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Bertrand Gondouin,
Claire Cerini,
Laetitia Dou,
Marion Sallée,
Ariane Duval-Sabatier,
Anneleen Pletinck,
Raymond Calaf,
Romaric Lacroix,
Noémie Jourde-Chiche,
Stéphane Poitevin,
Laurent Arnaud,
Raymond Vanholder, Philippe Brunet,
Françoise Dignat-George,
Stéphane Burtey
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ABSTRACT: In chronic kidney disease (CKD), uremic solutes accumulate in blood and tissues. These compounds probably contribute to the marked increase in cardiovascular risk during the progression of CKD. The uremic solutes indoxyl sulfate and indole-3-acetic acid (IAA) are particularly deleterious for endothelial cells. Here we performed microarray and comparative PCR analyses to identify genes in endothelial cells targeted by these two uremic solutes. We found an increase in endothelial expression of tissue factor in response to indoxyl sulfate and IAA and upregulation of eight genes regulated by the transcription factor aryl hydrocarbon receptor (AHR). The suggestion by microarray analysis of an involvement of AHR in tissue factor production was confirmed by siRNA inhibition and the indirect AHR inhibitor geldanamycin. These observations were extended to peripheral blood mononuclear cells. Tissue factor expression and activity were also increased by AHR agonist dioxin. Finally, we measured circulating tissue factor concentration and activity in healthy control subjects and in patients with CKD (stages 3-5d), and found that each was elevated in patients with CKD. Circulating tissue factor levels were positively correlated with plasma indoxyl sulfate and IAA. Thus, indolic uremic solutes increase tissue factor production in endothelial and peripheral blood mononuclear cells by AHR activation, evoking a 'dioxin-like' effect. This newly described mechanism of uremic solute toxicity may help understand the high cardiovascular risk of CKD patients.Kidney International advance online publication, 1 May 2013; doi:10.1038/ki.2013.133.
Kidney International 05/2013; · 6.61 Impact Factor
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ABSTRACT: Low power actuation of sessile droplets is of primary interest for portable
or hybrid lab-on-a-chip and harmless manipulation of biofluids. In this paper,
we show that the acoustic power required to move or deform droplets via surface
acoustic waves can be substantially reduced through the forcing of the drops
inertio-capillary modes of vibrations. Indeed, harmonic, superharmonic and
subharmonic (parametric) excitation of these modes are observed when the high
frequency acoustic signal (19.5 MHz) is modulated around Rayleigh-Lamb
inertio-capillary frequencies. This resonant behavior results in larger
oscillations and quicker motion of the drops than in the non-modulated case.
03/2012;
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Henri Vacher-Coponat,
Valerie Moal,
Monica Indreies,
Raj Purgus,
Anderson Loundou,
Stephane Burtey, Philippe Brunet,
Julie Moussi-Frances,
Laurent Daniel,
Bertrand Dussol,
Yvon Berland
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ABSTRACT: The best immunosuppressive regimen in benefit-risk ratio in renal transplantation is debated. Nowadays, tacrolimus (Tac) and mycophenolate mofetil (MMF) are considered more efficient than cyclosporine A (CsA) and MMF, but recent studies have challenged this assumption.
We conducted a monocentric, prospective, open-labeled, randomized, and controlled trial comparing CsA/azathioprine (Aza) versus Tac/MMF in 289 kidney transplant recipients treated with antithymocyte globulins and prednisone. Primary outcome was the number of patients with clinically suspected acute rejection at 1 year. Secondary outcomes were the number of patients with biopsy-proven acute rejection (BPAR), estimated glomerular filtration rate (eGFR), patient and graft survivals, and adverse events at 1 and 3 years.
During the first year, 21 patients had clinically suspected acute rejection with CsA/Aza (14.4%) vs. 11 (7.7%) with Tac/MMF (P=0.07). BPAR, including borderline, was more frequent in the CsA/Aza group (14.4%) than in the Tac/MMF group (5.6%; P=0.013). At 1 year, patient and graft survivals were not different, and eGFR was 48±1 in the CsA/Aza group and 53±1 mL/min/1.73 m in the Tac/MMF group (P=0.007). There was no significant difference in diabetes after transplantation (16.8% and 18.8%, respectively).
With antithymocyte globulins and steroids, clinically suspected acute rejections did not differ between CsA/Aza and Tac/MMF arms. Analysis of secondary endpoints showed a lower rate of BPAR, including border line, and a higher eGFR in the Tac/MMF group. CsA/Aza allowed a low acute rejection rate, but Tac/MMF seemed as a better regimen regarding severe secondary outcomes.
Transplantation 02/2012; 93(4):437-43. · 4.00 Impact Factor
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ABSTRACT: It has been suggested that clotting of the extracorporeal circuit during hemodialysis (HD) without heparin could be reduced by using the polyacrylonitrile AN69ST membrane. However, this has never been demonstrated in a controlled study. The objective of this study was to compare the AN69ST with a polysulfone membrane during HD without heparin in a controlled study.
This was a prospective, randomized, crossover study. Each patient had two 3-h test sessions without heparin, one with polysulfone F60 (Fresenius Medical Care, Bad Homburg, Germany), and the other with AN69ST (Hospal-Gambro, Meyzieu, France). The extracorporeal circuit was pre-rinsed with saline containing unfractionated heparin. The order of the test sessions was randomized. The test sessions were performed one week apart, during the midweek day. The participants were stable HD patients without bleeding risk. The measurements were the number of sessions with partial or complete circuit clotting.
Fifty-four patients were included in the study. The number of sessions interrupted for circuit clotting was 8 (15%) with AN69ST, and 10 (19%) with polysulfone (p=0.60). Complete circuit clotting occurred in 3 (6%) sessions with the two dialyzers. Partial circuit clotting manifested by a persistent increase in venous pressure occurred in 5 (9%) sessions with AN69ST, and in 7 (13%) sessions with polysulfone (p=0.54). Mean urea reduction ratio was 62±7% for AN69ST, and 63±7% for polysulfone (p=0.62).
The AN69ST membrane did not decrease the rate of circuit clotting during HD without heparin compared to the polysulfone F60 membrane.
The International journal of artificial organs 12/2011; 34(12):1165-71. · 1.86 Impact Factor
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Kidney International 11/2011; 80(10):1110. · 6.61 Impact Factor
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ABSTRACT: We analysed the trend of travel-times for haemodialysis patients in the Provence-Alpes-Côte-d'Azur region between 1995 and 2008 in relation with the reforms concerning the health care provision of haemodialysis.
We conducted this study using data from three cross sectional surveys for 1995, 1999 and 2002, including all dialysis patients, and from the Renal Epidemiology and Information Network register for 2008. The data focuses on sociodemographic, medical characteristics and travel-times for haemodialysis patients.
The number of haemodialysis patients increased from 1807 patients in 1995 to 3141 in 2008. The travel-time has decreased steadily between 1995 and 2008 (18.2 min versus 15, P<0.0001). The number of patients with a travel-time more than 45 min decreased from 7.2 to 3.5% between 1995 and 2008. The number of dialysis facilities has increased steadily between 1995 and 2008.
The favorable trend in the health care provision has resulted in an improvement of accessibility by reducing travel-times.
Néphrologie & Thérapeutique 10/2011; 8(3):156-62. · 0.47 Impact Factor
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Raymond Calaf,
Claire Cerini,
Cécile Génovésio,
Pierre Verhaeghe,
Noémie Jourde-Chiche,
David Bergé-Lefranc,
Bertrand Gondouin,
Laetitia Dou,
Sophie Morange,
Angel Argilés,
Pascal Rathelot,
Françoise Dignat-George, Philippe Brunet,
Philippe Charpiot
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ABSTRACT: During chronic kidney disease (CKD), solutes called uremic solutes, accumulate in blood and tissues of patients. We developed an HPLC method for the simultaneous determination of several uremic solutes of clinical interest in biological fluids: phenol (Pol), indole-3-acetic acid (3-IAA), p-cresol (p-C), indoxyl sulfate (3-INDS) and p-cresol sulfate (p-CS). These solutes were separated by ion-pairing HPLC using an isocratic flow and quantified with a fluorescence detection. The mean serum concentrations of 3-IAA, 3-INDS and p-CS were 2.12, 1.03 and 13.03 μM respectively in healthy subjects, 3.21, 17.45 and 73.47 μM in non hemodialyzed stage 3-5 CKD patients and 5.9, 81.04 and 120.54 μM in hemodialyzed patients (stage 5D). We found no Pol and no p-C in any population. The limits of quantification for 3-IAA, 3-INDS, and p-CS were 0.83, 0.72, and 3.2 μM respectively. The within-day CVs were between 1.23 and 3.12% for 3-IAA, 0.98 and 2% for 3-INDS, and 1.25 and 3.01% for p-CS. The between-day CVs were between 1.78 and 5.48% for 3-IAA, 1.45 and 4.54% for 3-INDS, and 1.19 and 6.36% for p-CS. This HPLC method permits the simultaneous and quick quantification of several uremic solutes for daily analysis of large numbers of samples.
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 08/2011; 879(23):2281-6. · 2.78 Impact Factor
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ABSTRACT: We analyzed, by home blood pressure (BP) self-measurement and conventional predialytic measurement of BP, a cohort of haemodialysis patients in two hospital units between 2008 and 2010. All patients who already own a BP self-measurement device were included in this study. BP was recorded by the two methods for one week. The number of patients with a validated self-measurement device was 69 of 350 (21%) and 60 patients were included in analyses. These patients were divided into 23 (38%) permanent uncontrolled hypertensive (elevated BP at home and in hospital), 13 (22%) masked hypertensive (normal BP in hospital and elevated at home), eight (13%) white coat hypertensive (elevated BP in hospital and normal at home), and 16 (27%) permanent controlled normotensive (normal BP in hospital and at home). Patient compliance with all the self BP measurements was 95%. We did not find in this cohort the factors associated with masked hypertension in the general population such as being male, smoking and high body mass index. These results obtained in an in-hospital dialysis unit should be extrapolated with caution to all haemodialysis patients. However it is, to our knowledge, the first study on home BP self-measurement published in patients undergoing haemodialysis in France. A significant proportion of patients have masked hypertension. This should alert clinicians because of the poor cardiovascular prognosis associated with masked hypertension.
Néphrologie & Thérapeutique 05/2011; 7(7):544-8. · 0.47 Impact Factor
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ABSTRACT: Patients with chronic kidney disease (CKD) have a much higher risk of cardiovascular diseases than the general population. Endothelial dysfunction, which participates in accelerated atherosclerosis, is a hallmark of CKD. Patients with CKD display impaired endothelium-dependent vasodilatation, elevated soluble biomarkers of endothelial dysfunction, and increased oxidative stress. They also present an imbalance between circulating endothelial populations reflecting endothelial injury (endothelial microparticles and circulating endothelial cells) and repair (endothelial progenitor cells). Endothelial damage induced by a uremic environment suggests an involvement of uremia-specific factors. Several uremic toxins, mostly protein-bound, have been shown to have specific endothelial toxicity: ADMA, homocysteine, AGEs, and more recently, p-cresyl sulfate and indoxyl sulfate. These toxins, all poorly removed by hemodialysis therapies, share mechanisms of endothelial toxicity: they promote pro-oxidant and pro-inflammatory response and inhibit endothelial repair. This article (i) reviews the evidence for endothelial dysfunction in CKD, (ii) specifies the involvement of protein-bound uremic toxins in this dysfunction, and (iii) discusses therapeutic strategies for lowering uremic toxin concentrations or for countering the effects of uremic toxins on the endothelium.
Seminars in Dialysis 05/2011; 24(3):327-37. · 2.27 Impact Factor
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ABSTRACT: Hydraulic permeability (KUF) is an intrinsic characteristic of dialysers, reported by the manufacturer as a single value, which drives and limits fluid removal. High-flux dialysers have been introduced with the appearance of convective techniques, aiming to increase fluid and solute removal. High convective volumes are being employed, although their advantages have not been fully demonstrated.
We assessed KUF over a pre-selected range of ultrafiltration rates (QUF) in post-dilutional haemodiafiltration and high-flux haemodialysis.
KUF vs QUF was neither a fixed value nor a linear function but followed a parabolic function with a vertex der (y)=0, which we have called KUF max. This also held true in high-flux routine dialysis.
These findings are completely new and have clear applications in clinics. The vertex point might be used to define the optimal QUF of a dialysis system, which would be that obtained at KUF max and corresponds to the best QUF/transmembrane pressure ratio, as opposed to the maximum QUF (which corresponds to the highest possible QUF), frequently associated with haemoconcentration, clotting, loss in dialyser surface area, and treatment problems. Determining KUF max in vivo could be of help in dialysis prescription and control with automatic systems.
Nephrology Dialysis Transplantation 02/2011; 26(2):636-40. · 3.40 Impact Factor
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ABSTRACT: Vascular dysfunction induced by uremia has 4 main aspects. (1) Atherosclerosis is increased. Intima-media thickness is increased, and animal studies have established that uremia accelerates atherosclerosis. Uremic toxins are involved in several steps of atherosclerosis. Leukocyte activation is stimulated by guanidines, advanced glycation end products (AGE), p-cresyl sulfate, platelet diadenosine polyphosphates, and indoxyl sulfate. Endothelial adhesion molecules are stimulated by indoxyl sulfate. Migration and proliferation of vascular smooth muscle cells (VSMC) are stimulated by local inflammation which could be triggered by indoxyl sulfate and AGE. Uremia is associated with an increase in von Willebrand factor, thrombomodulin, plasminogen activator inhibitor 1, and matrix metalloproteinases. These factors contribute to thrombosis and plaque destabilization. There is also a decrease in nitric oxide (NO) availability, due to asymmetric dimethylarginine (ADMA), AGE, and oxidative stress. Moreover, circulating endothelial microparticles (EMP) are increased in uremia, and inhibit the NO pathway. EMP are induced in vitro by indoxyl sulfate and p-cresyl sulfate. (2) Arterial stiffness occurs due to the loss of compliance of the vascular wall which induces an increase in pulse pressure leading to left ventricular hypertrophy and a decrease in coronary perfusion. Implicated uremic toxins are ADMA, AGE, and oxidative stress. (3) Vascular calcifications are increased in uremia. Their formation involves a transdifferentiation process of VSMC into osteoblast-like cells. Implicated uremic toxins are mainly inorganic phosphate, as well as reactive oxygen species, tumor necrosis factor and leptin. (4) Abnormalities of vascular repair and neointimal hyperplasia are due to VSMC proliferation and lead to severe reduction of vascular lumen. Restenosis after coronary angioplasty is higher in dialysis than in nondialysis patients. Arteriovenous fistula stenosis is the most common cause of thrombosis. Uremic toxins such as indoxyl sulfate and some guanidine compounds inhibit endothelial proliferation and wound repair. Endothelial progenitor cells which contribute to vessel repair are decreased and impaired in uremia, related to high serum levels of β(2)-microglobulin and indole-3 acetic acid. Overall, there is a link between kidney function and cardiovascular risk, as emphasized by recent meta-analyses. Moreover, an association has been reported between cardiovascular mortality and uremic toxins such as indoxyl sulfate, p-cresol and p-cresyl sulfate.
Kidney and Blood Pressure Research 01/2011; 34(4):284-90. · 1.46 Impact Factor
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Alain Ficheux,
Nathalie Gayrard,
Ilan Szwarc,
Daniel Andress,
Stéphan Soullier,
Yohan Duny,
Gilles Goubert,
Marie Thomas,
Johanna Bismuth-Mondolfo,
Jean-Pierre Daurès, Philippe Brunet,
Marie-Françoise Servel,
Angel Argilés
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ABSTRACT: Uraemic toxins in the 8 to 60 kDa molecular weight range have been attracting increasing attention in dialysis therapy. However, there are no available standardized methods to evaluate their removal. Using new filtering membranes, we evaluated SDS-PAGE of spent dialysate to assess cut-off ranges and removal capacities into dialysate, while also measuring classical markers of dialyser function.
Eighteen dialysis patients were washed out for 2 weeks with FX 100 (Helixone(®)), followed by randomization to Xevonta Hi 23 (Amembris(®)) or FX dialysers for 2 weeks, then crossed over for an additional 2 weeks, and finally placed on Xenium 210 (Purema(®)) for 2 weeks. SDS-PAGE scanning of the removed proteins contained in the spent dialysate was performed during all dialysis sessions. Total mass of urea, creatinine, total proteins, beta 2 microglobulin (β2m), retinol-binding protein (RBP) and albumin were measured. The reduction rates of serum urea, creatinine, β2m, leptin, RBP, alpha 1-antitrypsin, albumin and total proteins were also determined.
SDS-PAGE scanning identified four major protein peaks (10-18, 20-22.5, 23-30 and 60-80 kDa molecular weight) and showed clear differences in the amounts of removed proteins between the dialysers, particularly in the 20-22.5, 23-30 and 60-80 kDa ranges. Total mass of removed β2m, RBP and albumin were in agreement with SDS-PAGE, while serum assays showed differing results.
SDS-PAGE scanning provided a good characterization of protein patterns in the spent dialysate; it extended and agreed with protein determinations and allowed a better assessment of dialyser performance in removing 10 to 80 kDa molecular weight substances. It also identified differences between the three mainly filtrating polysulfone dialysers that were not detected with blood measurements.
Nephrology Dialysis Transplantation 12/2010; 26(7):2281-9. · 3.40 Impact Factor
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ABSTRACT: The persistence of manufacturing waste in hemodialysers is a neglected aspect of lack of hemodialysis biocompatibility. The effect of waste was tested on mitochondria isolated from rat liver.
After throwing the first two liters of the rinse solution of hemodialysers, the third liter is lyophilized. The waste is placed in the presence of mitochondria. The parameter V3 is the synthesis of ATP, the respiratory control (RC) is the ability to activate phosphorylation in the presence of ADP, ADP/O is the ratio of ADP used on oxygen consumption. The study was conducted on two hemodialyzers sterilized with gamma rays (Tricea and APS) and one hemodialyzer sterilized with flowing steam (FX60).
The respiratory parameters in the presence of waste are expressed as percentage of values obtained in the presence of control (sterile water). The respective values with Tricea, APS and the FX are for V3: 67±14, 79±10, and 81±8% (T vs A p=0.02; T vs F p=0.01; A vs F p=0.68) ; for CR : 44±6, 63±7, and 74±9% (T vs A p<0.001; T vs X p<0.001; A vs F p=0.004) ; for ADP/O : 75±11, 90±19, 91±11% (T vs A p=0.16; T vs F p=0.01; A vs F p=0.68). The dose-response curves confirm the differences concerning V3 and RC but not concerning ADP/O.
The hemodialyzers contain waste which has toxic effects on isolated mitochondria. This waste impairs the oxidative phosphorylation. The fact that this waste is still present in the dialyzers despite rinsing with two liters should alert users about the importance of extensive rinsing and manufacturers about the importance of effective procedures in order to eliminate manufacturing waste.
Néphrologie & Thérapeutique 12/2010; 6(7):576-80. · 0.47 Impact Factor
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Néphrologie & Thérapeutique 11/2010; 6(6):491-3. · 0.47 Impact Factor
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Eva Schepers,
Griet Glorieux,
Laetitia Dou,
Claire Cerini,
Nathalie Gayrard,
Loïc Louvet,
Charlotte Maugard,
Pierre Preus,
Maria Rodriguez-Ortiz,
Angel Argiles, Philippe Brunet,
Gerald Cohen,
Joachim Jankowski,
Vera Jankowski,
Ziad Massy,
Mariano Rodriguez,
Raymond Vanholder
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ABSTRACT: Chronic kidney disease is considered a major cause of cardiovascular risk and non-traditional risk factors remain largely unknown. The in vitro toxicity of 10 guanidino compounds (GCs) was evaluated via a standardized approach on different cell systems of relevance in cardiovascular disease. The parameters evaluated were production of reactive oxygen species, expression of surface molecules, cell proliferation, cytotoxicity and calcification. Several GCs had a stimulatory effect on monocytes and granulocytes (SDMA, creatine and guanidinobutyric acid (GBA)). Some GCs (guandine (G), guanidinosuccinic acid (GSA) and SDMA) inhibited endothelial cell proliferation or reduced calcification in osteoblast-like human VSMC (ADMA, GSA and SDMA). Stimulation of osteoclastogenesis could be demonstrated for ADMA, G, guanidinoacetic acid and GBA in a RAW264.7 cell line. No compounds were cytotoxic to AoSMC or endothelial cells, nor influenced their viability. GCs, especially SDMA, likely contribute to cardiovascular complications in uremia, mainly those related to microinflammation and leukocyte activation.
Blood Purification 11/2010; 30(4):277-87. · 2.10 Impact Factor
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Aurélie S Leroyer,
Francine Anfosso,
Romaric Lacroix,
Florence Sabatier,
Stéphanie Simoncini,
Sébastien M Njock,
Noémie Jourde, Philippe Brunet,
Laurence Camoin-Jau,
José Sampol,
Françoise Dignat-George
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ABSTRACT: Endothelial microparticles (EMP) are complex vesicular structures that can be shed by activated or apoptotic endothelial cells. EMP are composed of a phospholipid bilayer that exposes transmembrane proteins and receptors and encloses cytosolic components such as enzymes, transcription factors and mRNA derived from their parent cells. Thus, EMP behave as biological conveyors playing a key role in the tuning of vascular homeostasis. This review focuses on the multifaceted roles of EMP, notably in coagulation, inflammation and angiogenesis and also on the mechanisms that trigger their formation. In this context, EMP could compromise vascular homeostasis and then represent key players in the pathogenesis of several inflammatory and thrombotic diseases. Consequently, elucidating their role and their mechanisms of formation will bring new insights into the understanding of endothelial-associated diseases. Moreover, in the future, it can open novel therapeutic perspectives based on the inhibition of EMP release.
Thrombosis and Haemostasis 09/2010; 104(3):456-63. · 5.04 Impact Factor
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ABSTRACT: p-Cresylsulfate, a metabolite of p-cresol, is reported as prototypic protein-bound uremic toxin, inefficiently removed by haemodialysis. The binding between p-cresylsulfate or p-cresol and human serum albumin was studied using microcalorimetry. The results confirm that the two molecules are protein-bound. However, the affinity of p-cresylsulfate and p-cresol toward human serum albumin is moderate at 25 degrees C and becomes relatively weak at physiological temperature, 37 degrees C. The binding principally involves van der Waals type interactions, and the binding sites of the two molecules are the same or very close. The low fraction of bound toxin (13-20%) appears to be insufficient to link strong binding to poor removal of this toxin by hemodialysis.
The Journal of Physical Chemistry B 02/2010; 114(4):1661-5. · 3.70 Impact Factor
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ABSTRACT: Urea kinetic modelling-based methods are widely used to assess dialysis efficacy. However, they require blood sampling and are susceptible to a number of errors, mainly from the calculated parameters (particularly V). Spent dialysate determinations have been used and have been shown to be reliable and simple to use. In this study, we associated dialysate-based and clearance determinations along with Kt/V to estimate blood urea levels.
Urea kinetic modelling, continuous sampling of spent dialysate and ionic dialysance were determined in 18 stable dialysis patients during 126 dialysis sessions. Mean blood urea levels were estimated as follows: mean urea level = spent dialysate - urea mass/(dialysance T). Blood urea levels before and after dialysis were calculated based on the same determinations and extended formulae.
Estimated mean urea level was significantly correlated with measured mean blood urea level (R(2) = 0.957; P < 0.0001), and Bland and Altman analysis showed significant agreement between estimated and measured levels. Estimated and measured blood urea levels were also correlated before and after dialysis (R(2) = 0.972 , P < 0.0001 and R(2) = 0.903 , P < 0.0001, respectively), with good agreement for both blood urea before and after dialysis and their respective estimates.
Blood urea levels may be reliably estimated from the total mass of urea removed in the dialysate and the dialysance measured during dialysis. Coupling both measurements allows a precise monitoring of dialysis efficacy and a specific evaluation of the patient's urea metabolism status. Technical dysfunctions and patient variations may be easily identified using this approach without blood sampling.
Nephrology Dialysis Transplantation 10/2009; 25(3):873-9. · 3.40 Impact Factor
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ABSTRACT: Paracresol is a protein-bound toxin that is not efficiently eliminated by the hemodialysis method. Monte Carlo simulations in grand-canonical (GCMC) and canonical ensembles were performed to investigate the adsorption of paracresol and water in silicalite-1 zeolite. GCMC simulations using a configurational-biased algorithm show that four paracresol molecules are adsorbed at the channel intersections per unit cell of silicalite-1. The adsorption isotherms of water with and without the presence of paracresol at the intersections were investigated. A cooperative phenomenon in the process of coadsorption has been observed: at very low chemical potential, paracresol facilitates the penetration of water into silicalite-1. This mechanism is interpreted in terms of the properties of the zeolite and paracresol molecules. A thermodynamic cycle is used to calculate the adsorption energy of paracresol in silicalite-1. The calculated adsorption energy reasonably agrees with the experimental data.
Langmuir 09/2009; 25(19):11598-607. · 4.19 Impact Factor
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ABSTRACT: Protein-bound uremic retention solutes constitute a group whose common characteristic is their difficult removal by dialysis. In 2003, the EUTox group described 25 protein-bound solutes. They comprised six advanced glycation end products (AGE), four phenols (including p-cresol), six indoles (including indoxylsulfate), two hippurates, three polyamines, and two peptides, homocysteine and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF). As then, three new compounds have been added to the list: phenylacetic acid, dinucleoside polyphosphates, and IL-18. During the last years, protein-bound compounds have been identified as some of the main toxins involved in vascular lesions of chronic kidney disease. The removal of these solutes by conventional hemodialysis (HD) is low because only the free fraction of the solute is available for diffusion. The increase in the convective part with hemodiafiltration improves the performance of depuration but convection only applies to the free fraction and its benefit is limited. One possibility to improve the removal of a protein-bound solute would be to stimulate its dissociation from the binding protein. This could be obtained in experiments by setting the dialysate flow rate and the dialyzer mass transfer area coefficient (KoA) at much higher levels than the plasma flow rate, or by adding to the dialysate a sorbent such as activated charcoal or albumin. In the future, specific adsorbents may be developed. Today, the only possibility is to use approaches such as daily HD and long HD which could allow better equilibration between extravascular and vascular compartments and consequently result in greater removal of protein-bound compounds.
Seminars in Dialysis 08/2009; 22(4):334 - 339. · 2.27 Impact Factor
