Rituximab in Patients With Phospholipase A2 Receptor-Associated Membranous Nephropathy and Severe CKD.

INTRODUCTION: Patients with phospholipase A2 receptor (PLA2R)-associated membranous nephropathy and stage 4 or 5 chronic kidney disease are at high risk of end-stage kidney disease. In recent years, rituximab (RTX) emerged as a safe and efficient treatment for patients with PLA2R-associated membranous nephropathy. Whether its use is also appropriate in patients with an estimated glomerular filtration rate <30 ml/min per 1.73 m2 has not been investigated. METHODS: We retrospectively reviewed characteristics and outcome of 13 patients with PLA2R-associated membranous nephropathy and stage 4 or 5 chronic kidney disease who received a total of 14 consecutive RTX treatments from January 2012 to March 2018. The treatment regimen consisted of either 2 weekly infusions of 375 mg/m2 or 2 RTX infusions of 1 g/d two weeks apart. When needed, the regimen was repeated to achieve immunological remission. RESULTS: The mean estimated glomerular filtration rate, serum albumin level, and urinary protein level at the first RTX infusion were 18 ± 7 ml/min per 1.73 m2, 25.2 ± 5.4 g/l, and 13.2 ± 7.5 g/d, respectively, with all patients being tested positive for serum PLA2R antibodies. Ten treatment courses led to an increase in estimated glomerular filtration rate and remission of nephrotic syndrome after a median follow-up of 40.8 months (interquartile range, 14.8-46.8). Conversely, 4 RTX treatments were unsuccessful, with patients requiring chronic hemodialysis within 1 year. The urinary albumin-to-protein ratio before treatment was predictive of renal response. Immunological remission occurred after 11 treatment courses and was associated with clinical response in 10 of 11 patients. Three patients experienced severe adverse events. CONCLUSION: RTX seems effective and reasonably safe in PLA2R-associated membranous nephropathy with stage 4 or 5 chronic kidney disease. Immunological remission is associated with a good clinical outcome.

Application of a new dynamic transport model to predict the evolution of performances throughout the nanofiltration of single salt solutions in concentration and diafiltration modes.

Although many knowledge models describing the rejection of ionic compounds by nanofiltration membranes are available in literature, they are all used in full recycling mode. Indeed, both permeate and retentate streams are recycled in order to maintain constant concentrations in the feed solution. However, nanofiltration of real effluents is implemented either in concentration or diafiltration modes, for which the permeate stream is collected. In these conditions, concentrations progressively evolve during filtration and classical models fail to predict performances. In this paper, an improvement of the so called "Donnan Steric Pore Model", which includes both volume and concentration variations over time is proposed. This dynamic model is used here to predict the evolution of volumes and concentrations in both permeate and retentate streams during the filtration of salt solutions. This model was found to predict accurately the filtration performances with various salts whether the filtration is performed in concentration or diafiltration modes. The parameters of the usual model can be easily assessed from full batch experiments before being used in the dynamic version. Nevertheless, it is also highlighted that the variation of the membrane charge due to the evolution of feed concentration over time has to be taken into account in the model through the use of adsorption isotherms.

Elaboration of ammonia gas sensors based on electrodeposited polypyrrole--cobalt phthalocyanine hybrid films.

The electrochemical incorporation of a sulfonated cobalt phthalocyanine (sCoPc) in conducting polypyrrole (PPy) was done, in the presence or absence of LiClO4, in order to use the resulting hybrid material for the sensing of ammonia. After electrochemical deposition, the morphological features and structural properties of polypyrrole/phthalocyanine hybrid films were investigated and compared to those of polypyrrole films. A gas sensor consisting in platinum microelectrodes arrays was fabricated using silicon microtechnologies, and the polypyrrole and polypyrrole/phthalocyanine films were electrochemically deposited on the platinum microelectrodes arrays of this gas sensor. When exposed to ammonia, polymer-based gas sensors exhibited a decrease in conductance due to the electron exchange between ammonia and sensitive polymer-based layer. The characteristics of the gas sensors (response time, response amplitude, reversibility) were studied for ammonia concentrations varying from 1 ppm to 100 ppm. Polypyrrole/phthalocyanine films exhibited a high sensitivity and low detection limit to ammonia as well as a fast and reproducible response at room temperature. The response to ammonia exposition of polypyrrole films was found to be strongly enhanced thanks to the incorporation of the phthalocyanine in the polypyrrole matrix.

Concentration polarization phenomenon during the nanofiltration of multi-ionic solutions: influence of the filtrated solution and operating conditions.

One of the major difficulties for the prediction of separation performances in the case of multi-ionic mixtures nanofiltration lies in the description of the concentration polarization phenomenon. Usual models available in literature do not take account of the polarization phenomenon or only describe it cursorily. Very few studies dedicated to the understanding and the specific description of the concentration polarization phenomenon are available in literature and a 2-D multi-ionic model describing the layer heterogeneity along the membrane length has never been proposed yet. The model used in the present work, called Pore and Polarization Transport Model (PPTM), allows an accurate description of the concentration polarization layer occurring during the filtration of multi-ionic solutions by taking account of the radial electromigrative transport in the layer, the turbulence, as well as the axial heterogeneity. In this context, the present paper aims at proposing a numerical investigation of the influence of operating conditions on the behavior of the polarization layer occurring at the membrane vicinity. The input parameters governing the transport through the membrane have been assessed in a previous study in the same experimental conditions so that only the polarization layer is investigated here. The proposed model which was previously validated on experimental observed rejection curves is then used to understand how operating conditions, such as applied pressure, feed flow-rate, or divalent ion proportion, govern the polarization phenomenon. For this purpose, concentration and thickness axial profiles along the membrane length and radial profiles within the polarization layer are investigated for various conditions. Finally, the impact of the type of divalent ion and the number of ions is also studied on various mixtures.

[Treatment of iron deficiency in predialysis state by low molecular weight iron dextran high doses intravenously]. / Traitement de la carence martiale en prédialyse par l'administration intraveineuse de doses élevées de fer dextran de bas poids moléculaire.

Anemia is a common complication of chronic kidney disease (CKD) in predialysis stage. Iron deficiency is more common than in normal patients and plays a key role in the genesis of anemia. Its correction avoids the use of erythropoiesis stimulating agents (ESA) or reduces their dosage. Treatment with oral iron is often poorly tolerated and ineffective, necessitating the use of intravenous iron. New forms of injectable iron allow the use of high doses and correct iron deficiency in a single administration with consequent preservation of venous capital and lower costs. We studied the effectiveness of iron dextran of low molecular weight (LMWID) in high doses to correct iron deficiency and treat anemia in predialysis CKD patients. Twenty-nine doses of 500 to 1600 mg were administered to 25 patients followed for CKD (GFR between 60 and 10 ml/min per 1.73 m(2)), selected on biological criteria of iron deficiency defined by a ratio of transferrin saturation (TSAT) <20% and/or serum ferritin of less than 100 µg/L. Patients received treatment by ESA in 16 cases out of 29. One month after treatment, hemoglobin (Hb) increased significantly (11.4±1.6 vs 10.4±1.4 g/dL, P=0.0003) along with a significant increase in TSAT (21.3±7.3 vs 13.3±3.8%, P=0.000003) and serum ferritin (286±253 vs 91±60 µg/L, P=0.00005). Six patients had a serum ferritin greater than 500 µg/L after treatment, which may put them at risk of iron overload. Their serum ferritin was higher than the rest of the population before treatment, while the TSAT was no different, reflecting a functional deficiency. Their hemoglobin did not increase after treatment in contrast to the rest of the population suggesting the unavailability of iron for erythropoiesis with accumulation in the reticuloendothelial system. Renal function did not change significantly and there were no cases of acute renal failure. No immediate side effect was observed. Three patients presented delayed reactions to such self-limiting myalgia and arthralgia. No venous inflammatory reaction was noted. The administration of high doses of LMWID is effective in treating anemia of CKD in the predialysis stage with a satisfactory tolerance, without affecting kidney function and helps preserve the venous capital. It should be reserved for patients whose serum ferritin is less than or equal to 150 µg/L.

[Iron, hepcidin and chronic kidney disease]. / Fer, hepcidine et insuffisance rénale chronique.

Iron deficiency is commonly observed in chronic kidney disease. Blood loss and iron consumption under erythropiesis activating agents (ESA) induce absolute deficiency whereas defect of iron intestinal absorption and storage release account for functional deficiency. High hepcidin plasma levels are probably induced by inflammatory process and can explain functional deficiency. However, hepcidin is negatively correlated with ESA needs and hepcidin expression is influenced by other factors as degree of renal insufficiency, iron pool, treatments (iron IV and ESA). IV iron is the common therapeutic approach of iron deficiency and only normalized iron marrow supply cannot account for his efficiency. New IV iron products allow us to conceive new therapeutic schemes. Hepcidin inhibition is another therapeutic alternative.

Determining the dielectric constant inside pores of nanofiltration membranes from membrane potential measurements.

The membrane potential technique was applied to a nanofiltration polyamide membrane to determine its mean pore radius and the dielectric constant of electrolyte solutions inside pores. To our knowledge, this is the first attempt to assess these features from membrane potential measurements. Membrane potential data were analyzed by means of the SEDE (steric electric and dielectric exclusion) transport model. Experiments were conducted with single-salt solutions of NaCl and CaCl(2) and mixed-salt solutions of NaCl and CaCl(2) at various concentrations. It was shown that the pore-size values deduced from the high-concentration limit of the membrane potential measured with the two single-salt solutions are in good agreement. With this parameter being known, the membrane potential measured at high salt concentration with electrolyte mixtures was further used to compute the dielectric constant inside pores. The latter was found to be smaller than its bulk value and to decrease when sodium ions were replaced by calcium ions.

Charge properties of membranes modified by multilayer polyelectrolyte adsorption.

Alternate adsorption of polyanions and polycations on a polyethersulfone (PES) membrane was studied by the tangential streaming potential method using a parallel-plate channel to investigate the properties of the outer surface of the membrane. These streaming potential data were complemented by diffusion experiments and by membrane potential measurements in order to characterize the inner surface of the membrane. Tangential streaming potential measurements demonstrated that after completing a bilayer of poly(allylamine hydrochloride) (PAH) and poly(sodium 4-styrene sulfonate) (PSS), periodic variations in the zeta potential between positive and negative values appeared for multilayer films obtained from membrane dipped in polyelectrolyte (PE) solutions at 10 g/L. On the contrary, the zeta potential was always positive when multilayer films were obtained from 1 and 5 g/L polyelectrolyte concentration solutions. Diffusion experiments carried out with unmodified and modified membranes showed a decrease in the solute flux after functionalization of the membrane by several polyelectrolyte bilayers, indicating that the diffusional resistance of the PE layers contributes significantly to the overall resistance to diffusion of the modified membrane. By means of membrane potential measurements the pore walls of the membrane were functionalized since the charge of its pore walls was modified even if it is difficult to discriminate between the contribution of the membrane and that of the multilayer buildup.

PAH contaminated soil remediation by reusing an aqueous solution of cyclodextrins.

We studied the possibility to re-use an aqueous solution of methyl-beta-cyclodextrin (bpmCD) in order to decontaminate a soil polluted by phenanthrene and pyrene. The loss of bpmCD in the soil was insignificant. In order to eliminate polycylic aromatic hydrocarbons (PAHs) from the contaminated aqueous solution, on one hand we tested their photodegradation using TiO(2) suspensions. But it was inefficient, because of the stabilisation of PAHs within the cavity of bpmCD. On the other hand, we removed PAHs by liquid-liquid extraction with colza oil. This allowed the regeneration of cyclodextrins, by concentrating the pollutants in the organic phase with a small loss of carrier. Contaminated soils were almost completely de-polluted after 2d of re-circulation, using a 10mM solution of bpmCD. To reduce the amount of bpmCD loss in the oil phase, we set the fraction of colza oil low, by using a micro-emulsion or by impregnating an organic membrane with the oil. We found this last possibility more interesting.

Influence of steric, electric, and dielectric effects on membrane potential.

The membrane potential arising through nanofiltration membranes separating two aqueous solutions of the same electrolyte at identical hydrostatic pressures but different concentrations is investigated within the scope of the steric, electric, and dielectric exclusion model. The influence of the ion size and the so-called dielectric exclusion on the membrane potential arising through both neutral and electrically charged membranes is investigated. Dielectric phenomena have no influence on the membrane potential through neutral membranes, unlike ion size effects which increase the membrane potential value. For charged membranes, both steric and dielectric effects increase the membrane potential at a given concentration but the diffusion potential (that is the high-concentration limit of the membrane potential) is affected only by steric effects. It is therefore proposed that membrane potential measurements carried out at high salt concentrations could be used to determine the mean pore size of nanofiltration membranes. In practical cases, the membrane volume charge density and the dielectric constant inside pores depend on the physicochemical properties of both the membrane and the surrounding solutions (pH, concentration, and chemical nature of ions). It is shown that the Donnan and dielectric exclusions affect the membrane potential of charged membranes similarly; namely, a higher salt concentration is needed to screen the membrane fixed charge. The membrane volume charge density and the pore dielectric constant cannot then be determined unambiguously by means of membrane potential experiments, and additional independent measurements are in need. It is suggested to carry out rejection rate measurements (together with membrane potential measurements).

Tangential streaming potential as a tool in modeling of ion transport through nanoporous membranes.

Tangential streaming potential (TSP) measurements have been carried out so as to assess the electrokinetic properties of the active layer of organic nanofiltration (NF) membranes. Due to the porous structure of NF membranes, cares must be taken to convert the experimental data into zeta potential. Indeed, an assumption that is implicitly made in Smoluchowski's theory (or in related approaches accounting for the surface conduction phenomenon) is that both streaming and conduction currents involved in the streaming potential process flow through an identical path. Such an assumption does not hold with porous membranes since the conduction current is expected to flow wherever the electric conductivity differs from zero. Consequently, a non-negligible share of the conduction current is likely to flow through the membrane body filled with the electrolyte solution. This phenomenon has been taken into account by carrying out a series of TSP measurements at various channel heights. Experiments have been conducted with various electrolyte solutions. The inferred zeta potentials have been further converted into membrane volume charge densities which have been used to predict the membrane performances in terms of rejection rates. The conventional NF theory, i.e. based on a steric/Donnan exclusion mechanism, has been found to be unable to describe the experimental rejection rates. Using the volume charge density of the membrane as an adjustable parameter, it has been shown that the conventional theory even predicts the opposite sign for the membrane charge. On the other hand, the experimental rejection rates have been well described by including dielectric effects in the exclusion mechanism. In this case, a noticeable lowering of the effective dielectric constant of the electrolyte solution inside pores has been predicted (with respect to the bulk value).

Transport properties and electrokinetic characterization of an amphoteric nanofilter.

Transport properties of a tubular nanofilter with amphoteric properties have been investigated by means of the SEDE (steric, electric, and dielectric exclusion) homogeneous model. Within the scope of this 1D model, the separation of solutes results from transport effects (described by means of extended Nernst-Planck equations) and interfacial phenomena including steric hindrance, the Donnan effect, and dielectric exclusion (expressed in terms of (i) the Born dielectric effect, which is connected to the lowering of the dielectric constant of a solution inside nanodimensional pores, and (ii) the interaction between ions and the polarization charges induced at the dielectric boundary between the pore walls and the pore-filling solution). The effective volume charge density of the membrane has been determined from tangential streaming potential experiments coupled with conductance experiments in a potassium chloride solution at various pH values ranging from 2 to 11. The inferred values have been used in the SEDE model to compute the ion rejection rates with the dielectric constant of the solution inside the pores as a single adjustable parameter. The model provides a relatively good description of experimental data even at extreme pH values for which a ternary system has been considered (K+, Cl-, and H+ or OH- depending on the pH). The fit to experimental data at the membrane isoelectric point indicates that the confinement effect decreases the dielectric constant inside the pores only slightly (with respect to its bulk value). However, the (pH-dependent) ionization of surface sites has been found to lead to a substantial lowering of the dielectric constant inside the pores.

Removal of some divalent cations from water by membrane-filtration assisted with alginate.

The removal of divalent metal ions from hard waters or galvanic wastewater by polymer-assisted membrane filtration using alginate was investigated. The ability of this natural polymer to form aggregates and gels in presence of metal ions was studied, in order to carry out metal removal by ultra or micro-filtration. Alginate titrations have shown the presence of amine groups in addition to carboxylates onto the polymer backbone. The binding properties of alginate with divalent cations have been studied, showing an increasing affinity for Ca2+ over Mg2+ as polymer concentration increases, and the relative affinity Pb2+ > or = Cu2+ > Zn2+ > Ni2+. The softening of hard natural waters was achieved successfully and easily, but needs an optimal alginate concentration approximately 4 x 10(-2) M. The alginate powder can be directly added to hard waters. Except for Ni2+, metal-removal was efficient. Polymer regeneration has shown that Cu2+-complexes are labiles.

Analysis of the pressure-induced potential arising through composite membranes with selective surface layers.

When a pressure gradient is applied through a charged selective membrane, the transmembrane electrical potential difference, called the filtration potential, results from both the applied pressure and induced concentration difference across the membrane. In this work we investigate the electrokinetic properties relative to both active and support layers of a composite ceramic membrane close to the nanofiltration range. First, the volume charge density of the active layer is obtained by fitting a transport model to experimental rejection rates (which are controlled by the active layer only). Next, the value of the volume charge density is used to compute the theoretical filtration potential through the active layer. For sufficiently high permeate volume fluxes, the concentration difference across the active layer becomes constant, which allows assessing the membrane potential of the active layer. Experimental measurements of the overall filtration potential arising through the whole membrane are performed. The contribution of the support layer to this overall filtration potential is put in evidence. That implies that the membrane potential of the active layer cannot be deduced directly from the overall filtration potential measurements. Finally, the contribution of the support layer is singled out by subtracting the theoretical filtration potential of the active layer from the experimental filtration potential measured across the whole membrane (i.e., support + active layers). The amphoteric behavior of both layers is put in evidence, which is confirmed by electrophoretic measurements carried out with the powdered support layer and by recently reported tangential streaming potential measurements.

Effect of terlipressin (Glypressin) on hepatorenal syndrome in cirrhotic patients: results of a multicentre pilot study.

OBJECTIVES: Hepatorenal syndrome (HRS) is a severe complication of cirrhosis, leading to death in more than 90% of cases in the absence of liver transplantation. Several treatments have been attempted as a bridge to liver transplantation. Among such treatments, terlipressin has been studied in several reports, two prospective pilot studies and a double-blind, short-term, controlled haemodynamic study. Promising results have been shown with this drug. The purpose of this multicentre retrospective study was to evaluate the effects of terlipressin on renal function and survival of patients with HRS. PATIENTS AND METHODS: Eighteen patients recruited in three liver units with type 1 HRS in 16 cases and type 2 HRS in two cases were given 4 mg/day terlipressin (range 1.5-12) for 7 days (range 2-16). Electrolytes, renal function, mean urinary output, natriuresis, liver function tests, and tolerance of the treatment were monitored regularly. RESULTS: A total of 13/18 (72%) patients responded with a mean decline in serum creatinine ranging from 31 to 75% from day 0 to day 5. Eight of these 13 patients had a normal serum creatinine level at day 5. Liver function tests remained unaffected by terlipressin administration. Three local necrosis complications were noted in patients receiving terlipressin continuously via an infusion pump. Two responder patients survived: one of these underwent orthotopic liver transplantation with a follow-up of 24 months; the other is alive with a follow-up of more than 36 months. Patients who responded to terlipressin had lower baseline serum bilirubin and significantly higher serum sodium concentrations than patients who did not respond. CONCLUSION: In this pilot study, improvement in renal function was noted in 72% of cases after administration of terlipressin, and was associated with long-term survival in two patients. Parameters associated with response to terlipressin and increased survival should be defined better in a large cohort of cirrhotic patients with HRS.