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Paricalcitol AND CKD

C Torino, P Pizzini, S Cutrupi, G Tripepi, F Mallamaci, R Thadhani, C Zoccali
BACKGROUND AND AIMS: 1,25(OH)2Vitamin D increases the expression of the sclerostin gene. Whether vitamin D receptor activation (VDRA) influences serum sclerostin in CKD and whether compounds interfering with VDRA like Advanced Glycosylation End Products (AGEs) may alter the sclerostin response to VDRA is unknown. METHODS AND RESULTS: Eighty-eight stage G3-4 CKD patients randomly received 2 μg paricalcitol (PCT)/day (n = 44) or placebo (n = 44) for 12 weeks...
November 23, 2016: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
Kaichiro Sawada, J Ruth Wu-Wong, Yung-Wu Chen, Jerry L Wessale, Genta Kanai, Takatoshi Kakuta, Masafumi Fukagawa
Vitamin D receptor (VDR) agonists (VDRAs) are commonly used to treat secondary hyperparathyroidism (SHPT) associated with chronic kidney disease (CKD). Current VDRA therapy often causes hypercalcemia, which is a critical risk for vascular calcification. Previously we have shown that a novel VDRA, VS-105, effectively suppresses serum parathyroid hormone (PTH) without affecting serum calcium levels in 5/6 nephrectomized (NX) uremic rats. However, it is not known whether VS-105 directly regulates PTH gene expression...
March 2017: Journal of Steroid Biochemistry and Molecular Biology
Charlotte A Keyzer, G Fenna van Breda, Marc G Vervloet, Maarten A de Jong, Gozewijn D Laverman, Marc H Hemmelder, Wilbert M T Janssen, Hiddo J Lambers Heerspink, Arjan J Kwakernaak, Stephan J L Bakker, Gerjan Navis, Martin H de Borst
Reduction of residual albuminuria during single-agent renin-angiotensin-aldosterone blockade is accompanied by improved cardiorenal outcomes in CKD. We studied the individual and combined effects of the vitamin D receptor activator paricalcitol (PARI) and dietary sodium restriction on residual albuminuria in CKD. In a multicenter, randomized, placebo (PLAC)-controlled, crossover trial, 45 patients with nondiabetic CKD stages 1-3 and albuminuria >300 mg/24 h despite ramipril at 10 mg/d and BP<140/90 mmHg were treated for four 8-week periods with PARI (2 μg/d) or PLAC, each combined with a low-sodium (LS) or regular sodium (RS) diet...
November 17, 2016: Journal of the American Society of Nephrology: JASN
Hideki Fujii, Yuriko Yonekura, Kentaro Nakai, Keiji Kono, Shunsuke Goto, Shinichi Nishi
When using vitamin D, the most important clinical problems are hypercalcemia, hyperphosphatemia, and vascular calcification. VS-105 is a novel vitamin D receptor (VDR) analog. In the present study, we compared the effects of VS-105 and paricalcitol on chronic kidney disease-mineral bone disorder (CKD-MBD) in a CKD rat model. We used male Sprague-Dawley (SD) rats and performed 5/6 nephrectomy at 8-9 weeks. At 10 weeks, the rats were classified into five groups and administered vehicle, low-dose paricalcitol (LP, 0...
March 2017: Journal of Steroid Biochemistry and Molecular Biology
Inés Olaizola, Hena Caorsi, Laura Fajardo, Alejandro Ferreiro, Nieves Campistrus, Deyanira Dolinsky, Alicia Petraglia, Pablo Ambrosoni
Introduction: The mineral bone disorder, particularly secondary hyperparathyroidism, in chronic kidney disease (CKD) has a systemic impact affecting not only bone metabolism. Therefore its correction is important to prevent cardiovascular, inflammatory and immune diseases. Objective: To assess the effectiveness and safety of intravenous paricalcitol administered over a 6 month period for the treatment of secondary hyperparathyroidism (SHPT) in patients undergoing conventional hemodialysis, with close follow-up of treatment response...
July 2016: Jornal Brasileiro de Nefrologia: ʹorgão Oficial de Sociedades Brasileira e Latino-Americana de Nefrologia
Jonay Poveda, Ana B Sanz, Beatriz Fernandez-Fernandez, Susana Carrasco, Marta Ruiz-Ortega, Pablo Cannata-Ortiz, Alberto Ortiz, Maria D Sanchez-Niño
Current therapy for chronic kidney disease (CKD) is unsatisfactory because of an insufficient understanding of its pathogenesis. Matrix remodelling-associated protein 5 (MXRA5, adlican) is a human protein of unknown function with high kidney tissue expression, not present in rodents. Given the increased expression of MXRA5 in injured tissues, including the kidneys, we have suggested that MXRA5 may modulate kidney injury. MXRA5 immunoreactivity was observed in tubular cells in human renal biopsies and in urine from CKD patients...
January 2017: Journal of Cellular and Molecular Medicine
Luis Manjarres, Pilar Sanchez, María C Cabezas, Marco Fornasini, Valeria Freire, Adelin Albert
BACKGROUND: Chronic kidney disease (CKD) is a disorder with high morbidity and mortality worldwide whose complications generate multiple costs. In Ecuador, only a few healthcare institutions have implemented management protocols aimed to reduce costs and to improve the quality of life of patients. The aim of this study is to evaluate the short-term (1-year) and long-term (5-year) costs and savings in the management of secondary hyperparathyroidism (SHPT) of hemodialyzed CKD patients by comparing calcitriol and paricalcitol in a large social security hospital in Quito, Ecuador...
2016: BMC Health Services Research
Jacek Zawierucha, Jolanta Małyszko, Jacek Małyszko, Teresa Dryl-Rydzyńska, Tomasz Prystacki, Wojciech Marcinkowski
Secondary hyperparathyroidism (sHPT) is a common complication being a consequence of metabolic disorders associated with chronic kidney disease (CKD). Treatment of the sHPT should lead to calcium-phosphate management stabilization and parathyroid hormone levels reduction. The phosphate binders, synthetic vitamin D analogs and calcimimetics are used in sHPT treatment. In this paper we analyzed the results of three month paricalcitol treatment of 36 hemodialysis patients with sHPT (serum iPTH> 500 pg/ml). 11 patients have additionally received cinacalcet...
2016: Przegla̧d Lekarski
Giuseppe Cianciolo, Andrea Galassi, Irene Capelli, Maria Laura Angelini, Gaetano La Manna, Mario Cozzolino
Chronic kidney disease-mineral and bone disorder (CKD-MBD) is common in kidney transplant recipients (KTRs), where secondary hyperparathyroidism (HPTH) and post-transplantation bone disease (PTBD) are potential effectors of both graft and vascular aging. Reduced 25(OH)D levels are highly prevalent in KTRs. Experimental and clinical evidence support the direct involvement of deranged vitamin D metabolism in CKD-MBD among KTRs. This review analyzes the pathophysiology of vitamin D derangement in KTRs and its fall out on patient and graft outcome, highlighting the roles of both nutritional and active vitamin D compounds to treat PTBD, cardiovascular disease (CVD) and graft dysfunction...
2016: American Journal of Nephrology
C Zoccali, C Torino, G Curatola, V Panuccio, R Tripepi, P Pizzini, M Versace, D Bolignano, S Cutrupi, L Ghiadoni, R Thadhani, G Tripepi, F Mallamaci
BACKGROUND AND AIMS: Vitamin D receptor activation (VDRA) ameliorates endothelial dysfunction in CKD patients but also increases phosphate and FGF-23, which may attenuate the beneficial effect of VDRA on endothelial function. METHODS AND RESULTS: This is a pre-specified secondary analysis of the PENNY trial (NCT01680198) testing the effect of phosphate and FGF-23 on the flow mediated vasodilatory (FMD) response to paricalcitol (PCT, 2 μg/day) and placebo over a 12-weeks treatment period...
July 2016: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
Panpan Cai, Xiaohong Tang, Wei Qin, Ling Ji, Zi Li
PURPOSE: The goal of this systematic review is to evaluate the efficacy and safety of paricalcitol versus active non-selective vitamin D receptor activators (VDRAs) for secondary hyperparathyroidism (SHPT) management in chronic kidney disease (CKD) patients. METHODS: PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), (inception to September 2015), and ASN Web site were searched for relevant studies. A meta-analysis of randomized controlled trials (RCTs) and quasi-RCTs that assessed the effects and adverse events of paricalcitol and active non-selective VDRA in adult CKD patients with SHPT was performed using Review Manager 5...
April 2016: International Urology and Nephrology
Jesús Egido, Alberto Martínez-Castelao, Jordi Bover, Manuel Praga, José Vicente Torregrosa, Elvira Fernández-Giráldez, Carlos Solozábal
Secondary hyperparathyroidism (SHPT) is a common complication in patients with chronic kidney disease (CKD) that is characterised by elevated parathyroid hormone (PTH) levels and a series of bone-mineral metabolism anomalies. In patients with SHPT, treatment with paricalcitol, a selective vitamin D receptor activator, has been shown to reduce PTH levels with minimal serum calcium and phosphorus variations. The classic effect of paricalcitol is that of a mediator in mineral and bone homeostasis. However, recent studies have suggested that the benefits of treatment with paricalcitol go beyond PTH reduction and, for instance, it has a positive effect on cardiovascular disease and survival...
2016: Nefrología: Publicación Oficial de la Sociedad Española Nefrologia
Deirdre Hahn, Elisabeth M Hodson, Jonathan C Craig
BACKGROUND: Bone disease is common in children with chronic kidney disease (CKD) and when untreated may result in bone deformities, bone pain, fractures and reduced growth rates. This is an update of a review first published in 2010. OBJECTIVES: This review aimed to examine the benefits (improved growth rates, reduced risk of bone fractures and deformities, reduction in PTH levels) and harms (hypercalcaemia, blood vessel calcification, deterioration in kidney function) of interventions (including vitamin D preparations and phosphate binders) for the prevention and treatment of metabolic bone disease in children with CKD...
2015: Cochrane Database of Systematic Reviews
Kristina Lundwall, Gun Jörneskog, Stefan H Jacobson, Jonas Spaak
BACKGROUND: Vitamin D deficiency, sympathetic activation and endothelial dysfunction are associated with increased cardiovascular risk in patients with chronic kidney disease (CKD). Studies have so far failed to establish the role of vitamin D and vitamin D receptor activator (VDRA) treatment in moderate CKD. This trial was designed to assess whether VDRA treatment can ameliorate sympathetic activation and macro- and microvascular dysfunction in non-diabetic patients with moderate CKD...
2015: American Journal of Nephrology
Robert Ekart, Sebastjan Bevc, Radovan Hojs, Nina Hojs
Data on paricalcitol lowering albuminuria and proteinuria already exist; however, it is unclear how paricalcitol withdrawal affects both. Forty-two nondialysis chronic kidney disease (CKD) patients (29 men) aged 62.3 ± 12 years completed the study. CKD patients with proteinuria and intact parathyroid hormone ≥65 pg/mL received paricalcitol (1 μg/day po) for 6 months. After paricalcitol withdrawal we followed them for 6 more months. Paricalcitol treatment significantly reduced urinary albumin/creatinine ratio (UACR), 24-hour albuminuria (24hA), and 24-hour proteinuria (24hP)...
June 2016: Journal of Clinical Pharmacology
Silvia Lucisano, Adriana Arena, Giovanna Stassi, Daniela Iannello, Gaetano Montalto, Adolfo Romeo, Giuseppe Costantino, Rosaria Lupica, Valeria Cernaro, Domenico Santoro, Michele Buemi
Introduction. The aim was to highlight the existence of a relationship between vitamin D deficiency, chronic inflammation, and proteinuria, by measuring neutrophil gelatinase associated lipocalin (NGAL) and common inflammatory markers after administration of paricalcitol, a vitamin D analog, in vivo and in vitro. Methods. 40 patients with end-stage chronic kidney disease (CKD) and secondary hyperparathyroidism and 40 healthy subjects were enrolled. Serum calcium, phosphorus, 25(OH)-vitamin D, parathyroid hormone (PTH), erythrocyte sedimentation rate, high-sensitivity C-reactive protein, interleukin- (IL-) 17, IL-6, IL-1β, interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), plasmatic and urinary NGAL, and 24 h albuminuria and proteinuria were measured before and 24 h after an intravenous bolus of paricalcitol (5 mcg)...
2015: International Journal of Endocrinology
Mario Cozzolino, Adrian Covic, Blanca Martinez-Placencia, Konstantinos Xynos
BACKGROUND: In patients with chronic kidney disease (CKD), impaired renal function leads to decreased vitamin D levels, which causes an increase in parathyroid hormone (PTH) production and contributes to the development of secondary hyperparathyroidism (SHPT). This may result in adverse clinical effects such as bone disorders, vascular calcification, cardiovascular disease, and increased mortality. Current treatment practices and associated outcomes with active vitamin D treatment in patients with CKD were reviewed with the objective to assess parameters (such as PTH and serum calcium levels) that may be used to define the failure of vitamin D treatment...
2015: American Journal of Nephrology
Katarina Mirkovic, Anne-Roos S Frenay, Jacob van den Born, Harry van Goor, Gerjan Navis, Martin H de Borst
BACKGROUND: Renin-angiotensin-aldosterone system (RAAS) blockade provides renoprotective effects in chronic kidney disease (CKD); yet progressive renal function loss remains common. Dietary sodium restriction potentiates the renoprotective effects of RAAS blockade. Vitamin D receptor activator (VDRA) treatment reduces proteinuria, inflammation and fibrosis, but whether these effects depend on sodium intake has not been studied. We hypothesized that the renoprotective effects of VDRA treatment, with or without RAAS blockade, are modulated by sodium intake...
August 25, 2015: Nephrology, Dialysis, Transplantation
Maria Vanessa Perez-Gomez, Maria Dolores Sanchez-Niño, Ana Belen Sanz, Catalina Martín-Cleary, Marta Ruiz-Ortega, Jesus Egido, Juan F Navarro-González, Alberto Ortiz, Beatriz Fernandez-Fernandez
Diabetic kidney disease is the most frequent cause of end-stage renal disease. This implies failure of current therapeutic approaches based on renin-angiotensin system (RAS) blockade. Recent phase 3 clinical trials of paricalcitol in early diabetic kidney disease and bardoxolone methyl in advanced diabetic kidney disease failed to meet the primary endpoint or terminated on safety concerns, respectively. However, various novel strategies are undergoing phase 2 and 3 randomized controlled trials targeting inflammation, fibrosis and signaling pathways...
June 18, 2015: Journal of Clinical Medicine
Maciej Graczyk
Secondary hyperparathyroidism is a common disorder associated with chronic kidney disease (CKD). The increased parathormone (PTH) synthesis and secretion occur in response to: phosphate retention, decreased calcitriol (1,25(OH)2D) and increased fibroblast growth factor 23 (FGF 23) serum concentration, and--later on--decreased free ionized calcium concentration.There are several options of the management the choice depends on the CKD stage and the type of biochemical abnormalities. The initial treatment involve dietary phosphate restriction and phosphate binders...
2015: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
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