Effects of vitamin D and paricalcitol on murine cardiomyocytes

Severe alterations of Cacium-Phospate metabolism are frequently associated with chronic kidney diseases. High levels of Phospate and low levels of vitamin D in subjects affected by chronic kidney disease are, in many cases, correlated with high risk of mortality. For this reason, administration of vitamin D represents the elective treatment. Nevertheless, vitamin D in itself induces a variety of side effects which in many cases can be avoided by the administration of vitamin D analogues. In this study we treated murine cardiomyocytes with different concentrations of vitamin D and paricalcitol (one of its analogues) for 48 hours. Cell morphology, cell proliferation, intracellular Calcium deposition, and cAMP level were investigated respectively by light microscopy, immunoenzymatic assay and Von Kossa staining. Results show that, in comparison to paricalcitol, vitamin D induces stronger side effects on cardiomyocytes (such as cell proliferation, morphological changes, activation of signal transduction pathways). From our data emerges that paricalcitol induces less stressful effects on murine cardiomyocytes in comparison to what observed with vitamin D treatment

Effects of vitamin D and paricalcitol on murine cardiomyocytes

Severe alterations of Cacium-Phospate metabolism are frequently associated with chronic kidney diseases. High levels of Phospate and low levels of vitamin D in subjects affected by chronic kidney disease are, in many cases, correlated with high risk of mortality. For this reason, administration of vitamin D represents the elective treatment. Nevertheless, vitamin D in itself induces a variety of side effects which in many cases can be avoided by the administration of vitamin D analogues. In this study we treated murine cardiomyocytes with different concentrations of vitamin D and paricalcitol (one of its analogues) for 48 hours. Cell morphology, cell proliferation, intracellular Calcium deposition, and cAMP level were investigated respectively by light microscopy, immunoenzymatic assay and Von Kossa staining. Results show that, in comparison to paricalcitol, vitamin D induces stronger side effects on cardiomyocytes (such as cell proliferation, morphological changes, activation of signal transduction pathways). From our data emerges that paricalcitol induces less stressful effects on murine cardiomyocytes in comparison to what observed with vitamin D treatment

Effect of paricalcitol and GcMaf on angiogenesis and human peripheral blood mononuclear cell proliferation and signalling

Background: In addition to its role in calcium homeostasis and bone mineralization, vitamin D is involved in immune defence, cardiovascular function, inflammation and angiogenesis, and these pleiotropic effects are of interested in the treatment of chronic kidney disease. Here we investigated the effects of paricalcitol, a nonhypercalcemic vitamin D analogue, on human peripheral blood mononuclear cell proliferation and signaling, and on angiogenesis. These effects were compared with those of a known inhibitor of angiogenesis pertaining to the vitamin D axis, the vitamin D-binding protein-derived Gc-macrophage activating factor (GcMAF). Methods: Since the effects of vitamin D receptor agonists are associated with polymorphisms of the gene coding for the receptor, we measured the effects of both compounds on mononuclear cells harvested from subjects harboring different BsmI polymorphisms. Results: Paricalcitol inhibited mononuclear cell viability with the bb genotype showing the highest effect. GcMAF, on the contrary, stimulated cell proliferation, with the bb genotype showing the highest stimulatory effect. Both compounds stimulated 3'-5'-cyclic adenosine monophosphate formation in mononuclear cells with the highest effect on the bb genotype. Paricalcitol and GcMAF inhibited the angiogenesis induced by proinflammatory prostaglandin E1. Conclusions: Polymorphisms of the vitamin D receptor gene, known to be associated with the highest responses to vitamin D receptor agonists, are also associated with the highest responses to GcMAF. These results highlight the role of the vitamin D axis in chronic kidney disease, an axis which includes vitamin D, its receptor and vitamin D-binding protein-derived GcMAF

Vitamin D receptor gene polymorphism (BsmI) in uremic patients undergoing dialysis

Vitamin D receptor gene polymorphism (BsmI) in uremic patients undergoing dialysi

Nutritional-inflammation status and resistance to erythropoietin therapy in haemodialysis patients.

BACKGROUND: Chronic kidney disease patients who are resistant to erythropoietin (EPO) treatment may suffer from malnutrition and/or inflammation. METHODS: In a cross-sectional study of haemodialysis patients, we investigated the relationship between the natural logarithm of the weekly EPO dose normalized for post-dialysis body weight and outcome measures of nutrition and/or inflammation [BMI, albumin and C reactive protein (CRP)] by means of multiple linear regression analysis. On the basis of the decile distribution of weekly EPO doses, we also evaluated four groups of patients: untreated, hyper-responders, normo-responders and hypo-responders. RESULTS: Six hundred and seventy-seven adult haemodialysis patients were recruited from five Italian centres. BMI and albumin were lower in the hypo-responders than in the other groups (21.3+/-3.8 vs 24.4+/-4.7 kg/m(2), P<0.001; and 3.8+/-0.6 vs 4.1+/-0.4 g/dl, P<0.001), whereas the median CRP level was higher (1.9 vs 0.8 mg/dl, P = 0.004). The median weekly EPO dose ranged from 30 IU/kg/week in the hyper-responsive group to 263 IU/kg/week in the hypo-responsive group. Transferrin saturation linearly decreased from the hyper- to hypo-responsive group (37+/-15 to 25+/-10%, P = 0.003), without any differences in transferrin levels. Ferritin levels were lower in the hypo-responsive than in the other patients (median 318 vs 445 ng/ml, P = 0.01). At multiple linear regression analysis, haemoglobin, BMI, albumin, CRP and serum iron levels were independently associated with the natural logarithm of the weekly EPO dose (R(2) = 0.22). CONCLUSIONS: Our findings support a clear association between EPO responsiveness and nutritional and inflammation variables in haemodialysis patients; iron deficiency is still a major cause of hypo-responsiveness

Nutritional and Functional assessment of peritoneal dialysis patients in the clinical practice: Report from MITO-DP Group

Le problematiche nutrizionali e l’inattività fisica sono fattori di rischio di aumentata morbidità e mortalità nei pazienti affetti da insufficienza renale cronica. Individuare e definire la malnutrizione, in particolare una deplezione proteico-calorica (PEW) è un momento importante per la gestione e la prognosi dei nefropatici cronici. Obiettivo di questo studio osservazionale multicentrico è stato di implementare un protocollo di valutazione dello stato di nutrizione e delle capacità funzionali nei pazienti in dialisi peritoneale, comprendente test e metodiche validate, ripetibili, e di relativa facile applicazione nella pratica clinica. Lo studio comprende tutti i 133 pazienti (80 m, 53 f, età 65 ±14 anni) prevalenti in trattamento di dialisi peritoneale da 26 ±19 mesi, in 9 centri Toscani. Sono state eseguite: antropometria, bioimpedenziometria (BIA), biochimica clinica di routine, Valutazione Nutrizionale e Funzionale dei pazienti in dialisi peritoneale nella pratica clinica valutazione dell’attività fisica abituale (RAPA test) e di performance (Sit-To-Stand test), questionario di valutazione dell’appetito, ed indici tra i quali il Malnutrition Inflammation Score (MIS), Geriatric Nutrition Risk Index (GNRI), Charlson, Barthel e Karnowsky Il Barthel e Karnowsky hanno evidenziato una condizione di dipendenza nel 7.2% e 19.7% dei casi, rispettivamente. Scarso appetito è stato registrato nel 48.2%. La maggior parte dei pazienti rientrava nel sovrappeso/obesità (51 %) con valori di circonferenza vita associati a maggior rischio cardiovascolare nel 51% dei maschi e 60% delle femmine. Alla BIA, un BCMI &lt;8 Kg/m2 era presente nel 39% dei pazienti; un apporto stimato di proteine &lt; 1.0 g/Kg/d è stato riscontrato nel 59% dei casi. Il 34% dei pazienti aveva albuminemia &lt;3.5 g/dl; il controllo dell’acidosi è risultato buono (bicarbonatemia 25.4±3.8 mM) mentre iperfosforemia era presente nel 64.6% dei pazienti. Una condizione di sedentarietà o di leggera attività fisica è stata riportata dal 65.1% dei pazienti, attività vigorose solo dal 11.9%. L’86.5% dei pazienti in grado di eseguire il Sit-to-Stand test ha riportato un risultato inferiore ai valori di riferimento per età e sesso. Una diagnosi di PEW è stata possibile nel 8-13 % dei casi. Punteggio di MIS &gt; 11, indicativo di PEW, si è avuto nel 12.7% dei casi. Il valore del MIS ben correlava direttamente con l’età, ed il grado di comorbidità, ed inversamente con il Sit-to-Stand, RAPA test e livello di appetito. I dati di questo studio evidenziano che singole alterazioni indicative di malnutrizione sono relativamente frequenti, ma una chiara diagnosi di PEW era fattibile solo in una piccola percentuale di pazienti. Molti pazienti sono in sovrappeso, con aumento dell’adiposità addominale ma con massa cellulare ridotta e con un apporto proteico inferiore ai livelli raccomandati; il livello di attività fisica abituale è scarso, e ridotta è la capacità fisica. Appare quindi razionale un intervento di counseling nutrizionale per aumentare l’apporto di proteine, limitando quello di fosforo e (se indicato) di calorie, ed incentivare l’attività fisica spontanea / abituale o organizzare programmi assistiti di riabilitazione funzionale. Un attento monitoraggio dello stato di nutrizione e uno stimolo ad un’attività fisica adattata allo stato e alle capacità funzionali del paziente dovrebbero avere un ruolo preminente nella gestione clinica del paziente in dialisi peritoneal

Effects of different membranes and dialysis technologies on patient treatment tolerance and nutritional parameters

There is increasing evidence that the biochemical and cellular phenomena induced by blood/membrane/dialysate interactions contribute to dialysis-related intradialytic and long-term complications. However, there is a lack of large, prospective, randomized trials comparing biocompatible and bioincompatible membranes, and convective and diffusive treatment modalities. The primary aim of this prospective, randomized trial was to evaluate whether the use of polysulfone membrane with bicarbonate dialysate offers any advantages (in terms of treatment tolerance, nutritional parameters and pre-treatment beta(2)-microglobulin levels) over a traditional membrane (Cu-prophan(R)). A secondary aim was to assess whether the use of more sophisticated methods consisting of a biocompatible synthetic membrane with different hydraulic permeability at different ultrafiltration rate (high-flux hemodialysis and hemodiafiltration) offers any further advantages. Seventy-one Centers were involved and stratified according to the availability of only the first two or all four of the following techniques: Cuprophan(R) hemodialysis (Cu-HD), low flux polysulfone hemodialysis (LfPS-HD), high-flux polysulfone high-flux hemodialysis (HfPS-HD), and high-flux polysulfone hemodiafiltration (HfPS-HDF). The 380 eligible patients were randomized to one of the two or four treatments (132 to Cu-HD, 147 to LfPS-HD, 51 to HfPS-HD and 50 to HfPS-HDF). The follow-up was 24 months. No statistical difference was observed in the algebraic sum of the end points between bicarbonate dialysis with Cuprophan(R) or with low-flux polysulfone, or among the four dialysis methods under evaluation. There was a significant decrease in pre-dialysis plasma beta(2)-microglobulin levels in high-flux dialysis of 9.04+/-10.46 mg/liter (23%) and in hemodiafiltration of 6.35+/-12.28 mg/liter (16%), both using high-flux polysulfone membrane in comparison with Cuprophan(R) and low-flux polysulfone membranes (P=0.032). The significant decrease in pre-dialysis plasma beta(2)-microglobulin levels could have a clinical impact when one considers that beta(2)-microglobulin accumulation and amyloidosis are important long-term dialysis-related complications