2,861 research outputs found
Evaluating extended-release calcifediol as a treatment option for chronic kidney disease-mineral and bone disorder (CKD-MBD)
No full textIntroduction: Extended-release calcifediol (ERC) is an orally administered prohormone of active vitamin D (1,25-dihydroxyvitamin D [1,25D]) designed to safely and sufficiently increase serum total 25-hydroxyvitamin D (25D) to reduce elevated parathyroid hormone (PTH) in patients with non-dialysis-chronic kidney disease (ND-CKD). ERC is currently approved in the United States and Canada.Areas covered: Herein, key clinical data relating to the pharmacokinetics, pharmacodynamics, efficacy and safety of ERC are reviewed.Expert opinion: Currently available treatment options for secondary hyperparathyroidism (SHPT) in ND-CKD have limitations: the effectiveness of nutritional vitamin D supplements for reduction of PTH levels is unproven and active (1α-hydroxylated) vitamin D analogues elevate serum calcium, which increases the risk of hypercalcemia and vascular calcification. Clinical studies show that ERC is an effective, well tolerated treatment for SHPT in ND-CKD. ERC gradually raises serum 25D levels, resulting in physiologically regulated increases in serum 1,25D and sustained reductions in PTH, while avoiding clinically meaningful increases in serum phosphorus, calcium and fibroblast growth factor 23. ERC offers a new, effective and well tolerated treatment option for the early management of SHPT in patients with ND-CKD
An expert update on novel therapeutic targets for hyperphosphatemia in chronic kidney disease: preclinical and clinical innovations
No full textIntroduction: The management of hyperphosphatemia in patients with chronic kidney disease (CKD) is complicated, requiring a multidisciplinary approach that includes dietary phosphate restriction, dialysis, and phosphate binders.Areas covered: We describe key players involved in regulating inorganic phosphate homeostasis and their differential role in healthy people and different stages of CKD. The contribution of paracellular and transcellular intestinal absorptive mechanisms are also examined. Finally, we illuminate recent therapeutic approaches for hyperphosphatemia in CKD. We searched PubMed/Medline (up to November 2019) using the following terms: chronic kidney disease, dialysis, diet, hyperphosphatemia, NaPi2b, nicotinamide, phosphate binder, secondary hyperparathyroidism, tenapanor and vascular calcification.Expert opinion: The precise mechanisms regulating intestinal phosphate absorption in humans is not completely understood. However, it is now established that this process involves two independent pathways: a) active transport (i.e. transcellular route, via specific ion transporters) and inactive transport (i.e. paracellular route across tight junctions). Dietary phosphate restriction and phosphate-binder use can lead to an undesirable maladaptive increase in phosphate uptake and promote active phosphate transport by increased expression of the gastrointestinal sodium-dependent phosphate transporter, NaPi2b. Nicotinamide may overcome these limitations through the inhibition of NaPi2b, by improved efficacy and reduced phosphate binder use and better compliance
The vitamin D system : a crosstalk between the heart and kidney
No full textChronic kidney disease (CKD) independently increases the rates of cardiovascular disease, whereas the severity of kidney disease correlates with increased cardiovascular morbidity and death. Vitamin D is modified in the liver and the kidney to its active form (1,25-dihydroxyvitamin D) by the 25-hydroxy vitamin D 1-hydroxylase enzyme (CYP27B1). The activated vitamin D brings about its actions through the vitamin D receptor (VDR). The VDRs and CYP27B1 have recently been shown to be expressed in several tissues, not directly involved in mineral homeostasis, including the cardiovascular, immune, and epithelial systems. The action of vitamin D in these tissues is implicated in the regulation of endothelial, vascular smooth muscle, and cardiac cell function, the renin-angiotensin system, inflammatory and fibrotic pathways, and immune response. Impaired VDR activation and signalling results in cellular dysfunction in several organs and biological systems, which leads to reduced bone health, an increased risk for epithelial cancers, metabolic disease, and uncontrolled inflammatory responses. Failure of cardiovascular VDR activation results in hypertension, accelerated atherosclerosis and vascular calcification, cardiac hypertrophy with vascular rarification and fibrosis, and progressive renal dysfunction. An emerging body of evidence has prompted attention to the relationship between CKD, mineral bone disorder (CKD-MBD), and cardiovascular disease in the new guidelines from Kidney Disease: Improving Global Outcomes. Vitamin D receptor activators, commonly used to treat CKD-MBD, and an appropriate treatment of vitamin D hormonal system failure in patients with CKD, may help to reduce cardiovascular morbidity and mortality in these patients
Calciphylaxis: a still unmet challenge
No full textIntroduction: Calcific uremic arteriolopathy (CUA), also known as calciphylaxis, is a rare disease most frequently occurring in patients with advanced chronic kidney disease (CKD). The clinical picture is typically characterized by very painful skin lesions and ulcerations following calcification and occlusion of small cutaneous arterioles. CUA is life-threatening due to infections and concomitant cardiovascular diseases.
Methods: We performed a literature search for the terms calciphylaxis and calcific uremic arteriolopathy and summarized current state-of-the-art knowledge about pathophysiology, clinical picture, course of the disease, as well as treatment options. We have filled out the literature data with our personal treatment experiences.
Results: A combination of various local and systemic risk factors are necessary to cause the development of calciphylaxis. This pathophysiological cascade is still incompletely understood. Patients with advanced CKD and dialysis patients are especially at risk to develop CUA. Regarding therapy, no randomized prospective trials are available, and treatment is rather based on pathophysiological considerations as well as on evidence derived from case reports or case series. Therapy focuses on optimized dialysis treatment, control of chronic kidney disease-mineral and bone disorder parameters, experimental anticalcification strategies and wound care.
Conclusion: Facing the still deleterious outcome of patients with calciphylaxis, further studies on prophylaxis as well as treatment are urgently needed. Current treatment strategies may help ameliorate the course of the disease in some patients. However, it is still unclear if they are able to decrease mortality
The Phosphorus and the Vascular Calcification in ESRD between Old Adventures and New Horizons
No full textRazlike u fibrozi atrija po dobi i spolu među pacijentima s atrijskom fibrilacijom
No full textAim: Age and female sex are associated with a higher risk of stroke in atrial fibrillation (AF).
We sought to determine whether advancing age and female sex are associated with higher atrial
fibrosis.
Methods and results: We conducted an observational cohort study of patients with AF enrolled
in the University of Utah AF Database and a non-AF control group who underwent lategadolinium enhancement magnetic resonance imaging (LGE-MRI) for atrial fibrosis
quantification. Participants with contraindications for contrast MRI scanning were excluded.
Nine hundred and eight consecutive men and women with AF and 15 non-AF controls were
included in this study. Left atrial fibrosis increased with age in both men and women with AF.
Women with AF (n = 316) were older than men (n = 592): mean age 68.7±11.6 vs. 64.9±11.7
years; P < 0.01, and had higher left atrial fibrosis compared with men 17.5 ± 10.1% vs. 15.3 ±
8.9%; P < 0.001. Women also had a higher prevalence of prior stroke than men (15.8% vs.
6.5%; P < 0.001). Age and sex relationships with atrial fibrosis remained significant in
multivariate analysis. Compared with the non-AF control group, patients with AF they had
significantly higher atrial fibrosis: 16.0 ± 9.4 vs. 5.5 ± 5.8%; P < 0.001.
Conclusions: Advancing age and female sex are associated with a higher burden of atrial
fibrosis in patients with AF. Women with a prior history of stroke also have higher fibrosis
than women and men without a history of stroke. Advanced fibrosis may explain the female
and age association with stroke in AF.Cilj: Dob i ženski spol povezani su s većim rizikom za moždani udar u osoba s atrijskom
fibrilacijom (AF). Željeli smo utvrditi jesu li starija životna dob i ženski spol povezani s višom
razinom fibroze atrija.
Metode i rezultati: Proveli smo kohortnu studiju u koju smo uključili pacijente s AF koji su
bili upisani u bazu podataka na Sveučilištu Utah i kontrolnu skupinu bez AF, koja je
podvrgnuta magnetskoj rezonanciji s kasnim gadolinijskim kontrastnim pojačanjem prikaza
(engl. late-gadolinium enhancement magnetic resonance imaging, LGE-MRI) radi određivanja
atrijske fibroze. Osobe s kontraindikacijama za LGE-MRI pretragu su bile isključene. Devet
stotina i osam uzastopnih ispitanika muškog i ženskog spola s AF i 15 kontrola bez AF-a bilo
je uključeno u ovo istraživanje. Fibroza lijevog atrija se povećavala s dobi i kod muškaraca i
kod žena s AF. Žene s AF (n=316) bile su starije od muškaraca (n=592), s prosječnom dobi od
68,7 godina ± 11,6 u odnosu na 64,9 ± 11,7 godina u muškaraca (P<0,001) te su imale višu
razinu fibroze lijevog atrija u usporedbi s muškarcima (17,5 ± 10,1% nasuprot 15,3 ± 8,9%;
P<0,001). Žene su također imale veću prevalenciju prethodnog moždanog udara u usporedbi s
muškarcima (15,8% nasuprot 6,5%; P<0,001). Dob i spol bili su prediktori atrijske fibroze u
multivarijatnoj analizi. U usporedbi s kontrolnom skupinom koja nema AF, pacijenti s AF imali
su značajno višu razinu atrijske fibroze (16,0 ± 9,4 naspram 5,5 ± 5,8%; P<0,001).
Zaključci: Starija životna dob i ženski spol povezani su s većim teretom atrijske fibroze kod
pacijenata s AF. Žene koje imaju prethodni moždani udar također imaju i veću razinu atrijske
fibroze u usporedbi sa ženama i muškarcima koji nisu imali moždani udar. Uznapredovala
fibroza može objasniti povezanost između ženskog spola i starije životne dobi s moždanim
udarom kod AF
Kliničke koristi i prognostička vrijednost proteina koji veže masne kiseline srčanog tipa, miokardijalne kreatin kinaze i specifičnih ehokardiografskih parametara desne klijetke za stratifikaciju rizika normotenzivnih bolesnika s plućnom embolijom
No full textThe treatment of acute pulmonary artery embolism remains a challenge for modern medicine.
While the risk-adapted treatment strategies for the groups with high and low mortality risk are
essentially uncontroversial, uncertainty remains in patients with intermediate risk PE about the
appropriate risk stratification and management. Despite therapy, the mortality rate of this form
of pulmonary embolism is about 5-16%. It is possible that current concepts for risk
stratification, based on the use and combination of troponin I (TnI) with imaging techniques
such as echocardiography, only transfer to this patient group in limited capacity. Therefore,
clinical research is increasingly focusing on other cardiac-specific biomarkers, such as cardiac
muscle-specific fatty acid binding protein (H-FABP), which is already being used successfully
in early-stage cardiac infarction diagnostics.
Aim of the study
The present study investigates the prognostic value of new myocardial laboratory markers as
well as specific right ventricular echo parameters and contributes to risk stratification in PE
with intermediate mortality risk.
Material and Methods
Between 2005 and 2010, 161 patients with proven PE and an initial systolic blood pressure
above 90 mmHg were enrolled. All patients underwent TnI, creatine kinase isoenzyme MB
(CK-MB), CK and D-dimers determination at the routine cardiology laboratory. All patients
continued to receive a commercially available qualitative H-FABP rapid test (threshold 7
ng/ml). The routine echocardiographic examination with measurement of ventricular size ratios
(RV/LV index), the mTDI parameters, the TAPSE and other standard parameters took place on
the admission day. An intermediate mortality risk was based on the guidelines for
echocardiographic signs of right ventricular dysfunction (RVD) or elevated cardiac muscle
specific laboratory parameters. The primary endpoint was the 30-day mortality due to PE. The
secondary endpoint was the occurrence of a complicated clinical course, defined by therapy
escalation in the form of catecholamine administration, thrombolysis or embolectomy or
resuscitation.
Results
In total, 16 out of 161 (9.9%) patients died within 30 days after hospital admission. The
deceased had significantly higher plasma levels of TnI, and CK-MB compared to survivors. A positive H-FABP test was found in 26 patients, of whom 15 (57.7%) died. In contrast, one of
135 H-FABP-negative patients died (0.7%, H-FABP positive vs. negative P <0.001).
Stratification according to TnI resulted in a mortality rate of 19.7% (13 out of 66) among TnIpositive patients and 3.2% among those that were TnI-negative (3 out of 95, P = 0.001). In
echocardiography, H-FABP positives exhibited significantly greater RV/LV indices (1.02 ±
0.21 vs. 0.86 ± 0.22, P = 0.001) compared to H-FABP negatives, and a significantly lower
TAPSE (13.7 ± 4.0 mm vs. 19.1 ± 4.7 mm, P <0.001). There were no significant differences
for the mTDI parameters. Multivariate logistic regression analysis identified H-FABP (OR 27.1
95% CI 2.1 - 352.3), CK-MB (OR 5.3 95% CI 1.3 - 23.3) and the systolic blood pressure on
admisson (OR 1.2 95% CI 1.1 - 1.3) as independent predictors of 30-day mortality. The
combination of positive H-FABP test and increased CK-MB resulted in a particularly high
mortality risk: 14 of 16 patients with this laboratory constellation (87.5%) died. Conversely,
the survival probability of H-FABP-negative patients was over 99%.
There was an increased risk of a complicated clinical course with a positive H-FABP test
(OR 4.8 95% CI 1.1 - 21.1) and reduced TAPSE (OR 1.3 95% CI 1.2 - 1.5). TAPSE values
above 17.5mm made a complicated course unlikely in 98% of the cases.
Conclusion
Our data support the hypothesis that H-FABP could be a promising prognostic marker in
intermediate risk PE being highly associated with an unfavorable short-term outcome. Its
clinical value in risk stratification seems to be superior to that of cardiac troponins. The
combination of elevated H-FABP and CK-MB plasma levels indicates a particularly high risk
of mortality. The clinical value of CK-MB in risk stratification of PE is unclear and might be
underestimated and further studies are required. Increased H-FABP values correlate with
echocardiographic markers of RVD. MTDI is not suitable for risk stratification in this patient
group. Additional studies are necessary to identify which specific echocardiographic
parameters are the most useful in risk assessment in acute PE with intermediate risk mortality.Liječenje akutne embolije plućne arterije i dalje ostaje izazov za suvremenu medicinu. Iako su
strategije liječenja prilagođene riziku za skupine s visokim i niskim rizikom od smrtnosti u
osnovi nesporne, kod bolesnika sa srednjim rizikom za plućnu emboliju ostaje neizvjesnost o
odgovarajućoj stratifikaciji rizika i zbrinjavanja pacijenta. Unatoč terapiji, stopa smrtnosti od
ovog oblika plućne embolije je oko 5-16%. Moguće je da se trenutni koncepti za stratifikaciju
rizika, temeljeni na upotrebi i kombinaciji troponina I (TnI) s tehnikama slikovnog prikaza,
poput ehokardiografije, prenose na ovu grupu bolesnika u ograničenom kapacitetu. Stoga se
klinička istraživanja sve više fokusiraju na druge specifične srčane biomarkere, poput srčanomišićnog proteina koji veže masne kiseline (H-FABP), koji se već uspješno koristi u ranoj fazi
dijagnostičkog postupka srčanog infarkta.
Cilj studije
Ova studija istražuje prognostičku vrijednost novih laboratorijskih markera miokarda, kao i
specifične parametre ultrazvuka desnog ventrikula te doprinosi stratifikaciji rizika u pacijenata
s plućnom embolijom sa srednjim rizikom smrtnosti.
Materijali i metode
Između 2005. i 2010. godine u istraživanje je uključeno 161 pacijenta s dokazanom plućnom
ebmolijom i početnim sistoličkim krvnim tlakom većim od 90 mmHg. Za sve pacijente
provedeno je mjerenje TnI, kreatin kinaze MB (CK-MB), CK i D-dimera u laboratoriju za
rutinsku kardiologiju. Kod svih bolesnika učinjen je komercijalno dostupan kvalitativni brzi
test H-FABP (prag osjetljivosti od 7 ng/ml). Rutinski ultrazvučni pregled s mjerenjem omjera
veličine ventrikula (RV/LV indeks), mTDI parametrima, TAPSE i drugim standardnim
parametrima obavljen je na dan prijema. Definicija srednje razine rizika od smrtnog ishoda
zasnovana je na smjernicama za ultrazvučne znakove disfunkcije desne klijetke (RVD) ili na
povišenim vrijednostima specifičnih laboratorijskih parametara za srčani mišić. Primarni
promatrani ishod bila je smrtnost unutar 30 dana zbog plućne embolije. Sekundarni promatrani
ishod bila je pojava kompliciranog kliničkog tijeka, definiranog eskalacijom terapije u obliku
primjene kateholamina, trombolize ili embolektomije ili reanimacije.
Rezultati
Ukupno je 16 od 161 (9,9%) bolesnika umrlo u roku od 30 dana nakon prijema u bolnicu.
Ispitanici koji su preminuli imali su značajno više razine TnI i CK-MB u plazmi, u usporedbi s preživjelima. Pozitivan test H-FABP pronađen je kod 26 bolesnika, od kojih je njih 15 (57,7%)
umrlo. Suprotno tome, jedan od 135 bolesnika s negativnim H-FABP je umro (0,7%, pozitivan
H-FABP u odnosu na negativan P<0,001). Stratifikacija prema TnI rezultirala je pojavom
smrtnosti od 19,7% (13 od 66) među TnI-pozitivnim pacijentima i 3,2% među onima koji su
bili TnI-negativni (3 od 95; P=0,001). U ehokardiografiji, ispitanici s pozitivnim H-FABP
pokazali su značajno veće RV/LV indekse u usporedbi s H-FABP negativnima (1,02 ± 0,21 u
odnosu na 0,86 ± 0,22; P=0,001) i značajno niži TAPSE (13,7 ± 4,0 mm nasuprot 19,1 ± 4,7
mm; P<0,001). Nije bilo značajnih razlika za mTDI parametre. Multivarijantnom logističkom
regresijskom analizom utvrđeni su H-FABP (OR=27,1; 95% CI 2,1 - 352,3), CK-MB (OR=5,3;
95% CI 1,3 - 23,3) i sistolički krvni tlak pri prijemu (OR=1,2 95% CI 1,1 - 1.3) kao neovisni
prediktori 30-dnevne smrtnosti. Kombinacija pozitivnog H-FABP testa i povišenog CK-MB
rezultirala je s posebno visokim rizikom od smrtnosti: umrlo je 14 od 16 bolesnika s ovom
kombinacijom laboratorijskih nalaza (87,5%). Suprotno tome, vjerojatnost preživljavanja
bolesnika s negativnim H-FABP testom iznosila je preko 99%.
Zabilježen je povećan rizik od kompliciranog kliničkog tijeka u bolesnika s pozitivnim HFABP testom (OR=4,8; 95% CI 1,1- 21,1) i smanjenim TAPSE (OR=1,3; 95% CI 1,2 - 1,5).
Bolesnici s vrijednostima TAPSE iznad 17,5 mm imali su nekompliciran tijek bolesti u 98%
slučajeva.
Zaključak
Naši podaci podržavaju hipotezu da bi H-FABP mogao biti obećavajući prognostički biljeg za
plućnu emboliju s intermedijarnim rizikom jer je snažno povezan s nepovoljnim kratkoročnim
ishodom. Čini se da je njegova klinička vrijednost u stratifikaciji rizika veća od srčanih
troponina. Kombinacija povišene razine H-FABP i CK-MB u plazmi ukazuje na posebno visok
rizik od smrtnog ishoda. Klinička vrijednost CK-MB u stratifikaciji rizika od plućne embolije
je nejasna i moguće podcijenjena te su potrebne daljnje studije. Povećane vrijednosti H-FABP
koreliraju s ultrazvučnim markerima disfunkcije desne klijetke. MTDI nije pogodan za
stratifikaciju rizika u ovoj skupini bolesnika. Potrebne su dodatne studije kako bi se utvrdilo
koji su ultrazvučni parametri najkorisniji za procjenu rizika za smrtni ishod u bolesnika s
akutnom plućnom embolijom srednjeg rizika
Razlike u fibrozi atrija po dobi i spolu među pacijentima s atrijskom fibrilacijom
No full textAim: Age and female sex are associated with a higher risk of stroke in atrial fibrillation (AF).
We sought to determine whether advancing age and female sex are associated with higher atrial
fibrosis.
Methods and results: We conducted an observational cohort study of patients with AF enrolled
in the University of Utah AF Database and a non-AF control group who underwent lategadolinium enhancement magnetic resonance imaging (LGE-MRI) for atrial fibrosis
quantification. Participants with contraindications for contrast MRI scanning were excluded.
Nine hundred and eight consecutive men and women with AF and 15 non-AF controls were
included in this study. Left atrial fibrosis increased with age in both men and women with AF.
Women with AF (n = 316) were older than men (n = 592): mean age 68.7±11.6 vs. 64.9±11.7
years; P < 0.01, and had higher left atrial fibrosis compared with men 17.5 ± 10.1% vs. 15.3 ±
8.9%; P < 0.001. Women also had a higher prevalence of prior stroke than men (15.8% vs.
6.5%; P < 0.001). Age and sex relationships with atrial fibrosis remained significant in
multivariate analysis. Compared with the non-AF control group, patients with AF they had
significantly higher atrial fibrosis: 16.0 ± 9.4 vs. 5.5 ± 5.8%; P < 0.001.
Conclusions: Advancing age and female sex are associated with a higher burden of atrial
fibrosis in patients with AF. Women with a prior history of stroke also have higher fibrosis
than women and men without a history of stroke. Advanced fibrosis may explain the female
and age association with stroke in AF.Cilj: Dob i ženski spol povezani su s većim rizikom za moždani udar u osoba s atrijskom
fibrilacijom (AF). Željeli smo utvrditi jesu li starija životna dob i ženski spol povezani s višom
razinom fibroze atrija.
Metode i rezultati: Proveli smo kohortnu studiju u koju smo uključili pacijente s AF koji su
bili upisani u bazu podataka na Sveučilištu Utah i kontrolnu skupinu bez AF, koja je
podvrgnuta magnetskoj rezonanciji s kasnim gadolinijskim kontrastnim pojačanjem prikaza
(engl. late-gadolinium enhancement magnetic resonance imaging, LGE-MRI) radi određivanja
atrijske fibroze. Osobe s kontraindikacijama za LGE-MRI pretragu su bile isključene. Devet
stotina i osam uzastopnih ispitanika muškog i ženskog spola s AF i 15 kontrola bez AF-a bilo
je uključeno u ovo istraživanje. Fibroza lijevog atrija se povećavala s dobi i kod muškaraca i
kod žena s AF. Žene s AF (n=316) bile su starije od muškaraca (n=592), s prosječnom dobi od
68,7 godina ± 11,6 u odnosu na 64,9 ± 11,7 godina u muškaraca (P<0,001) te su imale višu
razinu fibroze lijevog atrija u usporedbi s muškarcima (17,5 ± 10,1% nasuprot 15,3 ± 8,9%;
P<0,001). Žene su također imale veću prevalenciju prethodnog moždanog udara u usporedbi s
muškarcima (15,8% nasuprot 6,5%; P<0,001). Dob i spol bili su prediktori atrijske fibroze u
multivarijatnoj analizi. U usporedbi s kontrolnom skupinom koja nema AF, pacijenti s AF imali
su značajno višu razinu atrijske fibroze (16,0 ± 9,4 naspram 5,5 ± 5,8%; P<0,001).
Zaključci: Starija životna dob i ženski spol povezani su s većim teretom atrijske fibroze kod
pacijenata s AF. Žene koje imaju prethodni moždani udar također imaju i veću razinu atrijske
fibroze u usporedbi sa ženama i muškarcima koji nisu imali moždani udar. Uznapredovala
fibroza može objasniti povezanost između ženskog spola i starije životne dobi s moždanim
udarom kod AF
Transkriptom-Analyse zirkulierender Monozyten zur Erforschung neuer Marker/Mediatoren akzelerierter Atherosklerose bei Hämodialyse-Patienten
No full textINTRODUCTION AND AIMS: Traditional risk factors of atherosclerosis inadequately explain the increased cardiovascular mortality in hemodialysis (HD) patients. Observations in humans and animal experiments underscore the pivotal role of the monocyte/macrophage system in the pathogenesis of atherosclerosis. Since circulating monocytes may serve as easily accessible reporters of vascular disease, we compared the transcriptomes of purified monocytes in HD patients and controls to search for new markers and potential mediators of atherosclerosis in HD patients.METHODS: Sequential monocyte purification via lymphoflot gradient centrifugation and CD14 bead separation was performed in 39 HD-patients (age: 65+13 years, HD-duration: 3,5 + 2,7 years, coronary artery disease (CAD): present: 21; absent 18) at the beginning of a HD session following a long interval and after 3h of hemodialysis. 30 age-matched healthy individuals served as controls (no coronary or peripheral artery disease, no diabetes, no continuous medication). To avoid pleiotropic effects of erythropoietin on monocytes all HD patients were off erythropoietin for more than 3 month. The amount and integrity of isolated RNA was checked using Agilentcapillary electrophoresis. 5 g of pooled RNA were hybridized on a GeneChip(U133 Plus 2.0). Differentially expressed genes were validated using absolute quantitative realtime PCR on the individual level. Serum clinical chemistry included serum levels of CRP, calcium, phosphate, PTH, ferritin, albumin, creatinine and a differential blood count.RESULTS: GeneChip-based analysis revealed about 33.000 transcripts expressed in circulating monocytes. Focussing on altered gene expression by a factor greater +/- 3 we detected 105 differentially regulated transcripts between controls and HD patients at the start of a hemodialysis session. This number increased to 469 genes after 3 hours of hemodialysis. Hitherto, we validated the pooled array results on the individual patient level focussing on differentially regulated genes between controls and patients at the start of hemodialysis with known function. Up to now we screened 16 differentially regulated transcripts on the individual patient level and identified 6 candidate genes discriminating between HD patients with CAD and controls: (HD-CAD vs. control, median [copies/1Mio18S; *T-test): cyclooxygenase2 (72 vs. 163; *<0.01); cannabinoid receptor 1 (1.1 vs. 0.27; *<0.01); interleukin-7 receptor (19 vs. 9; *<0.05); retinoic acid receptor-alpha (518 vs. 397; *<0.05); tissue factor (0.47 vs. 0.16; +<0.05); toll-like receptor 4 (1271 vs. 876; *<0.05).CONCLUSIONS: Our results suggest that transcriptome analysis of gene expression in circulating monocytes may provide a tool to detect new markers of atherosclerosis in HD patients. The potential pathomechanistic relevance in the context of accelerated atherosclerosis in the HD population is currently explored using functional in vitro studies
Fetuin-A-Serum-Spiegel und kardiovaskuläre Mortalität bei Dialysepatienten : eine Querschnittsuntersuchung
No full text- …
