical Pharmacology
M Rroji, G Spasovski
Secondary hyperparathyroidism (SHPT) is common among patients with end-stage renal disease (ESRD). SHPT is associated with high-turnover bone disease, interstitial and vascular calcifications, cardiovascular morbidity and mortality. The pharmacological management of SHPT has progressed in recent years. The introduction of targeted therapies, such as selective vitamin D receptors activators and calcium-sensing receptor modulators, offers an increased opportunity to adequately control elevated parathyroid hormone (PTH), especially in patients with chronic kidney disease under dialysis treatment...
March 12, 2018: International Urology and Nephrology
Shensen Li, Jianping Mao, Mengjing Wang, Minmin Zhang, Li Ni, Ye Tao, Bihong Huang, Jing Chen
SHPT is one of the most common complications of CKD-MBD. Recent studies indicate that oxyphil cell proliferation is related to SHPT progression, while not inhibited by current treatments. The aim of this study was to analysis the correlation between oxyphil cell and clinical indicators in SHPT, further explore the protein expression differences of oxyphil cell. Among 33 MHD patients, 84.8% patients have one or more oxyphil dominant glands and the overall oxyphil cells proportion was 39.5 ± 16.3%. Univariate correlation and multivariable linear regression analyze showed that oral calcitriol dose and treatment duration were independent indicators of oxyphil cell ratio...
March 8, 2018: Journal of Proteomics
Jürgen Floege, Kate Tsirtsonis, Jan Iles, Tilman B Drueke, Glenn M Chertow, Patrick Parfrey
The calcimimetic cinacalcet is used to treat secondary hyperparathyroidism in patients receiving dialysis, and asymptomatic hypocalcemia is often observed following its initiation. Here we investigated the incidence, predictors and therapeutic consequences of hypocalcemia by a post hoc analysis of the randomized, double-blind, placebo-controlled EValuation Of Cinacalcet Hydrochloride Therapy to Lower CardioVascular Events (EVOLVE) trial. Hypocalcemia was classified as mild (total serum calcium 8.0-8.39 mg/dL), moderate (7...
March 7, 2018: Kidney International
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
Alice Miriam Kitay, Marie-Therese Schneebacher, Anne Schmitt, Katharina Heschl, Sascha Kopic, Tariq I Alfadda, Abrar Alsaihati, Alexander Link, John P Geibel
The H+ ,K+ -ATPase was identified as the primary proton secretory pathway in the gastric parietal cell and is the pharmacological target of agents suppressing acid secretion. Recently, we identified a second acid secretory protein expressed in the parietal cell; the vacuolar H+ -ATPase (V-type ATPase). The aim of the present study was to further characterize the H+ -ATPase activation by modulations in extracellular calcium via the calcium sensing receptor (CaSR). Isolated gastric glands were loaded with the pH indicator dye BCECF [2', 7'-bis-(2- carboxyethyl)-5-(and-6)-carboxyfluorescein, acetoxymethyl ester to measure intracellular pH...
March 8, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Tibor Fülöp, Christian A Koch, Abdeen R Farah Musa, Christopher M Clark, Kamel A Gharaibeh, Zsolt Lengvársky, Mehrdad Hamrahian, Karen T Pitman, Mehul P Dixit
BACKGROUND: The long-term results of surgical parathyroidectomy (PTX) in end-stage renal disease (ESRD) patients are less well known in the modern era of newer activated vitamin-D analogs, calcimimetics and intraoperative monitoring of parathyroid hormone (PTH). METHODS: We performed a retrospective chart review of all ESRD patients undergoing PTX at the University of Mississippi Medical Center between January 2005 and August 2011, with follow-up data as available up to 4 years...
February 15, 2018: Hemodialysis International
Keith E Eidman, James B Wetmore
Secondary hyperparathyroidism (SHPT) is common in patients receiving maintenance hemodialysis and is associated with adverse outcomes. Currently, SHPT is managed by reducing circulating levels of phosphate with oral binders and parathyroid hormone (PTH) with vitamin D analogs and/or the calcimimetic cinacalcet. Etelcalcetide, a novel calcimimetic administered intravenously (IV) at the end of a hemodialysis treatment session, effectively reduces PTH in clinical trials when given thrice weekly. Additional clinical effects include reductions in circulating levels of phosphate and FGF-23 and an improved profile of markers of bone turnover...
2018: International Journal of Nephrology and Renovascular Disease
Cai-Mei Zheng, Chia-Chao Wu, Chi-Feng Hung, Min-Tser Liao, Jia-Fwu Shyu, Yung-Ho Hsu, Chien-Lin Lu, Yuan-Hung Wang, Jing-Quan Zheng, Tian-Jong Chang, Yuh-Feng Lin, Kuo-Cheng Lu
We evaluated the improvement of intact parathyroid hormone (iPTH) levels and bone parameters by supplementing nutritional vitamin D (cholecalciferol) to combined calcimimetic (cinacalcet) and active vitamin D analog (calcitriol) among severe secondary hyperparathyroidism (SHPT) hemodialysis (HD) patients. A randomized, controlled open-label study was undertaken in 60 HD patients with serum iPTH > 1000 pg/mL or persistently high iPTH ≥ 600 pg/mL even after >3 months of calcitriol (3 μg/week). The study group received oral cholecalciferol (5000 IU/ day) and the control group received a placebo...
February 10, 2018: Nutrients
Luciano Pereira, Catarina Meng, Daniela Marques, João M Frazão
Secondary hyperparathyroidism (SHPT) is associated with increased bone turnover, risk of fractures, vascular calcifications, and cardiovascular and all-cause mortality. The classical treatment for SHPT includes active vitamin D compounds and phosphate binders. However, achieving the optimal laboratory targets is often difficult because vitamin D sterols suppress parathyroid hormone (PTH) secretion, while also promoting calcium and phosphate intestinal absorption. Calcimimetics increase the sensitivity of the calcium-sensing receptor, so that even with lower levels of extracellular calcium a signal can still exist, leading to a decrease of the set-point for systemic calcium homeostasis...
February 2018: Clinical Kidney Journal
Mario Cozzolino
Patients with chronic kidney disease (CKD) are affected by mineral and bone disorder (MBD), resulting in abnormalities in serum calcium (Ca), phosphorous (P) and parathyroid hormone (PTH). Changes in mineral metabolism have also been associated with higher rates of both all-cause and cardiovascular-related mortality. The majority of haemodialysis patients are also deficient in the endogenous hormone 1,25-dihydroxyvitamin D (calcitriol), often contributing to increased secondary hyperparathyroidism (SHPT) and consequently to abnormal levels of Ca, P and PTH...
February 2018: Clinical Kidney Journal
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
Björn Stollenwerk, Sergio Iannazzo, Ron Akehurst, Michael Adena, Andrew Briggs, Bastian Dehmel, Patrick Parfrey, Vasily Belozeroff
INTRODUCTION: Etelcalcetide is a novel intravenous calcimimetic for the treatment of secondary hyperparathyroidism (SHPT) in haemodialysis patients. The clinical efficacy and safety of etelcalcetide (in addition to phosphate binders and vitamin D and/or analogues [PB/VD]) was evaluated in three phase III studies, including two placebo-controlled trials and a head-to-head study versus the oral calcimimetic cinacalcet. OBJECTIVE: The objective of this study was to develop a decision-analytic model for economic evaluation of etelcalcetide compared with cinacalcet...
February 2, 2018: PharmacoEconomics
Jie Gu, Shuya Dai, Yanmin Liu, Haitao Liu, Yao Zhang, Xingqi Ji, Feng Yu, Yang Zhou, Liang Chen, William Ka Fai Tse, Chris Kong Chu Wong, Binghai Chen, Haifeng Shi
Cadmium (Cd), as an extremely toxic metal could accumulate in kidney and induce renal injury. Previous studies have proved that Cd impact on renal cell proliferation, autophagy and apoptosis, but the detoxification drugs and the functional mechanism are still in study. In this study, we used mouse renal tubular epithelial cells (mRTECs) to clarify Cd-induced toxicity and signaling pathways. Moreover, we proposed to elucidate the prevent effect of activation of Ca2+ sensing receptor (CaSR) by Calcimimetic (R-467) on Cd-induced cytotoxicity and underlying mechanisms...
January 18, 2018: Scientific Reports
Kei Yoneki, Jun Kitagawa, Keika Hoshi, Manae Harada, Takaaki Watanabe, Takahiro Shimoda, Ryota Matsuzawa, Atsushi Yoshida, Yusuke Matsunaga, Yasuo Takeuchi, Kentaro Kamiya, Atsuhiko Matsunaga
Frailty is significantly associated with bone loss in the general population. However, it is unclear whether this association also exists in patients undergoing hemodialysis who have chronic kidney disease-mineral and bone disorder (CKD-MBD). This study aimed to assess the association between frailty and bone loss in patients undergoing hemodialysis. This cross-sectional study included 214 (90 women, 124 men) Japanese outpatients undergoing maintenance hemodialysis three times per week, with a mean age of 67...
January 15, 2018: Journal of Bone and Mineral Metabolism
Xiangrong Sun, Lieqi Tang, Steven Winesett, Wenhan Chang, Sam Xianjun Cheng
AIMS: Calcium-sensing receptor (CaSR) is expressed on neurons of both submucosal and myenteric plexuses of the enteric nervous system (ENS) and the CaSR agonist R568 inhibited Cl- secretion in intestine. The purpose of this study was to localize the primary site of action of R568 in the ENS and to explore how CaSR regulates secretion through the ENS. MATERIALS AND METHODS: Two preparations of rat proximal and distal colon were used. The full-thickness preparation contained both the submucosal and myenteric plexuses, whereas for the "stripped" preparation the myenteric plexus with the muscle layers was removed...
December 13, 2017: Life Sciences
P A Ureña Torres, J Bover, M Cohen-Solal
Chronic kidney disease is associated with mineral and bone disorders that are now considered as a syndrome. One of the major complications of this syndrome is secondary hyperparathyroidism (SHPT). SHPT increases bone turnover and the risk of fracture. SHPT is also associated with cardiovascular calcification and high mortality risk. The classical medical therapies of SHPT lack long-term efficacy and have undesirable effects on serum calcium and phosphate levels. Surgical parathyroidectomy is a radical therapeutic solution potentially exposing patients to a permanent state of hypoparathyroidism among other complications...
September 2017: Drugs of Today
Abhilash Koratala, Muhannad Leghrouz, Amir Kazory
In the current era of early detection of chronic kidney disease and efficient therapeutic options for management of its complications, skeletal manifestations of renal hyperparathyroidism are increasingly rare. A 31-year-old female patient presented for evaluation of severe pain in the left forearm, right hand, right knee, right hip, and lower back following a fall sustained 3 days prior to presentation. She had a history of end-stage renal disease and received maintenance hemodialysis. Review of the medical records revealed that she had poor compliance with her diet, medications, and dialysis treatments...
2017: SAGE Open Medical Case Reports
Yue Ding, Hongying Wang, Qiang Zou, Yiting Jin, Zijing Zhang, Junwen Huang
BACKGROUND: Renal hyperparathyroidism is a common complication of chronic kidney disease (CKD). Parathyroidectomy (PTX) for these patients continues to be a valuable option in the era of calcimimetics. Postoperative hypocalcemia is common after surgery. The aim of this study was to identify clinical factors to define postoperative calcium requirements. METHODS: From February 2013 to May 2017, 68 patients with chronic kidney disease 5 (CKD5) who underwent PTX were reviewed...
December 1, 2017: International Urology and Nephrology
Tarak Srivastava, Shahryar Jafri, William E Truog, Judith Sebestyen VanSickle, Winston M Manimtim, Uri S Alon
Secondary hyperparathyroidism (SHPT) is a rare complication of furosemide therapy that can occur in patients treated with the loop diuretic for a long period of time. We report a 6-month-old 28-weeks premature infant treated chronically with furosemide for his bronchopulmonary dysplasia, who developed hypocalcemia and severe SHPT, adversely affecting his bones. Discontinuation of the loop diuretic and the addition of supplemental calcium and calcitriol only partially reversed the SHPT, bringing serum parathyroid hormone level down from 553 to 238 pg/mL...
December 2017: Pediatrics
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