Haemodiafiltration elicits less platelet activation compared to haemodialysis

No significant changes (n.s.) were observed in platelet P-selectin (A), monocyte-platelet aggregates (B) and neutrophil-platelet aggregates (C) at different concentrations of unfractionated heparin (UFH) following 5 and 60 min of incubation. P values were calculated by Wilcoxon signed ranks test. (TIF 189 kb

Pharmacological induction of ferritin prevents osteoblastic transformation of smooth muscle cells

Vascular calcification is a frequent complication of atherosclerosis, diabetes and chronic kidney disease. In the latter group of patients, calcification is commonly seen in tunica media where smooth muscle cells (SMC) undergo osteoblastic transformation. Risk factors such as elevated phosphorus levels and vitamin D3 analogues have been identified. In the light of earlier observations by our group and others, we sought to inhibit SMC calcification via induction of ferritin. Human aortic SMC were cultured using β-glycerophosphate with activated vitamin D3 , or inorganic phosphate with calcium, and induction of alkaline phosphatase (ALP) and osteocalcin as well as accumulation of calcium were used to monitor osteoblastic transformation. In addition, to examine the role of vitamin D3 analogues, plasma samples from patients on haemodialysis who had received calcitriol or paricalcitol were tested for their tendency to induce calcification of SMC. Addition of exogenous ferritin mitigates the transformation of SMC into osteoblast-like cells. Importantly, pharmacological induction of heavy chain ferritin by 3H-1,2-Dithiole-3-thione was able to inhibit the SMC transition into osteoblast-like cells and calcification of extracellular matrix. Plasma samples collected from patients after the administration of activated vitamin D3 caused significantly increased ALP activity in SMC compared to the samples drawn prior to activated vitamin D3 and here, again induction of ferritin diminished the osteoblastic transformation. Our data suggests that pharmacological induction of ferritin prevents osteoblastic transformation of SMC. Hence, utilization of such agents that will cause enhanced ferritin synthesis may have important clinical applications in prevention of vascular calcification

Pharmacological induction of ferritin prevents osteoblastic transformation of smooth muscle cells

Vascular calcification is a frequent complication of atherosclerosis, diabetes and chronic kidney disease. In the latter group of patients, calcification is commonly seen in tunica media where smooth muscle cells (SMC) undergo osteoblastic transformation. Risk factors such as elevated phosphorus levels and vitamin D3 analogues have been identified. In the light of earlier observations by our group and others, we sought to inhibit SMC calcification via induction of ferritin. Human aortic SMC were cultured using β-glycerophosphate with activated vitamin D3, or inorganic phosphate with calcium, and induction of alkaline phosphatase (ALP) and osteocalcin as well as accumulation of calcium were used to monitor osteoblastic transformation. In addition, to examine the role of vitamin D3 analogues, plasma samples from patients on haemodialysis who had received calcitriol or paricalcitol were tested for their tendency to induce calcification of SMC. Addition of exogenous ferritin mitigates the transformation of SMC into osteoblast-like cells. Importantly, pharmacological induction of heavy chain ferritin by 3H-1,2-Dithiole-3-thione was able to inhibit the SMC transition into osteoblast-like cells and calcification of extracellular matrix. Plasma samples collected from patients after the administration of activated vitamin D3 caused significantly increased ALP activity in SMC compared to the samples drawn prior to activated vitamin D3 and here, again induction of ferritin diminished the osteoblastic transformation. Our data suggests that pharmacological induction of ferritin prevents osteoblastic transformation of SMC. Hence, utilization of such agents that will cause enhanced ferritin synthesis may have important clinical applications in prevention of vascular calcification

The disparate effect of hemodialysis and hemodiafiltration on T-wave-peak-to-end interval (Tpe) and Tpe/QT ratio of the surface electrocardiogram

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Examination of increased vascular risk factors in patients with end-stage renal disease

A krónikus vesebetegség legsúlyosabb stádiumában, amikor már végstádiumú veseelégtelenségről beszélhetünk, olyan mértékben csökken a salakanyagok kiválasztása és gyakran ezzel párhuzamosan a vizelet mennyisége is, hogy valamilyen formában már a kieső vesefunkciót pótolni szükséges. A vesepótló kezelésektől függetlenül is sajnos a betegeink fokozott kardiovaszkuláris rizikóval rendelkeznek. A megnövekedett rizikó hátterében már vannak jól ismert, kutatócsoportunk által is azonosított faktorok (pl.: inorganikus foszfát, vashiány, stb.), ill. irodalmi adatok alapján számos olyan tényező (pl.: D-vitamin és analóg vegyületei, kumarin származékok, stb.), melyek elősegítik a vaszkuláris kalcifikáció kialakulását, progresszióját. A vaszkuláris kalcifikáció speciális formájának számító Mönckeberg-féle mediasclerosis típusosan a krónikus vesebetegséghez társuló kórkép. Azonban a krónikus vesebetegség kialakulását előidéző, vagy „csak” a vesebetegséghez társultan jelentkező társbetegségek kapcsán gyakran az átlag populációban gyakori intimasclerosis is megfigyelhető betegeinknél. Ilyen esetekben a vaszkulatúra károsodása nagyságrendekkel gyorsabban zajlik. A vaszkuláris betegségek etiológiájában ugyancsak fontos szereppel bír a vérlemezkék számában és/vagy funkciójában bekövetkező változás. Vizsgálatunkban sikerült igazolni, hogy a dialízis kezelés önmagában képes a vérlemezkék aktivációját fokozni, de az irodalomban is újnak számító eredményként sikerült bizonyítanunk a hemodiafiltrációs kezelés kedvezőbb hatását a vérlemezke aktiváció vonatkozásában. Mindkét munkám során próbáltunk olyan területeket vizsgálni, melyek a végstádiumú veseelégtelen betegek fokozott kardiovaszkuláris rizikójának hátterében lejátszódó patofiziológiai folyamatok részletesebb megismerése révén segíthet a mindennapi gyakorlat számára is hasznos terápiás lehetőségek kidolgozásában.Cardiovascular risk is elevated among chronic kidney disease patients and it is independent from the modality of renal replacement therapy. Cardiovascular risk is increasing in parallel with the progression of CKD. There are many well-known pathophysiological factors in the background of increased CV risk, some of them are also confirmed by our research group (e.g. high inorganic phosphate, iron deficiency, etc.), while others can be found in the literature as inducers of vascular calcification (e.g. vitamin D and its analogues, coumarin derivatives, etc.). We demonstrated an in vitro model for Mönckeberg’s type mediasclerosis of vascular smooth muscle cells with activated vitamin D and beta-glycerophosphate. Induction of ferritin heavy chain expression and its ferroxidase activity inhibited succesfully the process of calcification. Among the inducers we used iron and other alternatives. The changes in platelet count and platelet function are also crucial in the aetiology of vascular diseases. We proved that platelet activation is increased in patients during the dialysis treatments. Our research group was the first to show that haemodiafiltration modality is more favourable in this respect. The aim of both studies was to recognize complex pathophysiological processes resulting in an increased cardiovascular risk of patients with end-stage renal disease and find new potential therapeutic strategies for everyday use

Pharmacological induction of ferritin prevents osteoblastic transformation of smooth muscle cells

Vascular calcification is a frequent complication of atherosclerosis, diabetes, and chronic kidney disease. In the latter group of patients, calcification is commonly seen in tunica media where smooth muscle cells (SMC) undergo osteoblastic transformation. Risk factors such as elevated phosphorus levels and vitamin D3 analogs have been identified. Inlight of earlier observations by our group and others, we sought to inhibit SMC calcification via induction of ferritin. Human aortic SMC were cultured using β-glycerophosphate with activated vitamin D3, or inorganic phosphate with calcium, and induction of alkaline phosphatase and osteocalcin as well as accumulation of calcium were used to monitor osteoblastic transformation. Additionally, to examine the role of vitamin D3 analogs, plasma samples from patients on hemodialysis who hadreceived calcitriol or paricalcitol were tested for their tendency to induce calcification of SMC. Addition of exogenous ferritin mitigates the transformation of SMC into osteoblast-like cells. Importantly, pharmacologic induction of heavy chain ferritin by 3H-1,2-Dithiole-3-thione was able to inhibit the SMC transition into osteoblast-like cells and calcification of extracellular matrix. Plasma samples collected from patients after administration of activated vitamin D3 caused significantly increased alkaline phosphatase activity in SMC compared to samples drawn prior to activated vitamin D3 and here, again induction of ferritin diminished the osteoblastic transformation. Our data suggests that pharmacologic induction of ferritin prevents osteoblastic transformation of SMC. Hence, utilization of such agents thatwill cause enhanced ferritin synthesis may have important clinical application in prevention of vascular calcification

Terminal Phase Components of the Clotting Cascade in Patients with End-Stage Renal Disease Undergoing Hemodiafiltration or Hemodialysis Treatment

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