HIV-1 Tat reduces nephrin in human podocytes: a potential mechanism for enhanced glomerular permeability in HIV-associated nephropathy.

PubMed

Doublier, Sophie; Zennaro, Cristina; Spatola, Tiziana; Lupia, Enrico; Bottelli, Antonella; Deregibus, Maria Chiara; Carraro, Michele; Conaldi, Pier Giulio; Camussi, Giovanni

2007-02-19

To determine whether HIV-1 Tat may directly alter glomerular permeability in HIV-associated nephropathy (HIVAN). Heavy proteinuria is a hallmark of HIVAN. The slit diaphragm is the ultimate glomerular filtration barrier critical for maintaining the efficiency of the ultrafiltration unit of the kidney. In this study, we evaluated the direct effect of Tat protein on the permeability of isolated glomeruli and on the expression of nephrin, the main slit diaphragm component, by human cultured podocytes. Permeability was studied by measuring the permeability to albumin in isolated rat glomeruli. We also evaluated the expression of nephrin in human cultured podocytes by using immunofluorescence and Western blot. We found that Tat increased albumin permeability in isolated glomeruli, and rapidly induced the redistribution and loss of nephrin in cultured podocytes. Pretreatment of glomeruli and podocytes with blocking antibodies showed that Tat reduced nephrin expression by engaging vascular endothelial growth factor receptors types 2 and 3 and the integrin alphavbeta3. Pre-incubation of podocytes with two platelet-activating factor (PAF) receptor antagonists prevented the loss and redistribution of nephrin induced by Tat, suggesting that PAF is an intracellular mediator of Tat action. Tat induced a rapid PAF synthesis by podocytes. When podocytes transfected to overexpress PAF-acetylhydrolase, the main catabolic enzyme of PAF, were stimulated with Tat, the redistribution and loss of nephrin was abrogated. The present results define a mechanism by which Tat may reduce nephrin expression in podocytes, thus increasing glomerular permeability. This provides new insights in the understanding of HIVAN pathogenesis.

Estimating individual glomerular volume in the human kidney: clinical perspectives.

PubMed

Puelles, Victor G; Zimanyi, Monika A; Samuel, Terence; Hughson, Michael D; Douglas-Denton, Rebecca N; Bertram, John F; Armitage, James A

2012-05-01

Measurement of individual glomerular volumes (IGV) has allowed the identification of drivers of glomerular hypertrophy in subjects without overt renal pathology. This study aims to highlight the relevance of IGV measurements with possible clinical implications and determine how many profiles must be measured in order to achieve stable size distribution estimates. We re-analysed 2250 IGV estimates obtained using the disector/Cavalieri method in 41 African and 34 Caucasian Americans. Pooled IGV analysis of mean and variance was conducted. Monte-Carlo (Jackknife) simulations determined the effect of the number of sampled glomeruli on mean IGV. Lin's concordance coefficient (R(C)), coefficient of variation (CV) and coefficient of error (CE) measured reliability. IGV mean and variance increased with overweight and hypertensive status. Superficial glomeruli were significantly smaller than juxtamedullary glomeruli in all subjects (P < 0.01), by race (P < 0.05) and in obese individuals (P < 0.01). Subjects with multiple chronic kidney disease (CKD) comorbidities showed significant increases in IGV mean and variability. Overall, mean IGV was particularly reliable with nine or more sampled glomeruli (R(C) > 0.95, <5% difference in CV and CE). These observations were not affected by a reduced sample size and did not disrupt the inverse linear correlation between mean IGV and estimated total glomerular number. Multiple comorbidities for CKD are associated with increased IGV mean and variance within subjects, including overweight, obesity and hypertension. Zonal selection and the number of sampled glomeruli do not represent drawbacks for future longitudinal biopsy-based studies of glomerular size and distribution.

Transport of Spherical Particles Through Fibrous Media and a Row of Parallel Cylinders: Applications to Glomerular Filtration.

PubMed

Punyaratabandhu, Numpong; Kongoup, Pimkhwan; Dechadilok, Panadda; Katavetin, Pisut; Triampo, Wannapong

2017-12-01

Viewed in renal physiology as a refined filtration device, the glomerulus filters large volumes of blood plasma while keeping proteins within blood circulation. Effects of macromolecule size and macromolecule hydrodynamic interaction with the nanostructure of the cellular layers of the glomerular capillary wall on the glomerular size selectivity are investigated through a mathematical simulation based on an ultrastructural model. The epithelial slit, a planar arrangement of fibers connecting the epithelial podocytes, is represented as a row of parallel cylinders with nonuniform spacing between adjacent fibers. The mean and standard deviation of gap half-width between its fibers are based on values recently reported from electron microscopy. The glomerular basement membrane (GBM) is represented as a fibrous medium containing fibers of two different sizes: the size of type IV collagens and that of glycosaminoglycans (GAGs). The endothelial cell layer is modeled as a layer full of fenestrae that are much larger than solute size and filled with GAGs. The calculated total sieving coefficient agrees well with the sieving coefficients of ficolls obtained from in vivo urinalysis in humans, whereas the computed glomerular hydraulic permeability also falls within the range estimated from human glomerular filtration rate (GFR). Our result indicates that the endothelial cell layer and GBM significantly contribute to solute and fluid restriction of the glomerular barrier, whereas, based on the structure of the epithelial slit obtained from electron microscopy, the contribution of the epithelial slit could be smaller than previously believed.

Agrin is a major heparan sulfate proteoglycan in the human glomerular basement membrane.

PubMed

Groffen, A J; Ruegg, M A; Dijkman, H; van de Velden, T J; Buskens, C A; van den Born, J; Assmann, K J; Monnens, L A; Veerkamp, J H; van den Heuvel, L P

1998-01-01

Agrin is a heparan sulfate proteoglycan (HSPG) that is highly concentrated in the synaptic basal lamina at the neuromuscular junction (NMJ). Agrin-like immunoreactivity is also detected outside the NMJ. Here we show that agrin is a major HSPG component of the human glomerular basement membrane (GBM). This is in addition to perlecan, a previously characterized HSPG of basement membranes. Antibodies against agrin and against an unidentified GBM HSPG produced a strong staining of the GBM and the NMJ, different from that observed with anti-perlecan antibodies. In addition, anti-agrin antisera recognized purified GBM HSPG and competed with an anti-GBM HSPG monoclonal antibody in ELISA. Furthermore, both antibodies recognized a molecule that migrated in SDS-PAGE as a smear and had a molecular mass of approximately 200-210 kD after deglycosylation. In immunoelectron microscopy, agrin showed a linear distribution along the GBM and was present throughout the width of the GBM. This was again different from perlecan, which was exclusively present on the endothelial side of the GBM and was distributed in a nonlinear manner. Quantitative ELISA showed that, compared with perlecan, the agrin-like GBM HSPG showed a sixfold higher molarity in crude glomerular extract. These results show that agrin is a major component of the GBM, indicating that it may play a role in renal ultrafiltration and cell matrix interaction. (J Histochem Cytochem 46:19-27, 1998)

Hindered transport of macromolecules in isolated glomeruli. II. Convection and pressure effects in basement membrane.

PubMed

Edwards, A; Daniels, B S; Deen, W M

1997-01-01

The filtration rates for water and a polydisperse mixture of Ficoll across films of isolated glomerular basement membrane (GBM) were measured to characterize convective transport across this part of the glomerular capillary wall. Glomeruli were isolated from rat kidneys and the cells were removed by detergent lysis, leaving a preparation containing almost pure GBM that could be consolidated into a layer at the base of a small ultrafiltration cell. A Ficoll mixture with Stokes-Einstein radii ranging from about 2.0 to 7.0 nm was labeled with fluorescein, providing a set of rigid, spherical test macromolecules with little molecular charge. Filtration experiments were performed at two physiologically relevant hydraulic pressure differences (delta P), 35 and 60 mmHg. The sieving coefficient (filtrate-to-retentate concentration ratio) for a given size of Ficoll tended to be larger at 35 than at 60 mmHg, the changes being greater for the smaller molecules. The Darcy permeability also varied inversely with pressure, averaging 1.48 +/- 0.10 nm2 at 35 mmHg and 0.82 +/- 0.07 nm2 at 60 mmHg. Both effects could be explained most simply by postulating that the intrinsic permeability properties of the GBM change in response to compression. The sieving data were consistent with linear declines in the hindrance factors for convection and diffusion with increasing pressure, and correlations were derived to relate those hindrance factors to molecular size and delta P. Comparisons with previous Ficoll sieving data for rats in vivo suggest that the GBM is less size-restrictive than the cell layers, but that its contribution to the overall size selectivity of the barrier is not negligible. Theoretical predictions of the Darcy permeability based on a model in which the GBM is a random fibrous network consisting of two populations of fibers were in excellent agreement with the present data and with ultrastructural observations in the literature.

Estimating individual glomerular volume in the human kidney: clinical perspectives

PubMed Central

Puelles, Victor G.; Zimanyi, Monika A.; Samuel, Terence; Hughson, Michael D.; Douglas-Denton, Rebecca N.; Bertram, John F.

2012-01-01

Background. Measurement of individual glomerular volumes (IGV) has allowed the identification of drivers of glomerular hypertrophy in subjects without overt renal pathology. This study aims to highlight the relevance of IGV measurements with possible clinical implications and determine how many profiles must be measured in order to achieve stable size distribution estimates. Methods. We re-analysed 2250 IGV estimates obtained using the disector/Cavalieri method in 41 African and 34 Caucasian Americans. Pooled IGV analysis of mean and variance was conducted. Monte-Carlo (Jackknife) simulations determined the effect of the number of sampled glomeruli on mean IGV. Lin’s concordance coefficient (RC), coefficient of variation (CV) and coefficient of error (CE) measured reliability. Results. IGV mean and variance increased with overweight and hypertensive status. Superficial glomeruli were significantly smaller than juxtamedullary glomeruli in all subjects (P < 0.01), by race (P < 0.05) and in obese individuals (P < 0.01). Subjects with multiple chronic kidney disease (CKD) comorbidities showed significant increases in IGV mean and variability. Overall, mean IGV was particularly reliable with nine or more sampled glomeruli (RC > 0.95, <5% difference in CV and CE). These observations were not affected by a reduced sample size and did not disrupt the inverse linear correlation between mean IGV and estimated total glomerular number. Conclusions. Multiple comorbidities for CKD are associated with increased IGV mean and variance within subjects, including overweight, obesity and hypertension. Zonal selection and the number of sampled glomeruli do not represent drawbacks for future longitudinal biopsy-based studies of glomerular size and distribution. PMID:21984554

Podocalyxin EBP50 Ezrin Molecular Complex Enhances the Metastatic Potential of Renal Cell Carcinoma Through Recruiting Rac1 Guanine Nucleotide Exchange Factor ARHGEF7

PubMed Central

Hsu, Yung-Ho; Lin, Wei-Ling; Hou, Yi-Ting; Pu, Yeong-Shiau; Shun, Chia-Tung; Chen, Chi-Ling; Wu, Yih-Yiing; Chen, Jen-Yau; Chen, Tso-Hsiao; Jou, Tzuu-Shuh

2010-01-01

Podocalyxin was initially identified in glomerular podocytes to critically maintain the structural and functional integrity of the glomerular ultrafiltrative apparatus. Lately, it has emerged as a malignant marker in tumors arising from a variety of tissue origins. By immunohistochemistry, we identified that 9.6% of renal cell carcinoma patients overexpress this protein. This subset of patients had significantly shorter disease-specific and overall survivals, and, importantly, we established podocalyxin overexpression as an independent prognostic factor for latent distant metastasis with multivariate analysis. Podocalyxin down-regulation by small interfering RNA led to defective migration in model renal tubular cells, which was corrected by re-expression of podocalyxin. The activity of the small GTPase Rac1, a well-characterized modulator of cell migration, was diminished by podocalyxin knock-down. Conversely, podocalyxin overexpression in human embryonic kidney cells up-regulated Rac1 activity, which depended on a complex formed by podocalyxin, ERM-binding phosphoprotein 50, ezrin, and ARHGEF7, a Rac1 activator. Therefore, podocalyxin can serve as a biomarker to identify renal cell carcinoma patients with higher metastatic potential for more aggressive intervention at earlier clinical stages. PMID:20395446

We Avoid RAAS Inhibitors in PD Patients with Residual Renal Function.

PubMed

Turner, Jeffrey M

2016-07-01

Preserving residual renal function in patients on peritoneal dialysis (PD) positively impacts mortality. While it is important to avoid nephrotoxic agents in this setting, clinicians should appreciate that inhibitors of the renin-angiotensin-aldosterone system (RAAS), including angiotensin converting enzyme inhibitors, and angiotensin receptor blockers are likely to preserve glomerular filtration rate and prolong the time until patients on PD reach anuria, and this may improve mortality in these patients. In addition, RAAS blockade favorably affects the peritoneal membrane by reducing morphologic changes that can lead to ultrafiltration failure. This in turn may delay or prevent modality failure in patients on PD. Thus, clinicians should avoid the impulse to stop RAAS inhibitors in the PD population. © 2016 Wiley Periodicals, Inc.

Differential regulation of glomerular and interstitial endothelial nitric oxide synthase expression in the kidney of hibernating ground squirrel.

PubMed

Sandovici, Maria; Henning, Robert H; Hut, Roelof A; Strijkstra, Arjen M; Epema, Anne H; van Goor, Harry; Deelman, Leo E

2004-09-01

Hibernating animals transiently reduce renal function during their hypothermic periods (torpor), while completely restoring it during their periodical rewarming to euthermia (arousal). Moreover, structural integrity of the kidney is preserved throughout the hibernation. Nitric oxide (NO) generated by endothelial nitric oxide synthase (eNOS) is a crucial vasodilatory mediator and a protective factor in the kidney. We investigated renal NOS expression in hibernating European ground squirrels after 1 day and 7 days of torpor (torpor short, TS, and torpor long, TL, respectively), at 1.5 and at 10 h of rewarming (arousal short, AS, and arousal long, AL, respectively), and in continuously euthermic animals after hibernation (EU). For that purpose, we performed NOS activity assay, immunohistochemistry and real-time PCR analysis. Immunohistochemistry revealed a decreased glomerular eNOS expression in hibernating animals (TS, TL, AS, and AL) compared to non-hibernating animals (EU, p < 0.05), whereas no difference was found in the expression of interstitial eNOS. Expression of iNOS and nNOS did not differ between all groups. The reduced glomerular eNOS was associated with a significantly lower eNOS mRNA levels and NOS activity of whole kidney during torpor and arousal (TS, TL, AS, and AL) compared to EU. In all methods used, torpid and aroused squirrels did not differ. These results demonstrate differential regulation of eNOS in glomeruli and interstitium of hibernating animals, which is unaffected during arousal. The differential regulation of eNOS may serve to reduce ultrafiltration without jeopardizing tubular structures during hibernation.

[Study on assistant cleaning of ultrasound for the ultrafiltration membrane].

PubMed

Zhang, Guojun; Liu, Zhongzhou

2003-11-01

The effects of ultrasounds with different frequency on membrane performance were investigated in this paper. The experimental results show that there were nearly no effects of 20 W ultrasound on membrane retention coefficient, but it decreased seriously when the ultrasound power was above 30 W. On the basis of these results, low frequency ultrasound (20 W) was introduced to assist the chemical cleaning in the ultrafiltration process of wastewater from bank note printing works. The cleaning time could be shortened from 20-30 min to 5 min by the ultra-liberation and ultra-blend effects of ultrasound, therefore, the cleaning efficiency was highly improved. However, the fouling substances could not be cleaned entirely in the simple physical cleaning process by SEM analysis.

Effects of plasma proteins on sieving of tracer macromolecules in glomerular basement membrane.

PubMed

Lazzara, M J; Deen, W M

2001-11-01

It was found previously that the sieving coefficients of Ficoll and Ficoll sulfate across isolated glomerular basement membrane (GBM) were greatly elevated when BSA was present at physiological levels, and it was suggested that most of this increase might have been the result of steric interactions between BSA and the tracers (5). To test this hypothesis, we extended the theory for the sieving of macromolecular tracers to account for the presence of a second, abundant solute. Increasing the concentration of an abundant solute is predicted to increase the equilibrium partition coefficient of a tracer in a porous or fibrous membrane, thereby increasing the sieving coefficient. The magnitude of this partitioning effect depends on solute size and membrane structure. The osmotic reduction in filtrate velocity caused by an abundant, mostly retained solute will also tend to elevate the tracer sieving coefficient. The osmotic effect alone explained only about one-third of the observed increase in the sieving coefficients of Ficoll and Ficoll sulfate, whereas the effect of BSA on tracer partitioning was sufficient to account for the remainder. At physiological concentrations, predictions for tracer sieving in the presence of BSA were found to be insensitive to the assumed shape of the protein (sphere or prolate spheroid). For protein mixtures, the theoretical effect of 6 g/dl BSA on the partitioning of spherical tracers was indistinguishable from that of 3 g/dl BSA and 3 g/dl IgG. This suggests that for partitioning and sieving studies in vitro, a good experimental model for plasma is a BSA solution with a mass concentration matching that of total plasma protein. The effect of plasma proteins on tracer partitioning is expected to influence sieving not only in isolated GBM but also in intact glomerular capillaries in vivo.

Ultrafiltration of pegylated proteins

NASA Astrophysics Data System (ADS)

Molek, Jessica R.

There is considerable clinical interest in the use of "second-generation" therapeutics produced by conjugation of a native protein with various polymers including polyethylene glycol (PEG). PEG--protein conjugates, so-called PEGylated proteins, can exhibit enhanced stability, half-life, and bioavailability. One of the challenges in the commercial production of PEGylated proteins is the purification required to remove unreacted polymer, native protein, and in many cases PEGylated proteins with nonoptimal degrees of conjugation. The overall objective of this thesis was to examine the use of ultrafiltration for the purification of PEGylated proteins. This included: (1) analysis of size-based separation of PEGylated proteins using conventional ultrafiltration membranes, (2) use of electrically-charged membranes to exploit differences in electrostatic interactions, and (3) examination of the effects of PEGylation on protein fouling. The experimental results were analyzed using appropriate theoretical models, with the underlying physical properties of the PEGylated proteins evaluated using size exclusion chromatography, capillary electrophoresis, dynamic light scattering, and reverse phase chromatography. PEGylated proteins were produced by covalent attachment of activated PEG to a protein via primary amines on the lysine residues. A simple model was developed for the reaction kinetics, which was used to explore the effect of reaction conditions and mode of operation on the distribution of PEGylated products. The effective size of the PEGylated proteins was evaluated using size exclusion chromatography, with appropriate correlations developed for the size in terms of the molecular weight of the native protein and attached PEG. The electrophoretic mobility of the PEGylated proteins were evaluated by capillary electrophoresis with the data in good agreement with a simple model accounting for the increase in protein size and the reduction in the number of protonated amine groups in the PEGylated proteins. Ultrafiltration experiments were performed using PEGylated alpha-lactalbumin, ovalbumin, and bovine serum albumin. In contrast to the size exclusion chromatography data, the sieving coefficient of the PEGylated proteins depended upon both the number and size of the attached PEG chains due to the elongation or deformation of the PEG associated with the filtrate flux. Sieving coefficients at low filtrate flux were in good agreement with predictions of available hydrodynamic models, with significant elongation occurring when the Deborah number for the PEG chain exceeded 0.001. The effects of electrostatic interactions on the ultrafiltration of PEGylated proteins were examined using electrically-charged membranes generated by covalent attachment of sulphonic acid groups to the base cellulosic membrane. Transmission of PEGylated proteins through charged membranes was dramatically reduced at low ionic strength due to strong electrostatic interactions, despite the presence of the neutral PEG. The experimental results were in good agreement with model calculations developed for the partitioning of charged spheres into charged cylindrical pores. The experimental and theoretical results provide the first quantitative analysis of the effects of PEGylation on transport through semipermeable ultrafiltration membranes. The results from small-scale ultrafiltration experiments were used to develop a two-stage diafiltration process to purify PEGylated alpha-lactalbumin. The first-stage used a neutral membrane to remove the unreacted protein by exploiting differences in size. The second stage used a negatively-charged membrane to remove hydrolyzed PEG, with the PEGylated product retained by strong electrostatic interactions. This process provided a purification factor greater than 1000 with respect to the unreacted protein and greater than 20-fold with respect to the PEG with an overall yield of PEGylated alpha-lactalbumin of 78%. These results provide the first demonstration of the potential of using ultrafiltration for the purification of protein-polymer conjugates.

Peritoneal fluid transport in CAPD patients with different transport rates of small solutes.

PubMed

Sobiecka, Danuta; Waniewski, Jacek; Weryński, Andrzej; Lindholm, Bengt

2004-01-01

Continuous ambulatory peritoneal dialysis (CAPD) patients with high peritoneal solute transport rate often have inadequate peritoneal fluid transport. It is not known whether this inadequate fluid transport is due solely to a too rapid fall of osmotic pressure, or if the decreased effectiveness of fluid transport is also a contributing factor. To analyze fluid transport parameters and the effectiveness of dialysis fluid osmotic pressure in the induction of fluid flow in CAPD patients with different small solute transport rates. 44 CAPD patients were placed in low (n = 6), low-average (n = 13), high-average (n = 19), and high (n = 6) transport groups according to a modified peritoneal equilibration test (PET). The study involved a 6-hour peritoneal dialysis dwell with 2 L 3.86% glucose dialysis fluid for each patient. Radioisotopically labeled serum albumin was added as a volume marker.The fluid transport parameters (osmotic conductance and fluid absorption rate) were estimated using three mathematical models of fluid transport: (1) Pyle model (model P), which describes ultrafiltration rate as an exponential function of time; (2) model OS, which is based on the linear relationship of ultrafiltration rate and overall osmolality gradient between dialysis fluid and blood; and (3) model G, which is based on the linear relationship between ultrafiltration rate and glucose concentration gradient between dialysis fluid and blood. Diffusive mass transport coefficients (K(BD)) for glucose, urea, creatinine, potassium, and sodium were estimated using the modified Babb-Randerson-Farrell model. The high transport group had significantly lower dialysate volume and glucose and osmolality gradients between dialysate and blood, but significantly higher K(BD) for small solutes compared with the other transport groups. Osmotic conductance, fluid absorption rate, and initial ultrafiltration rate did not differ among the transport groups for model OS and model P. Model G yielded unrealistic values of fluid transport parameters that differed from those estimated by models OS and P. The K(BD) values for small solutes were significantly different among the groups, and did not correlate with fluid transport parameters for model OS. The difference in fluid transport between the different transport groups was due only to the differences in the rate of disappearance of the overall osmotic pressure of the dialysate, which was a combined result of the transport rate of glucose and other small solutes. Although the glucose gradient is the major factor influencing ultrafiltration rate, other solutes, such as urea, are also of importance. The counteractive effect of plasma small solutes on transcapillary ultrafiltration was found to be especially notable in low transport patients. Thus, glucose gradient alone should not be considered the only force that shapes the ultrafiltration profile during peritoneal dialysis. We did not find any correlations between diffusive mass transport coefficients for small solutes and fluid transport parameters such as osmotic conductance or fluid and volume marker absorption. We may thus conclude that the pathway(s) for fluid transport appears to be partly independent from the pathway(s) for small solute transport, which supports the hypothesis of different pore types for fluid and solute transport.

Worsening renal function in patients with acute decompensated heart failure treated with ultrafiltration: predictors and outcomes.

PubMed

Raichlin, Eugenia; Haglund, Nicholas A; Dumitru, Ioana; Lyden, Elizabeth R; Johnston, Michael D; Mack, Joan M; Windle, John R; Lowes, Brian D

2014-05-01

Ultrafiltration (UF) is used to treat patients with diuretic-resistant acute decompensated heart failure. The aim of this study was to identify predictors and the effect of worsening renal failure(WRF) on mortality in patients treated with UF. Based on changes in serum creatinine, 99 patients treated with UF were divided into WRF and control groups. Overall creatinine increased from 1.9 ± 0.7 to 1.2 ± 1.0 mg/dL (P!.001),and WRF developed in 41% of the subjects. The peak UF rate was higher in the WRF group in univariate analysis (174 ± 75 vs 144 ± 52 mL/h; P = .03). Based on multivariate analysis, aldosterone antagonist treatment (odds ratio [OR] 3.38, 95% confidence interval [CI] 1.17-13.46, P = .04), heart rate ≤65 beats/min (OR 6.03, 95% CI 1.48-48.42; P = .03), and E/E0 ≥ 15 (OR 3.78, 95% CI 1.26-17.55; P 5 .04) at hospital admission were associated with WRF. Patients with baseline glomerular filtration rate (GFR) ≤60mg/dL who developed WRF during UF had a 75% 1-year mortality rate. WRF occurred frequently during UF. Increased LV filling pressures, lower heart rate, and treatment with aldosterone antagonist at hospital admission can identify patients at increased risk for WRF. Patients with baseline GFR ≤60 mg/dL and WRF during UF have an extremely high 1-year mortality rate.

Development of a Simple and Rapid Method to Measure the Free Fraction of Tacrolimus in Plasma Using Ultrafiltration and LC-MS/MS.

PubMed

Stienstra, Nicolaas A; Sikma, Maaike A; van Dapperen, Anouk L; de Lange, Dylan W; van Maarseveen, Erik M

2016-12-01

Tacrolimus is an immunosuppressant mainly used in the prophylaxis of solid organ transplant rejection. Therapeutic drug monitoring of tacrolimus is essential for avoiding toxicity related to overexposure and transplant rejection from underexposure. Previous studies suggest that unbound tacrolimus concentrations in the plasma may serve as a better predictor of tacrolimus-associated nephrotoxicity and neurotoxicity compared to tacrolimus concentration in whole blood. Monitoring the plasma concentrations of unbound tacrolimus might be of interest in preventing tacrolimus-related toxicity. Therefore, the aim was to develop a method for the measurement of total and unbound tacrolimus concentrations in plasma. The sample preparation for the determination of the plasma concentrations of unbound tacrolimus consisted of an easy-to-use ultrafiltration method followed by solid-phase extraction. To determine the total concentration of tacrolimus in plasma, a simple method based on protein precipitation was developed. The extracts were injected into a Thermo Scientific HyPurity C18 column using gradient elution. The analytes were detected by liquid chromatography-tandem mass spectrometry with positive ionization. The method was validated over a linear range of 1.00-200 ng/L for unbound tacrolimus concentrations in plasma and 100-3200 ng/L for total plasma concentrations. The lower limit of quantification was 1.00 ng/L in ultrafiltrate and 100 ng/L in plasma. The inaccuracy and imprecision for the determination of unbound tacrolimus concentrations in ultrafiltrate and plasma showed a maximum coefficients of variation (CV) of 11.7% and a maximum bias of 3.8%. A rapid and easy method based on ultrafiltration and liquid chromatography-tandem mass spectrometry was established to measure the total and unbound tacrolimus concentrations in plasma. This method can facilitate further investigations on the relationship between plasma concentrations of unbound tacrolimus and clinical outcomes in transplant recipients.

Estimation of Glomerular Filtration Rate from Plasma Clearance of 51-Chromium Edetic Acid

PubMed Central

Chantler, C.; Barratt, T. M.

1972-01-01

The glomerular filtration rate was estimated by a single compartment analysis of the rate of fall of plasma concentration of 51-chromium edetic acid after a single intravenous injection. This slope clearance consistently overestimated the simultaneously determined standard urinary clearance, but could be used to predict the latter with an accuracy of ±9% (95% confidence limits). The coefficient of variation of replicate estimates of the slope clearance in the same individual was 3·9%; thus two estimates of glomerular filtration rate by this technique which differ by 11% have a 95% probability of reflecting a genuine difference. The method requires an intravenous injection and blood samples at 2 and 4 hours; urine samples are not required. It is simple, safe, and precise, and is applicable to children. PMID:4625784

Centrifugal ultrafiltration of human serum for improving immunoglobulin A quantification using attenuated total reflectance infrared spectroscopy.

PubMed

Elsohaby, Ibrahim; McClure, J Trenton; Riley, Christopher B; Bryanton, Janet; Bigsby, Kathryn; Shaw, R Anthony

2018-02-20

Attenuated total reflectance infrared (ATR-IR) spectroscopy is a simple, rapid and cost-effective method for the analysis of serum. However, the complex nature of serum remains a limiting factor to the reliability of this method. We investigated the benefits of coupling the centrifugal ultrafiltration with ATR-IR spectroscopy for quantification of human serum IgA concentration. Human serum samples (n = 196) were analyzed for IgA using an immunoturbidimetric assay. ATR-IR spectra were acquired for whole serum samples and for the retentate (residue) reconstituted with saline following 300 kDa centrifugal ultrafiltration. IR-based analytical methods were developed for each of the two spectroscopic datasets, and the accuracy of each of the two methods compared. Analytical methods were based upon partial least squares regression (PLSR) calibration models - one with 5-PLS factors (for whole serum) and the second with 9-PLS factors (for the reconstituted retentate). Comparison of the two sets of IR-based analytical results to reference IgA values revealed improvements in the Pearson correlation coefficient (from 0.66 to 0.76), and the root mean squared error of prediction in IR-based IgA concentrations (from 102 to 79 mg/dL) for the ultrafiltration retentate-based method as compared to the method built upon whole serum spectra. Depleting human serum low molecular weight proteins using a 300 kDa centrifugal filter thus enhances the accuracy IgA quantification by ATR-IR spectroscopy. Further evaluation and optimization of this general approach may ultimately lead to routine analysis of a range of high molecular-weight analytical targets that are otherwise unsuitable for IR-based analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

Aging Selectively Modulates Vitamin C Transporter Expression Patterns in the Kidney.

PubMed

Forman, Katherine; Martínez, Fernando; Cifuentes, Manuel; Bertinat, Romina; Salazar, Katterine; Nualart, Francisco

2017-09-01

In the kidney, vitamin C is reabsorbed from the glomerular ultrafiltrate by sodium-vitamin C cotransporter isoform 1 (SVCT1) located in the brush border membrane of the proximal tubules. Although we know that vitamin C levels decrease with age, the adaptive physiological mechanisms used by the kidney for vitamin C reabsorption during aging remain unknown. In this study, we used an animal model of accelerated senescence (SAMP8 mice) to define the morphological alterations and aging-induced changes in the expression of vitamin C transporters in renal tissue. Aging induced significant morphological changes, such as periglomerular lymphocytic infiltrate and glomerular congestion, in the kidneys of SAMP8 mice, although no increase in collagen deposits was observed using 2-photon microscopy analysis and second harmonic generation. The most characteristic histological alteration was the dilation of intracellular spaces in the basolateral region of proximal tubule epithelial cells. Furthermore, a combination of laser microdissection, qRT-PCR, and immunohistochemical analyses allowed us to determine that SVCT1 expression specifically increased in the proximal tubules from the outer strip of the outer medulla (segment S3) and cortex (segment S2) during aging and that these tubules also express GLUT1. We conclude that aging modulates vitamin C transporter expression and that renal over-expression of SVCT1 enhances vitamin C reabsorption in aged animals that may synthesize less vitamin C. J. Cell. Physiol. 232: 2418-2426, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Worsening renal function in patients with acute decompensated heart failure treated with ultrafiltration: predictors and outcomes.

PubMed

Raichlin, Eugenia; Haglund, Nicholas A; Dumitru, Ioana; Lyden, Elizabeth R; Johnston, Michael D; Mack, Joan M; Windle, John R; Lowes, Brian D

2013-12-01

Ultrafiltration (UF) is used to treat patients with diuretic-resistant acute decompensated heart failure. The aim of this study was to identify predictors and the effect of worsening renal failure (WRF) on mortality in patients treated with UF. Based on changes in serum creatinine, 99 patients treated with UF were divided into WRF and control groups. Overall creatinine increased from 1.9 ± 9.7 to 2.2 ± 2.0 mg/dL (P < .001), and WRF developed in 41% of the subjects. The peak UF rate was higher in the WRF group in univariate analysis (174 ± 45 vs 144 ± 42 mL/h; P = .03). Based on multivariate analysis, aldosterone antagonist treatment (odds ratio [OR] 3.38, 95% confidence interval [CI] 1.17-13.46, P = .04), heart rate ≤65 beats/min (OR 6.03, 95% CI 1.48-48.42; P = .03), and E/E' ≥15 (OR 3.78, 95% CI 1.26-17.55; P = .04) at hospital admission were associated with WRF. Patients with baseline glomerular filtration rate (GFR) ≤60 mg/dL who developed WRF during UF had a 75% 1-year mortality rate. WRF occurred frequently during UF. Increased LV filling pressures, lower heart rate, and treatment with aldosterone antagonist at hospital admission can identify patients at increased risk for WRF. Patients with baseline GFR ≤60 mg/dL and WRF during UF have an extremely high 1-year mortality rate. Published by Elsevier Inc.

Evaluation of solute penetration across the polysulfone membrane with vitamin E coating.

PubMed

Yamashita, Akihiro C; Masaki, Hidenori; Kobayashi, Eisuke; Sukegawa, Takeshi

2015-10-01

Vitamin E (vit E) is coated on polysulfone (PS) dialysis membrane for antioxidative purpose. The membrane, however, has not yet been evaluated from the mass transfer point of view. We investigated this PS membrane with and without vit E coating in vitro ultrafiltration experiments to identify whether or not the coating influences the mass transfer. Dialyzers that included PS membrane with and without vit E coating were investigated. Aqueous test solution of various solutes including vitamin B12 (VB12 , MW1355), chymotrypsin (chymo, MW25000), and albumin (alb, MW66000) was prepared, and normal ultrafiltration experiments were performed at 310 K. Reverse ultrafiltration experiments in which test solution was filtered from outside to inside the hollow fiber were also performed. Sieving coefficients (SC) were computed for evaluation. SC for VB12 was the same regardless of vit E coating; however, chymo was 0.82 ± 0.01 and 0.86 ± 0.01, respectively, for the membrane with and without vit E. Thus, it would be understood that vit E coating reduces the pore size of the membrane, resulting the reduced transport of larger solutes. Like other PS membrane, SC for alb was decreased over time regardless of vit E coating. More importantly, although the steady-state SC for alb was almost identical in two membranes, PS without vit E showed much greater decrease for the first 2 h, while that with vit E showed very little decrease over time, which suggested the reduced fouling effect due to vit E coating. All the SC values found in reverse ultrafiltration were higher than those found in normal ultrafiltration; moreover, the degree of increase with chymo was approximately 5%, whereas that with alb was approximately 430%, which may be explained by a new model in which wedge effect is taken into consideration for the membrane transport. Vit E coating not only has antioxidative effect but also reduces the fouling that is usually caused by various proteins. © 2015 International Society for Hemodialysis.

Evaluation of erythrocyte dysmorphism by light microscopy with lowering of the condenser lens: A simple and efficient method.

PubMed

Barros Silva, Gyl Eanes; Costa, Roberto Silva; Ravinal, Roberto Cuan; Saraiva e Silva, Jucélia; Dantas, Marcio; Coimbra, Terezila Machado

2010-03-01

To demonstrate that the evaluation of erythrocyte dysmorphism by light microscopy with lowering of the condenser lens (LMLC) is useful to identify patients with a haematuria of glomerular or non-glomerular origin. A comparative double-blind study between phase contrast microscopy (PCM) and LMLC is reported to evaluate the efficacy of these techniques. Urine samples of 39 patients followed up for 9 months were analyzed, and classified as glomerular and non-glomerular haematuria. The different microscopic techniques were compared using receiver-operator curve (ROC) analysis and area under curve (AUC). Reproducibility was assessed by coefficient of variation (CV). Specific cut-offs were set for each method according to their best rate of specificity and sensitivity as follows: 30% for phase contrast microscopy and 40% for standard LMLC, reaching in the first method the rate of 95% and 100% of sensitivity and specificity, respectively, and in the second method the rate of 90% and 100% of sensitivity and specificity, respectively. In ROC analysis, AUC for PCM was 0.99 and AUC for LMLC was 0.96. The CV was very similar in glomerular haematuria group for PCM (35%) and LMLC (35.3%). LMLC proved to be effective in contributing to the direction of investigation of haematuria, toward the nephrological or urological side. This method can substitute PCM when this equipment is not available.

KNT-artificial neural network model for flux prediction of ultrafiltration membrane producing drinking water.

PubMed

Oh, H K; Yu, M J; Gwon, E M; Koo, J Y; Kim, S G; Koizumi, A

2004-01-01

This paper describes the prediction of flux behavior in an ultrafiltration (UF) membrane system using a Kalman neuro training (KNT) network model. The experimental data was obtained from operating a pilot plant of hollow fiber UF membrane with groundwater for 7 months. The network was trained using operating conditions such as inlet pressure, filtration duration, and feed water quality parameters including turbidity, temperature and UV254. Pre-processing of raw data allowed the normalized input data to be used in sigmoid activation functions. A neural network architecture was structured by modifying the number of hidden layers, neurons and learning iterations. The structure of KNT-neural network with 3 layers and 5 neurons allowed a good prediction of permeate flux by 0.997 of correlation coefficient during the learning phase. Also the validity of the designed model was evaluated with other experimental data not used during the training phase and nonlinear flux behavior was accurately estimated with 0.999 of correlation coefficient and a lower error of prediction in the testing phase. This good flux prediction can provide preliminary criteria in membrane design and set up the proper cleaning cycle in membrane operation. The KNT-artificial neural network is also expected to predict the variation of transmembrane pressure during filtration cycles and can be applied to automation and control of full scale treatment plants.

Fabrication of porous matrix membrane (PMM) using metal-organic framework as green template for water treatment.

PubMed

Lee, Jian-Yuan; Tang, Chuyang Y; Huo, Fengwei

2014-01-17

Pressure-driven membranes with high porosity can potentially be fabricated by removing template, such as low water stability metal-organic frameworks (MOFs) or other nanoparticles, in polymeric matrix. We report on the use of benign MOFs as green template to enhance porosity and interconnectivity of the water treatment membranes. Significantly enhanced separation performance was observed which might be attributed to the mass transfer coefficient of the substrate layer increased in ultrafiltration (UF) application.

Aldosterone and glomerular filtration--observations in the general population.

PubMed

Hannemann, Anke; Rettig, Rainer; Dittmann, Kathleen; Völzke, Henry; Endlich, Karlhans; Nauck, Matthias; Wallaschofski, Henri

2014-03-10

Increasing evidence suggests that aldosterone promotes renal damage. Since data on the association between aldosterone and renal function in the general population are sparse, we chose to address this issue. We investigated the associations between the plasma aldosterone concentration (PAC) or the aldosterone-to-renin ratio (ARR) and the estimated glomerular filtration rate (eGFR) in a sample of adult men and women from Northeast Germany. A study population of 1921 adult men and women who participated in the first follow-up of the Study of Health in Pomerania was selected. None of the subjects used drugs that alter PAC or ARR. The eGFR was calculated according to the four-variable Modification of Diet in Renal Disease formula. Chronic kidney disease (CKD) was defined as an eGFR < 60 ml/min/1.73 m2. Linear regression models, adjusted for sex, age, waist circumference, diabetes mellitus, smoking status, systolic and diastolic blood pressures, serum triglyceride concentrations and time of blood sampling revealed inverse associations of PAC or ARR with eGFR (ß-coefficient for log-transformed PAC -3.12, p < 0.001; ß-coefficient for log-transformed ARR -3.36, p < 0.001). Logistic regression models revealed increased odds for CKD with increasing PAC (odds ratio for a one standard deviation increase in PAC: 1.35, 95% confidence interval: 1.06-1.71). There was no statistically significant association between ARR and CKD. Our study demonstrates that PAC and ARR are inversely associated with the glomerular filtration rate in the general population.

Concentrating membrane proteins using ultrafiltration without concentrating detergents.

PubMed

Feroz, Hasin; Vandervelden, Craig; Ikwuagwu, Bon; Ferlez, Bryan; Baker, Carol S; Lugar, Daniel J; Grzelakowski, Mariusz; Golbeck, John H; Zydney, Andrew L; Kumar, Manish

2016-10-01

Membrane proteins (MPs) are of rapidly growing interest in the design of pharmaceutical products, novel sensors, and synthetic membranes. Ultrafiltration (UF) using commercially available centrifugal concentrators is typically employed for laboratory-scale concentration of low-yield MPs, but its use is accompanied by a concomitant increase in concentration of detergent micelles. We present a detailed analysis of the hydrodynamic processes that control detergent passage during ultrafiltration of MPs and propose methods to optimize detergent passage during protein concentration in larger-scale membrane processes. Experiments were conducted using nonionic detergents, octyl-β-D glucoside (OG), and decyl-β-D maltoside (DM) with the bacterial water channel protein, Aquaporin Z (AqpZ) and the light driven chloride pump, halorhodopsin (HR), respectively. The observed sieving coefficient (So ), a measure of detergent passage, was evaluated in both stirred cell and centrifugal systems. So for DM and OG increased with increasing filtrate flux and decreasing shear rates in the stirred cell, that is, with increasing concentration polarization (CP). Similar effects were observed during filtration of MP-detergent (MPD) micelles. However, lower transmission was observed in the centrifugal system for both detergent and MPD systems. This is attributed to free convection-induced shear and hence reduced CP along the membrane surface during centrifugal UF. Thus to concentrate MPs without retention of detergent, design of UF systems that promote CP is required. Biotechnol. Bioeng. 2016;113: 2122-2130. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Ultrafiltration technology with a ceramic membrane for reactive dye removal: optimization of membrane performance.

PubMed

Alventosa-deLara, E; Barredo-Damas, S; Alcaina-Miranda, M I; Iborra-Clar, M I

2012-03-30

An ultrafiltration (UF) ceramic membrane was used to decolorize Reactive Black 5 (RB5) solutions at different dye concentrations (50 and 500 mg/L). Transmembrane pressure (TMP) and cross-flow velocity (CFV) were modified to study their influence on initial and steady-state permeate flux (J(p)) and dye rejection (R). Generally, J(p) increased with higher TMP and CFV and lower feed concentration, up to a maximum steady-state J(p) of 266.81 L/(m(2)h), obtained at 3 bar, 3m/s and 50mg/L. However, there was a TMP value (which changed depending on operating CFV and concentration) beyond which slight or no further increase in steady-state J(p) was observed. Similarly, the higher the CFV was, the more slightly the steady-state J(p) increased. Furthermore, the effectiveness of ultrafiltration treatment was evaluated through dye rejection coefficient. The results showed significant dye removals, regardless of the tested conditions, with steady-state R higher than 79.8% for the 50mg/L runs and around 73.2% for the 500 mg/L runs. Finally response surface methodology (RSM) was used to optimize membrane performance. At 50mg/L, a TMP of 4 bar and a CFV of 2.53 m/s were found to be the conditions giving the highest steady-state J(p), 255.86 L/(m(2)h), and the highest R, 95.2% simultaneously. Copyright © 2012 Elsevier B.V. All rights reserved.

Discerning the role of mechanosensors in regulating proximal tubule function

PubMed Central

Weisz, Ora A.

2015-01-01

All cells in the body experience external mechanical forces such as shear stress and stretch. These forces are sensed by specialized structures in the cell known as mechanosensors. Cells lining the proximal tubule (PT) of the kidney are continuously exposed to variations in flow rates of the glomerular ultrafiltrate, which manifest as changes in axial shear stress and radial stretch. Studies suggest that these cells respond acutely to variations in flow by modulating their ion transport and endocytic functions to maintain glomerulotubular balance. Conceptually, changes in the axial shear stress in the PT could be sensed by three known structures, namely, the microvilli, the glycocalyx, and primary cilia. The orthogonal component of the force produced by flow exhibits as radial stretch and can cause expansion of the tubule. Forces of stretch are transduced by integrins, by stretch-activated channels, and by cell-cell contacts. This review summarizes our current understanding of flow sensing in PT epithelia, discusses challenges in dissecting the role of individual flow sensors in the mechanosensitive responses, and identifies potential areas of opportunity for new study. PMID:26662200

Aldosterone and glomerular filtration – observations in the general population

PubMed Central

2014-01-01

Background Increasing evidence suggests that aldosterone promotes renal damage. Since data on the association between aldosterone and renal function in the general population are sparse, we chose to address this issue. We investigated the associations between the plasma aldosterone concentration (PAC) or the aldosterone-to-renin ratio (ARR) and the estimated glomerular filtration rate (eGFR) in a sample of adult men and women from Northeast Germany. Methods A study population of 1921 adult men and women who participated in the first follow-up of the Study of Health in Pomerania was selected. None of the subjects used drugs that alter PAC or ARR. The eGFR was calculated according to the four-variable Modification of Diet in Renal Disease formula. Chronic kidney disease (CKD) was defined as an eGFR <60 ml/min/1.73 m2. Results Linear regression models, adjusted for sex, age, waist circumference, diabetes mellitus, smoking status, systolic and diastolic blood pressures, serum triglyceride concentrations and time of blood sampling revealed inverse associations of PAC or ARR with eGFR (ß-coefficient for log-transformed PAC −3.12, p < 0.001; ß-coefficient for log-transformed ARR −3.36, p < 0.001). Logistic regression models revealed increased odds for CKD with increasing PAC (odds ratio for a one standard deviation increase in PAC: 1.35, 95% confidence interval: 1.06-1.71). There was no statistically significant association between ARR and CKD. Conclusion Our study demonstrates that PAC and ARR are inversely associated with the glomerular filtration rate in the general population. PMID:24612948

Endocytosis of Albumin by Podocytes Elicits an Inflammatory Response and Induces Apoptotic Cell Death

PubMed Central

Okamura, Kayo; Dummer, Patrick; Kopp, Jeffrey; Qiu, Liru; Levi, Moshe; Faubel, Sarah; Blaine, Judith

2013-01-01

The presence of albuminuria is strongly associated with progression of chronic kidney disease. While albuminuria has been shown to injure renal proximal tubular cells, the effects of albumin on podocytes have been less well studied. We have addressed the hypothesis that exposure of podocytes to albumin initiates an injury response. We studied transformed human-urine derived podocytes-like epithelial cells (HUPECS, or podocytes). Upon differentiation, these cells retain certain characteristics of differentiated podocytes, including expression of synaptopodin, CD2AP, and nestin. We exposed podocytes to recombinant human albumin, which lacks lipids and proteins that bind serum albumin; this reagent allowed a direct examination of the effects of albumin. Podocytes endocytosed fluoresceinated albumin and this process was inhibited at 4°C, suggesting an energy-dependent process. Exposure to albumin at concentrations of 5 and 10 mg/ml was associated with increased cell death in a dose-dependent manner. The mechanism of cell death may involve apoptosis, as caspase 3/7 were activated and the pan-caspase inhibitor z-VAD reduced cell death. Albumin exposure also increased nuclear factor (NF)-κB activation and increased transcription and release of interleukin (IL-) 1β, tumor necrosis factor (TNF), and IL-6. We extended these findings to an in vivo model. Glomeruli isolated from mice with nephrotic syndrome also had increased expression of IL-1β and TNF RNA. These data suggest that while podocyte injury begets albuminuria, albumin in the glomerular ultrafiltrate may also beget podocyte injury. Thus, an additional mechanism by which anti-proteinuric therapies are beneficial in the treatment of glomerular diseases may be a reduction in injury to the podocyte by albumin. PMID:23382978

Performance of the chronic kidney disease-epidemiology study equations for estimating glomerular filtration rate before and after nephrectomy.

PubMed

Lane, Brian R; Demirjian, Sevag; Weight, Christopher J; Larson, Benjamin T; Poggio, Emilio D; Campbell, Steven C

2010-03-01

Accurate renal function determination before and after nephrectomy is essential for proper prevention and management of chronic kidney disease due to nephron loss and ischemic injury. We compared the estimated glomerular filtration rate using several serum creatinine based formulas against the measured rate based on (125)I-iothalamate clearance to determine which most accurately reflects the rate in this setting. Of 7,611 patients treated at our institution since 1975 the measured glomerular filtration rate was selectively determined before and after nephrectomy in 268 and 157, respectively. Performance of the Cockcroft-Gault, Modification of Diet in Renal Disease Study, re-expressed Modification of Diet in Renal Disease Study and Chronic Kidney Disease-Epidemiology Study equations, each of which estimates the glomerular filtration rate, were determined using serum creatinine, age, gender, weight and body surface area. The performance of serum creatinine, reciprocal serum creatinine and the 4 formulas was compared with the measured rate using Pearson's correlation, Lin's concordance coefficient and residual plots. Median serum creatinine was 1.4 mg/dl and the median measured glomerular filtration rate was 50 ml per minute per 1.73 m(2). The correlation between serum creatinine and the measured rate was poor (-0.66) compared with that of reciprocal serum creatinine (0.78) and the 4 equations (0.82 to 0.86). The Chronic Kidney Disease-Epidemiology Study equation performed with greatest precision and accuracy, and least bias of all equations. Stage 3 or greater chronic kidney disease ((125)I-iothalamate glomerular filtration rate 60 ml per minute per 1.73 m(2) or less) was present in 44% of patients with normal serum creatinine (1.4 mg/dl or less) postoperatively. Such missed diagnoses of chronic kidney disease decreased 42% using the Chronic Kidney Disease-Epidemiology Study equation. Glomerular filtration rate estimation equations outperform serum creatinine and better identify patients with perinephrectomy compromised renal function. The newly developed, serum creatinine based, Chronic Kidney Disease-Epidemiology Study equation has sufficient accuracy to render direct glomerular filtration rate measurement unnecessary before and after nephrectomy for cause in most circumstances. 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Clinical Relevance of Differences in Glomerular Filtration Rate Estimations in Frail Older People by Creatinine- vs. Cystatin C-Based Formulae.

PubMed

Jacobs, Anne; Benraad, Carolien; Wetzels, Jack; Rikkert, Marcel Olde; Kramers, Cornelis

2017-06-01

The risk of incorrect medication dosing is high in frail older people. Therefore, accurate assessment of the glomerular filtration rate is important. The objective of this study was to compare the estimated glomerular filtration rate using creatinine- and cystatin C-based formulae, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, in frail older people. We hypothesized that frailty determines the difference between the creatinine- and cystatin C-based formulae. The mean difference between CKD-EPI creatinine and cystatin C was determined using (cross-sectional) data of 55 patients (mean age 73 years) admitted to a psychiatric ward for older adults. The level of agreement of these estimations was assessed by a Bland-Altman analysis. In all patients, the Rockwood's Frailty Index was derived and correlated with the mean difference between CKD-EPI creatinine and cystatin C. The mean difference between CKD-EPI creatinine (mean 71.2 mL/min/1.73 m 2 ) and CKD-EPI cystatin C (mean 57.6 mL/min/1.73 m 2 ) was 13.6 mL/min/1.73 m 2 (p < 0.0001). The two standard deviation limit in the Bland-Altman plot was large (43.2 mL/min/1.73 m 2 ), which represents a low level of agreement. The Frailty Index did not correlate with the mean difference between the creatinine- and cystatin C-based glomerular filtration rate (Pearson correlation coefficient 0.182, p = 0.184). There was a significant gap between a creatinine- and cystatin C-based estimation of glomerular filtration rate, irrespective of frailty. The range of differences between the commonly used estimated glomerular filtration rate formulae might result in clinically relevant differences in drug prescription and differences in chronic kidney disease staging.

Extracorporeal Ultrafiltration for Fluid Overload in Heart Failure

PubMed Central

Costanzo, Maria Rosa; Ronco, Claudio; Abraham, William T.; Agostoni, Piergiuseppe; Barasch, Jonathan; Fonarow, Gregg C.; Gottlieb, Stephen S.; Jaski, Brian E.; Kazory, Amir; Levin, Allison P.; Levin, Howard R.; Marenzi, Giancarlo; Mullens, Wilfried; Negoianu, Dan; Redfield, Margaret M.; Tang, W.H. Wilson; Testani, Jeffrey M.; Voors, Adriaan A.

2017-01-01

More than 1 million heart failure hospitalizations occur annually, and congestion is the predominant cause. Rehospitalizations for recurrent congestion portend poor outcomes independently of age and renal function. Persistent congestion trumps serum creatinine increases in predicting adverse heart failure outcomes. No decongestive pharmacological therapy has reduced these harmful consequences. Simplified ultrafiltration devices permit fluid removal in lower-acuity hospital settings, but with conflicting results regarding safety and efficacy. Ultrafiltration performed at fixed rates after onset of therapy-induced increased serum creatinine was not superior to standard care and resulted in more complications. In contrast, compared with diuretic agents, some data suggest that adjustment of ultrafiltration rates to patients’ vital signs and renal function may be associated with more effective decongestion and fewer heart failure events. Essential aspects of ultrafiltration remain poorly defined. Further research is urgently needed, given the burden of congestion and data suggesting sustained benefits of early and adjustable ultrafiltration. PMID:28494980

Ultrafiltration and modified ultrafiltration in pediatric open heart operations.

PubMed

Elliott, M J

1993-12-01

The capillary leak associated with cardiopulmonary bypass results in an increase in content of water in the tissues measurable by an increase in total body water after cardiac operation. Following work by Magilligan in the 1970s, ultrafiltration was introduced during bypass as a means of hemoconcentrating patients and potentially removing water from the tissues. Conventional methods proved inconsistent; thus, we modified the technique to ultrafilter the patients immediately after cessation of bypass. Modified ultrafiltration takes 10 minutes and results in an elevation of the on-bypass hematocrit to about 35% or 40%. In pilot studies comparing bypass in absence of ultrafiltration with conventional ultrafiltration and modified ultrafiltration, only the modified technique was seen reliably to reduce the elevation in total body water to only 4%, within a narrow range. Subsequent prospective studies confirmed the reduction in accumulation of total body water and also demonstrated a reduction in blood loss and in requirements for blood transfusion. Systolic blood pressure was observed to increase uniformly in all patients undergoing modified ultrafiltration. This effect was investigated and found to be associated with a marked increase in cardiac index, no change in systemic vascular resistance, a decrease in heart rate, and a marked decrease in pulmonary vascular resistance. Recently, we have demonstrated an increase in contractility and a decrease in myocardial wall volume. The modified technique of ultrafiltration has been employed successfully in more than 400 patients in our institution, and represents an excellent option for perioperative management of both accumulation of fluid in the tissues and hemodynamics after hypothermic bypass.

Metal Ion Interactions with Immunoglobulin G (IgG). 1. Preliminary Studies with Electron Paramagnetic Resonance (EPR) Spectroscopy and Ultrafiltration

DTIC Science & Technology

1978-12-12

EPR and ultrafiltration studies are recommceided to conduct luture metal ion- IgG binding research. Using Scatchard plots, bind.ng levels can be...of the binding sites can be best pursued by EPR and ultrafiltration using the fragments of IgG . This report noted some difference in the binding...immunoelectrophoresis, ultrafiltration, UV spectroscopy, atomic absorption spectroscopy, and electron paramagnetic resonance (EPR). IgG used ,- ,is non

Effect of solvent and temperature on the size distribution of casein micelles measured by dynamic light scattering.

PubMed

Beliciu, C M; Moraru, C I

2009-05-01

The objectives of this study were to investigate the effect of the solvent on the accuracy of casein micelle particle size determination by dynamic light scattering (DLS) at different temperatures and to establish a clear protocol for these measurements. Dynamic light scattering analyses were performed at 6, 20, and 50 degrees C using a 90Plus Nanoparticle Size Analyzer (Brookhaven Instruments, Holtsville, NY). Raw and pasteurized skim milk were used as sources of casein micelles. Simulated milk ultrafiltrate, ultrafiltered water, and permeate obtained by ultrafiltration of skim milk using a 10-kDa cutoff membrane were used as solvents. The pH, ionic concentration, refractive index, and viscosity of all solvents were determined. The solvents were evaluated by DLS to ensure that they did not have a significant influence on the results of the particle size measurements. Experimental protocols were developed for accurate measurement of particle sizes in all solvents and experimental conditions. All measurements had good reproducibility, with coefficients of variation below 5%. Both the solvent and the temperature had a significant effect on the measured effective diameter of the casein micelles. When ultrafiltered permeate was used as a solvent, the particle size and polydispersity of casein micelles decreased as temperature increased. The effective diameter of casein micelles from raw skim milk diluted with ultrafiltered permeate was 176.4 +/- 5.3 nm at 6 degrees C, 177.4 +/- 1.9 nm at 20 degrees C, and 137.3 +/- 2.7 nm at 50 degrees C. This trend was justified by the increased strength of hydrophobic bonds with increasing temperature. Overall, the results of this study suggest that the most suitable solvent for the DLS analyses of casein micelles was casein-depleted ultrafiltered permeate. Dilution with water led to micelle dissociation, which significantly affected the DLS measurements, especially at 6 and 20 degrees C. Simulated milk ultrafiltrate seemed to give accurate results only at 20 degrees C. Results obtained in simulated milk ultrafiltrate at 6 degrees C could not be explained based on the known effects of temperature on the casein micelle, whereas at 50 degrees C, precipitation of amorphous calcium phosphate affected the DLS measurement.

[Comparison of essential oil enriched with ultrafiltration method and extraction method respectively from essential oil-in-water emulsion of Citri Reticulatae Pericarpium Viride by GC-MS].

PubMed

Yin, Ailing; Han, Zhifeng; Shen, Jie; Guo, Liwei; Cao, Guiping

2011-10-01

To study on the separation from essential oil-in-water emulsion of Citri Reticulatae Pericarpium Viride by ultrafiltration and acetoacetate extraction methods respectively, and the comparison of the oil yields and chemical compositions. Essential oil-in-water emulsion of Citri Reticulatae Pericarpium Viride was separated by ultrafiltration and acetoacetate extraction methods respectively, and the chemical compositions were analyzed and compared by GC-MS. Ultrafiltration method could enrich essential oil more and its chemical compositions were more similar to the essential oil prepared by steam distillation method. Ultrafiltration method is a good medium to separate essential oil from essential oil-in-water emulsion of Citri Reticulatae Pericarpium Viride.

Efficacy of cellulose triacetate dialyzer and polysulfone synthetic hemofilter for continuous venovenous hemofiltration in acute renal failure.

PubMed

Pichaiwong, Warangkana; Leelahavanichkul, Asada; Eiam-ong, Somchai

2006-08-01

To compare the clearance performances and biocompatibility between the modified cellulose membrane and the standard synthetic membrane in continuous renal replacement therapy (CRRT). Seventeen patients with acute renal failure (ARF) were treated with separated continuous veno venous hemofiltration (CVVH) system conducted with the pre-dilution mode. The modified cellulose used was a Sureflux150E (cellulose triacetate) and the standard synthetic membranes used was an AV-400. Blood and replacement flow rate were kept at 100 and 20 mL/min, respectively. Ultrafiltraion rate was 1,200 mL/hr. Samplings of blood and ultrafiltrate were collected at baseline, 2, 8, 16, and 24 hr. Patients in both methods could similarly tolerate CRRT with only minor complications. Sureflux 150E and AV-400 provided comparable values of sieving coefficients and clearances of small solutes. The albumin loss in ultrafiltrate by Sureflux 150E was greater than AV-400. The values of life span and biocompatability of both hemofilters were not different. Because of the excellent efficacy and the much cheaper cost, the modified cellulose membrane could be an appropriate alternative to standard synthetic membrane in CRRT.

Transepithelial ultrafiltration and fractal power diffusion of D-glucose in the perfused rat intestine.

PubMed

Kochak, Gregory M; Mangat, Surinder

2002-12-23

Despite an enormous body of research investigating the mass transfer of D-glucose through biological membranes, carrier-mediated and first-order models have remained the prevalent models describing glucose's quantitative behavior even though they have proven to be inadequate over extended concentration ranges. Recent evidence from GLUT2 knockout studies further questions our understanding of molecular models, especially those employing Michaelis-Menten (MM)-type kinetic models. In this report, evidence is provided that D-glucose is absorbed by rat intestinal epithelium by a combination of convective ultrafiltration and nonlinear diffusion. The diffusive component of mass transfer is described by a concentration-dependent permeability coefficient, modeled as a fractal power function. Glucose and sodium chloride-dependent-induced aqueous convection currents are the result of prevailing oncotic and osmotic pressure effects, and a direct effect of glucose and sodium chloride on intestinal epithelium resulting in enhanced glucose, sodium ion, and water mobility. The fractal power model of glucose diffusion was superior to the conventional MM description. A convection-diffusion model of mass transfer adequately characterized glucose mass transfer over a 105-fold glucose concentration range in the presence and absence of sodium ion.

Pharmacokinetics and pharmacodynamics of carboplatin administered in a high-dose combination regimen with thiotepa, cyclophosphamide and peripheral stem cell support.

PubMed Central

van Warmerdam, L. J.; Rodenhuis, S.; van der Wall, E.; Maes, R. A.; Beijnen, J. H.

1996-01-01

The aim of this pharmacokinetic/pharmacodynamic study was to define the relationships of the carboplatin exposure with the toxicity in patients treated with high dose carboplatin (400 mg m-2 day-1), cyclophosphamide (1500 mg m-2 day-1) and thiotepa (120 mg m-2 day-1) for four consecutive days, followed by peripheral stem cell transplantation. Exposure to carboplatin was studied in 200 treatment days by measuring the area under the carboplatin plasma ultrafiltrate (pUF) concentration vs time curve (AUC). The AUC was obtained by using a previously validated limited sampling model. A total of 31 patients was studied who received one, two or three courses of this high-dose chemotherapy regimen. The unbound, plasma ultrafiltrate carboplatin was almost completely cleared from the body before each next treatment day in a course; the day-to-day AUC variation was 3.3%. The mean cumulative AUC over 4 days was 19.6 (range 14.1-27.2) mg ml-1 min-1. In 97 treatment days the carboplatin dose was calculated using the Calvert formula with the creatinine clearance as the measure for the glomerular filtration rate (GFR). For these courses, the inter-patient variability in pharmacokinetics was significantly reduced from 21% to 15% (P = 0.007) in comparison with the schemes where it was given as a fixed dose of 400 mg m-2. There were no relationships found between toxicity and the AUC of carboplatin, which may be due to the influence of overlapping toxicities of cyclophosphamide and thiotepa. However, the ototoxicity was strongly related to the cumulative carboplatin AUC. This toxicity was dose limiting for carboplatin in this schedule. It appeared that the carboplatin pharmacokinetics in these regimens were similar to those reported at conventional dosages. To reduce the inter-patient variation, the carboplatin dose can be calculated using the Calvert-formula with the creatinine clearance as the measure for the GFR. PMID:8611435

Multiple Factors Influence Glomerular Albumin Permeability in Rats

PubMed Central

Sandoval, Ruben M.; Wagner, Mark C.; Patel, Monica; Campos-Bilderback, Silvia B.; Rhodes, George J.; Wang, Exing; Wean, Sarah E.; Clendenon, Sherry S.

2012-01-01

Different laboratories recently reported incongruous results describing the quantification of albumin filtration using two-photon microscopy. We investigated the factors that influence the glomerular sieving coefficient for albumin (GSCA) in an effort to explain these discordant reports and to develop standard operating procedures for determining GSCA. Multiple factors influenced GSCA, including the kidney depth of image acquisition (10–20 μm was appropriate), the selection of fluorophore (probes emitting longer wavelengths were superior), the selection of plasma regions for fluorescence measurements, the size and molecular dispersion characteristics of dextran polymers if used, dietary status, and the genetic strain of rat. Fasting reduced the GSCA in Simonsen Munich Wistar rats from 0.035±0.005 to 0.016±0.004 (P<0.01). Frömter Munich Wistar rats had a much lower GSCA in both the fed and the fasted states. Finally, we documented extensive albumin transcytosis with vesicular and tubular delivery to and fusion with the basolateral membrane in S1 proximal tubule cells. In summary, these results help explain the previously conflicting microscopy and micropuncture data describing albumin filtration and highlight the dynamic nature of glomerular albumin permeability. PMID:22223875

Serum Creatinine: Not So Simple!

PubMed

Delanaye, Pierre; Cavalier, Etienne; Pottel, Hans

2017-01-01

Measuring serum creatinine is cheap and commonly done in daily practice. However, interpretation of serum creatinine results is not always easy. In this review, we will briefly remind the physiological limitations of serum creatinine due notably to its tubular secretion and the influence of muscular mass or protein intake on its concentration. We mainly focus on the analytical limitations of serum creatinine, insisting on important concept such as reference intervals, standardization (and IDMS traceability), analytical interferences, analytical coefficient of variation (CV), biological CV and critical difference. Because the relationship between serum creatinine and glomerular filtration rate is hyperbolic, all these CVs will impact not only the precision of serum creatinine but still more the precision of different creatinine-based equations, especially in low or normal-low creatinine levels (or high or normal-high glomerular filtration rate range). © 2017 S. Karger AG, Basel.

Ultrafiltrative deinking of flexographic ONP : the role of surfactants

Treesearch

Bradley H. Upton; Gopal A. Krishnagopalan; Said Abubakr

1999-01-01

Ultrafiltration is a potentially viable method of removing finely dispersed flexographic pigments from the deinking water loop. This work examines the effects of surface-active materials on ultrafiltration efficiency. A logarithmic relationship between permeate flax and pigment concentration was demonstrated at ink concentrations above 0.4%, permeation rates becoming...

A novel membrane based process to isolate photosystem-I membrane complex from spinach.

PubMed

Liu, Jianguo; Yin, Mengmeng; Wang, Meng; Zhang, Xuefang; Ge, Baosheng; Liu, Shuang; Lu, Jianren; Cui, Zhanfeng

2011-02-01

The isolation of photosystem-I (PS-I) from spinach has been conducted using ultrafiltration with 300 kDa molecular weight cut-off polyethersulfone membranes. The effects of ultrafiltration operating conditions on PS-I activity were optimized using parameter scanning ultrafiltration. These conditions included solution pH, ionic strength, stirring speed, and permeate flux. The effects of detergent (Triton X-100 and n-dodecyl-beta-D-maltoside) concentration on time dependent activity of PS-I were also studied using an O(2) electrode. Under optimized conditions, the PS-I purity obtained in the retentate was about 84% and the activity recovery was greater than 94% after ultrafiltration. To our knowledge, this is the first report of the isolation of a membrane protein using ultrafiltration alone.

Evaluation of Ultrafiltration for Spacecraft Water Reuse

NASA Technical Reports Server (NTRS)

Pickering, Karen D.; Wiesner, Mark R.

2001-01-01

Ultrafiltration is examined for use as the first stage of a primary treatment process for spacecraft wastewater. It is hypothesized that ultrafiltration can effectively serve as pretreatment for a reverse osmosis system, removing the majority of organic material in a spacecraft wastewater. However, it is believed that the interaction between the membrane material and the surfactant found in the wastewater will have a significant impact on the fouling of the ultrafiltration membrane. In this study, five different ultrafiltration membrane materials are examined for the filtration of wastewater typical of that expected to be produced onboard the International Space Station. Membranes are used in an unstirred batch cell. Flux, organic carbon rejection, and recovery from fouling are measured. The results of this evaluation will be used to select the most promising membranes for further study.

Evolution of phospholipid contents during the production of quark cheese from buttermilk.

PubMed

Ferreiro, T; Martínez, S; Gayoso, L; Rodríguez-Otero, J L

2016-06-01

We report the evolution of phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylcholine (PC), phosphatidylserine (PS), and sphingomyelin (SM) contents during the production of quark cheese from buttermilk by successive ultrafiltration concentration, enrichment with cream, concurrent homogenization and pasteurization, fermentative coagulation, and separation of quark from whey by further ultrafiltration. Buttermilk is richer than milk itself in phospholipids that afford desirable functional and technological properties, and is widely used in dairy products. To investigate how phospholipid content is affected by end-product production processes such as ultrafiltration, homogenization, pasteurization or coagulation, we measured the phospholipids at several stages of each of 5 industrial-scale quark cheese production runs. In each run, 10,000L of buttermilk was concentrated to half volume by ultrafiltration, enriched with cream, homogenized, pasteurized, inoculated with lactic acid bacteria, incubated to coagulation, and once more concentrated to half volume by ultrafiltration. Phospholipid contents were determined by HPLC with evaporative light scattering detection in the starting buttermilk, concentrated buttermilk, ultrafiltrate, cream-enriched concentrated buttermilk (both before and after concurrent homogenization and pasteurization), coagulate, and quark, and also in the rinsings obtained when the ultrafiltration equipment was washed following initial concentration. The average phospholipid content of buttermilk was approximately 5 times that of milk, and the phospholipid content of buttermilk fat 26 to 29 times that of milk fat. Although phospholipids did not cross ultrafiltration membranes, significant losses occurred during ultrafiltration (due to retention on the membranes) and during the homogenization and pasteurization process. During coagulation, however, phospholipid content rose, presumably as a consequence of the proliferation of the inoculated lactic acid bacteria. In spite of these changes in total phospholipid content, the relative proportions of the phospholipids studied remain fairly stable throughout quark production (PE>PC>SM>PS>PI) and similar to those found in the milk of the region, except that SM content was lower than in milk. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Hollow-fiber ultrafiltration of Cryptosporidium parvum oocysts from a wide variety of 10-L surface water samples.

PubMed

Kuhn, Ryan C; Oshima, Kevin H

2002-06-01

An optimized hollow-fiber ultrafiltration system (50 000 MWCO) was developed to concentrate Cryptosporidium oocysts from 10-L samples of environmental water. Seeded experiments were conducted using a number of surface-water samples from the southwestern U.S.A. and source water from four water districts with histories of poor oocyst recovery. Ultrafiltration produced a mean recovery of 47.9% from 19 water samples (55.3% from 39 individual tests). We also compared oocyst recoveries using the hollow-fiber ultrafiltration system with those using the Envirochek filter. In limited comparison tests, the hollow-fiber ultrafiltration system produced recoveries similar to those of the Envirochek filter (hollow fiber, 74.1% (SD = 2.8); Envirochek, 71.9% (SD = 5.2)) in low-turbidity (3.9 NTU) samples and performed better than the Envirochek filter in high-turbidity (159.0 NTU) samples (hollow fiber, 27.5%; Envirochek, 0.4%). These results indicate that hollow-fiber ultrafiltration can efficiently recover oocysts from a wide variety of surface waters and may be a cost-effective alternative for concentrating Cryptosporidium from water, given the reusable nature of the filter.

The Effect of Cellulose Acetate Concentration from Coconut Nira on Ultrafiltration Membrane Characters

NASA Astrophysics Data System (ADS)

Vaulina, E.; Widyaningsih, S.; Kartika, D.; Romdoni, M. P.

2018-04-01

Cellulose acetate is one of material in produce ultrafiltration membrane. Many efforts have been done to produce cellulose acetate from natural product to replace commercial one. In this research, ultrafiltration membrane has been produced from coconut flower water (nira). Ultrafiltration membrane is widely used in separation processes. This research aims to determine the characteristics of ultrafiltration membrane at a various concentration of cellulose acetate. The ultrafiltration membrane is conducted by phase inversion method at various concentration of cellulose acetate. The cellulose acetate concentration was 20%, 23% and 25% (w/w) with formamide as additives. The results showed that the greater the concentration of cellulose acetate, the smaller the flux value. The highest flux was a membrane with 20% cellulose acetate concentration with water flux value 55.34 L/(m2. h). But the greater the concentration of cellulose acetate the greater the rejection. The highest rejection value was on a membrane with 25% cellulose acetate concentration of 82.82%. While from the tensile strength test and the pore size analysis, the greater the cellulose acetate concentration the greater the tensile strength and the smaller the pore size

Residual blood processing by centrifugation, cell salvage or ultrafiltration in cardiac surgery: effects on clinical hemostatic and ex-vivo rheological parameters.

PubMed

Vonk, Alexander B; Muntajit, Warayouth; Bhagirath, Pranav; van Barneveld, Laurentius J; Romijn, Johannes W; de Vroege, Roel; Boer, Christa

2012-10-01

The study compared the effects of three blood concentration techniques after cardiopulmonary bypass on clinical hemostatic and ex-vivo rheological parameters. Residual blood of patients undergoing elective cardiac surgery was processed by centrifugation, cell salvage or ultrafiltration, and retransfused (n = 17 per group). Study parameters included blood loss, (free) hemoglobin, hematocrit, fibrinogen and erythrocyte aggregation, deformability and 2,3-diphosphoglycerate content. Patient characteristics were similar between groups. Ultrafiltration was associated with the highest weight of the transfusion bag [649 ± 261 vs. 320 ± 134 g (centrifugation) and 391 ± 158 g (cell salvage); P < 0.01]. Cell salvage resulted in the lowest hemolysis levels in the transfusion bag. Retransfusion of cell saver blood induced the largest gain in postoperative patient hemoglobin levels when compared to centrifugation and ultrafiltration, and was associated with the largest increase in 2,3-diphosphoglycerate when compared to ultrafiltration (Δ2,3-diphosphoglycerate 1.34 ± 1.92 vs. -0.77 ± 1.56 mmol/l; P = 0.03). Cell salvage is superior with respect to postoperative hemoglobin gain and washout of free hemoglobin when compared to centrifugation or ultrafiltration.

Fouling reduction by ozone-enhanced backwashing process in ultrafiltration of petroleum-based oil in water emulsion

NASA Astrophysics Data System (ADS)

Aryanti, Nita; Prihatiningtyas, Indah; Kusworo, Tutuk Djoko

2017-06-01

Ultrafiltration membrane has been successfully applied for oily waste water treatment. However, one significant drawback of membrane technology is fouling which is responsible for permeate flux decline as well as reducing membrane performance. One method commonly used to reduce fouling is a backwashing process. The backwashing is carried out by a push of reversed flow from permeate side to the feed side of a membrane to remove fouling on the membrane pore and release fouling release fouling layer on the external side. However, for adsorptive fouling, the backwashing process was not effective. On the other hand, Ozone demonstrated great performance for reducing organics fouling. Hence this research was focused on backwashing process with ozone for removing fouling due to ultrafiltration of petroleum based oil emulsion. Gasoline and diesel oil were selected as dispersed phase, while as continuous phase was water added with Tween 80 as a surfactant. This research found that the Ozone backwashing was effective to improve flux recovery. In ultrafiltration of gasoline emulsion, the flux recovery after Ozone backwashing was in the range of 42-74%. For ultrafiltration of diesel oil emulsion, the permeate flux recovery was about 35-84%. In addition, foulant deposition was proposed and predicting that foulant deposition for ultrafiltration of gasoline-in-water emulsion was surfactant as the top layer and the oil was underneath the surfactant. On the other hand, for ultrafiltration of diesel oil-in-water emulsion, the oil was predicted as a top layer above the surfactant foulant.

ETV REPORT - PHYSICAL REMOVAL OF CRYPTOSPORIDIUM OOCYSTS AND GIARDIA CYSTS IN DRINKING WATER, LEOPOLD MEMBRANE SYSTEMS ULTRABAR ULTRAFILTRATION SYSTEM WITH 60 INCH MARK III ELEMENT AT PITTSBURG, PA - NSF/00/10/EPADW395

EPA Science Inventory

Verification testing of the Leopold Ultrabar Mark III Ultrafiltration Systems was conducted from February 3-March9, 1999. The performance claim evaluated during field testing of the Leopold Ultrabar Mark III Ultrafiltration system was that the system is capable of a minimum 3 log...

[Investigation on the phenomena of bacteria exceeding standards in rural pit water treated by ultrafiltration membrane].

PubMed

Yue, Yinling; Zhang, Lan; Ling, Bo

2011-11-01

To investigate the phenomenon of bacteria exceeding standards in rural pit water, which was intermittently operated by water pump equipped with ultrafiltration membrane, and to explore the solutions. Polyvinyl chloride (PVC) alloy capillary membranes combined with UV, disinfectant, one-way valve, water-seal, high water level-water tank and direct outlet were tested. The operation on water treatment was intermittent, simulating the ways of treating pit water in the rural. The combination modes of ultrafiltration membrane with UV, disinfectant and high water level-water tank are valid in solving the problem of high turbidity and microorganism of pit water stored in cellars, the quality of effluents was consistent with the requirements of the national standards. While the combination modes of ultrafiltration membrane with one-way valve or water-seal were less desirable, more bacteria in treated water than raw water were observed because of bacteria breeding on the membrane component. In order to avoid excessive bacteria in filtered pit water caused by intermittent operation, it is recommended that for the pit water in high water level water tanks, the ultrafiltration membranes should be cleaned with disinfectants on a regular basis. The effluent pit water from underground cellars should be disinfected with UV after ultrafiltration.

Identification of the Allergenic Ingredients in Reduning Injection by Ultrafiltration and High-Performance Liquid Chromatography.

PubMed

Wang, Fang; Li, Cun-yu; Zheng, Yun-feng; Li, Hong-yang; Xiao, Wei; Peng, Guo-ping

2016-01-01

Reduning injection is a traditional Chinese medicine injection which has multiple functions such as clearing heat, dispelling wind, and detoxification. Although Reduning injection was widely utilized, reports of its allergenicity emerged one after another. However, there is little research on its allergenic substances. The aim of this study is to evaluate the sensitization of Reduning injection and explore the underlying cause of the anaphylactic reaction. The main ingredients in Reduning injection were analyzed before and after ultrafiltration. Ultrafiltrate Reduning injection, unfiltered Reduning injection, egg albumin, Tween-80, and nine effective components in Reduning injection were utilized to sensitize guinea pigs. The serum 5-hydroxytryptamine level was used to assess the sensitization effect of Reduning injection. We found a significant decrease in Tween-80 content comparing to other components in the injection after ultrafiltration. Unfiltered Reduning injection, Tween-80, chlorogenic acid, and cryptochlorogenin acid caused remarkable anaphylactoid reaction on guinea pigs while ultrafiltration Reduning resulted in a significantly lower degree of sensitization. Our results suggest that ultrafiltration could significantly reduce the sensitization of Reduning injection, which is likely due to the decrease of Tween-80. We also conjectured that the form of chlorogenic acid and cryptochlorogenin acid within the complex solution mixture may also affect the sensitizing effect.

Trace element fractionation and transport in boreal rivers and soil porewaters of permafrost-dominated basaltic terrain in Central Siberia

NASA Astrophysics Data System (ADS)

Pokrovsky, O. S.; Schott, J.; Dupré, B.

2006-07-01

The chemical status of ˜40 major and trace elements (TE) and organic carbon (OC) in pristine boreal rivers draining the basaltic plateau of Central Siberia (Putorana) and interstitial solutions of permafrost soils was investigated. Water samples were filtered in the field through progressively decreasing pore size (5 μm → 0.22 μm → 0.025 μm → 10 kDa → 1 kDa) using cascade frontal filtration technique. Most rivers and soil porewaters exhibit 2-5 times higher than the world average concentration of dissolved (i.e., <0.22 μm) iron (0.03-0.4 mg/L), aluminum (0.03-0.4 mg/L), OC (10-20 mg/L) and various trace elements that are usually considered as immobile in weathering processes (Ti, Zr, Ga, Y, REEs). Ultrafiltration revealed strong relationships between concentration of TE and that of colloidal Fe and Al. According to their partition during filtration and association with colloids, two groups of elements can be distinguished: (i) those weakly dependent on ultrafiltration and that are likely to be present as truly dissolved inorganic species (Li, Na, K, Si, Mn, Mo, Rb, Cs, As, Sb) or, partially (20-30%) associated with small size Fe- and Al-colloids (Ca, Mg, Sr, Ba) and to small (<1-10 kDa) organic complexes (Co, Ni, Cu, Zn), and (ii) elements strongly associated with colloidal iron and aluminum in all ultrafiltrates largely present in 1-100 kDa fraction (Ga, Y, REEs, Pb, V, Cr, Ti, Ge, Zr, Th, U). TE concentrations and partition coefficients did not show any detectable variations between different colloidal fractions for soil porewaters, suprapermafrost flow and surface streams. TE concentration measurements in river suspended particles demonstrated significant contribution (i.e., ⩾30%) of conventionally dissolved (<0.22 μm) forms for usually "immobile" elements such as divalent transition metals, Cd, Pb, V, Sn, Y, REEs, Zr, Hf, Th. The Al-normalized accumulation coefficients of TE in vegetation litter compared to basalts achieve 10-100 for B, Mn, Zn, As, Sr, Sn, Sb, and the larch litter degradation is able to provide the major contribution to the annual dissolved flux of most trace elements. It is hypothesized that the decomposition of plant litter in the topsoil horizon leads to Fe(III)-, Al-organic colloids formation and serves as an important source of elements in downward percolating fluids.

Protein aggregation under high concentration/density state during chromatographic and ultrafiltration processes.

PubMed

Arakawa, Tsutomu; Ejima, Daisuke; Akuta, Teruo

2017-02-01

Local transient high protein concentration or high density condition can occur during processing of protein solutions. Typical examples are saturated binding of proteins during column chromatography and high protein concentration on the semi-permeable membrane during ultrafiltration. Both column chromatography and ultrafiltration are fundamental technologies, specially for production of pharmaceutical proteins. We summarize here our experiences related to such high concentration conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

Prevalence of and risk factors for reduced serum bicarbonate in chronic kidney disease.

PubMed

Raphael, Kalani L; Zhang, Yingying; Ying, Jian; Greene, Tom

2014-10-01

The prevalence of metabolic acidosis increases as glomerular filtration rate falls. However, most patients with stage 4 chronic kidney disease have normal serum bicarbonate concentration while some with stage 3 chronic kidney disease have low serum bicarbonate, suggesting that other factors contribute to generation of acidosis. The purpose of this study is to identify risk factors, other than reduced glomerular filtration rate, for reduced serum bicarbonate in chronic kidney disease. This is a cross-sectional analysis of baseline data from the Chronic Renal Insufficiency Cohort Study. Multivariable logistic and linear regression models were used to relate predictor variables to the odds of low serum bicarbonate (< 22 mM) compared with normal serum bicarbonate (22-30 mM) and the coefficients of Δ serum bicarbonate concentration. The prevalence of low serum bicarbonate at baseline was 17.3%. Lower estimated glomerular filtration rate had the strongest relationship with low serum bicarbonate. Factors associated with higher odds of low serum bicarbonate, independent of estimated glomerular filtration rate, were urinary albumin/creatinine ≥ 10 mg/g, smoking, anaemia, hyperkalaemia, non-diuretic use and higher serum albumin. These and younger age, higher waist circumference, and use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers associated with negative Δ serum bicarbonate in linear regression models. Several factors not typically considered to associate with reduced serum bicarbonate in chronic kidney disease were identified including albuminuria ≥ 10 mg/g, anaemia, smoking, higher serum albumin, higher waist circumference, and use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers. Future studies should explore the longitudinal effect of these factors on serum bicarbonate concentration. © 2014 Asian Pacific Society of Nephrology.

HYDROXYUREA TREATMENT DECREASES GLOMERULAR HYPERFILTRATION IN CHILDREN WITH SICKLE CELL ANEMIA

PubMed Central

Aygun, Banu; Mortier, Nicole A.; Smeltzer, Matthew P.; Shulkin, Barry L.; Hankins, Jane S.; Ware, Russell E.

2015-01-01

Background Glomerular hyperfiltration and microalbuminuria/proteinuria are early manifestations of sickle nephropathy. The effects of hydroxyurea therapy on these renal manifestations of sickle cell anemia (SCA) are not well defined. Objective To investigate the effects of hydroxyurea on glomerular filtration rate (GFR) measured by 99mTc-DTPA clearance, and on microalbuminuria/proteinuria in children with SCA. Study Design Hydroxyurea Study of Long-Term Effects (HUSTLE) is a prospective study (NCT00305175) with the goal of describing the long-term cellular, molecular, and clinical effects of hydroxyurea therapy in SCA. Glomerular filtration rate, urine microalbumin, and serum cystatin C were measured before initiating hydroxyurea therapy and then repeated after 3 years. Baseline and Year 3 values for HUSTLE subjects were compared using the Wilcoxon Signed Rank test. Associations between continuous variables were evaluated using Spearman correlation coefficient. Results Twenty-three children with SCA (median age 7.5 years, range 2.5–14.0 years) received hydroxyurea at maximum tolerated dose (MTD, 24.4 ± 4.5 mg/kg/day, range 15.3–30.6 mg/kg/day). After three years of treatment, GFR measured by 99mTc-DTPA decreased significantly from 167 ± 46 mL/min/1.73m2 to 145 ± 27 mL/min/1.73m2 (p=0.016). This decrease in GFR was significantly associated with increase in fetal hemoglobin (p= 0.042) and decrease in lactate dehydrogenase levels (p=0.035). Urine microalbumin and cystatin C levels did not change significantly. Conclusions Hydroxyurea at MTD is associated with a decrease in hyperfiltration in young children with SCA. PMID:23255310

Unilateral renal ischaemia in rats induces a rapid secretion of inflammatory markers to renal lymph and increased capillary permeability

PubMed Central

Bivol, Liliana Monica; Iversen, Bjarne Magnus; Hultström, Michael; Wallace, Paal William; Reed, Rolf Kåre

2015-01-01

Key points Transient reduction in renal blood flow results in inflammation and is a primary cause of acute kidney injury, thereby representing a major clinical problem.It is not known whether the inflammatory reaction is local only or part of a systemic response.We accessed the renal microenvironment through isolation of lymph and were in this way able to investigate whether the inflammatory reaction is local or systemic.Transient ischaemia followed by reperfusion resulted in a rapid production of inflammatory mediators locally in the renal interstitium.We moreover showed that the injury response affected the glomerular as well as the non‐glomerular barrier and resulted in a reduced size and charge selectivity of the glomerular capillaries. Abstract A better understanding of the inflammatory process associated with renal ischaemia–reperfusion (IR) injury may be clinically important. In this study we examined the role of the kidney in production of inflammatory mediators by analysing renal lymph after 30 min unilateral occlusion of renal artery followed by 120 min reperfusion, as well as the effect of IR on size selectivity for proteins in both glomerular and peritubular capillaries. All measured mediators increased dramatically in renal hilar lymph, plasma and renal cortical tissue samples and returned to control levels after 120 min reperfusion. The responses were differentiated; interleukin‐1β, monocyte chemoattractant protein‐1 and leptin were markedly increased in plasma before reperfusion, reflecting an extrarenal response possibly induced by afferent renal nerve activity from the ischaemic kidney. Tumour necrosis factor‐α  was the only mediator showing elevated lymph‐to‐plasma ratio following 30 min reperfusion, indicating that most cytokines were released directly into the bloodstream. The IR‐induced rise in cytokine levels was paralleled by a significant increase in high molecular weight plasma proteins in both lymph and urine. The latter was shown as a 14‐ to 166‐fold increase in glomerular sieving coefficient of plasma proteins assessed by a novel proteomic approach, and indicated a temporarily reduced size selectivity of both glomerular and peritubular capillaries. Collectively, our data suggest that cytokines from the ischaemic kidney explain most of the rise in plasma concentration, and that the locally produced substances enter the systemic circulation through transport directly to plasma and not via the interstitium to lymph. PMID:26584508

Making equipment to process paddy water for providing drinking water by using Ozone-UVC& Ultrafiltration

NASA Astrophysics Data System (ADS)

Styani, E.; Dja'var, N.; Irawan, C.; Hanafi

2018-01-01

This study focuses on making equipment which is useful to process paddy water to be consumable as drinking water by using ozone-UVC and ultrafiltration. The equipment which is made by the process of ozone-UVC and ultrafiltration or reverse osmosis is driven by electric power generated from solar panels. In the experiment, reverse osmosis system with ozone-UVC reactor proves to be good enough in producing high quality drinking water.

Limitations of salivary and blood cortisol determinations in pigs.

PubMed

Blackshaw, J K; Blackshaw, A W

1989-01-01

Blood and saliva samples were taken from groups of pigs maintained in intensive conditions. Multiple samples were taken from two unrestrained pregnant sows fitted with jugular cannulae. Single samples were taken from groups (mixed gilts and entire males; 70-90 kg) which were lightly exercised (7) or restrained (12). The rate of salivary secretion was low and collection of adequate samples took 5 min; in a number of pigs no saliva could be obtained. In order to stimulate salivary secretion, pigs (70-80 kg) were injected with pilocarpine nitrate (25 mg, subcutaneous) which produced a copious flow of saliva persisting for at least 15 min. Resting sows had higher mean levels of cortisol in plasma, ultrafiltrate and saliva than the other groups, which did not differ from each other. Within the pilocarpine group, males had a higher ultrafiltrate level of cortisol than females. In most instances salivary cortisol was significantly greater than ultrafiltrate cortisol. Ultrafiltrate and plasma cortisol were highly correlated (r = 0.883) but this correlation was low in the presence of pilocarpine (r = 0.260). Salivary cortisol was poorly correlated with either plasma (r = 0.167) or ultrafiltrate cortisol (r = 0.278) and the correlation with plasma was even lower following the administration of pilocarpine (r = 0.086). It was concluded that salivary estimates of cortisol in the pig were not usefully correlated with levels of ultrafiltrate (free) cortisol.

Fouling mechanism in ultrafiltration of vegetable oil

NASA Astrophysics Data System (ADS)

Ariono, D.; Wardani, A. K.; Widodo, S.; Aryanti, Putu T. P.; Wenten, I. G.

2018-03-01

Energy efficient and cost-effective separation of impurities from vegetable oil is a great challenge for vegetable oil processing. Several technologies have been developed, including pressurized membrane, chemical treatment, and chemical free separation methods. Among those technologies, ultrafiltration membrane is one of the most attractive processes with low operating pressure and temperature. In this work, hydrophobic polypropylene ultrafiltration membrane was used to remove impurities such as non-dissolved solids from palm kernel oil. Unfortunately, the hydrophobicity of polypropylene membrane leads to significant impact on the reduction of permeate flux due to membrane fouling. This fouling is associated with the accumulation of substances on the membrane surface or within the membrane pores. For better understanding, fouling mechanism that occurred during palm kernel oil ultrafiltration using hydrophobic polypropylene membrane was investigated. The effect of trans-membrane pressure and feed temperature on fouling mechanism was also studied. The result showed that cake formation became the dominant fouling mechanism up to 50 min operation of palm kernel oil ultrafiltration. Furthermore, the fouling mechanism was not affected by the increase of trans-membrane pressure and feed temperature.

Ultrafiltration by a compacted clay membrane-II. Sodium ion exclusion at various ionic strengths

USGS Publications Warehouse

Hanshaw, B.B.; Coplen, T.B.

1973-01-01

Several recent laboratory studies and field investigations have indicated that shales and compacted clay minerals behave as semipermeable membranes. One of the properties of semipermeable membranes is to retard or prevent the passage of charged ionic species through the membrane pores while allowing relatively free movement of uncharged species. This phenomenon is termed salt filtering, reverse osmosis, or ultrafiltration. This paper shows how one can proceed from the ion exchange capacity of clay minerals and, by means of Donnan membrane equilibrium concept and the Teorell-Meyer-Siever theory, develop a theory to explain why and to what extent ultrafiltration occurs when solutions of known concentration are forced to flow through a clay membrane. Reasonable agreement between theory and laboratory results were found. The concentration of the ultrafiltrate was always greater than predicted because of uncertainty in values of some parameters in the equations. Ultrafiltration phenomena may be responsible for the formation of some subsurface brines and mineral deposits. The effect should also be taken into consideration in any proposal for subsurface waste emplacement in an environment containing large quantities of clay minerals. ?? 1973.

Proximal Tubules Have the Capacity to Regulate Uptake of Albumin.

PubMed

Wagner, Mark C; Campos-Bilderback, Silvia B; Chowdhury, Mahboob; Flores, Brittany; Lai, Xianyin; Myslinski, Jered; Pandit, Sweekar; Sandoval, Ruben M; Wean, Sarah E; Wei, Yuan; Satlin, Lisa M; Wiggins, Roger C; Witzmann, Frank A; Molitoris, Bruce A

2016-02-01

Evidence from multiple studies supports the concept that both glomerular filtration and proximal tubule (PT) reclamation affect urinary albumin excretion rate. To better understand these roles of glomerular filtration and PT uptake, we investigated these processes in two distinct animal models. In a rat model of acute exogenous albumin overload, we quantified glomerular sieving coefficients (GSC) and PT uptake of Texas Red-labeled rat serum albumin using two-photon intravital microscopy. No change in GSC was observed, but a significant decrease in PT albumin uptake was quantified. In a second model, loss of endogenous albumin was induced in rats by podocyte-specific transgenic expression of diphtheria toxin receptor. In these albumin-deficient rats, exposure to diphtheria toxin induced an increase in albumin GSC and albumin filtration, resulting in increased exposure of the PTs to endogenous albumin. In this case, PT albumin reabsorption was markedly increased. Analysis of known albumin receptors and assessment of cortical protein expression in the albumin overload model, conducted to identify potential proteins and pathways affected by acute protein overload, revealed changes in the expression levels of calreticulin, disabled homolog 2, NRF2, angiopoietin-2, and proteins involved in ATP synthesis. Taken together, these results suggest that a regulated PT cell albumin uptake system can respond rapidly to different physiologic conditions to minimize alterations in serum albumin level. Copyright © 2016 by the American Society of Nephrology.

Proximal Tubules Have the Capacity to Regulate Uptake of Albumin

PubMed Central

Wagner, Mark C.; Campos-Bilderback, Silvia B.; Chowdhury, Mahboob; Flores, Brittany; Lai, Xianyin; Myslinski, Jered; Pandit, Sweekar; Sandoval, Ruben M.; Wean, Sarah E.; Wei, Yuan; Satlin, Lisa M.; Wiggins, Roger C.; Witzmann, Frank A.

2016-01-01

Evidence from multiple studies supports the concept that both glomerular filtration and proximal tubule (PT) reclamation affect urinary albumin excretion rate. To better understand these roles of glomerular filtration and PT uptake, we investigated these processes in two distinct animal models. In a rat model of acute exogenous albumin overload, we quantified glomerular sieving coefficients (GSC) and PT uptake of Texas Red-labeled rat serum albumin using two-photon intravital microscopy. No change in GSC was observed, but a significant decrease in PT albumin uptake was quantified. In a second model, loss of endogenous albumin was induced in rats by podocyte-specific transgenic expression of diphtheria toxin receptor. In these albumin-deficient rats, exposure to diphtheria toxin induced an increase in albumin GSC and albumin filtration, resulting in increased exposure of the PTs to endogenous albumin. In this case, PT albumin reabsorption was markedly increased. Analysis of known albumin receptors and assessment of cortical protein expression in the albumin overload model, conducted to identify potential proteins and pathways affected by acute protein overload, revealed changes in the expression levels of calreticulin, disabled homolog 2, NRF2, angiopoietin-2, and proteins involved in ATP synthesis. Taken together, these results suggest that a regulated PT cell albumin uptake system can respond rapidly to different physiologic conditions to minimize alterations in serum albumin level. PMID:26054544

21 CFR 177.2910 - Ultra-filtration membranes.

Code of Federal Regulations, 2014 CFR

2014-04-01

.... 1314-36-9). (4) Ultrafiltration membranes that consist of a microporous poly(vinylidene fluoride... gallons of potable water prior to their first use in contact with food. (g) Acrylonitrile copolymers...

The evaluation of hollow-fiber ultrafiltration and celite concentration of enteroviruses, adenoviruses and bacteriophage from different water matrices

EPA Pesticide Factsheets

The data to support the evaluation of hollow-fiber ultrafiltration and celite concentration of enteroviruses, adenoviruses and bacteriophage from different water matricesThis dataset is associated with the following publication:Rhodes , E., E. Huff, D. Hamilton, and J. Jones. The evaluation of hollow-fiber ultrafiltration and celite concentration of enteroviruses, adenoviruses and bacteriophage from different water matrices. JOURNAL OF VIROLOGICAL METHODS. Elsevier Science Ltd, New York, NY, USA, 228(2): 31-38, (2016).

Urine biomarkers informative of human kidney allograft rejection and tolerance.

PubMed

Nissaisorakarn, Voravech; Lee, John Richard; Lubetzky, Michelle; Suthanthiran, Manikkam

2018-05-01

We developed urinary cell messenger RNA (mRNA) profiling to monitor in vivo status of human kidney allografts based on our conceptualization that the kidney allograft may function as an in vivo flow cell sorter allowing access of graft infiltrating cells to the glomerular ultrafiltrate and that interrogation of urinary cells is informative of allograft status. For the profiling urinary cells, we developed a two-step preamplification enhanced real-time quantitative PCR (RT-QPCR) assays with a customized amplicon; preamplification compensating for the low RNA yield from urine and the customized amplicon facilitating absolute quantification of mRNA and overcoming the inherent limitations of relative quantification widely used in RT-QPCR assays. Herein, we review our discovery and validation of urinary cell mRNAs as noninvasive biomarkers prognostic and diagnostic of acute cellular rejection (ACR) in kidney allografts. We summarize our results reflecting the utility of urinary cell mRNA profiling for predicting reversal of ACR with anti-rejection therapy; differential diagnosis of kidney allograft dysfunction; and noninvasive diagnosis and prognosis of BK virus nephropathy. Messenger RNA profiles associated with human kidney allograft tolerance are also summarized in this review. Altogether, data supporting the idea that urinary cell mRNA profiles are informative of kidney allograft status and tolerance are reviewed in this report. Copyright © 2018. Published by Elsevier Inc.

Dynamic behaviour of river colloidal and dissolved organic matter through cross-flow ultrafiltration system.

PubMed

Wilding, Andrew; Liu, Ruixia; Zhou, John L

2005-07-01

Through cross-flow filtration (CFF) with a 1-kDa regenerated cellulose Pellicon 2 module, the ultrafiltration characteristics of river organic matter from Longford Stream, UK, were investigated. The concentration of organic carbon (OC) in the retentate in the Longford Stream samples increased substantially with the concentration factor (cf), reaching approximately 40 mg/L at cf 15. The results of dissolved organic carbon (DOC) and colloidal organic carbon (COC) analysis, tracking the isolation of colloids from river waters, show that 2 mg/L of COC was present in those samples and good OC mass balance (77-101%) was achieved. Fluorescence measurements were carried out for the investigation of retentate and permeate behaviour of coloured dissolved organic materials (CDOM). The concentrations of CDOM in both the retentate and permeate increased with increasing cf, although CDOM were significantly more concentrated in the retentate. The permeation model expressing the correlation between log[CDOM] in the permeate and logcf was able to describe the permeation behaviour of CDOM in the river water with regression coefficients (r(2)) of 0.94 and 0.98. Dry weight analysis indicated that the levels of organic colloidal particles were from 49 to 71%, and between 29 and 51% of colloidal particles present were inorganic. COC as a percentage of DOC was found to be 10-16% for Longford Stream samples.

Unloading therapy by intravenous diuretic in chronic heart failure: a double-edged weapon?

PubMed

De Vecchis, Renato; Ciccarelli, Antonio; Pucciarelli, Armando

2010-08-01

A well established part of therapeutic approaches applying to cases of chronic heart failure (CHF) with extreme fluid retention is represented by intensive intravenous (i.v.) therapy with loop diuretics. This kind of therapy, if appropriately modulated according to the individual clinical picture and biohumoral pattern, is able to decrease the abnormally high ventricular filling pressures, thereby relieving the breathlessness while being able to retrieve a suitable urine output, so as to propitiate regression or disappearance of edema without unfavorable influences on renal clearance of nitrogenous compounds. Nevertheless, the intensive i.v. diuretic therapy should be tailored on the basis of a close assessment of baseline hemodynamic data and hemodynamic response to the medications, in addition to the careful diuretic dose titration and cautious evaluation of risk/benefit ratio. Actually, by using this kind of therapy, there is a risk that a tubular or glomerular injury can be generated and that a frequently preexisting renal dysfunction can be aggravated, especially when excessive doses of loop diuretics are being erroneously administered, so as to cause hypotension, hypoperfusion and/or relative dehydration in patients with decompensated CHF who could have expressly benefitted from intensive unloading therapy. Recently, the genesis of CHF-related progressive renal deterioration has been highlighted by affirming that a major role may be played rather by neurovegetative disorders, that is, by increase in sympathetic tone and abnormalities in kidney's vasomotility than by cardiac inotropism deficiency. The measures, thought to be able to prevent renal arterial constriction and to impede deterioration of glomerular filtration rate (GFR) due to the ischemic-necrotic tubular injury, as occurring in the set of intensive unloading therapy with i.v. furosemide or other loop diuretic, are represented by application of inotropic and renal vasodilator support by dopamine i.v. infusion at low doses or by other inotropic agents provided with recognized renal vasodilator properties and/or by addition to i.v. furosemide of osmotic agents able to expand the hematic volume, so counteracting or minimizing the reflex renal vasoconstriction induced by furosemide-related reduction in intravascular circulating volume: i.v. infusion of small volumes of hypertonic saline solution, as well as administration of albumin, mannitol and/or plasma expanders. Because renal impairment, as developing in the setting of CHF, has proven to represent a very important indicator of adverse outcome, every effort should be addressed to prevent any significant (>25% of basal value) rise in serum creatinine consequent to diuretic unloading therapy or to other procedures (paracentesis of tense ascites, ultrafiltration) aimed at rapid fluid removal in edematous or ascitic CHF or cardiogenetic anasarca. Ultrafiltration, even though a promising technique highly valued for its acknowledged property to obtain a more rapid fluid and weight loss in CHF patients with marked fluid retention, has been demonstrated so far to produce neurohumoral activation, creatinine abnormalities and symptomatic hypotensions similar to those due to i.v. loop diuretics; thus, the hypothesized advantages of this technique remain to be further clarified and confirmed, with regard to its safety profile and cost-effectiveness.

Rationale and design of the Aquapheresis Versus Intravenous Diuretics and Hospitalization for Heart Failure (AVOID-HF) trial.

PubMed

Costanzo, Maria Rosa; Negoianu, Daniel; Fonarow, Gregg C; Jaski, Brian E; Bart, Bradley A; Heywood, J Thomas; Nabut, Jose L; Schollmeyer, Michael P

2015-09-01

In patients hospitalized with acutely decompensated heart failure, unresolved signs and symptoms of fluid overload have been consistently associated with poor outcomes. Regardless of dosing and type of administration, intravenous loop diuretics have not reduced heart failure events or mortality in patients with acutely decompensated heart failure. The results of trials comparing intravenous loop diuretics to mechanical fluid removal by isolated venovenous ultrafiltration have yielded conflicting results. Studies evaluating early decongestive strategies have shown that ultrafiltration removed more fluid and was associated with fewer heart failure-related rehospitalization than intravenous loop diuretics. In contrast, when used in the setting of worsening renal function, ultrafiltration was associated with poorer renal outcomes and no reduction in heart failure events. The AVOID-HF trial seeks to determine if an early strategy of ultrafiltration in patients with acutely decompensated heart failure is associated with fewer heart failure events at 90 days compared with a strategy based on intravenous loop diuretics. Study subjects from 40 highly experienced institutions are randomized to either early ultrafiltration or intravenous loop diuretics. In both treatment arms, fluid removal therapies are adjusted according to the patients' hemodynamic condition and renal function. The study was unilaterally terminated by the sponsor in the absence of futility and safety concerns after the enrollment of 221 subjects, or 27% of the originally planned sample size of 810 patients. The AVOID-HF trial's principal aim is to compare the safety and efficacy of ultrafiltration vs that of intravenous loop diuretics in patients hospitalized with acutely decompensated heart failure. Because stepped treatment approaches are applied in both ultrafiltration and intravenous loop diuretics groups and the primary end point is time to first heart failure event within 90 days, it is hoped that the AVOID-HF trial, despite its untimely termination by the sponsor, will provide further insight on how to optimally decongest patients with fluid-overloaded heart failure. Copyright © 2015. Published by Elsevier Inc.

Ultrafiltration of hemicellulose hydrolysate fermentation broth

NASA Astrophysics Data System (ADS)

Kresnowati, M. T. A. P.; Desiriani, Ria; Wenten, I. G.

2017-03-01

Hemicelulosic material is often used as the main substrate to obtain high-value products such as xylose. The five carbon sugar, xylose, could be further processed by fermentation to produce xylitol. However, not only the hemicellulose hydrolysate fermentation broth contains xylitol, but also metabolite products, residual substances, biomass and mineral salts. Therefore, in order to obtain the end products, various separation processes are required to separate and purify the desired product from the fermentation broth. One of the most promising downstream processing methods of fermentation broth clarification is ultrafiltration due to its potential for energy saving and higher purity. In addition, ultrafiltration membrane has a high performance in separating inhibitory components in the fermentation broth. This paper assesses the influence of operating conditions; including trans-membrane pressure, velocity, pH of the fermentation broth solutions, and also to the xylitol concentration in the product. The challenges of the ultrafiltration process will be pointed out.

[Dialysis and ultrafiltration therapy in patients with cardio-renal syndrome: recommendations of the working group "heart-kidney" of the German Cardiac Society and the German Society of Nephrology].

PubMed

Schwenger, V; Remppis, B A; Westenfeld, R; Weinreich, T; Brunkhorst, R; Schieren, G; Krumme, B; Haller, H; Schmieder, R; Schlieper, G; Frye, B; Hoppe, U C; Hoyer, J; Keller, T; Blumenstein, M; Schunkert, H; Mahfoud, F; Rump, L C

2014-02-01

Renal failure is common in patients with severe heart failure. This complex pathophysiological interaction has been classified as cardio-renal syndrome. In these patients hydropic decompensation is the main cause of hospitalization. In patients with refractory heart failure, characterized by diuretic resistance and congestion due to volume overload, ultrafiltration has to be considered. In acute decompensated heart failure with worsening of renal function, extracorporeal ultrafiltration is the preferred treatment modality. On the other hand, patients suffering from chronic decompensated heart failure, particularly patients with ascites, will profit from the treatment specific advantages of peritoneal ultrafiltration. Prerequisite for an optimized care of patients with cardio-renal syndrome is the close collaboration among intensive care doctors, cardiologists and nephrologists. © Georg Thieme Verlag KG Stuttgart · New York.

Physicochemical and Microbiological Properties of Yogurt-cheese Manufactured with Ultrafiltrated Cow's Milk and Soy Milk Blends

PubMed Central

Lee, Na-Kyoung; Mok, Bo Ram; Jeewanthi, Renda Kankanamge Chaturika; Yoon, Yoh Chang; Paik, Hyun-Dong

2015-01-01

The objective of this study was to develop yogurt-cheese using cow’s milk, ultrafiltrated cow’s milk, and soy milk. The addition of soy milk and ultrafiltrated milk increased the amount of protein in the yogurt-cheese. Yogurt-cheeses were made using cheese base using 10% and 20% soy milk with raw and ultrafiltrated cow’s milk, and stored at 4℃ during 2 wk. The yield of yogurt-cheeses made with added soy milk was decreased and the cutting point was delayed compared to yogurt-cheese made without soy milk. Yogurt-cheese made using ultrafiltrated cow’s milk showed the highest yield. However, yogurt-cheese made with added soy milk had higher protein content and titratable acidity than yogurt-cheese made using raw and ultrafiltrated cow’s milk. Fat and lactose contents in the yogurt-cheese made with added soy milk were lower. Yogurt-cheeses made with added soy milk contained several soy protein bands corresponding to the sizes of α2-, β-, and κ-casein band. Yogurt-cheese made with added soy milk had similar elasticity to yogurt-cheese made without soy milk but had lower cohesiveness. There was no significant difference in the number of lactic acid bacteria in the different cheeses, as all had over 8.0 Log CFU/g. Considering these data and the fact that proteins and fats of vegetable origin with high biological value were observed as well as unsaturated fats, yogurt-cheese made with added soy milk can be considered to be a functional food. PMID:26761829

Effect of Ultrafiltration on Pulmonary Function and Interleukins in Patients Undergoing Cardiopulmonary Bypass.

PubMed

Kosour, Carolina; Dragosavac, Desanka; Antunes, Nilson; Almeida de Oliveira, Rosmari Aparecida Rosa; Martins Oliveira, Pedro Paulo; Wilson Vieira, Reinaldo

2016-08-01

To evaluate the effect of ultrafiltration on interleukins, TNF-α levels, and pulmonary function in patients undergoing coronary artery bypass grafting (CABG). Prospective, randomized, controlled trial. University hospital. Forty patients undergoing CABG were randomized into a group assigned to receive ultrafiltration (UF) during cardiopulmonary bypass (CPB) or into another group (control) that underwent the same procedure but without ultrafiltration. Interleukins and TNF-α levels, pulmonary gas exchange, and ventilatory mechanics were measured in the preoperative, intraoperative, and postoperative periods. Interleukins and TNF-α also were analyzed in the perfusate of the test group. There were increases in IL-6 and IL-8 at 30 minutes after CPB and 6, 12, 24, and 36 hours after surgery, along with an increase in TNF-α at 30 minutes after CPB and 24, 36, and 48 hours after surgery in both groups. IL-1 increased at 30 minutes after CPB and 12 hours after surgery, while IL-6 increased 24 and 36 hours after surgery in the UF group. The analysis of the ultrafiltrate showed the presence of TNF-α and traces of IL-1β, IL-6, and IL-8. There were alterations in the oxygen index, alveolar-arterial oxygen difference, deadspace, pulmonary static compliance and airway resistance after anesthesia and sternotomy, as well as in airway resistance at 6 hours after surgery in both groups, with no difference between them. Ultrafiltration increased the serum level of IL-1 and IL-6, while it did not interfere with gas exchange and pulmonary mechanics in CABG. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation of Ultrafiltration Performance for Phospholipid Separation

NASA Astrophysics Data System (ADS)

Aryanti, N.; Wardhani, D. H.; Maulana, Z. S.; Roberto, D.

2017-11-01

Ultrafiltration membrane for degumming of crude palm oil has been applied as an alternative method since the membrane process required less procedure than the conventional degumming. This research focused on the examination of ultrafiltration performance for phospholipid separation from model crude palm oil degumming. Specifically, profile flux and rejection, as well as blocking mechanism, were investigated. Feed consisting of Refined Crude Palm Oil - Isopropanol - Lecithin mixtures were represented as crude palm oil degumming. Lecithin was denoted a phospholipid component, and the concentrations of lecithin in feed were varied to 0.1%, 0.2%, and 0.3%. The concentration of phospholipid was determined as phosphor content. At the concentration of lecithin in feed representing phospholipid concentration of 8,45 mg/kg, 8,45 mg/kg, 24,87 mg/kg and 57,58 mg/kg, respectively. Flux profiles confirmed that there was a flux decline during filtration. In addition, the lecithin concentrations do not significantly effect on further flux decline. Rejection characteristic and phospholipid concentration in the permeate showed that the phospholipid rejections by ultrafiltration were in the range of 23-79,5% representing permeate’s phospholipid concentration of 1,73 - 44,25 mg/kg. Evaluation of fouling mechanism by Hermia’s blocking model confirmed that the standard blocking is the dominant mechanism in the ultrafiltration of lecithin mixture.

Purification of Drug Loaded PLGA Nanoparticles Prepared by Emulsification Solvent Evaporation Using Stirred Cell Ultrafiltration Technique.

PubMed

Paswan, Suresh K; Saini, T R

2017-12-01

The emulsifiers in an exceedingly higher level are used in the preparation of drug loaded polymeric nanoparticles prepared by emulsification solvent evaporation method. This creates great problem to the formulator due to their serious toxicities when it is to be administered by parenteral route. The final product is therefore required to be freed from the used surfactants by the conventional purification techniques which is a cumbersome job. The solvent resistant stirred cell ultrafiltration unit (Millipore) was used in this study using polyethersulfone ultrafiltration membrane (Biomax®) having pore size of NMWL 300 KDa as the membrane filter. The purification efficiency of this technique was compared with the conventional centrifugation technique. The flow rate of ultrafiltration was optimized for removal of surfactant (polyvinyl alcohol) impurities to the acceptable levels in 1-3.5 h from the nanoparticle dispersion of tamoxifen prepared by emulsification solvent evaporation method. The present investigations demonstrate the application of solvent resistant stirred cell ultrafiltration technique for removal of toxic impurities of surfactant (PVA) from the polymeric drug nanoparticles (tamoxifen) prepared by emulsification solvent evaporation method. This technique offers added benefit of producing more concentrated nanoparticles dispersion without causing significant particle size growth which is observed in other purification techniques, e.g., centrifugation and ultracentrifugation.

Water hammer reduces fouling during natural water ultrafiltration.

PubMed

Broens, F; Menne, D; Pothof, I; Blankert, B; Roesink, H D W; Futselaar, H; Lammertink, R G H; Wessling, M

2012-03-15

Today's ultrafiltration processes use permeate flow reversal to remove fouling deposits on the feed side of ultrafiltration membranes. We report an as effective method: the opening and rapid closing of a valve on the permeate side of an ultrafiltration module. The sudden valve closure generates pressure fluctuations due to fluid inertia and is commonly known as "water hammer". Surface water was filtrated in hollow fiber ultrafiltration membranes with a small (5%) crossflow. Filtration experiments above sustainable flux levels (>125 l (m2h)(-1)) show that a periodic closure of a valve on the permeate side improves filtration performance as a consequence of reduced fouling. It was shown that this effect depends on flux and actuation frequency of the valve. The time period that the valve was closed proved to have no effect on filtration performance. The pressure fluctuations generated by the sudden stop in fluid motion due to the valve closure are responsible for the effect of fouling reduction. High frequency recording of the dynamic pressure evolution shows water hammer related pressure fluctuations to occur in the order of 0.1 bar. The pressure fluctuations were higher at higher fluxes (higher velocities) which is in agreement with the theory. They were also more effective at higher fluxes with respect to fouling mitigation. Copyright © 2011 Elsevier Ltd. All rights reserved.

Ultrafiltrate and microdialysis DL probe in vitro recoveries: electrolytes and metabolites

NASA Technical Reports Server (NTRS)

Janle, E. M.; Cregor, M.

1996-01-01

UF ultrafiltration and DL microdialysis probes are well-suited for sampling interstitial concentrations of ions and metabolites in peripheral tissue. The first step in utilization of membrane sampling techniques is to determine the recovery characteristics of the probes in vitro.

Tangential Ultrafiltration of Aqueous "Saccharomyces Cerevisiae" Suspensions

ERIC Educational Resources Information Center

Silva, Carlos M.; Neves, Patricia S.; Da Silva, Francisco A.; Xavier, Ana M. R. B.; Eusebio, M. F. J.

2008-01-01

Experimental work on ultrafiltration is presented to illustrate the practical and theoretical principles of this separation technique. The laboratory exercise comprises experiments with pure water and with aqueous "Saccharomyces cerevisiae" (from commercial Baker's yeast) suspensions. With this work students detect the characteristic phenomena…

Production of Hypoallergenic Antibacterial Peptides from Defatted Soybean Meal in Membrane Bioreactor: A Bioprocess Engineering Study with Comprehensive Product Characterization

PubMed Central

2017-01-01

Summary Hypoallergenic antibacterial low-molecular-mass peptides were produced from defatted soybean meal in a membrane bioreactor. In the first step, soybean meal proteins were digested with trypsin in the bioreactor, operated in batch mode. For the tryptic digestion of soybean meal protein, optimum initial soybean meal concentration of 75 g/L, temperature of 40 °C and pH=9.0 were determined. After enzymatic digestion, low-molecular-mass peptides were purified with cross-flow flat sheet membrane (pore size 100 µm) and then with tubular ceramic ultrafiltration membrane (molecular mass cut-off 5 kDa). Effects of transmembrane pressure and the use of a static turbulence promoter to reduce the concentration polarization near the ultrafiltration membrane surface were examined and their positive effects were proven. For the filtration with ultrafiltration membrane, transmembrane pressure of 3·105 Pa with 3-stage discontinuous diafiltration was found optimal. The molecular mass distribution of purified peptides using ultrafiltration membrane was determined by a liquid chromatography–electrospray ionization quadrupole time-of-flight mass spectrometry setup. More than 96% of the peptides (calculated as relative frequency) from the ultrafiltration membrane permeate had the molecular mass M≤1.7 kDa and the highest molecular mass was found to be 3.1 kDa. The decrease of allergenic property due to the tryptic digestion and membrane filtration was determined by an enzyme-linked immunosorbent assay and it was found to exceed 99.9%. It was also found that the peptides purified in the ultrafiltration membrane promoted the growth of Pediococcus acidilactici HA6111-2 and they possessed antibacterial activity against Bacillus cereus. PMID:29089846

Microfiltration and Ultrafiltration Membranes for Drinking Water

EPA Science Inventory

This article provides a concise and abbreviated summary of AWWA Manual of Practice M53, Microfiltration and Ultrafiltration Membranes for Drinking Water, to serve as a quick point of reference. For convenience, the article’s organization matches that of M53, as follows: • wate...

Class and Home Problems. The Lambert W Function in Ultrafiltration and Diafiltration

ERIC Educational Resources Information Center

Foley, Greg

2016-01-01

Novel analytical solutions based on the Lambert W function for two problems in ultrafiltration and diafiltration are described. Example problems, suitable for incorporation into an introductory module in unit operations, membrane processing, or numerical methods are provided in each case.

Microanatomy and ultrastructure of the excretory system of two pelagic opisthobranch species (Gastropoda: Gymnosomata and Thecosomata).

PubMed

Fahrner, A; Haszprunar, G

2000-04-01

The microanatomy and ultrastructure of the excretory system of Pneumoderma sp. (Gymnosomata) and Creseis virgula Rang, 1828 (Thecosomata) have been investigated by means of semithin serial sections, reconstructions and transmission electron microscopy. The studies revealed a functional metanephridial system consisting of a heart with a single ventricle and auricle in a pericardial cavity and a single kidney in both species. Podocytes in the atrial wall of the pericardial epithelium are the site of ultrafiltration, whereas the flat epithelium of the kidney with numerous basal infoldings and a dense microvillous border on the luminal surface suggests modification of the ultrafiltrate. In Pneumoderma sp., additional loci of ultrafiltration with identical fine structure (meandering slits with diaphragms covered by extracellular matrix) occur in the solitary rhogocytes (pore cells). The presence of podocytes situated on the atrial wall in representatives of two higher opisthobranch taxa contradicts former ideas on the loss of the primary site of ultrafiltration in the ancestors of the Opisthobranchia.

Separation of water-soluble polysaccharides from Cyclocarya paliurus by ultrafiltration process.

PubMed

Xie, Jian-Hua; Shen, Ming-Yue; Nie, Shao-Ping; Zhao, Qiang; Li, Chang; Xie, Ming-Yong

2014-01-30

In this study, ultrafiltration membrane process was employed to separate polysaccharides from Cyclocarya paliurus (Batal.) Iljinskaja (C. paliurus) to simulate industrial production. Meanwhile, the molecular weight distribution of C. paliurus polysaccharides was investigated by gel permeation chromatography. Four fractions were obtained and named as CPPS-A, CPPS-B, CPPS-C and CPPS-D, respectively. CPPS-A and CPPS-B contained approximately 69.5% and 12.7% of polysaccharides, whose molecular weight were in the range of 100-300 kDa and 120 kDa, respectively. CPPS-C was comprised of two polysaccharides with average molecular weight of 40 kDa and 15 kDa. Results showed that ultrafiltration resulted in the removal of parts of small molecule weight polysaccharides, the increase of proportion of high molecule weight ones and the obvious improvement of quality of products. Compared with ethanol precipitation and gel permeation chromatography techniques, ultrafiltration showed many advantages, and also provided theoretical support for industrial manufacturing of C. paliurus polysaccharides in separation. Copyright © 2013 Elsevier Ltd. All rights reserved.

The Mutual Relationship Between Peritonitis and Peritoneal Transport.

PubMed

van Esch, Sadie; van Diepen, Anouk T N; Struijk, Dirk G; Krediet, Raymond T

2016-01-01

♦ Preservation of the peritoneum is required for long-term peritoneal dialysis (PD). We investigated the effect of multiple peritonitis episodes on peritoneal transport. ♦ Prospectively collected data from 479 incident PD patients treated between 1990 and 2010 were analyzed, using strict inclusion criteria: follow-up of at least 3 years with the availability of a Standard Peritoneal Permeability Analysis (SPA) in the first year after start of PD and within the third year of PD, without peritonitis preceding the first SPA. For the purpose of the study, we only included patients who remained peritonitis-free (n = 28) or who experienced 3 or more peritonitis episodes (n = 16). ♦ At baseline the groups were similar with regard to small solute and fluid transport. However, the frequent peritonitis group had lower peritoneal protein clearances compared to the no peritonitis group, resulting in lower dialysate concentrations of proteins: albumin 196.5 mg/L vs 372.5 mg/L, IgG 36.4 mg/L vs 65.0 mg/L, and α-2-macroglobulin (A2M) 1.9 mg/L vs 3.6 mg/L, p <0.01. No differences in serum concentrations were present. A comparison between the transport slopes over time in both groups showed a positive time trend of mass transfer area coefficient (MTAC) creatinine (p = 0.03) and glucose absorption (p = 0.09) and a negative trend of transcapillary ultrafiltration (p = 0.06), when compared to the no peritonitis group. Frequent peritonitis did not affect free water transport. ♦ Slow initial peritoneal transport rates of serum proteins result in lower dialysate concentrations, and likely a lower opsonic activity, which is a risk factor for peritonitis. Patients with frequent peritonitis show an increase in small solute transport and a concomitant decrease of ultrafiltration. In long-term peritonitis-free PD patients, small solute transport decreased, while ultrafiltration increased. This suggests that frequent peritonitis leads to an increase of the vascular peritoneal surface area without all the structural membrane alterations that may develop after long-term PD. Copyright © 2016 International Society for Peritoneal Dialysis.

The Mutual Relationship Between Peritonitis and Peritoneal Transport

PubMed Central

van Esch, Sadie; van Diepen, Anouk T.N.; Struijk, Dirk G.; Krediet, Raymond T.

2016-01-01

♦ Background: Preservation of the peritoneum is required for long-term peritoneal dialysis (PD). We investigated the effect of multiple peritonitis episodes on peritoneal transport. ♦ Methods: Prospectively collected data from 479 incident PD patients treated between 1990 and 2010 were analyzed, using strict inclusion criteria: follow-up of at least 3 years with the availability of a Standard Peritoneal Permeability Analysis (SPA) in the first year after start of PD and within the third year of PD, without peritonitis preceding the first SPA. For the purpose of the study, we only included patients who remained peritonitis-free (n = 28) or who experienced 3 or more peritonitis episodes (n = 16). ♦ Results: At baseline the groups were similar with regard to small solute and fluid transport. However, the frequent peritonitis group had lower peritoneal protein clearances compared to the no peritonitis group, resulting in lower dialysate concentrations of proteins: albumin 196.5 mg/L vs 372.5 mg/L, IgG 36.4 mg/L vs 65.0 mg/L, and α-2-macroglobulin (A2M) 1.9 mg/L vs 3.6 mg/L, p <0.01. No differences in serum concentrations were present. A comparison between the transport slopes over time in both groups showed a positive time trend of mass transfer area coefficient (MTAC) creatinine (p = 0.03) and glucose absorption (p = 0.09) and a negative trend of transcapillary ultrafiltration (p = 0.06), when compared to the no peritonitis group. Frequent peritonitis did not affect free water transport. ♦ Conclusions: Slow initial peritoneal transport rates of serum proteins result in lower dialysate concentrations, and likely a lower opsonic activity, which is a risk factor for peritonitis. Patients with frequent peritonitis show an increase in small solute transport and a concomitant decrease of ultrafiltration. In long-term peritonitis-free PD patients, small solute transport decreased, while ultrafiltration increased. This suggests that frequent peritonitis leads to an increase of the vascular peritoneal surface area without all the structural membrane alterations that may develop after long-term PD. PMID:25395498

Definitions of differences and changes in peritoneal membrane water transport properties.

PubMed

Widerøe, T E; Smeby, L C; Dahl, K; Jörstad, S

1988-06-01

A survey is given comparing measurements of transperitoneal water transport in different clinical situations with analyses based on the so-called "pore theory." This model links the measured changes to physical alterations of the peritoneal membrane. The calculations include "equivalent pore radius," effective "membrane area" and diffusive length, the transport resistance of the unstirred dialysate layer, and the residual intraperitoneal volume after dialysate drainage. The clinical appearances include individual differences in transperitoneal transport characteristics, changes in transperitoneal transport over time on continuous ambulatory peritoneal dialysis (CAPD) and during peritonitis, the pharmacological effect on the transport properties, and the effect of peritoneal catheter dislocation on ultrafiltration capacity. The main conclusions are as follow: During CAPD treatment the measurement of intraperitoneal solute equilibration and "mass-transfer-area coefficients" for urea and creatinine is less sensitive than the measurement of ultrafiltration volume in revealing peritoneal membrane changes. Differences and changes found have mostly a combined physical explanation, but one is more or less dominant. Changes in peritoneal membrane area seem to be the most dominant cause of changes in transperitoneal transport during time on CAPD and when sodium nitroprusside was added to the peritoneal dialysate. Changes during peritonitis can be explained by changes in pore radius and depth. Individual differences can be explained by differences in "membrane" area and in resistance of the unstirred dialysate fluid. High residual dialysate volume can give rise to clinical problems and should be considered when placing the catheter in the peritoneal cavity.

Study to determine the technical and economic feasibility of reclaiming chemicals used in micellar polymer and low tension surfactant flooding. Final report. [Ultrafiltration membranes and reverse osmosis membranes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stephens, R.H.; Himmelblau, A.; Donnelly, R.G.

1978-02-01

Energy Resources Company has developed a technology for use with enhanced oil recovery to achieve emulsion breaking and surfactant recovery. By using ultrafiltration membranes, the Energy Resources Company process can dewater an oil-in-water type emulsion expected from enhanced oil recovery projects to the point where the emulsion can be inverted and treated using conventional emulsion-treating equipment. By using a tight ultrafiltration membrane or a reverse osmosis membrane, the Energy Resources Company process is capable of recovering chemicals such as surfactants used in micellar polymer flooding.

Treatment of silica effluents: ultrafiltration or coagulation-decantation.

PubMed

Ndiaye, P I; Moulin, P; Dominguez, L; Millet, J C; Charbit, F

2004-12-10

In the electronics industry, the preparation of silicon plates generates effluents that contain a great amount of colloidal silica. Two processes--decantation and ultrafiltration--are studied with in view the treatment of the effluents released by the firm Rockwood Electronic Materials. The feasibility of each of the two processes is studied separately and their operating parameters optimized. Both processes allow the recovery of a great proportion of the initial effluent (over 89%) as transparent and colorless water that can be reused at the start of a line. In view of the results and of the compared advantages and disadvantages of the two processes, ultrafiltration will be selected for the industrial unit.

[Ultrafiltration versus intravenous diuretics in decompensated heart failure: a meta-analysis of randomized controlled trials].

PubMed

Zhao, Yu-liang; Zhang, Ling; Yang, Ying-ying; Tang, Yi; Liu, Fang; Fu, Ping

2013-08-13

To explore whether ultrafiltration is superior to intravenous diuretics in ameliorating fluid overload and preserving renal functions in decompensated heart failure patients. By searching in Pubmed, Cochrane Library, Embase, Springer, WanFang, CQVIP, CNKI and CBM database as well as related Chinese journals, qualified randomized controlled trials (RCTs) were included for meta-analysis by Revman 5.0 and STATA 10.0. Six RCTs were included with 241 patients in ultrafiltration group and 240 patients in intravenous diuretics group. Pooled analyses demonstrated ultrafiltration was superior to intravenous diuretics in the aspects of weight loss (WMD = 1.44 kg, 95%CI:0.33-2.55 kg, P = 0.01) and fluid removal (WMD = 1.23 kg, 95%CI:0.63-1.82 kg, P < 0.01) while no significant difference was observed in serum creatinine level (WMD = -5.70 µmol/L, 95%CI: -35.02-23.61 µmol/L, P = 0.70), serum creatinine change from baseline (WMD = 4.74 µmol/L, 95%CI:-13.72-23.20 µmol/L, P = 0.61), mortality (RR = 1.09, 95%CI: 0.69-1.70, P = 0.72) or rehospitalization (RR = 0.92, 95%CI:0.53-1.61, P = 0.78). For decompensated heart failure patients, ultrafiltration is superior to intravenous diuretics in mitigating fluid overload. No intergroup difference was observed in renal function preservation, mortality or rehospitalization.

Removal of copper ions from aqueous solutions by means of micellar-enhanced ultrafiltration

NASA Astrophysics Data System (ADS)

Kowalska, Izabela; Klimonda, Aleksandra

2017-11-01

The aim of the study was to assess the usefulness of micellar-enhanced ultrafiltration (MEUF) for removal of copper ions from water solutions in comparison with classic ultrafiltration process. The tests were conducted in a semi-pilot membrane installation with the use of ultrafiltration module KOCH/ROMICON® at a transmembrane pressure of 0.05 MPa. The effect of concentration of copper ions on ultrafiltration process efficiency was investigated. The second part of the tests concerned the removal of copper ions by MEUF under wide range of anionic surfactant concentration (0.25, 1, and 5 CMC (critical micelle concentration)). Concentration of copper ions in model solutions was equal to 5, 20, and 50 mg Cu/L. Furthermore, the effect of surfactant leakage to the permeate side during filtration was evaluated. Conducted experiments confirmed effectiveness of MEUF in copper ions removal. For the highest copper concentration in the feed (i.e. 50 mg/L), the average concentration of copper ions in the permeate ranged from 1.2-4.7 mg Cu/L depending on surfactant concentration. During filtration experiments, UF module exhibited stable transport properties for model solutions containing copper. For the highest concentration of metal, the decrease of permeate flux did not exceed 11% after 60 minutes of filtration. In the presence of the surfactant, a slight deterioration of transport properties was observed.

Reexamining ultrafiltration and solute transport in groundwater

NASA Astrophysics Data System (ADS)

Neuzil, C. E.; Person, Mark

2017-06-01

Geologic ultrafiltration—slowing of solutes with respect to flowing groundwater—poses a conundrum: it is consistently observed experimentally in clay-rich lithologies, but has been difficult to identify in subsurface data. Resolving this could be important for clarifying clay and shale transport properties at large scales as well as interpreting solute and isotope patterns for applications ranging from nuclear waste repository siting to understanding fluid transport in tectonically active environments. Simulations of one-dimensional NaCl transport across ultrafiltering clay membrane strata constrained by emerging data on geologic membrane properties showed different ultrafiltration effects than have often been envisioned. In relatively high-permeability advection-dominated regimes, salinity increases occurred mostly within membrane units while their effluent salinity initially fell and then rose to match solute delivery. In relatively low-permeability diffusion-dominated regimes, salinity peaked at the membrane upstream boundary and effluent salinity remained low. In both scenarios, however, only modest salinity changes (up to ˜3 g L-1) occurred because of self-limiting tendencies; membrane efficiency declines as salinity rises, and although sediment compaction increases efficiency, it is also decreases permeability and allows diffusive transport to dominate. It appears difficult for ultrafiltration to generate brines as speculated, but widespread and less extreme ultrafiltration effects in the subsurface could be unrecognized. Conditions needed for ultrafiltration are present in settings that include topographically-driven flow systems, confined aquifer systems subjected to injection or withdrawal, compacting basins, and accretionary complexes.

Reexamining ultrafiltration and solute transport in groundwater

USGS Publications Warehouse

Neuzil, Christopher E.; Person, Mark

2017-01-01

Geologic ultrafiltration—slowing of solutes with respect to flowing groundwater—poses a conundrum: it is consistently observed experimentally in clay-rich lithologies, but has been difficult to identify in subsurface data. Resolving this could be important for clarifying clay and shale transport properties at large scales as well as interpreting solute and isotope patterns for applications ranging from nuclear waste repository siting to understanding fluid transport in tectonically active environments. Simulations of one-dimensional NaCl transport across ultrafiltering clay membrane strata constrained by emerging data on geologic membrane properties showed different ultrafiltration effects than have often been envisioned. In relatively high-permeability advection-dominated regimes, salinity increases occurred mostly within membrane units while their effluent salinity initially fell and then rose to match solute delivery. In relatively low-permeability diffusion-dominated regimes, salinity peaked at the membrane upstream boundary and effluent salinity remained low. In both scenarios, however, only modest salinity changes (up to ∼3 g L−1) occurred because of self-limiting tendencies; membrane efficiency declines as salinity rises, and although sediment compaction increases efficiency, it is also decreases permeability and allows diffusive transport to dominate. It appears difficult for ultrafiltration to generate brines as speculated, but widespread and less extreme ultrafiltration effects in the subsurface could be unrecognized. Conditions needed for ultrafiltration are present in settings that include topographically-driven flow systems, confined aquifer systems subjected to injection or withdrawal, compacting basins, and accretionary complexes.

Ceramic membrane fouling during ultrafiltration of oil/water emulsions: roles played by stabilization surfactants of oil droplets.

PubMed

Lu, Dongwei; Zhang, Tao; Ma, Jun

2015-04-07

Oil/water (O/W) emulsion stabilized by surfactants is the part of oily wastewater that is most difficult to handle. Ceramic membrane ultrafiltration presently is an ideal process to treat O/W emulsions. However, little is known about the fouling mechanism of the ceramic membrane during O/W emulsion treatment. This paper investigated how stabilization surfactants of O/W emulsions influence the irreversible fouling of ceramic membranes during ultrafiltration. An unexpected phenomenon observed was that irreversible fouling was much less when the charge of the stabilization surfactant of O/W emulsions is opposite to the membrane. The less ceramic membrane fouling in this case was proposed to be due to a synergetic steric effect and demulsification effect which prevented the penetration of oil droplets into membrane pores and led to less pore blockage. This proposed mechanism was supported by cross section images of fouled and virgin ceramic membranes taken with scanning electron microscopy, regression results of classical fouling models, and analysis of organic components rejected by the membrane. Furthermore, this mechanism was also verified by the existence of a steric effect and demulsification effect. Our finding suggests that ceramic membrane oppositely charged to the stabilization surfactant should be applied in ultrafiltration of O/W emulsions to alleviate irreversible membrane fouling. It could be a useful rule for ceramic membrane ultrafiltration of oily wastewater.

Flexographic newspaper deinking : treatment of wash filtrate effluent by membrane technology

Treesearch

B. Chabot; G.A. Krishnagopalan; S. Abubakr

1999-01-01

Ultrafiltration was investigated as a means to remove flexographic ink pigments from wash filtrate effluent generated from various mixtures of flexographic and offset old newspapers from deinking operations. Membrane separation efficiency was assessed from permeate flux, fouling rate, and ease of membrane regeneration (cleaning). Ultrafiltration was capable of...

NCL-01: Nanomedicine Drug Release Study in Human Plasma Using Stable Isotope Tracer Ultrafiltration Assay (SITUA)  | Frederick National Laboratory for Cancer Research

Cancer.gov

The Nanotechnology Characterization Laboratory will evaluate drug release from a nanoparticulate formulation in vitro in human plasma, using a novel stable isotope tracer ultrafiltration assay (SITUA) developed at the laboratory. The SITUA is a metho

EFFICIENT RECOVERY OF ENTEROCOCCI FROM MARINE AND FRESH WATER BEACHES BY A 30,000 MOLECULAR WEIGHT CUTOFF HOLLOW FIBER ULTRAFILTER

EPA Science Inventory

Ultrafiltration systems have been used to concentrate pathogens from various types of fresh water samples. However, less work has been done with marine waters for the concentration of pathogens or indicator bacteria. An ultrafiltration approach to concentrate indicator bacteria...

Coagulation pretreatment for ultrafiltration of deinking effluents containing flexographic inks

Treesearch

Bruno Chabot; Gopal A. Krishnagopalan; Said Abubakr

1999-01-01

This study was carried out to determine the potential of coagulation pretreatment with organic or inorganic coagulants to improve ultrafiltration performance during processing of wash deinking effluents containing flexographic inks. Wash filtrate effluents generated from mixtures of old flexographic and offset newspapers and old magazines were pretreated with a...

Evaluation of Hollow-Fiber Ultrafiltration Primary Concentration of Pathogens and Secondary Concentration of Viruses from Water

EPA Science Inventory

In this study, tangential hollow-fiber ultrafiltration (HFUF) was evaluated for virus and Cryptosporidium parvum concentration. Recovery of viruses at a low filtration rate was found to be significantly greater than at a higher filtration rate, with the recoveries of bacteriopha...

A Modified EPA Method 1623 that Uses Tangential Flow Hollow-Fiber Ultrafiltration and Heat Dissociation Steps to Detect Waterborne Cryptosporidum and Giardia spp.

EPA Science Inventory

This protocol describes the use of a tangential flow hollow-fiber ultrafiltration sample concentration system and a heat dissociation as alternative steps for the detection of waterborne Cryptosporidium and Giardia species using EPA Method 1623.

INVESTIGATION OF CONVENTIONAL MEMBRANE AND TANGENTIAL FLOW ULTRAFILTRATION ARTIFACTS AND THEIR APPLICATION TO THE CHARACTERIZATION OF FRESHWATER COLLOIDS

EPA Science Inventory

Artifacts associated with the fractionation of colloids in a freshwater sample were investigated for conventional membrane filtration (0.45 micron cutoff), and two tangential flow ultrafiltration cartridges (0.1 micron cutoff and 3000 MW cutoff). Membrane clogging during conventi...

Tumstatin peptide, an inhibitor of angiogenesis, prevents glomerular hypertrophy in the early stage of diabetic nephropathy.

PubMed

Yamamoto, Yoshihiko; Maeshima, Yohei; Kitayama, Hiroyuki; Kitamura, Shinji; Takazawa, Yuki; Sugiyama, Hitoshi; Yamasaki, Yasushi; Makino, Hirofumi

2004-07-01

In the early stage of diabetic nephropathy (one of the major microvascular complications of diabetes) glomerular hyperfiltration and hypertrophy are observed. It is clinically important to regulate glomerular hypertrophy for preventing glomerulosclerosis. The number of glomerular endothelial cells is known to be increased in diabetic nephropathy associated with enlarged glomerular tufts, suggesting that the mechanism is similar to that of angiogenesis. Tumstatin peptide is an angiogenesis inhibitor derived from type IV collagen and inhibits in vivo neovascularization induced by vascular endothelial growth factor (VEGF), one of the mediators of glomerular hypertrophy in diabetic nephropathy. Here, we show the effect of tumstatin peptide in inhibiting alterations in early diabetic nephropathy. Glomerular hypertrophy, hyperfiltration, and albuminuria were suppressed by tumstatin peptide (1 mg/kg) in streptozotocin-induced diabetic mice. Glomerular matrix expansion, the increase of total glomerular cell number and glomerular endothelial cells (CD31 positive), and monocyte/macrophage accumulation was inhibited by tumstatin peptide. Increase in renal expression of VEGF, flk-1, and angiopoietin-2, an antagonist of angiopoietin-1, was inhibited by tumstatin treatment in diabetic mice. Alteration of glomerular nephrin expression, a podocyte protein crucial for maintaining glomerular filtration barrier, was recovered by tumstatin in diabetic mice. Taken together, these results demonstrate the potential use of antiangiogenic tumstatin peptide as a novel therapeutic agent in early diabetic nephropathy.

Functional principal component analysis of glomerular filtration rate curves after kidney transplant.

PubMed

Dong, Jianghu J; Wang, Liangliang; Gill, Jagbir; Cao, Jiguo

2017-01-01

This article is motivated by some longitudinal clinical data of kidney transplant recipients, where kidney function progression is recorded as the estimated glomerular filtration rates at multiple time points post kidney transplantation. We propose to use the functional principal component analysis method to explore the major source of variations of glomerular filtration rate curves. We find that the estimated functional principal component scores can be used to cluster glomerular filtration rate curves. Ordering functional principal component scores can detect abnormal glomerular filtration rate curves. Finally, functional principal component analysis can effectively estimate missing glomerular filtration rate values and predict future glomerular filtration rate values.

Role of electrostatic interactions during protein ultrafiltration.

PubMed

Rohani, Mahsa M; Zydney, Andrew L

2010-10-15

A number of studies over the last decade have clearly demonstrated the importance of electrostatic interactions on the transport of charged proteins through semipermeable ultrafiltration membranes. This paper provides a review of recent developments in this field with a focus on the role of both protein and membrane charge on the rate of protein transport. Experimental results are analyzed using available theoretical models developed from the solution of the Poisson-Boltzmann equation for the partitioning of a charged particle into a charged pore. The potential of exploiting these electrostatic interactions for selective protein separations and for the development of ultrafiltration membranes with enhanced performance characteristics is also examined. Copyright © 2010 Elsevier B.V. All rights reserved.

[Pharmacokinetic properties of platinium derivatives].

PubMed

Boisdron-Celle, M; Lebouil, A; Allain, P; Gamelin, E

2001-08-01

The three platinum derivatives currently available share many pharmacokinetic and pharmacodynamic (PK-PD) properties but present also some distinct characteristics, due to their structural differences. They result in different systemic PK-PD and metabolic behaviour and toxicity profile. Oxaliplatin is quickly transformed into dach-platinum, the active metabolite, by loosing oxalate chain. Eighty to eighty-eight per cent of platinum are bound to proteins, as for cisplatin, whereas carboplatin is less reactive. Cisplatin and oxaliplatin active metabolites, i.e. monoaquo platin and dach-platin quickly react with small proteins with sulfhydryl groups, such as glutathione, cysteine and methionine, and then with high molecular weight proteins, such as albumin and gammaglobulins through covalent link. Thus, their terminal half lives are long, about ten days, but no platinum accumulation has been reported in plasma with oxaliplatin, whereas after cisplatin administration, both total and ultrafiltrable platinum progressively accumulate in plasma. This difference may play a role in the lack of oxaliplatin nephrotoxicity and its more delayed and reversible neurotoxicity. On the other hand, carboplatin is more stable, less bound to proteins and is largely excreted inchanged in urine. This can explain that it passes more easily through the blood brain barrier. Erythrocytes represent an important deep compartment, especially for oxaliplatin, a little bit less for cisplatin. Oxaliplatin is trapped in erythrocytes through a covalent binding to globin. There, its half life is identical to that of erythrocytes. According to certain authors, this trapping would be involved in the incidence of anemia. On the contrary, carboplatin is quickly extruded from erythrocytes. The three derivatives kinetics in plasma present a wide interindividual variability, resulting in differences in term of toxicity and efficacy. For the three of them, plasma clearance is correlated to creatinine clearance, but only carboplatin dosage can be individually adjusted, based on creatinine clearance measurement, thanks to its simple renal excretion, due to exclusive glomerular filtration, and after Calvert's, Egorin's and Chatelut's population kinetics studies. Cisplatin renal excretion is more complex, combining reabsorption and secretion processes. Therefore, individual dosage adjustment needs platinum concentration measurement in plasma, but there is no general agreement on the platinum species to measure, ultrafiltrable or bound. Oxaliplatin is too recent in clinical practice and still lacks of PK-PD data. These characteristics can help us for a better knowledge of the three platinum derivatives clinical properties, both in term of kinetics, behaviour and toxicity.

REMOVAL OF MICROBIAL CONTAMINANTS IN DRINKING WATER: KOCH MEMBRANE SYSTEMS, HF-82-35-PMPW™ ULTRAFILTRATION MEMBRANE

EPA Science Inventory

Two Koch Membrane Systems HF-82-35-PMPW ultrafiltration membrane cartridges were tested for removal of viruses, bacteria, and protozoan cysts at NSF’s Drinking Water Treatment Systems Laboratory. The ETV testing was conducted as part of a series of evaluations of the Expeditiona...

Structure and Activity of a New Low Molecular Weight Heparin Produced by Enzymatic Ultrafiltration

PubMed Central

FU, LI; ZHANG, FUMING; LI, GUOYUN; ONISHI, AKIHIRO; BHASKAR, UJJWAL; SUN, PEILONG; LINHARDT, ROBERT J.

2014-01-01

The standard process for preparing the low molecular weight heparin (LMWH) tinzaparin, through the partial enzymatic depolymerization of heparin, results in a reduced yield due to the formation of a high content of undesired disaccharides and tetrasaccharides. An enzymatic ultrafiltration reactor for LMWH preparation was developed to overcome this problem. The behavior, of the heparin oligosaccharides and polysaccharides using various membranes and conditions, was investigated to optimize this reactor. A novel product, LMWH-II, was produced from the controlled depolymerization of heparin using heparin lyase II in this optimized ultrafiltration reactor. Enzymatic ultrafiltration provides easy control and high yields (>80%) of LMWH-II. The molecular weight properties of LMWH-II were similar to other commercial LMWHs. The structure of LMWH-II closely matched heparin’s core structural features. Most of the common process artifacts, present in many commercial LWMHs, were eliminated as demonstrated by 1D and 2D nuclear magnetic resonance spectroscopy. The antithrombin III and platelet factor-4 binding affinity of LMWH-II were comparable to commercial LMWHs, as was its in vitro anticoagulant activity. PMID:24634007

Application of ultrafiltration in the pulp and paper industry: metals removal and whitewater reuse.

PubMed

Oliveira, C R; Silva, C M; Milanez, A F

2007-01-01

In the pulp and paper industry, the water use minimization is a constant target. One way to reduce water use is to recycle the effluent in a closed-cycle concept. In paper mills, the main source of liquid effluent is the so-called whitewater, which is the excess water, originated from pulp stock dewatering and other fibre contaminated water. This research studied the reuse of paper mill whitewater after membrane ultrafiltration (UF) in the paper machine and in the pulp bleach plant of an integrated mill. Contaminant removal and flux behaviour of the UF system were evaluated. The treatment by ultrafiltration was technically feasible and the treated whitewater had good potential to be reused in some processes in the paper machine. The reuse of ultrafiltered whitewater in the bleaching plant was not recommended because of the high level of soluble calcium present in this stream. Therefore, a combined treatment of the whitewater using the principle of precipitation and ultrafiltration was proposed showing good results and enabling the use of the treated whitewater in the bleach plant.

Preparation of ultrafiltration membrane by phase separation coupled with microwave irradiation

NASA Astrophysics Data System (ADS)

Suryani, Puput Eka; Purnama, Herry; Susanto, Heru

2015-12-01

Preparation of low fouling ultrafiltration membrane is still a big challenge in the membrane field. In this paper, polyether sulfone (PES) ultrafiltration membranes were prepared by non-solvent-induced phase separation (NIPS) coupled with microwave irradiation. Polyethylene glycol (PEG) and polyethylene glycol methacrylate (PEGMA) were used as additives to improve membrane hydrophilicity. In this study, the concentration of additive, irradiation time and microwave power was varied. The membranes were characterized by scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy, while the performances were tested by adsorptive and ultrafiltration fouling experiments. The results show that the irradiation time and irradiation power are very important parameter that influence the membrane characteristic. In addition, type and concentration of additive are other important parameters. The results suggest that microwave irradiation is the most important parameter influencing the membrane characteristic. Both pure water flux and fouling resistance increase with increasing irradiation time, power irradiation, and additive concentration. PES membrane with addition of 10% w/w PEG and irradiated by 130 W microwave power for 180 seconds is the best membrane performance.

Research on the experiment of reservoir water treatment applying ultrafiltration membrane technology of different processes.

PubMed

Zhang, Liyong; Zhang, Penghui; Wang, Meng; Yang, Kai; Liu, Junliang

2016-09-01

The processes and effects of coagulation-ultrafiltration (C-UF) and coagulation sedimentation-ultrafiltration (CS-UF) process used in the treatment of Dalangdian Reservoir water were compared. The experiment data indicated that 99% of turbidity removal and basically 100% of microorganism and algae removal were achieved in both C-UF and CS-UF process. The organic removal effect of CS-UF? process was slightly better than C-UF process. However, the organic removal effect under different processes was not obvious due to limitation of ultrafiltration membrane aperture. Polyaluminium chloride was taken as a coagulant in water plant. The aluminum ion removal result revealed that coagulant dosage was effectively saved by using membrane technology during megathermal high algae laden period. Within the range of certain reagent concentration and soaking time, air-water backwashing of every filtration cycle of membrane was conducted to effectively reduce membrane pollution. Besides, maintenance cleaning was conducted every 60 min. whether or not restorative cleaning was conducted depends on the pollution extent. After cleaning, recovery of membrane filtration effect was obvious.

Venoarterial modified ultrafiltration versus conventional arteriovenous modified ultrafiltration during cardiopulmonary bypass surgery.

PubMed

Mohanlall, Rakesh; Adam, Jamila; Nemlander, Arto

2014-01-01

Different types of modified ultrafiltration (MUF) systems evaluated showed that none of the MUF techniques adhered to the normal venous to arterial blood flow dynamics. This study compared a conventional arteriovenous modified ultrafiltration (AVMUF) system to a custom- designed venoarterial modified ultrafiltration (VAMUF) system. Randomized, controlled clinical study conducted at the Northwest Armed Forces Military hospital in Tabuk, Saudi Arabia. Sixty patients who underwent MUF during the years 2007 and 2009 were divided into 2 groups: the AVMUF (n=30) and the VAMUF (n=30) groups. MUF was performed for a mean time of 12 minutes in both groups. In AVMUF, blood was removed from the aorta, hemoconcentrated, and infused into the right atrium (RA). In VAMUF, blood flow was from the RA through a hemoconcentrator and re-infused into the aorta. Results of the study showed that the VAMUF group required a shorter ventilation time (P < .001), in.tensive care unit (ICU) (P=.003), and hospital stay (P=.007) than the AVMUF group. Results also demonstrated a lower percentage of fluid balance (P=.008) in the VAMUF group. The systolic (P < .001) and mean blood pres.sures (P < .001) were significantly higher after VAMUF, with a decrease in heart rate (P < .001) and central venous pressure (P=.002). The VAMUF group showed a significantly greater decrease of creatinine (P < .001), serum lactacte (P < .001), and uric acid (P < .027) over time with no significant differences in oximetry. Results prove that VAMUF is a more physiological technique than AVMUF.

Global Analysis Reveals the Complexity of the Human Glomerular Extracellular Matrix

PubMed Central

Byron, Adam; Humphries, Jonathan D.; Randles, Michael J.; Carisey, Alex; Murphy, Stephanie; Knight, David; Brenchley, Paul E.; Zent, Roy; Humphries, Martin J.

2014-01-01

The glomerulus contains unique cellular and extracellular matrix (ECM) components, which are required for intact barrier function. Studies of the cellular components have helped to build understanding of glomerular disease; however, the full composition and regulation of glomerular ECM remains poorly understood. We used mass spectrometry-based proteomics of enriched ECM extracts for a global analysis of human glomerular ECM in vivo and identified a tissue-specific proteome of 144 structural and regulatory ECM proteins. This catalog includes all previously identified glomerular components plus many new and abundant components. Relative protein quantification showed a dominance of collagen IV, collagen I, and laminin isoforms in the glomerular ECM together with abundant collagen VI and TINAGL1. Protein network analysis enabled the creation of a glomerular ECM interactome, which revealed a core of highly connected structural components. More than one half of the glomerular ECM proteome was validated using colocalization studies and data from the Human Protein Atlas. This study yields the greatest number of ECM proteins relative to previous investigations of whole glomerular extracts, highlighting the importance of sample enrichment. It also shows that the composition of glomerular ECM is far more complex than previously appreciated and suggests that many more ECM components may contribute to glomerular development and disease processes. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium with the dataset identifier PXD000456. PMID:24436468

Cell biology of mesangial cells: the third cell that maintains the glomerular capillary.

PubMed

Kurihara, Hidetake; Sakai, Tatsuo

2017-03-01

The renal glomerulus consists of glomerular endothelial cells, podocytes, and mesangial cells, which cooperate with each other for glomerular filtration. We have produced monoclonal antibodies against glomerular cells in order to identify different types of glomerular cells. Among these antibodies, the E30 clone specifically recognizes the Thy1.1 molecule expressed on mesangial cells. An injection of this antibody into rats resulted in mesangial cell-specific injury within 15 min, and induced mesangial proliferative glomerulonephritis in a reproducible manner. We examined the role of mesangial cells in glomerular function using several experimental tools, including an E30-induced nephritis model, mesangial cell culture, and the deletion of specific genes. Herein, we describe the characterization of E30-induced nephritis, formation of the glomerular capillary network, mesangial matrix turnover, and intercellular signaling between glomerular cells. New molecules that are involved in a wide variety of mesangial cell functions are also introduced.

Solution of Algebraic Equations in the Analysis, Design, and Optimization of Continuous Ultrafiltration

ERIC Educational Resources Information Center

Foley, Greg

2011-01-01

Continuous feed and bleed ultrafiltration, modeled with the gel polarization model for the limiting flux, is shown to provide a rich source of non-linear algebraic equations that can be readily solved using numerical and graphical techniques familiar to undergraduate students. We present a variety of numerical problems in the design, analysis, and…

Removal of Viruses in Drinking Water- Ultrafiltration Module with a Cut Fiber, Dow Chemical Company - Dow Water & Process Solutions, SFD-2880 - Ultrafiltration Module

EPA Science Inventory

The purpose of this verification was a cut fiber challenge study for the Dow Chemical Company SFD-2880 UF membrane module. MS2 coliphage virus was the surrogate challenge organism. The challenge tests followed the requirements of the Department of Health Victoria (Australia) Dr...

Hydrophobic asymmetric ultrafiltration PVDF membranes: an alternative separator for VFB with excellent stability.

PubMed

Wei, Wenping; Zhang, Huamin; Li, Xianfeng; Zhang, Hongzhang; Li, Yun; Vankelecom, Ivo

2013-02-14

Polyvinylidene fluoride (PVDF) ultrafiltration membranes were investigated for the first time in vanadium redox flow battery (VFB) applications. Surprisingly, PVDF ultrafiltration membranes with hydrophobic pore walls and relatively large pore sizes of several tens of nanometers proved able to separate vanadium ions and protons efficiently, thus being suitable as a VFB separator. The ion selectivity of this new type of VFB membrane could be tuned readily by controlling the membrane morphology via changes in the composition of the membrane casting solution, and the casting thickness. The results showed that the PVDF membranes offered good performances and excellent stability in VFB applications, where it could, performance-wise, truly substitute Nafion in VFB applications, but at a much lower cost.

Characterization of Natural Organic Matter in Conventional Water Treatment Processes and Evaluation of THM Formation with Chlorine

PubMed Central

Özdemır, Kadir

2014-01-01

This study investigates the fractions of natural organic matter (NOM) and trihalomethane (THM) formation after chlorination in samples of raw water and the outputs from ozonation, coagulation-flocculation, and conventional filtration treatment units. All the water samples are passed through various ultrafiltration (UF) membranes. UF membranes with different molecular size ranges based on apparent molecular weight (AMW), such as 1000, 3000, 10,000, and 30,000 Daltons (Da), are commonly used. The NOM fraction with AMW < 1000 Da (1 K) is the dominant fraction within all the fractionated water samples. Its maximum percentage is 85.86% after the filtration process and the minimum percentage is 65.01% in raw water samples. The total THM (TTHM) yield coefficients range from 22.5 to 42 μg-TTHM/mg-DOC in all fractionated samples, which is related to their specific ultraviolet Absorbance (SUVA) levels. As the molecular weight of the fractions decreased, the TTHM yield coefficients increased. The NOM fractions with AMW values less than 1 K had lower SUVA values (<3 L/mg·m) for all treatment stages and also they had higher yield of TTHM per unit of DOC. The NOM fraction with AMW < 1 K for chlorinated raw water samples has the highest yield coefficient (42 μg-TTHM/mg-DOC). PMID:24558323

Clinicopathological study of glomerular diseases associated with sarcoidosis: a multicenter study

PubMed Central

2013-01-01

Background The association between sarcoidosis and glomerular diseases has not been extensively investigated in a large series and the potential features of this uncommon association remain to be determined. Methods We retrospectively identified 26 patients with biopsy-proven glomerular lesions that occurred in a sarcoidosis context. Potential remission of glomerular disease and sarcoidosis under specific treatment (steroid and/or immunosuppressive agents) was recorded for all patients. Demographic, clinical and biological characteristics were assessed at the time of kidney biopsy for each patient. Therapeutic data were analyzed for all patients. Results Glomerular disease occurred after the diagnosis of sarcoidosis in 11 of 26 cases (42%) (mean delay of 9.7 years). In six patients (23%), the glomerulopathy preceded the sarcoidosis diagnosis (mean delay 8 years). In the last nine patients (35%), both conditions occurred simultaneously. The most frequent glomerular disease occurring in sarcoidosis patients was membranous nephropathy in eleven cases. Other glomerular lesions included IgA nephropathy in six cases, focal segmental glomerulosclerosis in four patients, minimal change nephrotic syndrome for three patients and proliferative lupus nephritis in two patients. Granulomatous interstitial nephritis was associated with glomerular disease in six patients and was exclusively found in patients in whom the both disease occurred simultaneously. In nine patients with simultaneous glomerular and sarcoidosis diseases, we observed a strong dissociation between glomerular disease and sarcoidosis in terms of steroid responsiveness. At the end of the follow-up (mean of 8.4 years), six patients had reached end-stage renal disease and three patients had died. Conclusions A wide spectrum of glomerular lesions is associated with sarcoidosis. The close temporal relationship observed in some patients suggests common causative molecular mechanisms of glomerular injury but complete remission of both diseases in response to exclusive steroid therapy is infrequent. PMID:23631446

Concentration polarization of hyaluronan on the surface of the synovial lining of infused joints

PubMed Central

Lu, Y; Levick, JR; Wang, W

2004-01-01

Hyaluronan (HA) in joints conserves the lubricating synovial fluid by making trans-synovial fluid escape almost insensitive to pressure elevation (e.g. effusions, joint flexion). This phenomenon, ‘outflow buffering’, was discovered during HA infusion into the rabbit knee joint cavity. It was also found that HA is partially reflected by the joint lining (molecular sieving), and that the reflected fraction R decreases as trans-synovial filtration rate Q is increased. It was postulated therefore that outflow buffering is mediated by HA reflection. Reflection creates a HA concentration polarization layer, the osmotic pressure of which opposes fluid loss. A steady-state, cross-flow ultrafiltration model was previously used to explain the outflow buffering and negative R-vs.-Q relation. However, the steady-state, cross-perfusion assumptions restricted the model's applicability for an infused, dead-end cavity or a non-infused joint during cyclical motion. We therefore developed a new, non-steady-state model which describes the time course of dead-end, partial HA ultrafiltration. The model describes the progressive build-up of a HA concentration polarization layer at the synovial surface over time. Using experimental parameter values, the model successfully accounts for the observed negative R-vs.-Q relation and shows that the HA reflected fraction (R) also depends on HA diffusivity, membrane area expansion and the synovial HA reflection coefficient. The non-steady-state model thus explains existing experimental work, and it is a key stage in understanding synovial fluid turnover in intact, moving, human joints or osteoarthritic joints treated by HA injections. PMID:15579541

An enquiry on appropriate selection of polymers for preparation of polymeric nanosorbents and nanofiltration/ultrafiltration membranes for hormone micropollutants removal from water effluents.

PubMed

Khansary, Milad Asgarpour; Mellat, Mostafa; Saadat, Seyed Hassan; Fasihi-Ramandi, Mahdi; Kamali, Mehdi; Taheri, Ramezan Ali

2017-02-01

To analyze polymeric nanosorbents and nanofiltration/ultrafiltration membranes for hormone micropollutants removal from water effluents, here an in-through investigation on the suitability and compatibility of various polymers has been carried out. For this work, estradiol, estrone, testosterone, progesterone, estriol, mestranol, and ethinylestradiol were considered. A total number of 452 polymers were analyzed and initially screened using Hansen solubility parameters. The identified good pairs of hormones and polymers then were examined to obtain the equilibrium capacity of hormones removal from water effluents using a modified Flory-Huggins model. A distribution coefficient was defined as the ratio of hormones in water effluent phase and polymer phase. For removal of mestranol, estradiol and ethinylestradiol, no compatible polymer was identified based on initial screening of collected database. Three compatible polymers were identified for estriol. For progesterone, a wide variety of polymers was identified as good matching of polar, dispersion and hydrogen forces contributions can be observed for these pairs. For estrone, only two polymers can be proposed due to the mismatch observed between polar, dispersion and hydrogen forces contributions of other polymers and this hormone. The phase calculations showed that not all the identified good pairs could be used for practical separation applications. The domain of applicability of each good pair was investigated and potential polymers for practical micropollutants removal together with their removal capacity were represented in terms of phase envelops. The theoretical approach follows fundamental chemical thermodynamic equations and then can be simply applied for any system of interest. Copyright © 2016 Elsevier Ltd. All rights reserved.

The impact of dialysis solution biocompatibility on ultrafiltration and on free water transport in rats.

PubMed

Aubertin, Gaëlle; Choquet, Philippe; Dheu, Céline; Constantinesco, André; Ratomponirina, Charline; Zaloszyc, Ariane; Passlick-Deetjen, Jutta; Fischbach, Michel

2012-01-01

This study compares different peritoneal dialysis fluids (PDF) in rats over a short contact time. For greater accuracy, net ultrafiltration (UF) and peritoneal transport indices, mass transfer area coefficient (MTAC) were scaled for the in vivo peritoneal surface area recruited (ivPSA) measured by microcomputerized tomography. Wistar rats underwent nephrectomy (5/6ths), were randomized into two groups and given 1.5% glucose PDF, either conventional acidic lactate (n = 14) or pH neutral bicarbonate (BicaVera) (n = 13); MTAC and UF were measured using a 90-min peritoneal equilibrium test (PET), fill volume (IPV) of 10 ml/100 g; small pore fluid transport was determined from sodium balance and used to calculate free water transport (FWT). Each ivPSA value was significantly correlated with the actual IPV, which varied from one rat to another. At 90 min of contact, there was no difference in recruited ivPSA in relation to PDFs. There was a difference (p < 0.01) in net UF/ivPSA 0.45 vs. 1.41 cm(2)/ml for bicarbonate versus lactate, as there was in the proportion of FWT with bicarbonate (42 ± 5% of net UF) compared to lactate (29 ± 4% of net UF). Net UF for individual values of ivPSA differs between conventional PDF and more biocompatible solutions, such as bicarbonate PDF. This observed change in UF cannot be fully explained by differences in glucose transport. The changes in FWT may be explained by the impact of the PDF biocompatibility on aquaporin function.

Documentation of angiotensin II receptors in glomerular epithelial cells

NASA Technical Reports Server (NTRS)

Sharma, M.; Sharma, R.; Greene, A. S.; McCarthy, E. T.; Savin, V. J.; Cowley, A. W. (Principal Investigator)

1998-01-01

Angiotensin II decreases glomerular filtration rate, renal plasma flow, and glomerular capillary hydraulic conductivity. Although angiotensin II receptors have been demonstrated in mesangial cells and proximal tubule cells, the presence of angiotensin II receptors in glomerular epithelial cells has not previously been shown. Previously, we have reported that angiotensin II caused an accumulation of cAMP and a reorganization of the actin cytoskeleton in cultured glomerular epithelial cells. Current studies were conducted to verify the presence of angiotensin II receptors by immunological and non-peptide receptor ligand binding techniques and to ascertain the activation of intracellular signal transduction in glomerular epithelial cells in response to angiotensin II. Confluent monolayer cultures of glomerular epithelial cells were incubated with angiotensin II, with or without losartan and/or PD-123,319 in the medium. Membrane vesicle preparations were obtained by homogenization of washed cells followed by centrifugation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of membrane proteins followed by multiscreen immunoblotting was used to determine the presence of angiotensin II receptor type 1 (AT1) or type 2 (AT2). Angiotensin II-mediated signal transduction in glomerular epithelial cells was studied by measuring the levels of cAMP, using radioimmunoassay. Results obtained in these experiments showed the presence of both AT1 and AT2 receptor types in glomerular epithelial cells. Angiotensin II was found to cause an accumulation of cAMP in glomerular epithelial cells, which could be prevented only by simultaneous use of losartan and PD-123,319, antagonists for AT1 and AT2, respectively. The presence of both AT1 and AT2 receptors and an increase in cAMP indicate that glomerular epithelial cells respond to angiotensin II in a manner distinct from that of mesangial cells or proximal tubular epithelial cells. Our results suggest that glomerular epithelial cells participate in angiotensin II-mediated control of the glomerular filtration barrier.

Head-to-head comparison of B-type natriuretic peptide (BNP) and NT-proBNP in daily clinical practice.

PubMed

Mair, Johannes; Gerda, Falkensammer; Renate, Hiemetzberger; Ulmer, Hanno; Andrea, Griesmacher; Pachinger, Otmar

2008-02-29

B-type natriuretic peptide (BNP; Abbott Diagnostics) and N-terminal proBNP (NT-proBNP, Roche Diagnostics) were compared in consecutive samples of 458 patients (mean age 60 years+/-16 years; 159 female, 299 male) sent for NT-proBNP measurement to investigate influences on both markers. BNP and NT-proBNP showed a close correlation with each other (r=0.89, p<0.0001). Using age- and gender-adjusted upper reference values the inter-rater agreement of both parameters was satisfactory (83%, Cohen's kappa coefficient=0.7). The combination of normal BNP and elevated NT-proBNP was significantly more frequent than vice versa (61 vs. 16 patients), and a calculated glomerular filtration rate<60 ml/min/1.73 m(2) was found in 39% of these patients. Multiple linear regression analysis revealed a significant influence of a reduced ejection fraction (<50%), renal dysfunction (calculated glomerular filtration rate<60 ml/min/1.73 m(2)), anemia, hypertension, age, and gender on both BNP and NT-proBNP. In conclusion, despite a close correlation and a satisfactory agreement between both markers in classification, frequent discrepancies in individual patients demonstrate that both markers are clinically not completely equivalent.

Determination of total and unbound concentrations of lopinavir in plasma using liquid chromatography-tandem mass spectrometry and ultrafiltration methods.

PubMed

Illamola, S M; Labat, L; Benaboud, S; Tubiana, R; Warszawski, J; Tréluyer, J M; Hirt, D

2014-08-15

Lopinavir is an HIV protease inhibitor with high protein binding (98-99%) in human plasma. This study was designed to develop an ultrafiltration method to measure the unbound concentrations of lopinavir overcoming the non-specific binding issue. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of total concentrations of lopinavir in plasma was developed and validated, and an adaptation was also optimized and validated for the determination of unbound concentrations. The chromatographic separation was performed with a C18 column (100 mm × 2.1mm i.d., 5 μm particle size) using a mobile phase containing deionized water with formic acid, and acetonitrile, with gradient elution at a flow-rate of 350 μL min(-1). Identification of the compounds was performed by multiple reaction monitoring, using electrospray ionization in positive ion mode. The method was validated over a clinical range of 0.01-1 μg/mL for human plasma ultrafiltrate and 0.1-15 μg/mL in human plasma. The inter and intra-assay accuracies and precisions were between 0.23% and 11.37% for total lopinavir concentrations, and between 3.50% and 13.30% for plasma ultrafiltrate (unbound concentration). The ultrafiltration method described allows an accurate separation of the unbound fraction of lopinavir, circumscribing the loss of drug by nonspecific binding (NSB), and the validated LC-MS/MS methodology proposed is suitable for the determination of total and unbound concentrations of lopinavir in clinical practice. Copyright © 2014 Elsevier B.V. All rights reserved.

Measurement of Murine Single-Kidney Glomerular Filtration Rate Using Dynamic Contrast-Enhanced MRI.

PubMed

Jiang, Kai; Tang, Hui; Mishra, Prasanna K; Macura, Slobodan I; Lerman, Lilach O

2018-06-01

To develop and validate a method for measuring murine single-kidney glomerular filtration rate (GFR) using dynamic contrast-enhanced MRI (DCE-MRI). This prospective study was approved by the Institutional Animal Care and Use Committee. A fast longitudinal relaxation time (T 1 ) measurement method was implemented to capture gadolinium dynamics (1 s/scan), and a modified two-compartment model was developed to quantify GFR as well as renal perfusion using 16.4T MRI in mice 2 weeks after unilateral renal artery stenosis (RAS, n = 6) or sham (n = 8) surgeries. This approach was validated by comparing model-derived GFR and perfusion to those obtained by fluorescein isothiocyanante (FITC)-inulin clearance and arterial spin labeling (ASL), respectively, using the Pearson's and Spearman's rank correlations and Bland-Altman analysis. The compartmental model provided a good fitting to measured gadolinium dynamics in both normal and RAS kidneys. The proposed DCE-MRI method offered assessment of single-kidney GFR and perfusion, comparable to the FITC-inulin clearance (Pearson's correlation coefficient r = 0.95 and Spearman's correlation coefficient ρ = 0.94, P < 0.0001, and mean difference -7.0 ± 11.0 μL/min) and ASL (r = 0.92 and ρ = 0.84, P < 0.0001, and mean difference 4.4 ± 66.1 mL/100 g/min) methods. The proposed DCE-MRI method may be useful for reliable noninvasive measurements of single-kidney GFR and perfusion in mice. Magn Reson Med 79:2935-2943, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

[Concordance of glomerular filtration rate with creatinine clearance in 24-hour urine and Schwartz and Schwartz updated].

PubMed

Salazar-Gutiérrez, María Luisa; Ochoa-Ponce, Cristina; Lona-Reyes, Juan Carlos; Gutiérrez-Íñiguez, Sara Ivonne

Reference methods for the quantification of the glomerular filtration rate (GFR) are difficult to use in clinical practice; formulas for evaluating GFR based on serum creatinine (SCr) and/or creatinine clearance are used. The aim of this study was to quantify the correlation and concordance of GFR with creatinine clearance in 24-hour urine (GFR24) and Schwartz and Schwartz updated formulas. Cross-sectional study involving healthy pediatric patients and with chronic kidney disease (CKD) from 5 to 16.9 years. Linear correlation between GFR 24 and two formulas was evaluated with the Pearson correlation coefficient (r) and intraclass correlation coefficient (ICC). We studied 134 patients, of which 59.7% were male. Mean age was 10.8 years. The average GFR24 was 140.34ml/min/1.73m 2 ; 34.3% (n=46) had GFR <90ml/min/1.73m 2 . Moderate linear correlation between GFR24 and Schwartz (r= 0.63) and Schwartz updated (r= 0.65) formulas was observed. There was good concordance between the GFR24 and Schwartz (ICC= 0.77) and updated Schwartz (ICC= 0.77) formulas. Schwartz classical formula in patients with GFR24 ≥ 90ml/min/1.73m 2 estimated higher values, while Schwartz updated underestimated values. There is moderate correlation and good concordance between the GFR24 and Schwartz and Schwartz updated formulas. The concordance was better in patients with obesity and lower in women, patients with hyperfiltration and normal weight. Copyright © 2016 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Estimating glomerular filtration rate in black South Africans by use of the modification of diet in renal disease and Cockcroft-Gault equations.

PubMed

van Deventer, Hendrick E; George, Jaya A; Paiker, Janice E; Becker, Piet J; Katz, Ivor J

2008-07-01

The 4-variable Modification of Diet in Renal Disease (4-v MDRD) and Cockcroft-Gault (CG) equations are commonly used for estimating glomerular filtration rate (GFR); however, neither of these equations has been validated in an indigenous African population. The aim of this study was to evaluate the performance of the 4-v MDRD and CG equations for estimating GFR in black South Africans against measured GFR and to assess the appropriateness for the local population of the ethnicity factor established for African Americans in the 4-v MDRD equation. We enrolled 100 patients in the study. The plasma clearance of chromium-51-EDTA ((51)Cr-EDTA) was used to measure GFR, and serum creatinine was measured using an isotope dilution mass spectrometry (IDMS) traceable assay. We estimated GFR using both the reexpressed 4-v MDRD and CG equations and compared it to measured GFR using 4 modalities: correlation coefficient, weighted Deming regression analysis, percentage bias, and proportion of estimated GFR within 30% of measured GFR (P(30)). The Spearman correlation coefficient between measured and estimated GFR for both equations was similar (4-v MDRD R(2) = 0.80 and CG R(2) = 0.79). Using the 4-v MDRD equation with the ethnicity factor of 1.212 as established for African Americans resulted in a median positive bias of 13.1 (95% CI 5.5 to 18.3) mL/min/1.73 m(2). Without the ethnicity factor, median bias was 1.9 (95% CI -0.8 to 4.5) mL/min/1.73 m(2). The 4-v MDRD equation, without the ethnicity factor of 1.212, can be used for estimating GFR in black South Africans.

Estimating equations for glomerular filtration rate in the era of creatinine standardization: a systematic review.

PubMed

Earley, Amy; Miskulin, Dana; Lamb, Edmund J; Levey, Andrew S; Uhlig, Katrin

2012-06-05

Clinical laboratories are increasingly reporting estimated glomerular filtration rate (GFR) by using serum creatinine assays traceable to a standard reference material. To review the performance of GFR estimating equations to inform the selection of a single equation by laboratories and the interpretation of estimated GFR by clinicians. A systematic search of MEDLINE, without language restriction, between 1999 and 21 October 2011. Cross-sectional studies in adults that compared the performance of 2 or more creatinine-based GFR estimating equations with a reference GFR measurement. Eligible equations were derived or reexpressed and validated by using creatinine measurements traceable to the standard reference material. Reviewers extracted data on study population characteristics, measured GFR, creatinine assay, and equation performance. Eligible studies compared the MDRD (Modification of Diet in Renal Disease) Study and CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations or modifications thereof. In 12 studies in North America, Europe, and Australia, the CKD-EPI equation performed better at higher GFRs (approximately >60 mL/min per 1.73 m(2)) and the MDRD Study equation performed better at lower GFRs. In 5 of 8 studies in Asia and Africa, the equations were modified to improve their performance by adding a coefficient derived in the local population or removing a coefficient. Methods of GFR measurement and study populations were heterogeneous. Neither the CKD-EPI nor the MDRD Study equation is optimal for all populations and GFR ranges. Using a single equation for reporting requires a tradeoff to optimize performance at either higher or lower GFR ranges. A general practice and public health perspective favors the CKD-EPI equation. Kidney Disease: Improving Global Outcomes.

Genetic Ablation of Calcium-independent Phospholipase A2γ Induces Glomerular Injury in Mice*

PubMed Central

Elimam, Hanan; Papillon, Joan; Kaufman, Daniel R.; Guillemette, Julie; Aoudjit, Lamine; Gross, Richard W.; Takano, Tomoko; Cybulsky, Andrey V.

2016-01-01

Glomerular visceral epithelial cells (podocytes) play a critical role in the maintenance of glomerular permselectivity. Podocyte injury, manifesting as proteinuria, is the cause of many glomerular diseases. We reported previously that calcium-independent phospholipase A2γ (iPLA2γ) is cytoprotective against complement-mediated glomerular epithelial cell injury. Studies in iPLA2γ KO mice have demonstrated an important role for iPLA2γ in mitochondrial lipid turnover, membrane structure, and metabolism. The aim of the present study was to employ iPLA2γ KO mice to better understand the role of iPLA2γ in normal glomerular and podocyte function as well as in glomerular injury. We show that deletion of iPLA2γ did not cause detectable albuminuria; however, it resulted in mitochondrial structural abnormalities and enhanced autophagy in podocytes as well as loss of podocytes in aging KO mice. Moreover, after induction of anti-glomerular basement membrane nephritis in young mice, iPLA2γ KO mice exhibited significantly increased levels of albuminuria, podocyte injury, and loss of podocytes compared with wild type. Thus, iPLA2γ has a protective functional role in the normal glomerulus and in glomerulonephritis. Understanding the role of iPLA2γ in glomerular pathophysiology provides opportunities for the development of novel therapeutic approaches to glomerular injury and proteinuria. PMID:27226532

Podocytes regulate the glomerular basement membrane protein nephronectin by means of miR-378a-3p in glomerular diseases.

PubMed

Müller-Deile, Janina; Dannenberg, Jan; Schroder, Patricia; Lin, Meei-Hua; Miner, Jeffrey H; Chen, Rongjun; Bräsen, Jan-Hinrich; Thum, Thomas; Nyström, Jenny; Staggs, Lynne Beverly; Haller, Hermann; Fiedler, Jan; Lorenzen, Johan M; Schiffer, Mario

2017-10-01

The pathophysiology of many proteinuric kidney diseases is poorly understood, and microRNAs (miRs) regulation of these diseases has been largely unexplored. Here, we tested whether miR-378a-3p is a novel regulator of glomerular diseases. MiR-378a-3p has two predicted targets relevant to glomerular function, the glomerular basement membrane matrix component, nephronectin (NPNT), and vascular endothelial growth factor VEGF-A. In zebrafish (Danio rerio), miR-378a-3p mimic injection or npnt knockdown by a morpholino oligomer caused an identical phenotype consisting of edema, proteinuria, podocyte effacement, and widening of the glomerular basement membrane in the lamina rara interna. Zebrafish vegf-A protein could not rescue this phenotype. However, mouse Npnt constructs containing a mutated 3'UTR region prevented the phenotype caused by miR-378a-3p mimic injection. Overexpression of miR-378a-3p in mice confirmed glomerular dysfunction in a mammalian model. Biopsies from patients with focal segmental glomerulosclerosis and membranous nephropathy had increased miR-378a-3p expression and reduced glomerular levels of NPNT. Thus, miR-378a-3p-mediated suppression of the glomerular matrix protein NPNT is a novel mechanism for proteinuria development in active glomerular diseases. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

ENVIRONMENTAL TECHNOLOGY VERIFICATION REPORT - PHYSICAL REMOVAL OF PARTICULATE CONTAMINANTS IN DRINKING WATER: POLYMEM UF 120 S2 ULTRAFILTRATION MEMBRANE MODULE, LUXENBURG, WISCONSIN

EPA Science Inventory

Verification testing of the Polymem UF120 S2 Ultrafiltration Membrane Module was conducted over a 46-day period at the Green Bay Water Utility Filtration Plant, Luxemburg, Wisconsin. The ETV testing described herein was funded in conjunction with a 12-month membrane pilot study f...

Nutrient Recovery from the Dry Grind Process Using Sequential Micro and Ultrafiltration of Thin Stillage

USDA-ARS?s Scientific Manuscript database

The effectiveness of microfiltration (MF) and ultrafiltration (UF) for nutrient recovery from a thin stillage stream was determined. When a stainless steel MF membrane (0.1 um pore size) was used, the content of solids increased from 7.0% to 22.8% with a mean permeate flux rate of 45 L/m**2/h (LMH)...

Structure and activity of a new low-molecular-weight heparin produced by enzymatic ultrafiltration.

PubMed

Fu, Li; Zhang, Fuming; Li, Guoyun; Onishi, Akihiro; Bhaskar, Ujjwal; Sun, Peilong; Linhardt, Robert J

2014-05-01

The standard process for preparing the low-molecular-weight heparin (LMWH) tinzaparin, through the partial enzymatic depolymerization of heparin, results in a reduced yield because of the formation of a high content of undesired disaccharides and tetrasaccharides. An enzymatic ultrafiltration reactor for LMWH preparation was developed to overcome this problem. The behavior, of the heparin oligosaccharides and polysaccharides using various membranes and conditions, was investigated to optimize this reactor. A novel product, LMWH-II, was produced from the controlled depolymerization of heparin using heparin lyase II in this optimized ultrafiltration reactor. Enzymatic ultrafiltration provides easy control and high yields (>80%) of LMWH-II. The molecular weight properties of LMWH-II were similar to other commercial LMWHs. The structure of LMWH-II closely matched heparin's core structural features. Most of the common process artifacts, present in many commercial LWMHs, were eliminated as demonstrated by 1D and 2D nuclear magnetic resonance spectroscopy. The antithrombin III and platelet factor-4 binding affinity of LMWH-II were comparable to commercial LMWHs, as was its in vitro anticoagulant activity. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Effect of electrostatic interactions on the ultrafiltration behavior of charged bacterial capsular polysaccharides.

PubMed

Hadidi, Mahsa; Buckley, John J; Zydney, Andrew L

2016-11-01

Charged polysaccharides are used in the food industry, as cosmetics, and as vaccines. The viscosity, thermodynamics, and hydrodynamic properties of these charged polysaccharides are known to be strongly dependent on the solution ionic strength because of both inter- and intramolecular electrostatic interactions. The goal of this work was to quantitatively describe the effect of these electrostatic interactions on the ultrafiltration behavior of several charged capsular polysaccharides obtained from Streptococcus pneumoniae and used in the production of Pneumococcus vaccines. Ultrafiltration data were obtained using various Biomax™ polyethersulfone membranes with different nominal molecular weight cutoffs. Polysaccharide transmission decreased with decreasing ionic strength primarily because of the expansion of the charged polysaccharide associated with intramolecular electrostatic repulsion. Data were in good agreement with a simple theoretical model based on solute partitioning in porous membranes, with the effective size of the different polysaccharide serotypes evaluated using size exclusion chromatography at the same ionic conditions. These results provide fundamental insights and practical guidelines for exploiting the effects of electrostatic interactions during the ultrafiltration of charged polysaccharides. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1531-1538, 2016. © 2016 American Institute of Chemical Engineers.

Impact of ozonation, anion exchange resin and UV/H2O2 pre-treatments to control fouling of ultrafiltration membrane for drinking water treatment.

PubMed

Pramanik, Biplob Kumar; Pramanik, Sagor Kumar; Sarker, Dipok Chandra; Suja, Fatihah

2017-06-01

The effects of ozonation, anion exchange resin (AER) and UV/H 2 O 2 were investigated as a pre-treatment to control organic fouling (OF) of ultrafiltration membrane in the treatment of drinking water. It was found that high molecular weight (MW) organics such as protein and polysaccharide substances were majorly responsible for reversible fouling which contributed to 90% of total fouling. The decline rate increased with successive filtration cycles due to deposition of protein content over time. All pre-treatment could reduce the foulants of a Ultrafiltration membrane which contributed to the improvement in flux, and there was a greater improvement of flux by UV/H 2 O 2 (61%) than ozonation (43%) which in turn was greater than AER (23%) treatment. This was likely due to the effective removal/breakdown of high MW organic content. AER gave greater removal of biofouling potential components (such as biodegradable dissolved organic carbon and assimilable organic carbon contents) compared to UV/H 2 O 2 and ozonation treatment. Overall, this study demonstrated the potential of pre-treatments for reducing OF of ultrafiltration for the treatment of drinking water.

[Study on the interface of human hepatocyte/micropore polypropylene ultrafiltration membrane].

PubMed

Peng, Cheng-Hong; Han, Bao-San; Gao, Chang-You; Ma, Zu-Wei; Zhao, Zhi-Ming; Wang, Yong; Liu, Hong; Zhang, Gui-di; Yang, Mei-Juan

2004-09-02

To found a new interface of human hepatocyte/micropore polypropylene ultrafiltration membrane (MPP) with good cytocompatibility so as to construct bioartificial bioreactor with polypropylene hollow fibers in future. MPP ultrafiltration membrane underwent chemical grafting modification through ultraviolet irradiation and Fe(2+) reduction. The contact angles of MPP and the modified MPP membranes were measured. Human hepatic cells L-02 were cultured. MPP and modified MPP membranes were spread on the wells of culture plate and human hepatic cells and cytodex 3 were inoculated on them. Different kinds of microscopy were used to observe the morphology of these cells. The water contact angle of MPP and the modified MPP membranes decreased from 78 degrees +/- 5 degrees to 27 degrees +/- 4 degrees (P < 0.05), which indicated that the hydrophilicity of the membrane was improved obviously after the grafting modification. Human hepatocyte L-02 did not adhere to and spread on the modified MPP membrane surface, and only grew on the microcarrier cytodex 3 with higher density and higher proliferation ratio measured by MTT. Grafting modification of acrylamide on MPP membrane is a good method to improve the human hepatocyte cytocompatibility with MPP ultrafiltration membrane.

Thermoase-Derived Flaxseed Protein Hydrolysates and Membrane Ultrafiltration Peptide Fractions Have Systolic Blood Pressure-Lowering Effects in Spontaneously Hypertensive Rats

PubMed Central

Nwachukwu, Ifeanyi D.; Girgih, Abraham T.; Malomo, Sunday A.; Onuh, John O.; Aluko, Rotimi E.

2014-01-01

Thermoase-digested flaxseed protein hydrolysate (FPH) samples and ultrafiltration membrane-separated peptide fractions were initially evaluated for in vitro inhibition of angiotensin I-converting enzyme (ACE) and renin activities. The two most active FPH samples and their corresponding peptide fractions were subsequently tested for in vivo antihypertensive activity in spontaneously hypertensive rats (SHR). The FPH produced with 3% thermoase digestion showed the highest ACE- and renin-inhibitory activities. Whereas membrane ultrafiltration resulted in significant (p < 0.05) increases in ACE inhibition by the <1 and 1–3 kDa peptides, only a marginal improvement in renin-inhibitory activity was observed for virtually all the samples after membrane ultrafiltration. The FPH samples and membrane fractions were also effective in lowering systolic blood pressure (SBP) in SHR with the largest effect occurring after oral administration (200 mg/kg body weight) of the 1–3 kDa peptide fraction of the 2.5% FPH and the 3–5 kDa fraction of the 3% FPH. Such potent SBP-lowering capacity indicates the potential of flaxseed protein-derived bioactive peptides as ingredients for the formulation of antihypertensive functional foods and nutraceuticals. PMID:25302619

Ceramic membrane by tape casting and sol-gel coating for microfiltration and ultrafiltration application

NASA Astrophysics Data System (ADS)

Das, Nandini; Maiti, H. S.

2009-11-01

Alumina membrane filters in the form of thin (0.3-0.8 mm) discs of 25-30 mm diameter suitable for microfiltration application have been fabricated by tape-casting technique. Further using this microfiltration membrane as substrate, boehmite sol coating was applied on it and ultrafiltration membrane with very small thickness was formed. The pore size of the microfiltration membrane could be varied in the range of 0.1-0.7 μm through optimisation of experimental parameter. In addition, each membrane shows a very narrow pore size distribution. The most important factor, which determines the pore size of the membrane, is the initial particle size and its distribution of the ceramic powder. The top thin ultrafiltration, boehmite layer was prepared by sol-gel method, with a thickness of 0.5 μm. Particle size of the sol was approximately 30-40 nm. The structure and formation of the layer was analysed through TEM. At 550 °C formation of the top layer was completed. The pore size of the ultrafiltration membrane measured from TEM micrograph was almost 10 nm. Results of microbial (Escherichia coli—smallest-sized water-borne bacteria) test confirm the possibility of separation through this membrane

Peritoneal fluid transport: mechanisms, pathways, methods of assessment.

PubMed

Waniewski, Jacek

2013-11-01

Fluid removal during peritoneal dialysis is controlled by many mutually dependent factors and therefore its analysis is more complex than that of the removal of small solutes used as markers of dialysis adequacy. Many new tests have been proposed to assess quantitatively different components of fluid transport (transcapillary ultrafiltration, peritoneal absorption, free water, etc.) and to estimate the factors that influence the rate of fluid transport (osmotic conductance). These tests provide detailed information about indices and parameters that describe fluid transport, especially those concerning the problem of the permanent loss of ultrafiltration capacity (ultrafiltration failure). Different theories and respective mathematical models of mechanisms and pathways of fluid transport are presently discussed and applied, and some fluid transport issues are still debated. Copyright © 2013 IMSS. Published by Elsevier Inc. All rights reserved.

The determination of ultrafiltrable calcium and magnesium in serum.

PubMed

Danielson, B G; Pallin, E; Sohtell, M

1982-01-01

Ultrafiltrate of human serum was investigated in order to evaluate the serum content of calcium and magnesium. The acid and base concentrations and pH of the serum was altered through titration with HCl- or NaOH-solutions. The Pco2 was varied in the titrated serum using different carbon dioxide tensions. This was performed when serum was filtered in a recycling system. It is shown that the analysis of calcium and magnesium have to be done under anaerobic conditions or at standardized pH and Pco2 situations, as the concentrations vary with both pH and Pco2. The concentration ratio between ultrafiltrate and serum for calcium and magnesium was found to be 0.56 and 0.74 respectively at pH=7.41 and Pco2=40 mmHg.

High-throughput protein concentration and buffer exchange: comparison of ultrafiltration and ammonium sulfate precipitation.

PubMed

Moore, Priscilla A; Kery, Vladimir

2009-01-01

High-throughput protein purification is a complex, multi-step process. There are several technical challenges in the course of this process that are not experienced when purifying a single protein. Among the most challenging are the high-throughput protein concentration and buffer exchange, which are not only labor-intensive but can also result in significant losses of purified proteins. We describe two methods of high-throughput protein concentration and buffer exchange: one using ammonium sulfate precipitation and one using micro-concentrating devices based on membrane ultrafiltration. We evaluated the efficiency of both methods on a set of 18 randomly selected purified proteins from Shewanella oneidensis. While both methods provide similar yield and efficiency, the ammonium sulfate precipitation is much less labor intensive and time consuming than the ultrafiltration.

Performance in Measurement of Serum Cystatin C by Laboratories Participating in the College of American Pathologists 2014 CYS Survey.

PubMed

Eckfeldt, John H; Karger, Amy B; Miller, W Greg; Rynders, Gregory P; Inker, Lesley A

2015-07-01

Cystatin C is becoming an increasingly popular biomarker for estimating glomerular filtration rate, and accurate measurements of cystatin C concentrations are necessary for accurate estimates of glomerular filtration rate. To assess the accuracy of cystatin C concentration measurements in laboratories participating in the College of American Pathologists CYS Survey. Two fresh frozen serum pools, the first from apparently healthy donors and the second from patients with chronic kidney disease, were prepared and distributed to laboratories participating in the CYS Survey along with the 2 usual processed human plasma samples. Target values were established for each pool by using 2 immunoassays and ERM DA471/IFCC international reference material. For the normal fresh frozen pool (ERM-DA471/IFCC-traceable target of 0.960 mg/L), the all-method mean (SD, % coefficient of variation [CV]) reported by all of the 123 reporting laboratories was 0.894 mg/L (0.128 mg/L, 14.3%). For the chronic kidney disease pool (ERM-DA471/IFCC-traceable target of 2.37 mg/L), the all-method mean (SD, %CV) was 2.258 mg/L (0.288 mg/L, 12.8%). There were substantial method-specific biases (mean milligram per liter reported for the normal pool was 0.780 for Siemens, 0.870 for Gentian, 0.967 for Roche, 1.061 for Diazyme, and 0.970 for other/not specified reagents; and mean milligram per liter reported for the chronic kidney disease pool was 2.052 for Siemens, 2.312 for Gentian, 2.247 for Roche, 2.909 for Diazyme, and 2.413 for other/not specified reagents). Manufacturers need to improve the accuracy of cystatin C measurement procedures if cystatin C is to achieve its full potential as a biomarker for estimating glomerular filtration rate.

Measurement of glomerular filtration rate using dynamic magnetic resonance imaging in patients with chronic kidney disease.

PubMed

Artunc, Ferruh; Yildiz, Serdar; Boss, Andreas; Frenzel, Thomas; Schlemmer, Heinz-Peter; Schick, Fritz; Risler, Teut; Häring, Hans-Ulrich; Rossi, Cristina

2011-01-01

Determination of glomerular filtration rate (GFR) using plasma disappearance curves requires the injection of a filtration marker and repeated timed blood collections. Gadolinium-containing contrast media are excreted exclusively by glomerular filtration and could provide a novel approach to quantifying GFR using magnetic resonance (MR) imaging. The aim of this study was to demonstrate the feasibility of measuring GFR by the clearance of gadolinium-containing contrast medium in patients with chronic kidney disease (CKD). Informed consent was obtained from stable CKD patients in stages 1, 2 or 3 (n=16; 5 women, 11 men; median age 54 years). GFR was measured after a bolus injection of gadobutrol (4 mL, approximately 0.05 mmol/kg) and calculated from the washout of the signal intensity obtained over the liver. The obtained MR-GFR was compared with simultaneously measured plasma clearance of inulin and gadobutrol. Technical failure occurred in 2 patients. The mean obtained MR-GFR was 71 ± 25 (SD) mL/min per 1.73 m² and agreed well with the mean inulin-GFR (70 ± 24 mL/min per 1.73 m²). Pearson's correlation coefficient was r=0.91. The mean of the paired differences was 1 ± 10 mL/min per 1.73 m² and not significantly different from zero. GFR obtained from gadobutrol plasma clearance also agreed well with inulin-GFR and MR-GFR (r=0.92 and r=0.75, respectively). We describe a novel method of determining GFR from MR imaging using a low dose of gadobutrol in patients with reduced GFR that enables the absolute quantification of GFR after routine contrast-enhanced MR imaging.

Glomerular enlargement assessed by paired donor and early protocol renal allograft biopsies.

PubMed

Alperovich, Gabriela; Maldonado, Rafael; Moreso, Francesc; Fulladosa, Xavier; Grinyó, Josep M; Serón, Daniel

2004-04-01

The aim of the study was to evaluate the evolution of glomerular volume 4 months after transplantation. Mean glomerular volume (Vg) was estimated according to the Weibel and Gomez method in a donor and a protocol biopsy done at 139 +/- 58 d in 41 stable grafts. Biopsies were also evaluated according to the Banff schema. Vg increased after transplantation from 4.1 +/- 1.4 to 5.1 +/- 2.4 x 10(6) micro3 (p=0.02). In patients with chronic allograft nephropathy in the protocol biopsy (n=14), the Vg enlargement was -0.3 +/-x 10(6) micro3 while in patients without chronic allograft nephropathy (n=27), glomerular enlargement was 1.6 +/- 2.1 x 10(6) micro3 (p=0.01). There was a negative association between glomerular volume in the donor biopsy and glomerular enlargement after transplantation (R=- 0.34, p=0.03). Multivariate regression analysis confirmed that Vg in the donor biopsy and chronic allograft nephropathy in the protocol biopsy were independent predictors of glomerular enlargement after transplantation (R=0.48, p=0.01). Moreover, Vg in the protocol biopsy correlated with creatinine clearance at the time of biopsy (R=0.38, p=0.01). Glomeruli enlarge after transplantation and glomerular volume after 4 months correlates with creatinine clearance, suggesting that glomerular enlargement is a necessary condition for renal adaptation to the recipient. Glomerular enlargement is impaired in patients with chronic allograft nephropathy.

Muscarinic Receptors Modulate Dendrodendritic Inhibitory Synapses to Sculpt Glomerular Output

PubMed Central

Shao, Zuoyi; Puche, Adam; Wachowiak, Matt; Rothermel, Markus

2015-01-01

Cholinergic [acetylcholine (ACh)] axons from the basal forebrain innervate olfactory bulb glomeruli, the initial site of synaptic integration in the olfactory system. Both nicotinic acetylcholine receptors (nAChRs) and muscarinic acetylcholine receptors (mAChRs) are expressed in glomeruli. The activation of nAChRs directly excites both mitral/tufted cells (MTCs) and external tufted cells (ETCs), the two major excitatory neurons that transmit glomerular output. The functional roles of mAChRs in glomerular circuits are unknown. We show that the restricted glomerular application of ACh causes rapid, brief nAChR-mediated excitation of both MTCs and ETCs in the mouse olfactory bulb. This excitation is followed by mAChR-mediated inhibition, which is blocked by GABAA receptor antagonists, indicating the engagement of periglomerular cells (PGCs) and/or short axon cells (SACs), the two major glomerular inhibitory neurons. Indeed, selective activation of glomerular mAChRs, with ionotropic GluRs and nAChRs blocked, increased IPSCs in MTCs and ETCs, indicating that mAChRs recruit glomerular inhibitory circuits. Selective activation of glomerular mAChRs in the presence of tetrodotoxin increased IPSCs in all glomerular neurons, indicating action potential-independent enhancement of GABA release from PGC and/or SAC dendrodendritic synapses. mAChR-mediated enhancement of GABA release also presynaptically suppressed the first synapse of the olfactory system via GABAB receptors on sensory terminals. Together, these results indicate that cholinergic modulation of glomerular circuits is biphasic, involving an initial excitation of MTC/ETCs mediated by nAChRs followed by inhibition mediated directly by mAChRs on PGCs/SACs. This may phasically enhance the sensitivity of glomerular outputs to odorants, an action that is consistent with recent in vivo findings. PMID:25855181

Muscarinic receptors modulate dendrodendritic inhibitory synapses to sculpt glomerular output.

PubMed

Liu, Shaolin; Shao, Zuoyi; Puche, Adam; Wachowiak, Matt; Rothermel, Markus; Shipley, Michael T

2015-04-08

Cholinergic [acetylcholine (ACh)] axons from the basal forebrain innervate olfactory bulb glomeruli, the initial site of synaptic integration in the olfactory system. Both nicotinic acetylcholine receptors (nAChRs) and muscarinic acetylcholine receptors (mAChRs) are expressed in glomeruli. The activation of nAChRs directly excites both mitral/tufted cells (MTCs) and external tufted cells (ETCs), the two major excitatory neurons that transmit glomerular output. The functional roles of mAChRs in glomerular circuits are unknown. We show that the restricted glomerular application of ACh causes rapid, brief nAChR-mediated excitation of both MTCs and ETCs in the mouse olfactory bulb. This excitation is followed by mAChR-mediated inhibition, which is blocked by GABAA receptor antagonists, indicating the engagement of periglomerular cells (PGCs) and/or short axon cells (SACs), the two major glomerular inhibitory neurons. Indeed, selective activation of glomerular mAChRs, with ionotropic GluRs and nAChRs blocked, increased IPSCs in MTCs and ETCs, indicating that mAChRs recruit glomerular inhibitory circuits. Selective activation of glomerular mAChRs in the presence of tetrodotoxin increased IPSCs in all glomerular neurons, indicating action potential-independent enhancement of GABA release from PGC and/or SAC dendrodendritic synapses. mAChR-mediated enhancement of GABA release also presynaptically suppressed the first synapse of the olfactory system via GABAB receptors on sensory terminals. Together, these results indicate that cholinergic modulation of glomerular circuits is biphasic, involving an initial excitation of MTC/ETCs mediated by nAChRs followed by inhibition mediated directly by mAChRs on PGCs/SACs. This may phasically enhance the sensitivity of glomerular outputs to odorants, an action that is consistent with recent in vivo findings. Copyright © 2015 the authors 0270-6474/15/355680-13$15.00/0.

Hemoglobin Decline in Children with Chronic Kidney Disease: Baseline Results from the Chronic Kidney Disease in Children Prospective Cohort Study

PubMed Central

Fadrowski, Jeffrey J.; Pierce, Christopher B.; Cole, Stephen R.; Moxey-Mims, Marva; Warady, Bradley A.; Furth, Susan L.

2008-01-01

Background and objectives: The level of glomerular filtration rate at which hemoglobin declines in chronic kidney disease is poorly described in the pediatric population. Design, setting, participants, & measurements: This cross-sectional study of North American children with chronic kidney disease examined the association of glomerular filtration rate, determined by the plasma disappearance of iohexol, and hemoglobin concentration. Results: Of the 340 patients studied, the mean age was 11 ± 4 yr, the mean glomerular filtration rate was 42 ± 14 ml/min per 1.73 m2, and the mean hemoglobin was 12.5 ± 1.5. Below a glomerular filtration rate of 43, the hemoglobin declined by 0.3 g/dl (95% confidence interval −0.2 to −0.5) for every 5-ml/min per 1.73 m2 decrease in glomerular filtration rate. Above a glomerular filtration rate of 43 ml/min per 1.73 m2, the hemoglobin showed a nonsignificant decline of 0.1 g/dl for every 5-ml/min per 1.73 m2 decrease in glomerular filtration rate. Conclusions: In pediatric patients with chronic kidney disease, hemoglobin declines as an iohexol-determined glomerular filtration rate decreases below 43 ml/min per 1.73 m2. Because serum creatinine–based estimated glomerular filtration rates may overestimate measured glomerular filtration rate in this population, clinicians need to be mindful of the potential for hemoglobin decline and anemia even at early stages of chronic kidney disease, as determined by current Schwartz formula estimates. Future longitudinal analyses will further characterize the relationship between glomerular filtration rate and hemoglobin, including elucidation of reasons for the heterogeneity of this association among individuals. PMID:18235140

Hollow-Fiber Ultrafiltration and PCR Detection of Human-Associated Genetic Markers from Various Types of Surface Water in Florida ▿

PubMed Central

Leskinen, Stephaney D.; Brownell, Miriam; Lim, Daniel V.; Harwood, Valerie J.

2010-01-01

Hollow-fiber ultrafiltration (HFUF) and PCR were combined to detect human-associated microbial source tracking marker genes in large volumes of fresh and estuarine Florida water. HFUF allowed marker detection when membrane filtration did not, demonstrating HFUF's ability to facilitate detection of diluted targets by PCR in a variety of water types. PMID:20435774

Glomerulopathy Associated with Parasitic Infections

PubMed Central

van Velthuysen, M.-L. F.; Florquin, S.

2000-01-01

Although parasitic infections do not usually present with disturbance in renal function, glomerular lesions can be seen in most of these infections. The glomerular lesions observed in parasitic infections cover the whole range of glomerular lesions known, but most of them are proliferative. Little is known of the exact pathogenic mechanisms. In this review, we try to explain the glomerular lesions associated with parasitic infections in terms of the specific immunologic events observed during these diseases against the background of recent developments in the general knowledge of the pathogenesis of glomerular disease. PMID:10627491

A mass balance approach for calculation of recovery and binding enables the use of ultrafiltration as a rapid method for measurement of plasma protein binding for even highly lipophilic compounds.

PubMed

Wang, Changguang; Williams, Noelle S

2013-03-05

The aim of this study is to further validate the use of ultrafiltration (UF) as a method for determining plasma protein binding (PPB) by demonstrating that non-specific binding (NSB) is not a limitation, even for highly lipophilic compounds, because NSB sites on the apparatus are passivated in the presence of plasma. Mass balance theory was used to calculate recovery of 20 commercial and seven investigational compounds during ultrafiltration in the presence and absence of plasma. PPB was also measured using this mass balance approach for comparison to PPB determined by rapid equilibrium dialysis (RED) and as found in the literature. Compound recovery during UF was dramatically different in the presence and absence of plasma for compounds with high NSB in PBS only. A comparison of PPB calculated by ultrafiltration with literature values or calculated by RED gave concordant results. Discrepancies could be explained by changes in pH, insufficient time to equilibrium, or compound instability during RED, problems which were circumvented by ultrafiltration. Therefore, NSB, as measured by the traditional incubation of compound in PBS, need not be an issue when choosing UF as a PPB assay method. It is more appropriate to calculate compound recovery from the device in plasma as measured by mass balance to determine the suitability of the method for an individual compound. The speed with which UF can be conducted additionally avoids changes in pH or compound loss that can occur with other methods. The mass balance approach to UF is thus a preferred method for rapid determination of PPB. Copyright © 2012 Elsevier B.V. All rights reserved.

Influence of continuous haemofiltration-related hypothermia on haemodynamic variables and gas exchange in septic patients.

PubMed

Matamis, D; Tsagourias, M; Koletsos, K; Riggos, D; Mavromatidis, K; Sombolos, K; Bursztein, S

1994-07-01

To investigate the influence of continuous haemofiltration (CHF) on haemodynamics, gas exchange and core temperature in critically ill septic patients with acute renal failure. In 20 patients (17 male, 3 female) ultrafiltration rate, core temperature, gas exchange and haemodynamic variables were measured at regular intervals during the first 48 h of haemofiltration. Baseline data were compared to those obtained 30 min after initiating CHF and also to those during hypothermia (if observed). Haemodynamic variables remained remarkably constant throughout the study period. In patients with a relatively low ultrafiltration rate (855 +/- 278 ml/h) temperature did not change, while in patients with a high ultrafiltration rate (1468 +/- 293 ml/h) core temperature significantly decreased from 37.6 +/- 0.9 degrees C to 34.8 +/- 0.8 degrees C (p < 0.001). There was a statistically significant correlation between temperature decrease and ultrafiltration rate (r = -0.68, Y = 1.8-0.003 X, p < 0.01). Hypothermic patients also showed a mean decrease in VO2 from 141 +/- 22 ml/min/m2 to 112 +/- 22 ml/min/m2 (p < 0.01) with a concomitant increase in PaO2 from 103 +/- 37 mmHg to 140 +/- 42 mmHg (p < 0.001) and in PvO2 from 35 +/- 4 mmHg to 41 +/- 5 mmHg (p < 0.001). 1) Continuous haemofiltration does not cause significant alternations in haemodynamic variables. 2) Hypothermia frequently occurs in patients undergoing continuous haemofiltration with high ultrafiltration rates. These hypothermic patients show a reduction in VO2 leading to an increase in PvO2 and PaO2. This mild hypothermia in these circumstances has no evident deleterious effects.

The processing of used cooking oil (yellow grease) using combination of adsorption and ultrafiltration membrane processes

NASA Astrophysics Data System (ADS)

Rosnelly, C. M.; Sofyana; Amalia, D.; Sarah, S.

2018-03-01

Yellow grease is used cooking oil whose quality has degraded due to the oxidation, polymerization, or hydrolysis process. In previous studies, yellow grease refining had been conducted either by adsorption or by using membrane. In this study, adsorption process using adsorbent from bagasse activated with H3PO4 12.5%, and ultrafiltration using Polyethersulfone (PES) membrane were combined. In adsorption stage, several variation of bagasse mass was fed into 200 ml of yellow grease and stirred for 60 minutes at 60 rpm. Yellow grease produced from adsorption with best condition was then processed using ultrafiltration membran that is PES membran with concentration by 15 wt % with transmembrane pressure variation by 0.5; 1; 1.5; 2; and 2.5 Bar. Analysis of yellow grease characteristics before refined showed its acid number, peroxide number, iodine number, and water content respectively by 2.68 mgKOH/Kg; 5.97 Meq/Kg; 51,48; and 1.29%. Characteristics of yellow grease after adsorption at its best condition on the parameters of acid number, peroxide number, iodine number, and water content are respectively by 2.55 mgKOH/Kg; 4.19 Meq/Kg; 40,02; and 0.27%. Characteristics of yellow grease after ultrafiltration at its best condition on the parameters of acid number, peroxide number, iodine number, and water content are respectively by 1.12 mgKOH/Kg; 1.8 Meq/Kg; 41,36; and 0.02%. Combination of adsorption and ultrafiltration processes for yellow grease processing showed decreasing value on the parameters of acid number, peroxide number, and water content that conforms to the SNI quality standard, but has not been able to increase the iodine number.

Icodextrin as salvage therapy in peritoneal dialysis patients with refractory fluid overload

PubMed Central

Johnson, David Wayne; Arndt, Mary; O'Shea, Amanda; Watt, Rhonda; Hamilton, Jan; Vincent, Kaia

2001-01-01

Background Icodextrin is a high molecular weight, starch-derived glucose polymer, which is capable of inducing sustained ultrafiltration over prolonged (12–16 hour) peritoneal dialysis (PD) dwells. The aim of this study was to evaluate the ability of icodextrin to alleviate refractory, symptomatic fluid overload and prolong technique survival in PD patients. Methods A prospective, open-label, pre-test/post-test study was conducted in 17 PD patients (8 females/9 males, mean age 56.8 ± 2.9 years) who were on the verge of being transferred to haemodialysis because of symptomatic fluid retention that was refractory to fluid restriction, loop diuretic therapy, hypertonic glucose exchanges and dwell time optimisation. One icodextrin exchange (2.5 L 7.5%, 12-hour dwell) was substituted for a long-dwell glucose exchange each day. Results Icodextrin significantly increased peritoneal ultrafiltration (885 ± 210 ml to 1454 ± 215 ml, p < 0.05) and reduced mean arterial pressure (106 ± 4 to 96 ± 4 mmHg, p < 0.05), but did not affect weight, plasma albumin concentration, haemoglobin levels or dialysate:plasma creatinine ratio. Diabetic patients (n = 12) also experienced improved glycaemic control (haemoglobin Alc decreased from 8.9 ± 0.7% to 7.9 ± 0.7%, p < 0.05). Overall PD technique survival was prolonged by a mean of 11.6 months (95% CI 6.0–17.3 months). On multivariate Cox proportional hazards analysis, extension of technique survival by icodextrin was only significantly predicted by baseline net daily peritoneal ultrafiltration (adjusted HR 2.52, 95% CI 1.13–5.62, p < 0.05). Conclusions Icodextrin significantly improved peritoneal ultrafiltration and extended technique survival in PD patients with symptomatic fluid overload, especially those who had substantially impaired peritoneal ultrafiltration. PMID:11737871

Development and application of novelty pretreatment method for the concurrent quantitation of eleven water-soluble B vitamins in ultrafiltrates after renal replacement therapy.

PubMed

Wirkus, Dorota; Jakubus, Aleksandra; Owczuk, Radosław; Stepnowski, Piotr; Paszkiewicz, Monika

2017-02-01

Continous renal replacement therapy (CRRT) is particularly recommended for septic shock patients in intensive care units. The CRRT technique used most frequently is high volume continuous veno-venous haemofiltration. It provides a high rate of clearance of uremic toxins and inflammatory cytokines. However, it should also be taken into account that substances important for homeostasis may be concurrently unintentionally removed. Accordingly, water-soluble vitamins can be removed during continuous renal replacement therapy, and the estimate of the loss is critical to ensure appropriate supplementation. The aim of this work was to develop a simple methodology for a purification step prior to the LC-MS/MS determination of water-soluble vitamins in ultrafiltrate samples. For this purpose, two types of resin and a mix of resins were used as sorbents for the purification step. Moreover, parameters such as the amount of resin and the extraction time were optimized. The LC-MS/MS method was developed and validated for final determination of 11 vitamins. The results demonstrated the high purification capability of DEAE Sephadex resin with recoveries between 65 and 101% for water-soluble vitamins from ultrafiltrate samples. An optimized method was applied to assess the loss of B-group vitamins in patients after 24h of renal replacement therapy. The loss of vitamins B2, B6 pyridoxamine, B6 pyridoxal, B7, B1, and B5 in ultrafiltrates was similar in all patients. In the native ultrafiltrates, vitamins B6 pyridoxine, B9 and B12 were not detected. Copyright © 2016 Elsevier B.V. All rights reserved.

A Decrease in Glomerular Endothelial Cells and Endothelial-mesenchymal Transition during Glomerulosclerosis in the Tensin2-deficient Mice (ICGN strain).

PubMed

Kato, Takashi; Mizuno, Shinya; Ito, Akihiko

2014-01-01

The ICR-derived glomerulonephritis (ICGN) mouse is a unique model of nephrotic syndrome, and albuminuria becomes evident in a neonatal stage, due to a genetic mutation of tensin2. We previously provided evidence that an apparent decrease in nephrin, caused by tensin2-deficiencient states, leads to podocytopathy, albuminuria and eventually, chronic renal failure. In general, glomerular endothelial cells (ECs) function as a barrier through tight attachment of glomerular basement membrane to podocytes, while decreased ECs can worsen renal failure. Nevertheless, it is still unknown whether glomerular ECs are altered under the tensin-2-deficient states during the manifestation of chronic renal failure. Herein, we examined the changes of glomerular ECs, with focus on the expression of PECAM-1 and VE-cadherin (EC-specific markers), or of α-SMA (myofibroblast marker) in this mouse model by histological methods. Compared with the non-nephrotic (+/nep) mice, the nephrotic (nep/nep) mice exhibited the reduced expression of PECAM-1, or of VE-cadherin, in glomerular area. Notably, some glomerular ECs showed the positive stainings for both PECAM-1 and α-SMA, suggesting endothelial-to-mesenchymal transition (EndoMT) during progression of glomerular sclerosis. This is the first report showing that a decrease in glomerular ECs, at least in part, via EndoMT is involved in tensin2-deficient pathological conditions.

Platelet-activating factor mediates monocyte chemoattractant protein-1 expression in glomerular immune injury.

PubMed

Jocks, T; Freudenberg, J; Zahner, G; Stahl, R A

1998-01-01

These studies were designed to determine the possible role of platelet-activating factor (PAF) in the production of monocyte chemoattractant protein-1 (MCP-1) in glomerular immune injury. The glomerular lesion was induced in isolated perfused rat kidneys by a rabbit anti-rat-thymocyte serum (ATS) and rat serum (RS) as a complement source. Perfusion of kidneys with ATS and RS results in the selective binding of the antiserum to the glomerular mesangium with consecutive intraglomerular activation of complement. Antibody binding and complement activation induced a significant increase in glomerular MCP-1 mRNA levels when assessed by Northern blotting or RT-PCR. Decomplemented RS or non antibody rabbit IgG had only moderate effects on glomerular MCP-1 mRNA levels. The PAF receptor antagonist WEB 2170 almost completely blocked the ATS and RS induced MCP-1 mRNA levels. Perfusion of control kidneys with PAF increased MCP-1 mRNA expression, an effect which was blocked by WEB 2170. Glomerular MCP-1 protein formation, assessed by Western blotting, was stimulated following ATS and RS and PAF, respectively, was blocked by WEB 2170. These data show that PAF, derived from glomerular resident cells following antibody and complement induced injury, stimulates MCP-1 expression. In addition to the direct effects on leukocyte adhesion and activation PAF may mediate inflammatory cell influx in glomerular injuries due to the release of MCP-1.

ENVIRONMENTAL TECHNOLOGY VERIFICATION REPORT - PHYSICAL REMOVAL OF MICROBIOLOGICAL AND PARTICULATE CONTAMINANTS IN DRINKING WATER, HYDRANAUTICS HYDRACAP ULTRAFILTRATION MEMBRANE SYSTEM AT THE AQUA2000 RESEARCH CENTER - NSF 00/04/EPADW395

EPA Science Inventory

Verification testing of the Hydranautics HYDRA Cap(TM) Ultrafiltration Membrane System (Hydranautics UF unit) was conducted over two test periods at the Aqua 2000 Research Center in San Diego, CA. The first test period, from 8/3/99-9/13/99, represented summer/fall conditions. The...

ETV REPORT - PHYSICAL REMOVAL OF CRYPTOSPORIDIUM OOCYSTS AND GIARDIA CYSTS IN DRINKING WATER AQUASOURCE NORTH AMERICA ULTRAFILTRATION SYSTEM A35 AT PITTSBURGH, PA. - NSF00/07/EPADW395

EPA Science Inventory

Verification testing of the Aquasource Ultrafiltration Treatment System Model A35 was conducted from 12/1 - 12/31/98. The treatment system underwent microbial challenge testing on 1/22/99 and demonstrated a 5.5 log10 removal of Giardia cysts and a 6.5 log10 removal of Cryptospori...

Tangential-flow ultrafiltration with integrated inhibition detection for recovery of surrogates and human pathogens from large-volume source water and finished drinking water.

PubMed

Gibson, Kristen E; Schwab, Kellogg J

2011-01-01

Tangential-flow ultrafiltration was optimized for the recovery of Escherichia coli, Enterococcus faecalis, Clostridium perfringens spores, bacteriophages MS2 and PRD1, murine norovirus, and poliovirus seeded into 100-liter surface water (SW) and drinking water (DW) samples. SW and DW collected from two drinking water treatment plants were then evaluated for human enteric viruses.

Comparison of 2 ultrafiltration systems for the concentration of seeded viruses from environmental waters.

PubMed

Olszewski, John; Winona, Linda; Oshima, Kevin H

2005-04-01

The use of ultrafiltration as a concentration method to recover viruses from environmental waters was investigated. Two ultrafiltration systems (hollow fiber and tangential flow) in a large- (100 L) and small-scale (2 L) configuration were able to recover greater than 50% of multiple viruses (bacteriophage PP7 and T1 and poliovirus type 2) from varying water turbidities (10-157 nephelometric turbidity units (NTU)) simultaneously. Mean recoveries (n = 3) in ground and surface water by the large-scale hollow fiber ultrafiltration system (100 L) were comparable to recoveries observed in the small-scale system (2 L). Recovery of seeded viruses in highly turbid waters from small-scale tangential flow (2 L) (screen and open channel) and hollow fiber ultrafilters (2 L) (small pilot) were greater than 70%. Clogging occurred in the hollow fiber pencil module and when particulate concentrations exceeded 1.6 g/L and 5.5 g/L (dry mass) in the screen and open channel filters, respectively. The small pilot module was able to filter all concentrates without clogging. The small pilot hollow fiber ultrafilter was used to test recovery of seeded viruses from surface waters from different geographical regions in 10-L volumes. Recoveries >70% were observed from all locations.

Determination of moxifloxacin in human plasma, plasma ultrafiltrate, and cerebrospinal fluid by a rapid and simple liquid chromatography- tandem mass spectrometry method.

PubMed

Pranger, Arianna D; Alffenaar, Jan-Willem C; Wessels, A Mireille A; Greijdanus, Ben; Uges, Donald R A

2010-04-01

Moxifloxacin (MFX) is a useful agent in the treatment of multi-drug-resistant tuberculosis (MDR-TB). At Tuberculosis Centre Beatrixoord, a referral center for tuberculosis in the Netherlands, approximately 36% of the patients have received MFX as treatment. Based on the variability of MFX AUC, the variability of in vitro susceptibility to MFX of M. tuberculosis, and the variability of penetration into sanctuary sites, measuring the concentration of MFX in plasma and cerebrospinal fluid (CSF) could be recommended. Therefore, a rapid and validated liquid chromatography-tandem mass spectrometry (LC-MS-MS) analyzing method with a simple pretreatment procedure was developed for therapeutic drug monitoring of MFX in human plasma and CSF. Because of the potential influence of protein binding on efficacy, we decided to determine both bound and unbound (ultrafiltrate) fraction of MFX. The calibration curves were linear in the therapeutic range of 0.05 to 5.0 mg/L plasma and CSF with CV in the range of -5.4% to 9.3%. MFX ultrafiltrate samples could be determined with the same method setup for analysis of MFX in CSF. The LC-MS-MS method developed in this study is suitable for monitoring MFX in human plasma, plasma ultrafiltrate, and CSF.

Acute symptoms during and between hemodialysis: the relative role of speed, duration, and biocompatibility of dialysis.

PubMed

Skroeder, N R; Jacobson, S H; Lins, L E; Kjellstrand, C M

1994-12-01

The relationship between hemodialysis (HD) symptoms and dialyzer membrane composition and area, blood-flow, treatment duration, urea removal, ultrafiltration volume, leukocyte activation, and complement generation (C3a) was studied in 20 patients undergoing 234 HD treatments by 12 different modes in random order using Cuprophan, hemophane, or polyamide membranes with small or large membrane areas with high Qb (400 ml/min) and short duration (2 h) or low Qb (200 ml/min) and long duration (4 h). Fewer symptoms occurred during the 2-h HD at high Qb than during the 4-h HD with low Qb (19% vs. 32%, p = 0.0351). No differences were observed between different dialyzer membranes or areas. More intradialytic symptoms occurred when urea elimination was high than it was low (p = 0.0044). Leukocyte activation (leukocyte drop) after 15 min of dialysis and complement generation did not influence symptom incidence. Blood pressure changes were mainly influenced by ultrafiltration volume (p < 0.001). Symptoms between dialyses were determined by urea removal and ultrafiltration. Membrane, area, or Qb were of no importance. Thus, duration of dialysis, urea removal, and demand for ultrafiltration, but not membrane composition, area, or biocompatability, are important for the development of HD-related symptoms.

Flux enhancement during ultrafiltration of produced water using turbulence promoter.

PubMed

Zhen, Xiang-hua; Yu, Shui-li; Wang, Bei-fu; Zheng, Hai-feng

2006-01-01

Concentration polarization and membrane fouling remain one of the major hurdles for the implementation of ultrafiltration of produced water. Although many applications for ultrafiltration were already suggested, only few were implemented on an industrial scale. Among those techniques, turbulence promoter can be more simple and effective in overcoming membrane fouling and enhancing membrane flux. As for the result that turbulence promoter increase fluid velocity, wall shear rates and produce secondary flows or instabilities, the influence of turbulence promoter was investigated on permeate flux during produced water ultrafiltration and the potential application of this arrangement for an industrial development. Experimental investigations were performed on 100 KDa molecular weight cut-off PVDF single-channel tubular membrane module using four kinds of turbulence promoters. It is observed that the significant flux enhancement in the range of 83%-164% was achieved while the hydraulic dissipated power per unit volume of permeate decreased from 31%-42%, which indicated that the using of turbulence promoter is more efficient than operation without the turbulence promoter. The effects of transmembrane pressure and cross-flow velocity with and without turbulence promoter were studied as well. Among the four kinds of turbulence promoters, winding inserts with 20.0 mm pitch and 1.0 mm wire diameter showed better performances than the others did.

Controlling Legionella and Pseudomonas aeruginosa re-growth in therapeutic spas: implementation of physical disinfection treatments, including UV/ultrafiltration, in a respiratory hydrotherapy system.

PubMed

Leoni, E; Sanna, T; Zanetti, F; Dallolio, L

2015-12-01

The study aimed to assess the efficacy of an integrated water safety plan (WSP) in controlling Legionella re-growth in a respiratory hydrotherapy system located in a spa centre, supplied with sulphurous water, which was initially colonized by Legionella pneumophila. Heterotrophic plate counts, Pseudomonas aeruginosa, Legionella spp. were detected in water samples taken 6-monthly from the hydrotherapy equipment (main circuit, entry to benches, final outlets). On the basis of the results obtained by the continuous monitoring and the changes in conditions, the original WSP, including physical treatments of water and waterlines, environmental surveillance and microbiological monitoring, was integrated introducing a UV/ultrafiltration system. The integrated treatment applied to the sulphurous water (microfiltration/UV irradiation/ultrafiltration), waterlines (superheated stream) and distal outlets (descaling/disinfection of nebulizers and nasal irrigators), ensured the removal of Legionella spp. and P. aeruginosa and a satisfactory microbiological quality over time. The environmental surveillance was successful in evaluating the hazard and identifying the most suitable preventive strategies to avoid Legionella re-growth. Ultrafiltration is a technology to take into account in the control of microbial contamination of therapeutic spas, since it does not modify the chemical composition of the water, thus allowing it to retain its therapeutic properties.

Exploration of zwitterionic cellulose acetate antifouling ultrafiltration membrane for bovine serum albumin (BSA) separation.

PubMed

Liu, Yang; Huang, Haitao; Huo, Pengfei; Gu, Jiyou

2017-06-01

This study focused on the preparation of a new kind of membrane material, zwitterionic cellulose acetate (ZCA), via a three-step procedure consist of oxidization, Schiff base and quaternary amination reaction, and the fabrication of antifouling ZCA ultrafiltration membrane by the non-solvent-induced phase separation method (NIPS). The morphologies, surface chemical structures and compositions of the obtained CA and ZCA membranes were thoroughly characterized by field emission scanning electron microscopy (FE-SEM) with energy dispersive X-ray (EDX) spectroscopy, Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS), respectively. Meanwhile, the thermal stability, porosity and average pore size of two investigated membranes were also studied. As a result, the ZCA membrane displayed significantly improved hydrophilicity and water permeability compared with those of the reference CA membrane, despite a slight decrease in the protein rejection ratio. According to the cycle ultrafiltration performance of bovine serum albumin (BSA) solution and protein adsorption experiment, ZCA membrane exhibited better flux recovery property and fouling resistant ability, especially irreversible fouling resistant ability, suggesting superior antifouling performance. This new approach gives polymer-based membrane a long time life and excellent ultrafiltration performance, and seems promising for potential applications in the protein separation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prostaglandin E1 inhibits collagen expression in anti-thymocyte antibody-induced glomerulonephritis: possible role of TGF beta.

PubMed

Schneider, A; Thaiss, F; Rau, H P; Wolf, G; Zahner, G; Jocks, T; Helmchen, U; Stahl, R A

1996-07-01

To test whether or not prostaglandins mediate extracellular matrix formation in immune-mediated glomerular disease, rats with anti-thymocyte antibody-induced glomerulonephritis were treated with prostaglandin E1 (PGE1) (250 micrograms/twice daily/s.c.). Glomerular expression of collagen types III and IV was assessed by Northern blotting, immunohistology and Western blotting. Proliferation of glomerular cells was evaluated by staining for the proliferating cell nuclear antigen (PCNA) and consecutive cell counting. At day five after induction of the disease, glomerular mRNA levels of collagen types III and IV were three- to fivefold higher compared with non-nephritic controls. Similarly glomerular deposition of these collagens was markedly increased when assessed by immunohistology. The treatment of nephritic rats with PGE1 reduced the increased glomerular mRNA levels as well as the protein concentration and the deposition of extracellular collagens. The number of PCNA positive cells which was significantly higher in nephritic rats when compared with control animals (24 hr, nephritis 2.53 +/- 0.33 and Control 0.26 +/- 0.06, P = 0.011; 5 days, nephritis 5.10 +/- 1.13 and Control 0.75 +/- 0.08, cells per glomerular cross section, P = 0.03) was reduced by PGE1 (24 hr, nephritis+PGE1 0.44 +/- 0.30, P = 0.0001; 5 days, nephritis +/- PGE1 1.91 +/- 1.84 cells per glomerular cross section, P = 0.001). Prostaglandin E1 also ameliorated the glomerular infiltration of monocytes at 24 hours (nephritis 4.36 +/- 2.82, nephritis + PGE1 2.20 +/- 1.82, cells per glomerular cross section) and five days (nephritis 1.51 +/- 0.58, nephritis+PGE1 1.12 +/- 0.61, cells per glomerular cross section). To further characterize possible mechanisms by which PGE1 reduces extracellular matrix deposition, the glomerular expression of transforming growth factor (TGF-beta), and interleukin 1 beta (IL-1 beta) was assessed by Northern blotting. Nephritic glomeruli showed increased mRNA levels of TGF-beta at day 5 and IL-1 beta at 24 hours when compared with control kidneys. Treatment of the animals with PGE1 inhibited the mRNA expression of TGF-beta and IL-1 beta. These data demonstrate that PGE1 reduces the glomerular expression of extracellular matrix proteins in anti-thymocyte antibody-induced glomerulonephritis, suggesting a beneficial role of prostaglandins in this proliferative glomerular immune injury. The effects of PGE1 might be mediated by inhibition of TGF-beta and IL-1 beta production.

The Prediction of Key Cytoskeleton Components Involved in Glomerular Diseases Based on a Protein-Protein Interaction Network.

PubMed

Ding, Fangrui; Tan, Aidi; Ju, Wenjun; Li, Xuejuan; Li, Shao; Ding, Jie

2016-01-01

Maintenance of the physiological morphologies of different types of cells and tissues is essential for the normal functioning of each system in the human body. Dynamic variations in cell and tissue morphologies depend on accurate adjustments of the cytoskeletal system. The cytoskeletal system in the glomerulus plays a key role in the normal process of kidney filtration. To enhance the understanding of the possible roles of the cytoskeleton in glomerular diseases, we constructed the Glomerular Cytoskeleton Network (GCNet), which shows the protein-protein interaction network in the glomerulus, and identified several possible key cytoskeletal components involved in glomerular diseases. In this study, genes/proteins annotated to the cytoskeleton were detected by Gene Ontology analysis, and glomerulus-enriched genes were selected from nine available glomerular expression datasets. Then, the GCNet was generated by combining these two sets of information. To predict the possible key cytoskeleton components in glomerular diseases, we then examined the common regulation of the genes in GCNet in the context of five glomerular diseases based on their transcriptomic data. As a result, twenty-one cytoskeleton components as potential candidate were highlighted for consistently down- or up-regulating in all five glomerular diseases. And then, these candidates were examined in relation to existing known glomerular diseases and genes to determine their possible functions and interactions. In addition, the mRNA levels of these candidates were also validated in a puromycin aminonucleoside(PAN) induced rat nephropathy model and were also matched with existing Diabetic Nephropathy (DN) transcriptomic data. As a result, there are 15 of 21 candidates in PAN induced nephropathy model were consistent with our predication and also 12 of 21 candidates were matched with differentially expressed genes in the DN transcriptomic data. By providing a novel interaction network and prediction, GCNet contributes to improving the understanding of normal glomerular function and will be useful for detecting target cytoskeleton molecules of interest that may be involved in glomerular diseases in future studies.

The Prediction of Key Cytoskeleton Components Involved in Glomerular Diseases Based on a Protein-Protein Interaction Network

PubMed Central

Ju, Wenjun; Li, Xuejuan; Li, Shao; Ding, Jie

2016-01-01

Maintenance of the physiological morphologies of different types of cells and tissues is essential for the normal functioning of each system in the human body. Dynamic variations in cell and tissue morphologies depend on accurate adjustments of the cytoskeletal system. The cytoskeletal system in the glomerulus plays a key role in the normal process of kidney filtration. To enhance the understanding of the possible roles of the cytoskeleton in glomerular diseases, we constructed the Glomerular Cytoskeleton Network (GCNet), which shows the protein-protein interaction network in the glomerulus, and identified several possible key cytoskeletal components involved in glomerular diseases. In this study, genes/proteins annotated to the cytoskeleton were detected by Gene Ontology analysis, and glomerulus-enriched genes were selected from nine available glomerular expression datasets. Then, the GCNet was generated by combining these two sets of information. To predict the possible key cytoskeleton components in glomerular diseases, we then examined the common regulation of the genes in GCNet in the context of five glomerular diseases based on their transcriptomic data. As a result, twenty-one cytoskeleton components as potential candidate were highlighted for consistently down- or up-regulating in all five glomerular diseases. And then, these candidates were examined in relation to existing known glomerular diseases and genes to determine their possible functions and interactions. In addition, the mRNA levels of these candidates were also validated in a puromycin aminonucleoside(PAN) induced rat nephropathy model and were also matched with existing Diabetic Nephropathy (DN) transcriptomic data. As a result, there are 15 of 21 candidates in PAN induced nephropathy model were consistent with our predication and also 12 of 21 candidates were matched with differentially expressed genes in the DN transcriptomic data. By providing a novel interaction network and prediction, GCNet contributes to improving the understanding of normal glomerular function and will be useful for detecting target cytoskeleton molecules of interest that may be involved in glomerular diseases in future studies. PMID:27227331

Isolation and characterization of conditionally immortalized mouse glomerular endothelial cell lines.

PubMed

Rops, Angelique L; van der Vlag, Johan; Jacobs, Cor W; Dijkman, Henry B; Lensen, Joost F; Wijnhoven, Tessa J; van den Heuvel, Lambert P; van Kuppevelt, Toin H; Berden, Jo H

2004-12-01

The culture and establishment of glomerular cell lines has proven to be an important tool for the understanding of glomerular cell functions in glomerular physiology and pathology. Especially, the recent establishment of a conditionally immortalized visceral epithelial cell line has greatly boosted the research on podocyte biology. Glomeruli were isolated from H-2Kb-tsA58 transgenic mice that contain a gene encoding a temperature-sensitive variant of the SV40 large tumor antigen, facilitating proliferative growth at 33 degrees C and differentiation at 37 degrees C. Glomerular endothelial cells were isolated from glomerular outgrowth by magnetic beads loaded with CD31, CD105, GSL I-B4, and ULEX. Clonal cell lines were characterized by immunofluorescence staining with antibodies/lectins specific for markers of endothelial cells, podocytes, and mesangial cells. Putative glomerular endothelial cell lines were analyzed for (1) cytokine-induced expression of adhesion molecules; (2) tube formation on Matrigel coating; and (3) the presence of fenestrae. As judged by immunostaining for Wilms tumor-1, smooth muscle actin (SMA), podocalyxin, and von Willebrand factor (vWF), we obtained putative endothelial, podocyte and mesangial cell lines. The mouse glomerular endothelial cell clone #1 (mGEnC-1) was positive for vWF, podocalyxin, CD31, CD105, VE-cadherin, GSL I-B4, and ULEX, internalized acetylated-low-density lipoprotein (LDL), and showed increased expression of adhesion molecules after activation with proinflammatory cytokines. Furthermore, mGEnC-1 formed tubes and contained nondiaphragmed fenestrae. The mGEnC-1 represents a conditionally immortalized cell line with various characteristics of differentiated glomerular endothelial cells when cultured at 37 degrees C. Most important, mGEnC-1 contains nondiaphragmed fenestrae, which is a unique feature of glomerular endothelial cells.

Distribution of volumes of individual glomeruli in kidneys at autopsy: association with age, nephron number, birth weight and body mass index.

PubMed

Hoy, W E; Hughson, M D; Zimanyi, M; Samuel, T; Douglas-Denton, R; Holden, L; Mott, S; Bertram, J F

2010-11-01

Glomerular hypertrophy occurs in a number of normal and pathological states. Glomerular volume in kidneys at autopsy is usually indirectly derived from estimates of total glomerular mass and nephron number, and provides only a single value per kidney, with no indication of the range of volumes of glomeruli within the kidney of any given subject. We review findings of the distribution of volumes of different glomeruli within subjects without kidney disease, and their correlations with age, nephron number, birth weight and body mass index (BMI). The study describes findings from autopsy kidneys of selected adult white males from the Southeast USA who had unexpected deaths, and who did not have renal scarring or renal disease. Total glomerular (nephron) number and total glomerular volume were estimated using the disector/fractionator combination, and mean glomerular volume (Vglom) was derived. The volumes of 30 individual glomeruli (IGV) in each subject were determined using the disector/Cavalieri method. IGV values were compared by categories of age, nephron number, birth weight and BMI. There was substantial variation in IGV within subjects. Older age, lower nephron number, lower birth weight and gross obesity were associated with higher mean IGV and with greater IGV heterogeneity. High Vglom and high IGVs were associated with more glomerulosclerosis. However, amongst the generally modest numbers of sclerosed glomeruli, the pattern was uniformly of ischemic collapse of the glomerular tuft. There was no detectable focal segmental glomerular tuft injury. In this series of people without overt renal disease, greater age, nephron deficit, lower birth weight and obesity were marked by glomerular enlargement and greater glomerular volume heterogeneity within individuals.

Distinct Contributions of TNF Receptor 1 and 2 to TNF-Induced Glomerular Inflammation in Mice

PubMed Central

Taubitz, Anela; Schwarz, Martin; Eltrich, Nuru; Lindenmeyer, Maja T.; Vielhauer, Volker

2013-01-01

TNF is an important mediator of glomerulonephritis. The two TNF-receptors TNFR1 and TNFR2 contribute differently to glomerular inflammation in vivo, but specific mechanisms of TNFR-mediated inflammatory responses in glomeruli are unknown. We investigated their expression and function in murine kidneys, isolated glomeruli ex vivo, and glomerular cells in vitro. In normal kidney TNFR1 and TNFR2 were preferentially expressed in glomeruli. Expression of both TNFRs and TNF-induced upregulation of TNFR2 mRNA was confirmed in murine glomerular endothelial and mesangial cell lines. In vivo, TNF exposure rapidly induced glomerular accumulation of leukocytes. To examine TNFR-specific inflammatory responses in intrinsic glomerular cells but not infiltrating leukocytes we performed microarray gene expression profiling on intact glomeruli isolated from wildtype and Tnfr-deficient mice following exposure to soluble TNF ex vivo. Most TNF-induced effects were exclusively mediated by TNFR1, including induced glomerular expression of adhesion molecules, chemokines, complement factors and pro-apoptotic molecules. However, TNFR2 contributed to TNFR1-dependent mRNA expression of inflammatory mediators in glomeruli when exposed to low TNF concentrations. Chemokine secretion was absent in TNF-stimulated Tnfr1-deficient glomeruli, but also significantly decreased in glomeruli lacking TNFR2. In vivo, TNF-induced glomerular leukocyte infiltration was abrogated in Tnfr1-deficient mice, whereas Tnfr2-deficiency decreased mononuclear phagocytes infiltrates, but not neutrophils. These data demonstrate that activation of intrinsic glomerular cells by soluble TNF requires TNFR1, whereas TNFR2 is not essential, but augments TNFR1-dependent effects. Previously described TNFR2-dependent glomerular inflammation may therefore require TNFR2 activation by membrane-bound, but not soluble TNF. PMID:23869211

Simultaneous assessment of glomerular filtration and barrier function in live zebrafish

PubMed Central

Kotb, Ahmed M.; Müller, Tobias; Xie, Jing; Anand-Apte, Bela; Endlich, Nicole

2014-01-01

The zebrafish pronephros is a well-established model to study glomerular development, structure, and function. A few methods have been described to evaluate glomerular barrier function in zebrafish larvae so far. However, there is a need to assess glomerular filtration as well. In the present study, we extended the available methods by simultaneously measuring the intravascular clearances of Alexa fluor 647-conjugated 10-kDa dextran and FITC-conjugated 500-kDa dextran as indicators of glomerular filtration and barrier function, respectively. After intravascular injection of the dextrans, mean fluorescence intensities of both dextrans were measured in the cardinal vein of living zebrafish (4 days postfertilization) by confocal microscopy over time. We demonstrated that injected 10-kDa dextran was rapidly cleared from the circulation, became visible in the lumen of the pronephric tubule, quickly accumulated in tubular cells, and was detectably excreted at the cloaca. In contrast, 500-kDa dextran could not be visualized in the tubule at any time point. To check whether alterations in glomerular function can be quantified by our method, we injected morpholino oligonucleotides (MOs) against zebrafish nonmuscle myosin heavy chain IIA (zMyh9) or apolipoprotein L1 (zApol1). While glomerular filtration was reduced in zebrafish nonmuscle myosin heavy chain IIA MO-injected larvae, glomerular barrier function remained intact. In contrast, in zebrafish apolipoprotein L1 MO-injected larvae, glomerular barrier function was compromised as 500-kDa dextran disappeared from the circulation and became visible in tubular cells. In summary, we present a novel method that allows to simultaneously assess glomerular filtration and barrier function in live zebrafish. PMID:25298528

Ultrafiltration membrane reactors for enzymatic resolution of amino acids: design model and optimization.

PubMed

Bódalo, A; Gómez, J L.; Gómez, E; Bastida, J; Máximo, M F.; Montiel, M C.

2001-03-08

In this paper the possibility of continuous resolution of DL-phenylalanine, catalyzed by L-aminoacylase in a ultrafiltration membrane reactor (UFMR) is presented. A simple design model, based on previous kinetic studies, has been demonstrated to be capable of describing the behavior of the experimental system. The model has been used to determine the optimal experimental conditions to carry out the asymmetrical hydrolysis of N-acetyl-DL-phenylalanine.

Enhancing performance and surface antifouling properties of polysulfone ultrafiltration membranes with salicylate-alumoxane nanoparticles

NASA Astrophysics Data System (ADS)

Mokhtari, Samaneh; Rahimpour, Ahmad; Shamsabadi, Ahmad Arabi; Habibzadeh, Setareh; Soroush, Masoud

2017-01-01

To improve the hydrophilicity and antifouling properties of polysulfone (PS) ultrafiltration membranes, we studied the use of salicylate-alumoxane (SA) nanoparticles as a novel hydrophilic additive. The effects of SA nanoparticles on the membrane characteristics and performance were investigated in terms of membrane structure, permeation flux, solute rejection, hydrophilicity, and antifouling ability. The new mixed-matrix membranes (MMMs) possess asymmetric structures. They have smaller finger-like pores and smoother surfaces than the neat PS membranes. The embedment of SA nanoparticles in the polymer matrix and the improvement of surface hydrophilicity were investigated. Ultrafiltration experiments indicated that the pure-water flux of the new MMMs initially increases with SA nanoparticles loading followed by a decrease at high loadings. Higher BSA solution flux was achieved for the MMMs compared to the neat PS membranes. Membranes with 1 wt.% SA nanoparticles exhibit the highest flux recovery ratio of 87% and the lowest irreversible fouling of 13%.

Novelties of combustion synthesized titania ultrafiltration membrane in efficient removal of methylene blue dye from aqueous effluent.

PubMed

Doke, Suresh M; Yadav, Ganapati D

2014-12-01

In this study, titania nanoparticles were synthesized by combustion and used to make ultrafiltration membrane. Characteristics of titania membranes such as textural evaluation, surface morphology, pure water permeability and protein rejection were investigated. Titania membrane sintered at 450 °C showed pure water permeability 11 × 10−2 L h−1 m−2 kPa−1 and 76% protein rejection. The membrane presented good water flux and retention properties with regards to protein and methylene blue dye. Ultrafiltration process was operated at lower pressure (100 kPa) and showed 99% removal of methylene blue using adsorptive micellar flocculation at sodium dodecyl sulfate concentration below its critical micellar concentration. Ferric chloride was used as the coagulant. The method of making titania membrane and its use are new. These studies can be extended to other dyes and pollutants.

Enhanced permeability and antifouling performance of cellulose acetate ultrafiltration membrane assisted by l-DOPA functionalized halloysite nanotubes.

PubMed

Mu, Keguang; Zhang, Dalun; Shao, Ziqiang; Qin, Dujian; Wang, Yalong; Wang, Shuo

2017-10-15

l-Dopa functionalized halloysite nanotubes (HNTs) were prepared by the self-polymerization of l-dopa in the weak alkaline condition. Then different contents of l-dopa coated HNTs (LPDHNTs) were blended into cellulose acetate to prepare enhanced performance ultrafiltration membranes via the phase inversion method. The HNTs and LPDHNTs were characterized by FTIR, XPS, and TEM anysis. And the membranes morphologies, separation performance, antifouling performance, mechanical properties and hydrophilicity were also investigated. It was found that the composite membranes exhibited excellent antifouling performance. The pure water flux of 3.0wt% LPDHNTs/CA membrane increased from 11.4Lm -2 h -1 to 92.9Lm -2 h -1 , while the EA rejection ratio of the membrane was about 91.2%. In addition, the mechanical properties of the resultant membranes were strengthened compared with the CA ultrafiltration membrane. Copyright © 2017 Elsevier Ltd. All rights reserved.

Use of the Hemobag® for Modified Ultrafiltration in a Jehovah’s Witness Patient Undergoing Cardiac Surgery

PubMed Central

Moskowitz, David M.; Klein, James J.; Shander, Aryeh; Perelman, Seth I.; McMurtry, Kirk A.; Cousineau, Katherine M.; Ergin, M. Arisan

2006-01-01

Abstract: Modified ultrafiltration is an important technique to concentrate the patient’s circulating blood volume and the residual whole blood in the extracorporeal circuit post-cardiopulmonary bypass. The Hemobag system is a device cleared by the US Food and Drug Administration and represents a novel and safe modification of traditional modified ultrafiltration systems. It is quick and easy to operate by the perfusionist during the hemoconcentration process. Hemoconcentration is accomplished by having the Hemobag “recovery loop” circuit separate from the extracorporeal circuit. This allows the surgeons to continue with surgery, decannulate, and administer protamine simultaneously while the Hemobag is in use. The successful use of the Hemobag in a Jehovah’s Witness patient has not been previously described in the literature. This case report describes how to set up and operate the Hemobag in a Jehovah’s Witness patient undergoing cardiac surgery that requires an extracorporeal circuit. PMID:17089515

Subfractionation, characterization and in-depth proteomic analysis of glomerular membrane vesicles in human urine

PubMed Central

Hogan, Marie C.; Johnson, Kenneth L.; Zenka, Roman M.; Charlesworth, M. Cristine; Madden, Benjamin J.; Mahoney, Doug W.; Oberg, Ann L.; Huang, Bing Q.; Nesbitt, Lisa L.; Bakeberg, Jason L.; Bergen, H. Robert; Ward, Christopher J.

2014-01-01

Urinary exosome-like vesicles (ELVs) are a heterogenous mixture (diameter 40–200nm) containing vesicles shed from all segments of the nephron including glomerular podocytes. Contamination with Tamm Horsfall protein (THP) oligomers has hampered their isolation and proteomic analysis. Here we improved ELV isolation protocols employing density centrifugation to remove THP and albumin, and isolated a glomerular membranous vesicle (GMV) enriched subfraction from 7 individuals identifying 1830 proteins and in 3 patients with glomerular disease identifying 5657 unique proteins. The GMV fraction was composed of podocin/podocalyxin positive irregularly shaped membranous vesicles and podocin/podocalyxin negative classical exosomes. Ingenuity pathway analysis identified integrin, actin cytoskeleton and RhoGDI signaling in the top three canonical represented signaling pathways and 19 other proteins associated with inherited glomerular diseases. The GMVs are of podocyte origin and the density gradient technique allowed isolation in a reproducible manner. We show many nephrotic syndrome proteins, proteases and complement proteins involved in glomerular disease are in GMVs and some were shed in the disease state (nephrin, TRPC6 and INF2 and PLA2R). We calculated sample sizes required to identify new glomerular disease biomarkers, expand the ELV proteome and provide a reference proteome in a database that may prove useful in the search for biomarkers of glomerular disease. PMID:24196483

Effect of picric acid and enzymatic creatinine on the efficiency of the glomerular filtration rate predicator formula.

PubMed

Qiu, Ling; Guo, Xiuzhi; Zhu, Yan; Shou, Weilin; Gong, Mengchun; Zhang, Lin; Han, Huijuan; Quan, Guoqiang; Xu, Tao; Li, Hang; Li, Xuewang

2013-01-01

To investigate the impact of serum creatinine measurement on the applicability of glomerular filtration rate (GFR) evaluation equations. 99mTc-DTPA plasma clearance rate was used as GFR reference (rGFR) in patients with chronic kidney disease (CKD). Serum creatinine was measureded using enzymatic or picric acid creatinine reagent. The GFR of the patients were estimated using the Cockcroft-Gault equation corrected for body surface area, simplified Modification of Diet in Renal Disease (MDRD) equation, simplified MDRD equation corrected to isotopes dilution mass spectrometry, the CKD epidemiology collaborative research equation, and two Chinese simplified MDRD equations. Significant differences in the eGFR results estimated through enzymatic and picric acid methods were observed for the same evaluation equation. The intraclass correlation coefficient (ICC) of eGFR when the creatinine was measured by the picric acid method was significantly lower than that of the enzymatic method. The assessment accuracy of every equation using the enzymatic method to measure creatinine was significantly higher than that measured by the picric acid method when rGFR was > or = 60 mL/min/1.73m2. A significant difference was demonstrated in the same GFR evaluation equation using the picric acid and enzymatic methods. The enzymatic creatinine method was better than the picric acid method.

Glomerular Endothelial Mitochondrial Dysfunction Is Essential and Characteristic of Diabetic Kidney Disease Susceptibility.

PubMed

Qi, Haiying; Casalena, Gabriella; Shi, Shaolin; Yu, Liping; Ebefors, Kerstin; Sun, Yezhou; Zhang, Weijia; D'Agati, Vivette; Schlondorff, Detlef; Haraldsson, Börje; Böttinger, Erwin; Daehn, Ilse

2017-03-01

The molecular signaling mechanisms between glomerular cell types during initiation/progression of diabetic kidney disease (DKD) remain poorly understood. We compared the early transcriptome profile between DKD-resistant C57BL/6J and DKD-susceptible DBA/2J (D2) glomeruli and demonstrated a significant downregulation of essential mitochondrial genes in glomeruli from diabetic D2 mice, but not in C57BL/6J, with comparable hyperglycemia. Diabetic D2 mice manifested increased mitochondrial DNA lesions (8-oxoguanine) exclusively localized to glomerular endothelial cells after 3 weeks of diabetes, and these accumulated over time in addition to increased urine secretion of 8-oxo-deoxyguanosine. Detailed assessment of glomerular capillaries from diabetic D2 mice demonstrated early signs of endothelial injury and loss of fenestrae. Glomerular endothelial mitochondrial dysfunction was associated with increased glomerular endothelin-1 receptor type A (Ednra) expression and increased circulating endothelin-1 (Edn1). Selective Ednra blockade or mitochondrial-targeted reactive oxygen species scavenging prevented mitochondrial oxidative stress of endothelial cells and ameliorated diabetes-induced endothelial injury, podocyte loss, albuminuria, and glomerulosclerosis. In human DKD, increased urine 8-oxo-deoxyguanosine was associated with rapid DKD progression, and biopsies from patients with DKD showed increased mitochondrial DNA damage associated with glomerular endothelial EDNRA expression. Our studies show that DKD susceptibility was linked to mitochondrial dysfunction, mediated largely by Edn1-Ednra in glomerular endothelial cells representing an early event in DKD progression, and suggest that cross talk between glomerular endothelial injury and podocytes leads to defects and depletion, albuminuria, and glomerulosclerosis. © 2017 by the American Diabetes Association.

Screening a fragment cocktail library using ultrafiltration

PubMed Central

Shibata, Sayaka; Zhang, Zhongsheng; Korotkov, Konstantin V.; Delarosa, Jaclyn; Napuli, Alberto; Kelley, Angela M.; Mueller, Natasha; Ross, Jennifer; Zucker, Frank H.; Buckner, Frederick S.; Merritt, Ethan A.; Verlinde, Christophe L. M. J.; Van Voorhis, Wesley C.; Hol, Wim G. J.; Fan, Erkang

2011-01-01

Ultrafiltration provides a generic method to discover ligands for protein drug targets with millimolar to micromolar Kd, the typical range of fragment-based drug discovery. This method was tailored to a 96-well format, and cocktails of fragment-sized molecules, with molecular masses between 150 and 300 Da, were screened against medical structural genomics target proteins. The validity of the method was confirmed through competitive binding assays in the presence of ligands known to bind the target proteins. PMID:21750879

Plasma ultrafiltrates from Fanconi Anemia patients induces chromosomal breakages in donor lymphocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Emerit, I.; Levy, A.; Pagano, G.

1994-09-01

The present study investigated the occurrence, if any, of transferable clastogenic activity in the plasma from Fanconi Anemia (FA) patients and their families. A total of 13 FA homozygotes, 25 parents, and 12 siblings were studied for their: (a) spontaneous and DEB-induced chromosomal instability, and (b) induction of chromosomal breaks in peripheral blood lymphocytes (PBL) from healthy donors, following exposure to plasma ultrafiltrates from FA subjects, their parents or siblings. Plasma was ultrafiltered through membranes with a cutoff at 10,000 daltons (YM 10 Amicon) and 0.25 ml-aliquote added to PBL from 14 healthy donors. DEB test provided FA confirmatory diagnosis.more » The occurrence of clastogenic factors (CF) was evident in all FA patients, except for one. In two out of three patients, who died during this study, very high CF levels were observed. Clastogenic activity was significantly higher in male than in female patients (p<0.05). No correlation was observed between CF data and spontaneous or DEB-induced chromosomal instability. Ultrafiltrates from parents and siblings showed less CF than FA homozygotes; however, concentration by ultrafiltration through YM 2 (3x to 5x) led to excess clastogenic activity. The control plasmas were lacking CF even after an 8x concentration. The present data suggest that CF formation in the plasma of FA patients is consistent with an in vivo prooxident state in FA.« less

Optimization of the elution buffer and concentration method for detecting hepatitis E virus in swine liver using a nested reverse transcription-polymerase chain reaction and real-time reverse transcription-polymerase chain reaction.

PubMed

Son, Na Ry; Seo, Dong Joo; Lee, Min Hwa; Seo, Sheungwoo; Wang, Xiaoyu; Lee, Bog-Hieu; Lee, Jeong-Su; Joo, In-Sun; Hwang, In-Gyun; Choi, Changsun

2014-09-01

The aim of this study was to develop an optimal technique for detecting hepatitis E virus (HEV) in swine livers. Here, three elution buffers and two concentration methods were compared with respect to enhancing recovery of HEV from swine liver samples. Real-time reverse transcription-polymerase chain reaction (RT-PCR) and nested RT-PCR were performed to detect HEV RNA. When phosphate-buffered saline (PBS, pH 7.4) was used to concentrate HEV in swine liver samples using ultrafiltration, real-time RT-PCR detected HEV in 6 of the 26 samples. When threonine buffer was used to concentrate HEV using polyethylene glycol (PEG) precipitation and ultrafiltration, real-time RT-PCR detected HEV in 1 and 3 of the 26 samples, respectively. When glycine buffer was used to concentrate HEV using ultrafiltration and PEG precipitation, real-time RT-PCR detected HEV in 1 and 3 samples of the 26 samples, respectively. When nested RT-PCR was used to detect HEV, all samples tested negative regardless of the type of elution buffer or concentration method used. Therefore, the combination of real-time RT-PCR and ultrafiltration with PBS buffer was the most sensitive and reliable method for detecting HEV in swine livers. Copyright © 2014 Elsevier B.V. All rights reserved.

Sequential peritoneal equilibration test: a new method for assessment and modelling of peritoneal transport.

PubMed

Galach, Magda; Antosiewicz, Stefan; Baczynski, Daniel; Wankowicz, Zofia; Waniewski, Jacek

2013-02-01

In spite of many peritoneal tests proposed, there is still a need for a simple and reliable new approach for deriving detailed information about peritoneal membrane characteristics, especially those related to fluid transport. The sequential peritoneal equilibration test (sPET) that includes PET (glucose 2.27%, 4 h) followed by miniPET (glucose 3.86%, 1 h) was performed in 27 stable continuous ambulatory peritoneal dialysis patients. Ultrafiltration volumes, glucose absorption, ratio of concentration in dialysis fluid to concentration in plasma (D/P), sodium dip (Dip D/P Sodium), free water fraction (FWF60) and the ultrafiltration passing through small pores at 60 min (UFSP60), were calculated using clinical data. Peritoneal transport parameters were estimated using the three-pore model (3p model) and clinical data. Osmotic conductance for glucose was calculated from the parameters of the model. D/P creatinine correlated with diffusive mass transport parameters for all considered solutes, but not with fluid transport characteristics. Hydraulic permeability (L(p)S) correlated with net ultrafiltration from miniPET, UFSP60, FWF60 and sodium dip. The fraction of ultrasmall pores correlated with FWF60 and sodium dip. The sequential PET described and interpreted mechanisms of ultrafiltration and solute transport. Fluid transport parameters from the 3p model were independent of the PET D/P creatinine, but correlated with fluid transport characteristics from PET and miniPET.

Novel Functional Whey-Based Drinks with Great Potential in the Dairy Industry

PubMed Central

Pereira, Carlos; Gomes, David; Gomez-Zavaglia, Andrea; de Antoni, Graciela

2015-01-01

Summary This work focuses on the production of liquid whey protein concentrates by ultrafiltration followed by thermal denaturation and homogenization of the ultrafiltrated concentrate, as well as on the production of ultrafiltrated permeates concentrated by reverse osmosis. Kefir grains (fresh and thawed) and/or commercial probiotic bacteria were inoculated in both liquid whey protein concentrates and concentrated ultrafiltrated permeates and grown at 25 °C for 24 h for the manufacture of fermented drinks. The physicochemical characterization (pH, titratable acidity, viscosity, and content of total solids, ash, fat and proteins) of the obtained drinks was then assessed and compared. Enumeration of viable microorganisms was carried out immediately after inoculation (at 0 h), during the fermentation period (at 12 and 24 h) and during refrigerated storage (at 48, 168 and 336 h). The fermented drinks showed acceptable physicochemical and sensorial properties, and contained above 7 log CFU/mL of lactococci and lactobacilli and 6 log CFU/mL of yeasts after 14 days of refrigerated storage, which is in agreement with the standards required by international organizations like European Food Safety Authority (EFSA) and Food and Drug Administration (FDA) for products containing probiotics. In summary, the strategy developed in this work contributes to the expansion of the applications of products derived from whey fractionation for the design of novel functional foods. PMID:27904362

Marine microalgae Nannochloropsis oculata biomass harvesting using ultrafiltration in cross-flow mode

NASA Astrophysics Data System (ADS)

Devianto, L. A.; Aprilia, D. N.; Indriani, D. W.; Sukarni, S.; Sumarlan, S. H.; Wibisono, Y.

2018-03-01

Microalgae is a potential bioenergy source. It can grows rapidly, even it could be harvested within 7 days. Harvesting is an important part of microalgae cultivation due to the method used. It should be undamaging toward essential content of microalgae and should produces high yields of biomass. In this study, the harvesting of Nannochloropsis oculata was carried out using capillary ultrafiltration in cross flow mode. This study aims to test ultrafiltration membrane performance in Nannochloropsis oculata harvesting accompanied by Backwash and Non-Backwash modes and to analyse its total lipid content. The harvest was done under 1; 1.5; and 2 bar of trans membrane pressure. Some observed parameters were permeate flux, cell density, biomass recovery, microalgae’s dry weight, yield, and total lipid content. The application of high pressure and backwashed treatment have boosted slurry production time which lead to microalgae’s biomass abundance. The result showed that the best treatment of Nannochloropsis oculata harvesting using capillary ultrafiltration membrane in cross flow mode is under 2 bar of pressure with backwashed treatment. This is the fastest condition to produce slurry within 1800 s with the highest recovery percentage 79.50%, 16.05 × 106 cell/ml of post-treatment cell density, 6.8 grams of biomass’ dry weight, 22.66 % of yield, and 2.52 % of total lipid content.

Novel Functional Whey-Based Drinks with Great Potential in the Dairy Industry.

PubMed

Pereira, Carlos; Henriques, Marta; Gomes, David; Gomez-Zavaglia, Andrea; de Antoni, Graciela

2015-09-01

This work focuses on the production of liquid whey protein concentrates by ultrafiltration followed by thermal denaturation and homogenization of the ultrafiltrated concentrate, as well as on the production of ultrafiltrated permeates concentrated by reverse osmosis. Kefir grains (fresh and thawed) and/or commercial probiotic bacteria were inoculated in both liquid whey protein concentrates and concentrated ultrafiltrated permeates and grown at 25 °C for 24 h for the manufacture of fermented drinks. The physicochemical characterization (pH, titratable acidity, viscosity, and content of total solids, ash, fat and proteins) of the obtained drinks was then assessed and compared. Enumeration of viable microorganisms was carried out immediately after inoculation (at 0 h), during the fermentation period (at 12 and 24 h) and during refrigerated storage (at 48, 168 and 336 h). The fermented drinks showed acceptable physicochemical and sensorial properties, and contained above 7 log CFU/mL of lactococci and lactobacilli and 6 log CFU/mL of yeasts after 14 days of refrigerated storage, which is in agreement with the standards required by international organizations like European Food Safety Authority (EFSA) and Food and Drug Administration (FDA) for products containing probiotics. In summary, the strategy developed in this work contributes to the expansion of the applications of products derived from whey fractionation for the design of novel functional foods.

Laboratory Tests on Post-Filtration Precipitation in the WTP Pretreatment Process

DOE Office of Scientific and Technical Information (OSTI.GOV)

Russell, Renee L.; Peterson, Reid A.; Rinehart, Donald E.

Pacific Northwest National Laboratory (PNNL) has been tasked by Bechtel National Inc. (BNI) on the River Protection Project-Hanford Tank Waste Treatment and Immobilization Plant (RPP-WTP) project to perform research and development activities to resolve technical issues identified for the Pretreatment Facility (PTF). The Pretreatment Engineering Platform (PEP) was designed, constructed, and operated as part of a plan to respond to issue M12, "Undemonstrated Leaching Processes," of the External Flowsheet Review Team (EFRT) issue response plan (Barnes et al. 2006). The PEP is a 1/4.5-scale test platform designed to simulate the WTP pretreatment caustic leaching, oxidative leaching, ultrafiltration solids concentration, andmore » slurry washing processes. The PEP replicates the WTP leaching processes using prototypic equipment and control strategies. A simplified flow diagram of the PEP system is shown in Figure 1.1. Two operating scenarios are currently being evaluated for the ultrafiltration process (UFP) and leaching operations. The first scenario has caustic leaching performed in the UFP-2 ultrafiltration feed vessels (i.e., vessel UFP-VSL-T02A in the PEP; and vessels UFP-VSL-00002A and B in the WTP PTF). The second scenario has caustic leaching conducted in the UFP-1 ultrafiltration feed preparation vessels (i.e., vessels UFP-VSL-T01A and B in the PEP; vessels UFP-VSL-00001A and B in the WTP PTF).« less

THE GLOMERULAR MESANGIUM

PubMed Central

Mauer, S. Michael; Sutherland, David E. R.; Howard, Richard J.; Fish, Alfred J.; Najarian, John S.; Michael, Alfred F.

1973-01-01

A mechanism of immune glomerular injury is described based on the fixation of antibody (Ab) to an antigen (Ag) that has localized in the glomerular mesangium. Rabbits were given, intravenously (i.v.), aggregated human IgG (AHIgG) or albumin (AHSA) and 10 h later, when the Ag by immunofluorescent microscopy was present in the mesangium, a kidney was removed and transplanted into a normal rabbit. The recipient then received, i.v., rabbit anti-HIgG or anti-HSA. Within minutes of Ab infusion, glomeruli of the donor kidney had polymorphonuclear (PMN) infiltration that over the next few hours became marked and was associated with glomerular cell swelling. At 24 h a decrease in PMN's and early mesangial proliferation was seen. By 3 days there was marked mesangial hypercellularity and increased mesangial matrix. Within minutes after Ab administration rabbit IgG, C3, and fibrin were seen in the glomerular mesangium. There was a fall in complement titer by 1 min after Ab infusion that was due to complement consumption by the donor kidney. Complement then returned to normal levels by 48 h. Significant glomerular injury did not occur (a) in the recipient's own kidney, (b) from Ag administration and transplantation without recipient Ab administration, or (c) from transplantation and Ab administration without prior Ag administration. These studies demonstrated that Ag localized in the glomerular mesangium can react with circulating Ab and complement resulting in severe glomerular injury. PMID:4570015

Distribution of endogenous albumin in the glomerular wall of proteinuric patients.

PubMed Central

Russo, P. A.; Bendayan, M.

1990-01-01

Glomerular proteinuria seems to be related, in part, to loss or impairment of the normal barrier function of the glomerular capillary wall. To investigate the functional properties of this barrier, endogenous albumin was revealed in the glomerular wall of proteinuric patients and compared with a nonproteinuric control by immunoelectron microscopy using the protein A-gold method. In the control biopsy, peaks of albumin accumulation were noted in the subendothelial area and in the inner portion of the lamina densa, with gradual tapering of the distribution toward the epithelial side of the basement membrane. The urinary space and epithelial cells were weakly labeled. In tissues from proteinuric patients, albumin was distributed throughout the entire width of the glomerular basement membrane, although the pattern of accumulation varied between patients. The urinary space showed significant labeling associated with some flocculent material. Mesangial areas were heavily labeled in tissues from both control and proteinuric patients. In the latter, lysozomes in glomerular and tubular epithelial cells also accumulated albumin, which is evidence of reabsorption. These results reveal the existence, in normal conditions, of a barrier located in the subendothelial area of the glomerular basement membrane, the loss of which, as in the idiopathic nephrotic syndrome, leads to diffuse distribution of albumin in the glomerular capillary wall. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:2260634

Genetic Background is a Key Determinant of Glomerular Extracellular Matrix Composition and Organization

PubMed Central

Randles, Michael J.; Woolf, Adrian S.; Huang, Jennifer L.; Byron, Adam; Humphries, Jonathan D.; Price, Karen L.; Kolatsi-Joannou, Maria; Collinson, Sophie; Denny, Thomas; Knight, David; Mironov, Aleksandr; Starborg, Toby; Korstanje, Ron; Humphries, Martin J.; Long, David A.

2015-01-01

Glomerular disease often features altered histologic patterns of extracellular matrix (ECM). Despite this, the potential complexities of the glomerular ECM in both health and disease are poorly understood. To explore whether genetic background and sex determine glomerular ECM composition, we investigated two mouse strains, FVB and B6, using RNA microarrays of isolated glomeruli combined with proteomic glomerular ECM analyses. These studies, undertaken in healthy young adult animals, revealed unique strain- and sex-dependent glomerular ECM signatures, which correlated with variations in levels of albuminuria and known predisposition to progressive nephropathy. Among the variation, we observed changes in netrin 4, fibroblast growth factor 2, tenascin C, collagen 1, meprin 1-α, and meprin 1-β. Differences in protein abundance were validated by quantitative immunohistochemistry and Western blot analysis, and the collective differences were not explained by mutations in known ECM or glomerular disease genes. Within the distinct signatures, we discovered a core set of structural ECM proteins that form multiple protein–protein interactions and are conserved from mouse to man. Furthermore, we found striking ultrastructural changes in glomerular basement membranes in FVB mice. Pathway analysis of merged transcriptomic and proteomic datasets identified potential ECM regulatory pathways involving inhibition of matrix metalloproteases, liver X receptor/retinoid X receptor, nuclear factor erythroid 2-related factor 2, notch, and cyclin-dependent kinase 5. These pathways may therefore alter ECM and confer susceptibility to disease. PMID:25896609

Prostaglandin E1 reduces the glomerular mRNA expression of monocyte-chemoattractant protein 1 in anti-thymocyte antibody-induced glomerular injury.

PubMed

Jocks, T; Zahner, G; Freudenberg, J; Wolf, G; Thaiss, F; Helmchen, U; Stahl, R A

1996-06-01

To study whether prostaglandins (PG) can regulate the mRNA expression of monocyte-chemoattractant protein 1 (MCP-1) in glomerular immune injury, MCP-1 mRNA levels were evaluated in anti-thymocyte antibody (ATS) -induced glomerular injury by Northern blotting and reverse transcription-polymerase chain reaction. Immune injury was induced in vivo by the intravenous application of ATS to male Wistar rats and in vitro by the perfusion of isolated rat kidneys with ATS and rat serum. In vivo 3 h and 5 days after antibody application, glomerular mRNA expression of MCP-1 was markedly enhanced compared with controls. In the isolated perfused kidney, antibody and complement also induced an increase in MCP-1 expression at 10 min and 60 min after antibody perfusion. When the rats were treated with PGE (250 micrograms, twice daily), the increase in MCP-1 expression was reduced. This was associated with a reduction of intraglomerular recruitment of monocytes/macrophages. In the isolated perfused kidneys, PGE1 (1 mg/L) prevented the antibody- and rat serum-stimulated increase in glomerular MCP-1 mRNA expression. These data demonstrate that PGE1 reduces glomerular MCP-1 mRNA expression in glomerulonephritis and in the isolated perfused rat kidney after induction of immune injury with antibody and complement. The data suggest that prostaglandins might mediate MCP-1 effects in glomerular immune injuries.

A validated inductively coupled plasma mass spectrometry (ICP-MS) method for the quantification of total platinum content in plasma, plasma ultrafiltrate, urine and peritoneal fluid.

PubMed

Lemoine, Lieselotte; Thijssen, Elsy; Noben, Jean-Paul; Adriaensens, Peter; Carleer, Robert; Speeten, Kurt Van der

2018-04-15

Oxaliplatin is a platinum (Pt) 1 containing antineoplastic agent that is applied in current clinical practice for the treatment of colon and appendiceal neoplasms. A fully validated, highly sensitive, high throughput inductively coupled plasma mass spectrometry (ICP-MS) method is provided to quantify the total Pt content in plasma, plasma ultrafiltrate, urine and peritoneal fluid. In this ICP-MS approach, the only step of sample preparation is a 1000-fold dilution in 0.5% nitric acid, allowing the analysis of 17 samples per hour. Detection of Pt was achieved over a linear range of 0.01-100 ng/mL. The limit of quantification was 18.0 ng/mL Pt in plasma, 8.0 ng/mL in ultrafiltrate and 6.1 ng/mL in urine and peritoneal fluid. The ICP-MS method was further validated for inter-and intraday precision and accuracy (≤15%), recovery, robustness and stability. Short-term storage of the biofluids, for 14 days, can be performed at -4 °C, -24 °C and -80 °C. As to long-term stability, up to 5 months, storage at -80 °C is encouraged. Furthermore, a timeline assessing the total and unbound Pt fraction in plasma and ultrafiltrate over a period of 45 h is provided. Following an incubation period of 5 h at 37 °C, 19-21% of Pt was recovered in the ultrafiltrate, emphasizing the extensive and rapid binding of oxaliplatin-derived Pt to plasma proteins. The described method can easily be implemented in a routine setting for pharmacokinetic studies in patients treated with oxaliplatin-based hyperthermic intraperitoneal perioperative chemotherapy. Copyright © 2018 Elsevier B.V. All rights reserved.

Excess Podocyte Semaphorin-3A Leads to Glomerular Disease Involving PlexinA1–Nephrin Interaction

PubMed Central

Reidy, Kimberly J.; Aggarwal, Pardeep K.; Jimenez, Juan J.; Thomas, David B.; Veron, Delma; Tufro, Alda

2014-01-01

Semaphorin-3A (Sema3a), a guidance protein secreted by podocytes, is essential for normal kidney patterning and glomerular filtration barrier development. Here, we report that podocyte-specific Sema3a gain-of-function in adult mice leads to proteinuric glomerular disease involving the three layers of the glomerular filtration barrier. Reversibility of the glomerular phenotype upon removal of the transgene induction provided proof-of-principle of the cause-and-effect relationship between podocyte Sema3a excess and glomerular disease. Mechanistically, excess Sema3a induces dysregulation of nephrin, matrix metalloproteinase 9, and αvβ3 integrin in vivo. Sema3a cell-autonomously disrupts podocyte shape. We identified a novel direct interaction between the Sema3a signaling receptor plexinA1 and nephrin, linking extracellular Sema3a signals to the slit-diaphragm signaling complex. We conclude that Sema3a functions as an extracellular negative regulator of the structure and function of the glomerular filtration barrier in the adult kidney. Our findings demonstrate a crosstalk between Sema3a and nephrin signaling pathways that is functionally relevant both in vivo and in vitro. PMID:23954273

Different methods of hilar clamping during partial nephrectomy: Impact on renal function.

PubMed

Lee, Jeong Woo; Kim, Hwanik; Choo, Minsoo; Park, Yong Hyun; Ku, Ja Hyeon; Kim, Hyeon Hoe; Kwak, Cheol

2014-03-01

To evaluate the impact of different hilar clamping methods on changes in renal function after partial nephrectomy. We analyzed the clinical data of 369 patients who underwent partial nephrectomy for a single renal tumor of size ≤4.0 cm and a normal contralateral kidney. Patients were separated into three groups depending on hilar clamping method: non-clamping, cold ischemia and warm ischemia. Estimated glomerular filtration rate was examined at preoperative, nadir and 1 year postoperatively. Percent change in estimated glomerular filtration rate was used as the parameter to assess the renal functional outcome. Percent change in nadir estimated glomerular filtration rate in the non-clamping group was significantly less compared with the cold ischemia and warm ischemia groups (P < 0.001). However, no significant differences among the groups were noted in percent change of estimated glomerular filtration rate at 1 year (P = 0.348). The cold ischemia group had a similar serial change of postoperative renal function compared with the warm ischemia group. Percent change in 1-year estimated glomerular filtration rate increased with increasing ischemia time in the cold ischemia (P for trend = 0.073) and warm ischemia groups (P for trend = 0.010). On multivariate analysis, hilar clamping (both warm ischemia and cold ischemia) were significantly associated with percent change in nadir estimated glomerular filtration rate, but not in 1-year estimated glomerular filtration rate. Non-clamping partial nephrectomy results in a lower percent change in nadir estimated glomerular filtration rate, whereas it carries an estimated glomerular filtration rate change at 1 year that is similar to partial nephrectomy with cold ischemia and warm ischemia. Cold ischemia and warm ischemia provide a similar effect on renal function. Therefore, when hilar clamping is required, minimization of ischemia time is necessary. © 2013 The Japanese Urological Association.

A general diagram for estimating pore size of ultrafiltration and reverse osmosis membranes

NASA Technical Reports Server (NTRS)

Sarbolouki, M. N.

1982-01-01

A slit sieve model has been used to develop a general correlation between the average pore size of the upstream surface of a membrane and the molecular weight of the solute which it retains by better than 80%. The pore size is determined by means of the correlation using the high retention data from an ultrafiltration (UF) or a reverse osmosis (RO) experiment. The pore population density can also be calculated from the flux data via appropriate equations.

"All that glisters is not gold": Ultrafiltration and free thyroxine measurement With apologies to W Shakespeare.

PubMed

Midgley, John E M

2011-02-01

To examine the merits of measuring free analytes by ultrafiltration using either diluted or undiluted serum. Confidence in the accuracy of measurements is affected both by problems identified in current systems using semipermeable membranes, the sensitivity of the system to artefacts and comparisons with other imperfect assays. All "gold standard" methods must robustly obey sound physicochemical principles if valid conclusions are to be drawn. Copyright © 2010 Elsevier Inc. All rights reserved.

A Low Cost Environmentally Benign Waste Lubricants Recycling/Re-refining Technology.

DTIC Science & Technology

1999-05-01

EXPERIMENTAL 3 2.1 Ceramic Membrane Ultrafiltration Pilot Unit 3 2.2 Polishing/Finishing Pilot Unit 3 2.3 Feed Samples 3 2.4 Sample...development of an additional 2 to 3 sites in the US. 2. EXPERIMENTAL 2.1. Ceramic Membrane Ultrafiltration Pilot Unit A photograph of the pilot...scale ceramic membrane system used in this work is shown in Figure la. Samples of spent turbine oil were charged to the feed tank and heated to 150°C

Falsely Elevated Plasma Creatinine Due to an Immunoglobulin M Paraprotein.

PubMed

McGill, Mitchell R; Vijayan, Anitha; Trulock, Elbert P; Witt, Chad A; Kohler, Giselle D; Scott, Mitchell G

2016-11-01

The most common method for measuring plasma creatinine is based on its reaction with picric acid. However, enzymatic methods are becoming more popular due to improved specificity. We present a case of falsely elevated plasma creatinine values obtained by an enzymatic method that turned out to be due to a monoclonal immunoglobulin M (IgM) paraprotein. A 63-year-old woman evaluated for lung transplantation had falsely increased plasma creatinine levels (1.54-1.71mg/dL; corresponding to estimated glomerular filtration rates of 32-36 mL/min/1.73m 2 ) as measured by the Roche Creatinine plus enzymatic assay when compared with the picric acid-based procedure and several other enzymatic methods, which gave plasma creatinine values of 0.7 to 0.8mg/dL. Serum protein electrophoresis revealed an IgM κ light chain paraprotein. Removal of high-molecular-weight (>30kDa) proteins by ultrafiltration reduced the patient's plasma creatinine level by the Roche enzymatic method to 0.7mg/dL. Addition of the patient's immunoglobulin fraction to plasma from other patients with normal plasma creatinine levels resulted in values that were increased by 0.58 to 0.62mg/dL. Furthermore, removal of non-IgM immunoglobulins with protein G-coupled beads did not eliminate the interference from the patient's plasma. Taken together, these studies demonstrate that falsely elevated plasma creatinine values by the Roche enzymatic method can be due to an IgM paraprotein. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Effector CD4+ T cells recognize intravascular antigen presented by patrolling monocytes.

PubMed

Westhorpe, Clare L V; Norman, M Ursula; Hall, Pam; Snelgrove, Sarah L; Finsterbusch, Michaela; Li, Anqi; Lo, Camden; Tan, Zhe Hao; Li, Songhui; Nilsson, Susan K; Kitching, A Richard; Hickey, Michael J

2018-02-21

Although effector CD4 + T cells readily respond to antigen outside the vasculature, how they respond to intravascular antigens is unknown. Here we show the process of intravascular antigen recognition using intravital multiphoton microscopy of glomeruli. CD4 + T cells undergo intravascular migration within uninflamed glomeruli. Similarly, while MHCII is not expressed by intrinsic glomerular cells, intravascular MHCII-expressing immune cells patrol glomerular capillaries, interacting with CD4 + T cells. Following intravascular deposition of antigen in glomeruli, effector CD4 + T-cell responses, including NFAT1 nuclear translocation and decreased migration, are consistent with antigen recognition. Of the MHCII + immune cells adherent in glomerular capillaries, only monocytes are retained for prolonged durations. These cells can also induce T-cell proliferation in vitro. Moreover, monocyte depletion reduces CD4 + T-cell-dependent glomerular inflammation. These findings indicate that MHCII + monocytes patrolling the glomerular microvasculature can present intravascular antigen to CD4 + T cells within glomerular capillaries, leading to antigen-dependent inflammation.

Early chronic low-level lead exposure produces glomerular hypertrophy in young C57BL/6J mice☆

PubMed Central

Basgen, John M.; Sobin, Christina

2014-01-01

Early chronic lead exposure continues to pose serious health risks for children, particularly those living in lower socioeconomic environments. This study examined effects on developing glomeruli in young C57BL/6J mice exposed to low (30 ppm), higher (330 ppm) or no lead via dams’ drinking water from birth to sacrifice on post-natal day 28. Low-level lead exposed mice [BLL mean (SD); 3.19 (0.70) μg/dL] had an increase in glomerular volume but no change in podocyte number compared to control mice [0.03 (0.01) μg/dL]. Higher-level lead exposed mice [14.68 (2.74) μg/dL] had no change in either glomerular volume or podocyte number. The increase in glomerular volume was explained by increases in glomerular capillary and mesangial volumes with no change in podocyte volume. Early chronic lead exposure yielding very low blood lead levels alters glomerular development in pre-adolescent animals. PMID:24300173

Cobalt treatment does not prevent glomerular morphological alterations in type 1 diabetic rats.

PubMed

Singh, Gaaminepreet; Krishan, Pawan

2018-06-02

Early renal morphological alterations including glomerular hypertrophy and mesangial expansion occur in diabetic kidney disease and correlate with various clinical manifestations of diabetes. The present study was designed to investigate the influence of pharmacological modulation of HIF-1α (hypoxia inducible factor-1 alpha) protein levels, on these glomerular changes in rodent model of type 1 diabetes. Male wistar rats were made diabetic (Streptozotocin 45 mg/kg; i.p.) and afterwards treated with HIF activator cobalt chloride for 4 weeks. Renal function was assessed by serum creatinine, albumin, proteinuria levels, oxidative stress: reduced glutathione levels and catalase activity, and renal tissue HIF-1α protein levels were determined by ELISA assay. Histological analysis of kidney sections was done by haematoxylin and eosin (glomeruli diameter), periodic acid Schiff (mesangial expansion and glomerulosclerosis) and sirius red (fibrosis, tubular dilation) staining. Diabetes rats displayed reduced serum albumin levels, marked proteinuria, lower kidney reduced glutathione content, glomerular hypertrophy, glomerulosclerosis, mesangial expansion, tubular dilation and renal fibrosis. Cobalt chloride treatment normalised renal HIF-1α protein levels, reduced development of proteinuria and tubulo-interstitial fibrosis, but the glomerular morphological alterations such as glomerulosclerosis, mesangial expansion, increased glomerular diameter and tubular vacoulations were not abrogated in diabetic kidneys. Glomerular morphological abnormalities might precede the development of proteinuria and renal fibrosis in experimental model of type 1 diabetes. Pharmacological modulation of renal HIF-1α protein levels does not influence glomerular and tubular dilatory changes in diabetic kidney disease.

Genetic Background is a Key Determinant of Glomerular Extracellular Matrix Composition and Organization.

PubMed

Randles, Michael J; Woolf, Adrian S; Huang, Jennifer L; Byron, Adam; Humphries, Jonathan D; Price, Karen L; Kolatsi-Joannou, Maria; Collinson, Sophie; Denny, Thomas; Knight, David; Mironov, Aleksandr; Starborg, Toby; Korstanje, Ron; Humphries, Martin J; Long, David A; Lennon, Rachel

2015-12-01

Glomerular disease often features altered histologic patterns of extracellular matrix (ECM). Despite this, the potential complexities of the glomerular ECM in both health and disease are poorly understood. To explore whether genetic background and sex determine glomerular ECM composition, we investigated two mouse strains, FVB and B6, using RNA microarrays of isolated glomeruli combined with proteomic glomerular ECM analyses. These studies, undertaken in healthy young adult animals, revealed unique strain- and sex-dependent glomerular ECM signatures, which correlated with variations in levels of albuminuria and known predisposition to progressive nephropathy. Among the variation, we observed changes in netrin 4, fibroblast growth factor 2, tenascin C, collagen 1, meprin 1-α, and meprin 1-β. Differences in protein abundance were validated by quantitative immunohistochemistry and Western blot analysis, and the collective differences were not explained by mutations in known ECM or glomerular disease genes. Within the distinct signatures, we discovered a core set of structural ECM proteins that form multiple protein-protein interactions and are conserved from mouse to man. Furthermore, we found striking ultrastructural changes in glomerular basement membranes in FVB mice. Pathway analysis of merged transcriptomic and proteomic datasets identified potential ECM regulatory pathways involving inhibition of matrix metalloproteases, liver X receptor/retinoid X receptor, nuclear factor erythroid 2-related factor 2, notch, and cyclin-dependent kinase 5. These pathways may therefore alter ECM and confer susceptibility to disease. Copyright © 2015 by the American Society of Nephrology.

Compensatory Structural and Functional Adaptation after Radical Nephrectomy for Renal Cell Carcinoma According to Preoperative Stage of Chronic Kidney Disease.

PubMed

Choi, Don Kyoung; Jung, Se Bin; Park, Bong Hee; Jeong, Byong Chang; Seo, Seong Il; Jeon, Seong Soo; Lee, Hyun Moo; Choi, Han-Yong; Jeon, Hwang Gyun

2015-10-01

We investigated structural hypertrophy and functional hyperfiltration as compensatory adaptations after radical nephrectomy in patients with renal cell carcinoma according to the preoperative chronic kidney disease stage. We retrospectively identified 543 patients who underwent radical nephrectomy for renal cell carcinoma between 1997 and 2012. Patients were classified according to preoperative glomerular filtration rate as no chronic kidney disease--glomerular filtration rate 90 ml/minute/1.73 m(2) or greater (230, 42.4%), chronic kidney disease stage II--glomerular filtration rate 60 to less than 90 ml/minute/1.73 m(2) (227, 41.8%) and chronic kidney disease stage III--glomerular filtration rate 30 to less than 60 ml/minute/1.73 m(2) (86, 15.8%). Computerized tomography performed within 2 months before surgery and 1 year after surgery was used to assess functional renal volume for measuring the degree of hypertrophy of the remnant kidney, and the preoperative and postoperative glomerular filtration rate per unit volume of functional renal volume was used to calculate the degree of hyperfiltration. Among all patients (mean age 56.0 years) mean preoperative glomerular filtration rate, functional renal volume and glomerular filtration rate/functional renal volume were 83.2 ml/minute/1.73 m(2), 340.6 cm(3) and 0.25 ml/minute/1.73 m(2)/cm(3), respectively. The percent reduction in glomerular filtration rate was statistically significant according to chronic kidney disease stage (no chronic kidney disease 31.2% vs stage II 26.5% vs stage III 12.8%, p <0.001). However, the degree of hypertrophic functional renal volume in the remnant kidney was not statistically significant (no chronic kidney disease 18.5% vs stage II 17.3% vs stage III 16.5%, p=0.250). The change in glomerular filtration rate/functional renal volume was statistically significant (no chronic kidney disease 18.5% vs stage II 20.1% vs stage III 45.9%, p <0.001). Factors that increased glomerular filtration rate/functional renal volume above the mean value were body mass index (p=0.012), diabetes mellitus (p=0.023), hypertension (p=0.015) and chronic kidney disease stage (p <0.001). Patients with a lower preoperative glomerular filtration rate had a smaller reduction in postoperative renal function than those with a higher preoperative glomerular filtration rate due to greater degrees of functional hyperfiltration. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Cystatin C-Based Equation Does Not Accurately Estimate the Glomerular Filtration in Japanese Living Kidney Donors.

PubMed

Tsujimura, Kazuma; Ota, Morihito; Chinen, Kiyoshi; Adachi, Takayuki; Nagayama, Kiyomitsu; Oroku, Masato; Nishihira, Morikuni; Shiohira, Yoshiki; Iseki, Kunitoshi; Ishida, Hideki; Tanabe, Kazunari

2017-06-23

BACKGROUND Precise evaluation of a living donor's renal function is necessary to ensure adequate residual kidney function after donor nephrectomy. Our aim was to evaluate the feasibility of estimating glomerular filtration rate (GFR) using serum cystatin-C prior to kidney transplantation. MATERIAL AND METHODS Using the equations of the Japanese Society of Nephrology, we calculated the GFR using serum creatinine (eGFRcre) and cystatin C levels (eGFRcys) for 83 living kidney donors evaluated between March 2010 and March 2016. We compared eGFRcys and eGFRcre values against the creatinine clearance rate (CCr). RESULTS The study population included 27 males and 56 females. The mean eGFRcys, eGFRcre, and CCr were, 91.4±16.3 mL/min/1.73 m² (range, 59.9-128.9 mL/min/1.73 m²), 81.5±14.2 mL/min/1.73 m² (range, 55.4-117.5 mL/min/1.73 m²) and 108.4±21.6 mL/min/1.73 m² (range, 63.7-168.7 mL/min/1.73 m²), respectively. eGFRcys was significantly lower than CCr (p<0.001). The correlation coefficient between eGFRcys and CCr values was 0.466, and the mean difference between the two values was -17.0 (15.7%), with a root mean square error of 19.2. Thus, eGFRcre was significantly lower than CCr (p<0.001). The correlation coefficient between eGFRcre and CCr values was 0.445, and the mean difference between the two values was -26.9 (24.8%), with a root mean square error of 19.5. CONCLUSIONS Although eGFRcys provided a better estimation of GFR than eGFRcre, eGFRcys still did not provide an accurate measure of kidney function in Japanese living kidney donors.

More Efficient Sodium Removal by Ultrafiltration Compared to Diuretics in Acute Heart Failure; Underexplored and Overstated.

PubMed

Kazory, Amir

2016-01-01

Enhanced removal of sodium has often been cited as an advantage of ultrafiltration (UF) therapy over diuretic-based medical treatment in the management of acute decompensated heart failure. However, so far clinical studies have rarely evaluated the precise magnitude of sodium removal, and this assumption is largely based on the physiologic mechanisms and anecdotal observations that predate the contemporary management of heart failure. Recent data suggest that patients treated with UF experience substantial reduction in urinary sodium excretion possibly due to prolonged intravascular volume contraction. Consequently, the efficient sodium extraction through production of isotonic ultrafiltrate can be offset by urine hypotonicity. Based on the limited currently available data, it seems unlikely that the persistent benefits of UF could be solely explained by its greater efficiency in sodium removal. The design of the future studies should include frequent measurements of urine sodium to precisely compare the impact of UF and diuretics on sodium balance. © 2016 S. Karger AG, Basel.

Ultrafiltration of skimmed goat milk increases its nutritional value by concentrating nonfat solids such as proteins, Ca, P, Mg, and Zn.

PubMed

Moreno-Montoro, Miriam; Olalla, Manuel; Giménez-Martínez, Rafael; Bergillos-Meca, Triana; Ruiz-López, María Dolores; Cabrera-Vique, Carmen; Artacho, Reyes; Navarro-Alarcón, Miguel

2015-11-01

Goat milk has been reported to possess good nutritional and health-promoting properties. Usually, it must be concentrated before fermented products can be obtained. The aim of this study was to compare physicochemical and nutritional variables among raw (RM), skimmed (SM), and ultrafiltration-concentrated skimmed (UFM) goat milk. The density, acidity, ash, protein, casein, whey protein, Ca, P, Mg, and Zn values were significantly higher in UFM than in RM or SM. Dry extract and fat levels were significantly higher in UFM than in SM, and Mg content was significantly higher in UFM than in RM. Ultrafiltration also increased the solubility of Ca and Mg, changing their distribution in the milk. The higher concentrations of minerals and proteins, especially caseins, increase the nutritional value of UFM, which may therefore be more appropriate for goat milk yogurt manufacturing in comparison to RM or SM. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Ultrafiltration and thermal processing effects on Maillard reaction products and biological properties of date palm sap syrups (Phoenix dactylifera L.).

PubMed

Makhlouf-Gafsi, Ines; Krichen, Fatma; Mansour, Riadh Ben; Mokni, Abir; Sila, Assad; Bougatef, Ali; Blecker, Christophe; Attia, Hamadi; Besbes, Souhail

2018-08-01

The effect of ultrafiltration process and temperature concentration on MRPs content and antioxidant, antimicrobial and cytotoxic properties of date palm sap syrups were investigated. MRPs were analyzed by HPLC. Antioxidant activity was evaluated by reducing power and DPPH free radical and H 2 O 2 scavenging activities. Antimicrobial activity was evaluated by the agar disk diffusion method. In vitro cytotoxic activity was examined by cell proliferation assay. Date sap syrups displayed strong antioxidant activities which are correlated 5HMF and 2F contents. In addition, concentration at 100 °C, unlike ultrafiltration process, enhanced significantly the antioxidant activities sap syrups and total phenolic contents. The antimicrobial activities showed marked activity against S. enterica, P. aeruginosa, S. aureus, L. monocytogenes with an inhibition zone of 21, 34, 27 and 34 mm respectively. Cytotoxicity assays showed that sap syrups can inhibit the proliferation of HeLa cell lines at high concentration. Published by Elsevier Ltd.

Fabrication of TiO2-modified polytetrafluoroethylene ultrafiltration membranes via plasma-enhanced surface graft pretreatment

NASA Astrophysics Data System (ADS)

Qian, Yingjia; Chi, Lina; Zhou, Weili; Yu, Zhenjiang; Zhang, Zhongzhi; Zhang, Zhenjia; Jiang, Zheng

2016-01-01

Surface hydrophilic modification of polymer ultrafiltration membrane using metal oxide represents an effective yet highly challenging solution to improve water flux and antifouling performance. Via plasma-enhanced graft of poly acryl acid (PAA) prior to coating TiO2, we successfully fixed TiO2 functional thin layer on super hydrophobic polytetrafluoroethylene (PTFE) ultrafiltration (UF) membranes. The characterization results evidenced TiO2 attached on the PTFE-based UF membranes through the chelating bidentate coordination between surface-grafted carboxyl group and Ti4+. The TiO2 surface modification may greatly reduce the water contact angle from 115.8° of the PTFE membrane to 35.0° without degradation in 30-day continuous filtration operations. The novel TiO2/PAA/PTFE membranes also exhibited excellent antifouling and self-cleaning performance due to the intrinsic hydrophilicity and photocatalysis properties of TiO2, which was further confirmed by the photo-degradation of MB under Xe lamp irradiation.

Chronic Kidney Disease Screening Methods and Its Implication for Malaysia: An in Depth Review

PubMed Central

Almualm, Yasmin; Huri, Hasniza Zaman

2015-01-01

Chronic Kidney Disease has become a public health problem, imposing heath, social and human cost on societies worldwide. Chronic Kidney Disease remains asymptomatic till late stage when intervention cannot stop the progression of the disease. Therefore, there is an urgent need to detect the disease early. Despite the high prevalence of Chronic Kidney Disease in Malaysia, screening is still lacking behind. This review discusses the strengths and limitations of current screening methods for Chronic Kidney Disease from a Malaysian point of view. Diabetic Kidney Disease was chosen as focal point as Diabetes is the leading cause of Chronic Kidney Disease in Malaysia. Screening for Chronic Kidney Disease in Malaysia includes a urine test for albuminuria and a blood test for serum creatinine. Recent literature indicates that albuminuria is not always present in Diabetic Kidney Disease patients and serum creatinine is only raised after substantial kidney damage has occurred. Recently, cystatin C was proposed as a potential marker for kidney disease but this has not been studied thoroughly in Malaysia. Glomerular Filtration Rate is the best method for measuring kidney function and is widely estimated using the Modification of Diet for Renal Disease equation. Another equation, the Chronic Kidney Disease Epidemiology Collaboration Creatinine equation was introduced in 2009. The new equation retained the precision and accuracy of the Modification of Diet for Renal Disease equation at GFR < 60ml/min/1.73m2, showed less bias and improved precision at GFR>60ml/min/1.73m2. In Asian countries, adding an ethnic coefficient to the equation enhanced its performance. In Malaysia, a multi-ethnic Asian population, the Chronic Kidney Disease Epidemiology Collaboration equation should be validated and the Glomerular Filtration Rate should be reported whenever serum creatinine is ordered. Reporting estimated Glomerular Filtration Rate will help diagnose patients who would have been otherwise missed if only albuminuria and serum creatinine are measured. PMID:25946939

Chronic kidney disease screening methods and its implication for Malaysia: an in depth review.

PubMed

Almualm, Yasmin; Zaman Huri, Hasniza

2015-01-01

Chronic Kidney Disease has become a public health problem, imposing heath, social and human cost on societies worldwide. Chronic Kidney Disease remains asymptomatic till late stage when intervention cannot stop the progression of the disease. Therefore, there is an urgent need to detect the disease early. Despite the high prevalence of Chronic Kidney Disease in Malaysia, screening is still lacking behind. This review discusses the strengths and limitations of current screening methods for Chronic Kidney Disease from a Malaysian point of view. Diabetic Kidney Disease was chosen as focal point as Diabetes is the leading cause of Chronic Kidney Disease in Malaysia. Screening for Chronic Kidney Disease in Malaysia includes a urine test for albuminuria and a blood test for serum creatinine. Recent literature indicates that albuminuria is not always present in Diabetic Kidney Disease patients and serum creatinine is only raised after substantial kidney damage has occurred.  Recently, cystatin C was proposed as a potential marker for kidney disease but this has not been studied thoroughly in Malaysia.  Glomerular Filtration Rate is the best method for measuring kidney function and is widely estimated using the Modification of Diet for Renal Disease equation. Another equation, the Chronic Kidney Disease Epidemiology Collaboration Creatinine equation was introduced in 2009. The new equation retained the precision and accuracy of the Modification of Diet for Renal Disease equation at GFR < 60ml/min/1.73m2, showed less bias and improved precision at GFR>60ml/min/1.73m2. In Asian countries, adding an ethnic coefficient to the equation enhanced its performance. In Malaysia, a multi-ethnic Asian population, the Chronic Kidney Disease Epidemiology Collaboration equation should be validated and the Glomerular Filtration Rate should be reported whenever serum creatinine is ordered. Reporting estimated Glomerular Filtration Rate will help diagnose patients who would have been otherwise missed if only albuminuria and serum creatinine are measured.

Experimental autologous immune deposit nephritis in rats associated with mercuric chloride administration.

PubMed

Kelchner, J; McIntosh, J R; Boedecker, E; Guggenheim, S; McIntosh, R M

1976-09-15

Serial administration of mercuric chloride to rats was followed by development of antibodies to tubular basement membrane and renal tubular epithelial antigen (RTE) and glomerulonephritis characterized by granular deposits of hosts IgG, C3 and RTE along the glomerular capillary walls. The glomerular fixed antibody was directed against RTE. These studies suggest that tubular injury by mercury may lead to release of RTE and autosensitization and subsequent antibody production to this antigen result in formation of and glomerular deposition of circulating immunopathogenic complexes (RTE-anti-RTE) and glomerular morphologic alterations.

Endothelin A receptor activation on mesangial cells initiates Alport glomerular disease

PubMed Central

Dufek, Brianna; Meehan, Daniel; Delimont, Duane; Cheung, Linda; Gratton, Michael Anne; Phillips, Grady; Song, Wenping; Liu, Shiguang; Cosgrove, Dominic

2016-01-01

Recent work demonstrates that Alport glomerular disease is mediated through a biomechanical strain-sensitive activation of mesangial actin dynamics. This occurs through a Rac1/CDC42 cross-talk mechanism that results in the invasion of the sub-capillary spaces by mesangial filopodia. The filopodia deposit mesangial matrix proteins in the glomerular basement membrane, including laminin 211, which activates focal adhesion kinase in podocytes culminating in the up-regulation of pro-inflammatory cytokines and metalloproteinases. These events drive the progression of glomerulonephritis. Here we test whether endothelial cell-derived endothelin-1 is upregulated in Alport glomeruli, and further elevated by hypertension. Treatment of cultured mesangial cells with endothelin-1 activates the formation of drebrin-positive actin microspikes. These microspikes do not form when cells are treated with the endothelin A receptor antagonist sitaxentan, or under conditions of siRNA knockdown of endothelin A receptor mRNA. Treatment of Alport mice with sitaxentan results in delayed onset of proteinuria, normalized glomerular basement membrane morphology, inhibition of mesangial filopodial invasion of the glomerular capillaries, normalization of glomerular expression of metalloproteinases and pro-inflammatory cytokines, increased lifespan, and prevention of glomerulosclerosis and interstitial fibrosis. Thus endothelin A receptor activation on mesangial cells is a key event in initiation of Alport glomerular disease in this model. PMID:27165837

Study on the interaction of plasma protein binding rate between edaravone and taurine in human plasma based on HPLC analysis coupled with ultrafiltration technique.

PubMed

Tang, Dao-quan; Li, Yin-jie; Li, Zheng; Bian, Ting-ting; Chen, Kai; Zheng, Xiao-xiao; Yu, Yan-yan; Jiang, Shui-shi

2015-08-01

In this work, two high-performance liquid chromatography (HPLC) assays were developed and validated for the independent determination of edaravone and taurine using 3-methyl-1-p-tolyl-5-pyrazolone and L-glutamine as internal standards. In in vitro experiments, human plasma was separately spiked with a mixture of edaravone and taurine, edaravone or taurine alone. Plasma was precipitated with acetonitrile containing 0.1% formic acid. Ultrafiltration was employed to obtain the unbound ingredients of the two drugs. The factors that might influence the ultrafiltration effiency were elaborately optimized. Plasma supernatant and ultrafiltrate containing taurine were derivated with o-phthalaldehyde and ethanethiol in the presence of 40 mmol/L sodium borate buffer (pH 10.2) at room temperature within 1 min. Chromatographic separations were achieved on an InertSustain C18 column (250 × 4.6 mm, 5 µm). Isocratic 50 mmol/L ammonium acetate-acetonitrile and gradient 50 mmol/L sodium acetate (pH 5.3)-methanol were respectively selected as the mobile phase for the determination of edaravone and taurine. All of the validation data including linearity, extraction recovery, precision, accuracy and stability conformed to the requirements. Results showed that there were no significant alterations in the plasma protein binding rate of taurine and edaravone, implying that the proposed combination therapy was pharmacologically feasible. Copyright © 2014 John Wiley & Sons, Ltd.

Supported mesoporous carbon ultrafiltration membrane and process for making the same

DOEpatents

Strano, Michael; Foley, Henry C.; Agarwal, Hans

2004-04-13

A novel supported mesoporous carbon ultrafiltration membrane and process for producing the same. The membranes comprise a mesoporous carbon layer that exists both within and external to the porous support. A liquid polymer precursor composition comprising both carbonizing and noncarbonizing templating polymers is deposited on the porous metal support. The coated support is then heated in an inert-gas atmosphere to pyrolyze the polymeric precursor and form a mesoporous carbon layer on and within the support. The pore-size of the membranes is dependent on the molecular weight of the noncarbonizing templating polymer precursor. The mesoporous carbon layer is stable and can withstand high temperatures and exposure to organic chemicals. Additionally, the porous metal support provides excellent strength properties. The composite structure of the membrane provides novel structural properties and allows for increased operating pressures allowing for greater membrane flow rates. The invention also relates to the use of the novel ultrafiltration membrane to separate macromolecules from solution. An example is shown separating bovine serum albumin from water. The membrane functions by separating and by selective adsorption. Because of the membrane's porous metal support, it is well suited to industrial applications. The unique properties of the supported mesoporous carbon membrane also allow the membrane to be used in transient pressure or temperature swing separations processes. Such processes were not previously possible with existing mesoporous membranes. The present invention, however, possesses the requisite physical properties to perform such novel ultrafiltration processes.

Improved antifouling performance of ultrafiltration membrane via preparing novel zwitterionic polyimide

NASA Astrophysics Data System (ADS)

Huang, Haitao; Yu, Jiayu; Guo, Hanxiang; Shen, Yibo; Yang, Fan; Wang, Han; Liu, Rong; Liu, Yang

2018-01-01

On the basis of the outstanding fouling resistance of zwitterionic polymers, an antifouling ultrafiltration membrane was fabricated through phase inversion induced by immersion precipitation method, directly using the novel zwitterionic polyimide (Z-PI), which was synthesized via a two-step procedure including polycondensation and quaternary amination reaction, as membrane material. The chemical structure and composition of the obtained polymer were confirmed by using FTIR, 1H NMR and XPS analysis, and its thermal stability was thoroughly characterized by TGA measurement, respectively. The introduction of zwitterionic groups into polyimide could effectively increase membrane pore size, porosity and wettability, and convert the membrane surface from hydrophobic to highly hydrophilic. As a result, Z-PI membrane displayed significantly improved water permeability compared with that of the reference polyimide (R-PI) membrane without having an obvious compromise in protein rejection. According to the static adsorption and dynamic cycle ultrafiltration experiments of bovine serum albumin (BSA) solution, Z-PI membrane exhibited better fouling resistant ability, especially irreversible fouling resistant ability, suggesting superior antifouling property and long-term performance stability. Moreover, Z-PI membrane had a water flux recovery ratio of 93.7% after three cycle of BSA solution filtration, whereas only about 68.5% was obtained for the control R-PI membrane. These findings demonstrated the advantages of Z-PI membrane material and aimed to provide a facile and scalable method for the large-scale preparation of low fouling ultrafiltration membranes for potential applications.

The Players: Cells Involved in Glomerular Disease.

PubMed

Kitching, A Richard; Hutton, Holly L

2016-09-07

Glomerular diseases are common and important. They can arise from systemic inflammatory or metabolic diseases that affect the kidney. Alternately, they are caused primarily by local glomerular abnormalities, including genetic diseases. Both intrinsic glomerular cells and leukocytes are critical to the healthy glomerulus and to glomerular dysregulation in disease. Mesangial cells, endothelial cells, podocytes, and parietal epithelial cells within the glomerulus all play unique and specialized roles. Although a specific disease often primarily affects a particular cell type, the close proximity, and interdependent functions and interactions between cells mean that even diseases affecting one cell type usually indirectly influence others. In addition to those cells intrinsic to the glomerulus, leukocytes patrol the glomerulus in health and mediate injury in disease. Distinct leukocyte types and subsets are present, with some being involved in different ways in an individual glomerular disease. Cells of the innate and adaptive immune systems are important, directing systemic immune and inflammatory responses, locally mediating injury, and potentially dampening inflammation and facilitating repair. The advent of new genetic and molecular techniques, and new disease models means that we better understand both the basic biology of the glomerulus and the pathogenesis of glomerular disease. This understanding should lead to better diagnostic techniques, biomarkers, and predictors of prognosis, disease severity, and relapse. With this knowledge comes the promise of better therapies in the future, directed toward halting pathways of injury and fibrosis, or interrupting the underlying pathophysiology of the individual diseases that lead to significant and progressive glomerular disease. Copyright © 2016 by the American Society of Nephrology.

Heterogeneous targeting of centrifugal inputs to the glomerular layer of the main olfactory bulb.

PubMed

Gómez, C; Briñón, J G; Barbado, M V; Weruaga, E; Valero, J; Alonso, J R

2005-06-01

The centrifugal systems innervating the olfactory bulb are important elements in the functional regulation of the olfactory pathway. In this study, the selective innervation of specific glomeruli by serotonergic, noradrenergic and cholinergic centrifugal axons was analyzed. Thus, the morphology, distribution and density of positive axons were studied in the glomerular layer of the main olfactory bulb of the rat, using serotonin-, serotonin transporter- and dopamine-beta-hydroxylase-immunohistochemistry and acetylcholinesterase histochemistry in serial sections. Serotonin-, serotonin transporter-immunostaining and acetylcholinesterase-staining revealed a higher heterogeneity in the glomerular layer of the main olfactory bulb than previously reported. In this sense, four types of glomeruli could be identified according to their serotonergic innervation. The main distinctive feature of these four types of glomeruli was their serotonergic fibre density, although they also differed in their size, morphology and relative position throughout the rostro-caudal main olfactory bulb. In this sense, some specific regions of the glomerular layer were occupied by glomeruli with a particular morphology and a characteristic serotonergic innervation pattern that was consistent from animal to animal. Regarding the cholinergic system, we offer a new subclassification of glomeruli based on the distribution of cholinergic fibres in the glomerular structure. Finally, the serotonergic and cholinergic innervation patterns were compared in the glomerular layer. Sexual differences concerning the density of serotonergic fibres were observed in the atypical glomeruli (characterized by their strong cholinergic innervation). The present report provides new data on the heterogeneity of the centrifugal innervation of the glomerular layer that constitutes the morphological substrate supporting the existence of differential modulatory levels among the entire glomerular population.

Species-specific inflammatory responses as a primary component for the development of glomerular lesions in mice and monkeys following chronic administration of a second-generation antisense oligonucleotide.

PubMed

Frazier, Kendall S; Sobry, Cécile; Derr, Victoria; Adams, Mike J; Besten, Cathaline Den; De Kimpe, Sjef; Francis, Ian; Gales, Tracy L; Haworth, Richard; Maguire, Shaun R; Mirabile, Rosanna C; Mullins, David; Palate, Bernard; Doorten, Yolanda Ponstein-Simarro; Ridings, James E; Scicchitano, Marshall S; Silvano, Jérémy; Woodfine, Jennie

2014-07-01

Chronic administration of drisapersen, a 2'-OMe phosphorothioate antisense oligonucleotide (AON) to mice and monkeys resulted in renal tubular accumulation, with secondary tubular degeneration. Glomerulopathy occurred in both species with species-specific characteristics. Glomerular lesions in mice were characterized by progressive hyaline matrix accumulation, accompanied by the presence of renal amyloid and with subsequent papillary necrosis. Early changes involved glomerular endothelial hypertrophy and degeneration, but the chronic glomerular amyloid and hyaline alterations in mice appeared to be species specific. An immune-mediated mechanism for the glomerular lesions in mice was supported by early inflammatory changes including increased expression of inflammatory cytokines and other immunomodulatory genes within the renal cortex, increased stimulation of CD68 protein, and systemic elevation of monocyte chemotactic protein 1. In contrast, kidneys from monkeys given drisapersen chronically showed less severe glomerular changes characterized by increased mesangial and inflammatory cells, endothelial cell hypertrophy, and subepithelial and membranous electron-dense deposits, with ultrastructural and immunohistochemical characteristics of complement and complement-related fragments. Lesions in monkeys resembled typical features of C3 glomerulopathy, a condition described in man and experimental animals to be linked to dysregulation of the alternative complement pathway. Thus, inflammatory/immune mechanisms appear critical to glomerular injury with species-specific sensitivities for mouse and monkey. The lower observed proinflammatory activity in humans as compared to mice and monkeys may reflect a lower risk of glomerular injury in patients receiving AON therapy. © 2014 by The Author(s).

Influence of thyroid function on glomerular filtration rate and other estimates of kidney function in two pediatric patients.

PubMed

Uemura, Osamu; Iwata, Naoyuki; Nagai, Takuhito; Yamakawa, Satoshi; Hibino, Satoshi; Yamamoto, Masaki; Nakano, Masaru; Tanaka, Kazuki

2018-05-01

To determine the optimal method of evaluating kidney function in patients with thyroid dysfunction, this study compared the estimated glomerular filtration rate derived from serum creatinine, cystatin C, or β2-microglobulin with inulin or creatinine clearance in two pediatric patients, one with hypothyroidism and the other with hyperthyroidism. It was observed that the kidney function decreased in a hypothyroid child and enhanced in a hyperthyroid child, with their kidney function becoming normalized by treatment with drugs, which normalized their thyroid function. Kidney function cannot be accurately evaluated using cystatin C-based or β2-microglobulin-based estimated glomerular filtration rate in patients with thyroid dysfunction, as these tests overestimated glomerular filtration rate in a patient with hypothyroidism and underestimated glomerular filtration rate in a patient with hyperthyroidism, perhaps through a metabolic rate-mediated mechanism. In both our patients, 24-h urinary creatinine secretion was identical before and after treatment, suggesting that creatinine production is not altered in patients with thyroid dysfunction. Therefore, kidney function in patients with thyroid dysfunction should be evaluated using creatinine-based estimated glomerular filtration rate.

Role of mTOR in podocyte function and diabetic nephropathy in humans and mice

PubMed Central

Gödel, Markus; Hartleben, Björn; Herbach, Nadja; Liu, Shuya; Zschiedrich, Stefan; Lu, Shun; Debreczeni-Mór, Andrea; Lindenmeyer, Maja T.; Rastaldi, Maria-Pia; Hartleben, Götz; Wiech, Thorsten; Fornoni, Alessia; Nelson, Robert G.; Kretzler, Matthias; Wanke, Rüdiger; Pavenstädt, Hermann; Kerjaschki, Dontscho; Cohen, Clemens D.; Hall, Michael N.; Rüegg, Markus A.; Inoki, Ken; Walz, Gerd; Huber, Tobias B.

2011-01-01

Chronic glomerular diseases, associated with renal failure and cardiovascular morbidity, represent a major health issue. However, they remain poorly understood. Here we have reported that tightly controlled mTOR activity was crucial to maintaining glomerular podocyte function, while dysregulation of mTOR facilitated glomerular diseases. Genetic deletion of mTOR complex 1 (mTORC1) in mouse podocytes induced proteinuria and progressive glomerulosclerosis. Furthermore, simultaneous deletion of both mTORC1 and mTORC2 from mouse podocytes aggravated the glomerular lesions, revealing the importance of both mTOR complexes for podocyte homeostasis. In contrast, increased mTOR activity accompanied human diabetic nephropathy, characterized by early glomerular hypertrophy and hyperfiltration. Curtailing mTORC1 signaling in mice by genetically reducing mTORC1 copy number in podocytes prevented glomerulosclerosis and significantly ameliorated the progression of glomerular disease in diabetic nephropathy. These results demonstrate the requirement for tightly balanced mTOR activity in podocyte homeostasis and suggest that mTOR inhibition can protect podocytes and prevent progressive diabetic nephropathy. PMID:21606591

The effect of a low potassium diet on the glomerular zone of the adrenal cortex of rats.

PubMed

Kawai, K; Sugihara, H; Tsuchiyama, H

1979-05-01

Rats were fed on low potassium diets in order to observe the effect of dietary low potassium on the adrenal cortex. The authors clarified morphological changes of the hypofunctional glomerular zone and compared these changes with those of the hyperfunctional glomerular zone. Three weeks after or 2 months after the start of a low potassium diet, slight narrowing of the glomerular zone of the adrenal cortex was observed followed by miniaturization of cells, presence of binuclear cells and an increase of lipid with enlarged lipid drops. Electron microscope mainly disclosed changes of mitochondrial cristae consisting of markedly reduced, enlarged and irregularly dilated cristae with shortening or elongation. Granules appeared in mitochondria. Lysosomes or dense bodies were enlarged. The Golgi's apparatus was atrophied but endoplasmic reticulum did not show remarkable changes. These changes were directly opposite to those of the hyperfunctional glomerular zone noted after a pottasium load or seen in sodium deficiency. Consequently, these changes were considered to be the changes of the hypofunctional glomerular zone associated with decrease of aldosterone production.

Ceramic membrane ultrafiltration of natural surface water with ultrasound enhanced backwashing.

PubMed

Boley, A; Narasimhan, K; Kieninger, M; Müller, W-R

2010-01-01

Ultrafiltration membrane cleaning with ultrasound enhanced backwashing was investigated with two ceramic membrane systems in parallel. One of them was subjected to ultrasound during backwashing, the other acted as a reference system. The feed water was directly taken from a creek with a sedimentation process as only pre-treatment. The cleaning performance was improved with ultrasound but after 3 weeks of operation damages occurred on the membranes. These effects were studied with online measurements of flux, trans-membrane-pressure and temperature, but also with integrity tests, turbidity measurements and visual examination.

α1β1 Integrin/Rac1-Dependent Mesangial Invasion of Glomerular Capillaries in Alport Syndrome

PubMed Central

Zallocchi, Marisa; Johnson, Brianna M.; Meehan, Daniel T.; Delimont, Duane; Cosgrove, Dominic

2014-01-01

Alport syndrome, hereditary glomerulonephritis with hearing loss, results from mutations in type IV collagen COL4A3, COL4A4, or COL4A5 genes. The mechanism for delayed glomerular disease onset is unknown. Comparative analysis of Alport mice and CD151 knockout mice revealed progressive accumulation of laminin 211 in the glomerular basement membrane. We show mesangial processes invading the capillary loops of both models as well as in human Alport glomeruli, as the likely source of this laminin. l-NAME salt–induced hypertension accelerated mesangial cell process invasion. Cultured mesangial cells showed reduced migratory potential when treated with either integrin-linked kinase inhibitor or Rac1 inhibitor, or by deletion of integrin α1. Treatment of Alport mice with Rac1 inhibitor or deletion of integrin α1 reduced mesangial cell process invasion of the glomerular capillary tuft. Laminin α2–deficient Alport mice show reduced mesangial process invasion, and cultured laminin α2–null cells showed reduced migratory potential, indicating a functional role for mesangial laminins in progression of Alport glomerular pathogenesis. Collectively, these findings predict a role for biomechanical insult in the induction of integrin α1β1–dependent Rac1-mediated mesangial cell process invasion of the glomerular capillary tuft as an initiation mechanism of Alport glomerular pathology. PMID:23911822

Involvement of Renal Corpuscle microRNA Expression on Epithelial-to-Mesenchymal Transition in Maternal Low Protein Diet in Adult Programmed Rats

PubMed Central

Sene, Letícia de Barros; Mesquita, Flávia Fernandes; de Moraes, Leonardo Nazário; Santos, Daniela Carvalho; Carvalho, Robson; Gontijo, José Antônio Rocha; Boer, Patrícia Aline

2013-01-01

Prior study shows that maternal protein-restricted (LP) 16-wk-old offspring have pronounced reduction of nephron number and arterial hypertension associated with unchanged glomerular filtration rate, besides enhanced glomerular area, which may be related to glomerular hyperfiltration/overflow and which accounts for the glomerular filtration barrier breakdown and early glomerulosclerosis. In the current study, LP rats showed heavy proteinuria associated with podocyte simplification and foot process effacement. TGF-β1 glomerular expression was significantly enhanced in LP. Isolated LP glomeruli show a reduced level of miR-200a, miR-141, miR-429 and ZEB2 mRNA and upregulated collagen 1α1/2 mRNA expression. By western blot analyzes of whole kidney tissue, we found significant reduction of both podocin and nephrin and enhanced expression of mesenchymal protein markers such as desmin, collagen type I and fibronectin. From our present knowledge, these are the first data showing renal miRNA modulation in the protein restriction model of fetal programming. The fetal-programmed adult offspring showed pronounced structural glomerular disorders with an accentuated and advanced stage of fibrosis, which led us to state that the glomerular miR-200 family would be downregulated by TGF-β1 action inducing ZEB 2 expression that may subsequently cause glomeruli epithelial-to-mesenchymal transition. PMID:23977013

Relationship between dietary protein intake and the changes in creatinine clearance and glomerular cross-sectional area in patients with IgA nephropathy.

PubMed

Wada, Toshikazu; Nakao, Toshiyuki; Matsumoto, Hiroshi; Okada, Tomonari; Nagaoka, Yume; Iwasawa, Hideaki; Gondo, Asako; Niwata, Ami; Kanno, Yoshihiko

2015-08-01

Dietary protein intake (PI) induces glomerular hyperfiltration and reduced dietary PI can be effective in preserving kidney function. However, there is limited information regarding the relationship between dietary PI and glomerular histological changes in chronic kidney disease. We investigated the relationship between changes in dietary PI and both the changes in creatinine clearance and glomerular histomorphometry in adult patients with IgA nephropathy (IgAN). A total of 24 consecutive adult patients with biopsy-confirmed IgAN were enrolled and glomerular histomorphometric variables and clinical variables were investigated. The main clinical variables were differences in creatinine clearance (Ccr) (dCcr) and in PI (dPI) which were calculated by subtracting PI and Ccr values in patients on a controlled diet during hospitalization for kidney biopsy from the respective values in patients on daily diets as outpatients. These values of PI were estimated from urinary urea excretion measured by 24-h urine collection. The main renal histomorphometric variable was glomerular tuft area (GTA) (μm(2)). dCcr positively correlated with dPI (r = 0.726, P < 0.001). GTA correlated positively with dPI (r = 0.556, P = 0.013). Multiple regression analysis showed that dPI was independently associated with both dCcr and GTA. Additionally, GTA positively correlated with dietary PI as outpatients (r = 0.457, P = 0.043). Changes in dietary PI were associated with the changes in glomerular filtration rate. Furthermore, histomorphometric findings suggested that a greater dietary PI can affect the glomerular size at the time of the initial diagnostic biopsy for IgAN.

CXC Chemokine Receptor 7 (CXCR7) Regulates CXCR4 Protein Expression and Capillary Tuft Development in Mouse Kidney

PubMed Central

Haege, Sammy; Mueller, Wiebke; Nietzsche, Sandor; Lupp, Amelie; Mackay, Fabienne; Schulz, Stefan; Stumm, Ralf

2012-01-01

Background The CXCL12/CXCR4 axis is involved in kidney development by regulating formation of the glomerular tuft. Recently, a second CXCL12 receptor was identified and designated CXCR7. Although it is established that CXCR7 regulates heart and brain development in conjunction with CXCL12 and CXCR4, little is known about the influence of CXCR7 on CXCL12 dependent kidney development. Methodology/Principal Findings We provided analysis of CXCR7 expression and function in the developing mouse kidney. Using in situ hybridization, we identified CXCR7 mRNA in epithelial cells including podocytes at all nephron stages up to the mature glomerulus. CXCL12 mRNA showed a striking overlap with CXCR7 mRNA in epithelial structures. In addition, CXCL12 was detected in stromal cells and the glomerular tuft. Expression of CXCR4 was complementary to that of CXCR7 as it occurred in mesenchymal cells, outgrowing ureteric buds and glomerular endothelial cells but not in podocytes. Kidney examination in CXCR7 null mice revealed ballooning of glomerular capillaries as described earlier for CXCR4 null mice. Moreover, we detected a severe reduction of CXCR4 protein but not CXCR4 mRNA within the glomerular tuft and in the condensed mesenchyme. Malformation of the glomerular tuft in CXCR7 null mice was associated with mesangial cell clumping. Conclusions/Significance We established that there is a similar glomerular pathology in CXCR7 and CXCR4 null embryos. Based on the phenotype and the anatomical organization of the CXCL12/CXCR4/CXCR7 system in the forming glomerulus, we propose that CXCR7 fine-tunes CXCL12/CXCR4 mediated signalling between podocytes and glomerular capillaries. PMID:22880115

CXC chemokine receptor 7 (CXCR7) regulates CXCR4 protein expression and capillary tuft development in mouse kidney.

PubMed

Haege, Sammy; Einer, Claudia; Thiele, Stefanie; Mueller, Wiebke; Nietzsche, Sandor; Lupp, Amelie; Mackay, Fabienne; Schulz, Stefan; Stumm, Ralf

2012-01-01

The CXCL12/CXCR4 axis is involved in kidney development by regulating formation of the glomerular tuft. Recently, a second CXCL12 receptor was identified and designated CXCR7. Although it is established that CXCR7 regulates heart and brain development in conjunction with CXCL12 and CXCR4, little is known about the influence of CXCR7 on CXCL12 dependent kidney development. We provided analysis of CXCR7 expression and function in the developing mouse kidney. Using in situ hybridization, we identified CXCR7 mRNA in epithelial cells including podocytes at all nephron stages up to the mature glomerulus. CXCL12 mRNA showed a striking overlap with CXCR7 mRNA in epithelial structures. In addition, CXCL12 was detected in stromal cells and the glomerular tuft. Expression of CXCR4 was complementary to that of CXCR7 as it occurred in mesenchymal cells, outgrowing ureteric buds and glomerular endothelial cells but not in podocytes. Kidney examination in CXCR7 null mice revealed ballooning of glomerular capillaries as described earlier for CXCR4 null mice. Moreover, we detected a severe reduction of CXCR4 protein but not CXCR4 mRNA within the glomerular tuft and in the condensed mesenchyme. Malformation of the glomerular tuft in CXCR7 null mice was associated with mesangial cell clumping. We established that there is a similar glomerular pathology in CXCR7 and CXCR4 null embryos. Based on the phenotype and the anatomical organization of the CXCL12/CXCR4/CXCR7 system in the forming glomerulus, we propose that CXCR7 fine-tunes CXCL12/CXCR4 mediated signalling between podocytes and glomerular capillaries.

Identification of a major sialoprotein in the glycocalyx of human visceral glomerular epithelial cells.

PubMed Central

Kerjaschki, D; Poczewski, H; Dekan, G; Horvat, R; Balzar, E; Kraft, N; Atkins, R C

1986-01-01

Glomerular visceral epithelial cells are endowed with a sialic acid-rich surface coat (the "glomerular epithelial polyanion"), which in rat tissue contains the sialoprotein podocalyxin. We have identified a major membrane sialoprotein in human glomeruli that is similar to rat podocalyxin in its sialic acid-dependent binding of wheat germ agglutinin and in its localization on the surface of glomerular epithelial and endothelial cells, as shown by immunoelectron microscopy, using the monoclonal antibody PHM5. Differences in the sialoproteins of the two species are indicated by the discrepancy of their apparent molecular weights in sodium dodecyl sulfate gels, by the lack of cross reactivity of their specific antibodies, and by the lack of homology of their proteolytic peptide maps. It is therefore possible that the human glomerular sialoprotein and rat podocalyxin are evolutionarily distinct, but have similar functions. Images PMID:3533998

PEP Support Laboratory Leaching and Permeate Stability Tests

DOE Office of Scientific and Technical Information (OSTI.GOV)

Russell, Renee L.; Peterson, Reid A.; Rinehart, Donald E.

2009-09-25

Pacific Northwest National Laboratory (PNNL) has been tasked by Bechtel National Inc. (BNI) on the River Protection Project-Hanford Tank Waste Treatment and Immobilization Plant (RPP-WTP) project to perform research and development activities to resolve technical issues identified for the Pretreatment Facility (PTF). The Pretreatment Engineering Platform (PEP) was designed, constructed, and operated as part of a plan to respond to issue M12, "Undemonstrated Leaching Processes," of the External Flowsheet Review Team (EFRT) issue response plan.( ) The PEP is a 1/4.5-scale test platform designed to simulate the WTP pretreatment caustic leaching, oxidative leaching, ultrafiltration solids concentration, and slurry washing processes.more » The PEP replicates the WTP leaching processes using prototypic equipment and control strategies. A simplified flow diagram of the PEP system is shown in Figure 1.1. Two operating scenarios are currently being evaluated for the ultrafiltration process (UFP) and leaching operations. The first scenario has caustic leaching performed in the UFP-2 ultrafiltration feed vessels (i.e., vessel UFP-VSL-T02A in the PEP and vessels UFP-VSL-00002A and B in the WTP PTF). The second scenario has caustic leaching conducted in the UFP-1 ultrafiltration feed preparation vessels (i.e., vessels UFP-VSL-T01A and B in the PEP and vessels UFP-VSL-00001A and B in the WTP PTF). In both scenarios, 19-M sodium hydroxide solution (NaOH, caustic) is added to the waste slurry in the vessels to leach solid aluminum compounds (e.g., gibbsite, boehmite). Caustic addition is followed by a heating step that uses direct injection of steam to accelerate the leach process. Following the caustic leach, the vessel contents are cooled using vessel cooling jackets and/or external heat exchangers. The main difference between the two scenarios is that for leaching in UFP-VSL-T01A and B, the 19-M NaOH is added to un-concentrated waste slurry (3 to 8 wt% solids), while for leaching in UFP-VSL-T02A, the slurry is concentrated to nominally 20 wt% solids using cross-flow ultrafiltration before adding caustic.« less

Efficient removal of nickel(II) from high salinity wastewater by a novel PAA/ZIF-8/PVDF hybrid ultrafiltration membrane.

PubMed

Li, Ting; Zhang, Weiming; Zhai, Shu; Gao, Guandao; Ding, Jie; Zhang, Wenbin; Liu, Yang; Zhao, Xin; Pan, Bingcai; Lv, Lu

2018-06-15

The development of highly efficient membranes, especially those aimed at the removal of trace (ppm, 10 -6 ) heavy metals from high salinity wastewater, is one of the principal challenges in the wastewater treatment field. In this study, a new metal-organic frameworks-based hybrid ultrafiltration membrane (PAA/ZIF-8/PVDF membrane) was prepared, which outperformed some other adsorption materials and owned the first and highest reported nickel ion (Ni(II)) adsorption capacity (219.09 mg/g) in high salinity ([Na + ] = 15000 mg/L) wastewater. Novel and highly efficient hybrid ultrafiltration membrane was facilely fabricated by physically immobilizing zeolitic imidazolate framework-8 (ZIF-8) particles onto the surface of trimesoyl chloride (TMC)-modified polyvinylidene fluoride (PVDF) membrane under the protection of polyacrylic acid (PAA) layer, and possessed a relatively high water flux of ∼460 L m -2 h -1 . The XPS studies revealed that the Ni(II) uptake was mainly attributed to the specific hydrogen bonding interaction between Ni(II) and hydroxyl on ZIF-8 frameworks as well as the electrostatic adsorption by carboxyl groups in PAA layer. Especially, compared to PAA, ZIF-8 could selectively bind with Ni(II) effectively, which was almost not affected by concentrated sodium ion. The filtration study showed that the membrane with an area of 12.56 cm 2 could treat 5.76 L of Ni(II)-contained high salinity wastewater ([Ni(II) = 2 mg/L, [Na + ] = 15000 mg/L) to meet the maximum contaminant level of 0.1 mg/L Ni(II). Moreover, the hybrid membrane can be regenerated several times by HCl-NaCl solution (pH = 5.5) for repeated use under direct current electric field. Thus, the newly developed ZIF-8 hybrid ultrafiltration membrane showed a promising potential for heavy metals containing wastewater treatment. This work provides a worthy reference for designing highly efficient ultrafiltration membranes modified by metal-organic frameworks. Copyright © 2018 Elsevier Ltd. All rights reserved.

Concentration of infectious aquatic rhabdoviruses from freshwater and seawater using ultrafiltration.

PubMed

Grant, Amelia A M; Jakob, Eva; Richard, Jon; Garver, Kyle A

2011-12-01

Infectious hematopoietic necrosis virus (IHNV), viral hemorrhagic septicemia virus, and spring viremia of carp virus were concentrated and detected from freshwater and seawater samples by using hollow-fiber ultrafiltration. Within 60 min, virus in a 50-L freshwater or saltwater sample was concentrated more than 70-fold, and virus retention efficiencies were consistently greater than 88%. Retention efficiency was highly dependent upon concentrations of column blocking and sample stabilization solutions. A large column with a surface area of 1.15 m2 and a filtration capacity of 5-200 L exhibited optimal viral retention when blocked with 2% fetal bovine serum (FBS) and when the samples were supplemented with 0.1% FBS. Conversely, a small column with 100-fold less surface area and a filtering capacity of 0.5-2.0 L was optimized when blocked with 1% FBS and when the samples were supplemented with 0.1% FBS. The optimized ultrafiltration procedure was further validated with water from a tank that contained IHNV-exposed juvenile sockeye salmon Oncorhynchus nerka, resulting in an average virus retention efficiency of 91.6 +/- 4.1% (mean +/- SE). Virus quantification of concentrated samples demonstrated that IHNV shedding in sockeye salmon preceded mortality; shedding of the virus was observed to increase significantly as early as 7 d postchallenge and peaked at day 14, when virus levels reached 4.87 x 10(3) plaque-forming units/mL. We conclude that ultrafiltration is a reliable and effective method for concentrating viable aquatic rhabdoviruses from large volumes of water and has application for the analysis of environmental water samples.

Xanthan gum recovery from fermentation broth using ultrafiltration: Kinetics and process evaluation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lo, Y.M.; Yang, S.T.; Min, D.B.

1995-12-01

Ultrafiltration of xanthan gum solution as an alternative method to alcohol precipitation for xanthan gum recovery from dilute fermentation broth was studied. A polysulfone membrane (with 500,000 MWCO) hollow fiber (106 mil fiber diameter) tubular cartridge was used to concentrate xanthan broth from less than 3 (w/v) % to {approximately}13.5 (w/v) %, with the xanthan recovery yield of {approximately}95 % or higher. During ultrafiltration, the filtrate flux was one order of magnitude lower for xanthan broth than for water, However, the flux remained almost constant for xanthan concentrations up to {approximately}8%. It was then reduced dramatically as the xanthan concentrationmore » increased beyond 8%. The reduced filtrate flux was caused by the reduced pumping (shear) rate and higher viscosities at higher xanthan concentrations. At constant xanthan concentration, the filtrate flux remained almost unchanged for the entire period studied, suggesting that the process is not subject to membrane fouling. In general, the filtrate flux decreased with increasing the xanthan concentration and increased with increasing the pumping (shear) rate and the trans-membrane pressure difference. Changing the solution pH had a slight effect on the viscosity of xanthan solution, but did not affect the filtration performance. Even under high-shear-rate conditions, ultrafiltration did not give any adverse effects on the rheological properties and molecular weight of the xanthan polymer. Thus, ultra filtration can be used to concentrate xanthan broth from fermentation by a factor of four or higher and to reduce the subsequent alcohol recovery costs by at least 75 %.« less

Acute effects of ultrafiltration on aortic mechanical properties determined by measurement of pulse wave velocity and pulse propagation time in hemodialysis patients

PubMed Central

Yıldız, Banu Şahin; Şahin, Alparslan; Aladağ, Nazire Başkurt; Arslan, Gülgün; Kaptanoğulları, Hakan; Akın, İbrahim; Yıldız, Mustafa

2015-01-01

Objective: The effects of acute hemodialysis session on pulse wave velocity are conflicting. The aim of the current study was to assess the acute effects of ultrafiltration on the aortic mechanical properties using carotid-femoral (aortic) pulse wave velocity and pulse propagation time. Methods: A total of 26 (12 women, 14 men) consecutive patients on maintenance hemodialysis (mean dialysis duration: 40.7±25.6 (4-70) months) and 29 healthy subjects (13 women, 16 men) were included in this study. Baseline blood pressure, carotid-femoral (aortic) pulse wave velocity, and pulse propagation time were measured using a Complior Colson device (Createch Industrie, France) before and immediately after the end of the dialysis session. Results: While systolic blood pressure, diastolic blood pressure, mean blood pressure, pulse pressure, and pulse wave velocity were significantly higher in patients on hemodialysis than in healthy subjects, pulse propagation time was significantly higher in healthy subjects. Although body weight, systolic blood pressure, diastolic blood pressure, mean blood pressure, pulse pressure, and pulse wave velocity were significantly decreased, heart rate and pulse propagation time were significantly increased after ultrafiltration. There was a significant positive correlation between pulse wave velocity and age, body height, waist circumference, systolic blood pressure, diastolic blood pressure, mean blood pressure, pulse pressure, and heart rate. Conclusion: Although hemodialysis treatment may chronically worsen aortic mechanical properties, ultrafiltration during hemodialysis may significantly improve aortic pulse wave velocity, which is inversely related to aortic distensibility and pulse propagation time. PMID:25413228

New Insights into Glomerular Parietal Epithelial Cell Activation and Its Signaling Pathways in Glomerular Diseases

PubMed Central

Su, Hua; Chen, Shan; He, Fang-Fang; Wang, Yu-Mei; Bondzie, Philip; Zhang, Chun

2015-01-01

The glomerular parietal epithelial cells (PECs) have aroused an increasing attention recently. The proliferation of PECs is the main feature of crescentic glomerulonephritis; besides that, in the past decade, PEC activation has been identified in several types of noninflammatory glomerulonephropathies, such as focal segmental glomerulosclerosis, diabetic glomerulopathy, and membranous nephropathy. The pathogenesis of PEC activation is poorly understood; however, a few studies delicately elucidate the potential mechanisms and signaling pathways implicated in these processes. In this review we will focus on the latest observations and concepts about PEC activation in glomerular diseases and the newest identified signaling pathways in PEC activation. PMID:25866774

Pattern of glomerular diseases in Oman: a study based on light microscopy and immunofluorescence.

PubMed

Alwahaibi, Nasar Yousuf; Alhabsi, Taiseer Ahmed; Alrawahi, Samira Abdullah

2013-03-01

Light microscopy and immunofluorescence play an important part in the final diagnosis of renal biopsy. The aim of this study was to analyze the pattern of various glomerular diseases in Oman. A total of 424 renal biopsies were retrospectively analyzed at the Sultan Qaboos University Hospital between 1999 and 2010. Focal and segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranous glomerulopathy (MGN) and IgA nephropathy were the most common primary glomerular diseases encountered, accounting for 21.2%, 17%, 12.3% and 8.3%, respectively, of all cases. Lupus nephritis was the most common secondary glomerular disease and was the most prevalent among all biopsies, accounting for 30.4% of all biopsies. Amyloidosis was seen in only two cases. The presence of fluorescein isothiocyanatefibrin in all renal cases was low when compared with IgG, IgA, IgM, C3 and C1q markers. In conclusion, based on the findings of this study, lupus nephritis was the most common of all glomerular diseases and FSGS was the most common primary glomerular disease. The importance of fluorescein isothiocyanate-fibrin in the diagnosis of renal biopsy needs to be further investigated.

Effect of alterations in glomerular charge on deposition of cationic and anionic antibodies to fixed glomerular antigens in the rat.

PubMed

Adler, S; Baker, P; Pritzl, P; Couser, W G

1985-07-01

Reduction of the negative charge of the glomerular capillary wall alters its charge- and size-selective properties. To investigate the effect of alteration in glomerular charge properties on antibody localization, we prepared cationic and anionic fractions of antibodies to subepithelial and glomerular basement membrane (GBM) antigens, and compared their deposition in normal rats and rats treated with protamine sulfate or aminonucleoside of puromycin to reduce capillary wall charge. IgG antibodies were eluted from kidneys of rats with active Heymann's nephritis (AICN), passive Heymann's nephritis (PHN), or anti-GBM nephritis (NTN), separated into cationic and anionic fractions, and radiolabeled with iodine 125 or iodine 131. Relative antibody content of each fraction was determined by incubation with an excess of glomerular antigen. Varying amounts of cationic and anionic IgG eluted from kidneys of rats with AICN or PHN were injected into 24 normal or protamine sulfate-treated rats. Glomerular binding of all antibodies was highly correlated with IgG delivery to the kidney. The ratio of cationic to anionic antibody deposited in the glomeruli of normal rats after 4 hours was 1.08 +/- 0.07 for AICN eluate and 0.37 +/- 0.04 for PHN eluate. The ratios were not significantly different in animals pretreated with protamine sulfate (1.15 +/- 0.06 and 0.44 +/- 0.06, respectively; P greater than 0.05). Varying amounts of cationic and anionic IgG eluted from kidneys of rats with NTN were injected into 10 normal rats and four rats treated with aminonucleoside of puromycin. Glomerular binding of antibody was again highly correlated with IgG delivery to the kidney. The ratio of cationic to anionic antibody deposited in the glomeruli of normal rats after 1 hour was 1.03 +/- 0.06, and was not significantly altered in rats treated with aminonucleoside of puromycin (1.05 +/- 0.03, P greater than 0.5). Proteinuria in PHN rats was also unaffected by treatment with protamine sulfate for 5 days (controls: 68 +/- 21 mg/day; protamine sulfate-treated: 65 +/- 14 mg/day; n = 25, P greater than 0.08). These results demonstrate that treatment to reduce glomerular polyanion does not significantly alter the ratio of cationic to anionic antibodies to fixed glomerular antigens that deposit in the glomerulus, or reduce proteinuria caused by deposition of antibody to a fixed subepithelial antigen.

Antimicrobial compounds of porcine mucosa

NASA Astrophysics Data System (ADS)

Kotenkova, E. A.; Lukinova, E. A.; Fedulova, L. V.

2017-09-01

The aim of the study was to investigate porcine oral cavity mucosa (OCM), nasal cavity mucosa (NCM), rectal mucosa (RM) and tongue mucosa (TM) as sources of antimicrobial compounds. Ultrafiltrates with MW >30 kDa, MW 5-30 kDa and MW <5 kDa were obtained. All ultrafiltrates had antimicrobial activity against Escherichia coli and Proteus vulgaris. NCM ultrafiltrates revealed the highest antibacterial activity in respect to negative control: for the fraction with MW >30 kDa, the zone of microbial growth inhibition was 7.5 mm, for the MW<5 kDa fraction, it was 7 mm, and for MW 5-30 kDa fraction, it was 4.5 mm. No significant differences were found in high molecular weight proteomic profile, while qualitative and quantitative differences were observed in the medium and low molecular weight areas, especially in OCM and NCM. HPLC showed 221 tissue-specific peptides in OCM, 156 in NCM, 225 in RM, but only 5 in TM. The results observed confirmed porcine mucous tissues as a good source of antimicrobial compounds, which could be an actual alternative for reduction of microbial spoilage of foods.

Treatment of laundry wastewater using polyethersulfone/polyvinylpyrollidone ultrafiltration membranes.

PubMed

Sumisha, A; Arthanareeswaran, G; Lukka Thuyavan, Y; Ismail, A F; Chakraborty, S

2015-11-01

In this study, laundry wastewater filtration was studied using hydrophilic polyvinylpyrollidone (PVP) modified polyethersulfone (PES) ultrafiltration membranes. The performances of PES/PVP membranes were assessed using commercial PES membrane with 10kDa in ultrafiltration. Operating parameters The influence of transmembrane pressure (TMP) and stirring speed on laundry wastewater flux was investigated. A higher permeate flux of 55.2L/m(2)h was obtained for modified PES membrane with high concentration of PVP at TMP of 500kPa and 750rpm of stirring speed. The separation efficiencies of membranes were also studied with respect to chemical oxygen demand (COD), total dissolved solids (TDS), turbidity and conductivity. Results showed that PES membrane with 10% of PVP had higher permeate flux, flux recovery and less fouling when compared with other membranes. Higher COD and TDS rejection of 88% and 82% were also observed for modified membranes due to the improved surface property of membranes. This indicated that modified PES membranes are suitable for the treatment of surfactant, detergent and oil from laundry wastewater. Copyright © 2015 Elsevier Inc. All rights reserved.

Preparation and characterization of a novel highly hydrophilic and antifouling polysulfone/nanoporous TiO2 nanocomposite membrane.

PubMed

Bidsorkhi, H Cheraghi; Riazi, H; Emadzadeh, D; Ghanbari, M; Matsuura, T; Lau, W J; Ismail, A F

2016-10-14

In this research, novel ultrafiltration nanocomposite membranes were prepared by incorporating self-synthesized nanoporous titanium dioxide (NTiO2) nanoparticles into polysulfone. The surface of the nanoparticle was treated with a silane-based modifier to improve its distribution in the host polymer. Atomic-force microscopy, scanning electron microscopy, Fourier transform infrared spectroscopy, Brunauer-Emmett-Teller, transmission electron microscopy, energy-dispersive x-ray spectroscopy, porosity and contact angle tests were conducted to characterize the properties of the particles as well as the fabricated nanocomposite membranes. The effects of the nanoparticle incorporation were evaluated by conducting ultrafiltration experiments. It was reported that the membrane pure water flux was increased with increasing NTiO2 loading owing to the high porosity of the nanoparticles embedded and/or formation of enlarged pores upon addition of them. The antifouling capacity of the membranes was also tested by ultrafiltration of bovine serum albumin fouling solution. It was found that both water flux and antifouling capacity tended to reach desired level if the NTiO2 added was at optimized loading.

Differential natural organic matter fouling of ceramic versus polymeric ultrafiltration membranes.

PubMed

Lee, Seung-Jin; Kim, Jae-Hong

2014-01-01

Ceramic ultrafiltration membranes has drawn increasing attention in drinking water treatment sectors as an alternative to traditional polymeric counterparts, yet only limited information has been made available about the characteristics of ceramic membrane fouling by natural organic matter. The effects of solution chemistry including ionic strength, divalent ion concentration and pH on the flux behavior were comparatively evaluated for ceramic and polymeric ultrafiltration of synthetic water containing model natural organic matter. Filtration characteristics were further probed via resistance-in-series model analysis, fouling visualization using quantum dots, batch adsorption test, contact angle measurement, solute-membrane surface adhesion force measurement, and quantitative comparison of fouling characteristics between ceramic and polymeric membranes. The results collectively suggested that the effects of solution chemistry on fouling behavior of ceramic membranes were generally similar to polymeric counterparts in terms of trends, while the extent varied significantly depending on water quality parameters. Lower fouling tendency and enhanced cleaning efficiency were observed with the ceramic membrane, further promoting the potential for ceramic membrane application to surface water treatment. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Blood gas and acid-base changes and rhythmologic tolerance of acetate and bicarbonate hemodialysis using a standard dialyser with high sodium and control of ultrafiltration].

PubMed

Westeel, P F; Coevoet, B; Bens, J L; Neuville, M; Morinière, P; Fievet, P; Dkhissi, H; Fournier, A

1983-01-01

In order to demonstrate a possible superiority of bicarbonate dialysis (HDB) over acetate dialysis (HDA) in conditions of standard dialysis (4 hours on a 1 m2 cuprophan dialyser) but with a bath rich in sodium (143 mEq/l) and control of ultrafiltration, we have compared 2 sequences of 3 runs of HDA and HDB with these conditions in 8 patients as regards their acido-basic and cardiologic parameters (continuous monitoring of ECG by Holter, regular measurement of blood pressure). Acid base balance study in AHD led to the distinction of 2 groups according to wether their plasma bicarbonate increased or decreased during the run. Rythmological tolerance was the same in BHD and AHD, wether all patients or both groups were considered. Heart rate was however slightly but significantly higher during AHD than during BHD, in the patients whose plasma bicarbonate decreased. In conclusion, the benefit of HDB is not remarkable when HDA is performed not only in standard conditions but also with a bath rich in sodium and with control of ultrafiltration.

Efficient Preparation of Super Antifouling PVDF Ultrafiltration Membrane with One Step Fabricated Zwitterionic Surface.

PubMed

Zhao, Xinzhen; He, Chunju

2015-08-19

On the basis of the excellent fouling resistance of zwitterionic materials, the super antifouling polyvinylidene fluoride (PVDF) membrane was efficiently prepared though one-step sulfonation of PVDF and polyaniline blend membrane in situ. The self-doped sulfonated polyaniline (SPANI) was generated as a novel zwitterionic polymer to improve the antifouling property of PVDF ultrafiltration membrane used in sewage treatment. Surface attenuated total reflection Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, surface zeta potential, and water contact angle demonstrated the successful fabrication of zwitterionic interface by convenient sulfonation modification. The static adsorption fouling test showed the quantified adsorption mass of bovine serum albumin (BSA) pollutant on the PVDF/SPANI membrane surface decreases to 3(±2) μg/cm(2), and the water flux recovery ratio (FRR) values were no less than 95% for the three model pollutants of BSA, sodium alginate (SA), and humic acid (HA), which were corresponding hydrophobic, hydrophilic, and natural pollutants in sewage, respectively. This Research Article demonstrated the antifouling advantages of zwitterionic SPANI and aimed to provide a simple method for the large scale preparation of zwitterionic antifouling ultrafiltration membranes.

Influence of pH and temperature of dip-coating solution on the properties of cellulose acetate-ceramic composite membrane for ultrafiltration.

PubMed

Kaur, Harjot; Bulasara, Vijaya Kumar; Gupta, Raj Kumar

2018-09-01

Polymer-ceramic composite membranes were prepared by dip coating technique using 5 wt.% cellulose acetate (CA) solution at different temperatures (15 °C, 25 °C and 40 °C). The effect of pH (2-12) of the polymeric solution on the properties of the membranes was studied using SEM, EDAX, FTIR, gas and liquid permeation. The thickness of the polymeric layer depended on the interaction of CA solution with the surface of ceramic support. Membrane permeability decreased with increase in pH because of decrease in pore size and porosity resulting from strong interaction of the polymer layer with the ceramic support. The porosity and mean pore size of the prepared membranes were found to be 28-60% and 30-47 nm (ultrafiltration range), respectively. The optimized membrane (pH 7) was used for ultrafiltration of oil in water emulsions (100 and 200 mg/L). Oil rejection of 99.61% was obtained for 100 mg/L of oil concentration in water. Copyright © 2018 Elsevier Ltd. All rights reserved.

Plutonium partitioning in water-granite and water-α-FeOOH systems: from a viewpoint of a three-phase system.

PubMed

Lin, Jianfeng; Dang, Haijun; Xie, Jinchuan; Zhou, Guoqing; Li, Mei; Zhang, Jihong

2015-09-01

Traditional sorption experiments commonly treat the colloidal species of low-solubility contaminants as immobile species when separated by centrifugation or ultrafiltration. This study shows that, from a viewpoint of a three-phase system, the mobile Pu species, especially the colloidal species, play an important role in Pu partitioning in water-granite and water-α-FeOOH systems. A new distribution coefficient term Ks/(d+c) was defined to take the mobile colloidal species into consideration, and it differs to the traditional distribution coefficient Ks/d by orders of magnitude in the water-granite and water-α-FeOOH systems. This term, Ks/(d+c), can quantitatively describe Pu partitioning in the suspension, in particular the fraction of mobile species that dominate Pu migration in the environment. The effects of ionic strength (I) and pH on the Pu partitioning in water-granite and water-α-FeOOH systems are well interpreted with respect to the zeta potential change of granite grains, α-FeOOH colloid particles and polymeric Pu. It is concluded that the presence of the α-FeOOH colloid with a low concentration (<10 mg L(-1)) is favorable for the stability of colloidal Pu and leads to large proportion of mobile Pu, especially colloid-associated Pu, which will migrate much faster than dissolved Pu in groundwater.

The Gne M712T mouse as a model for human glomerulopathy.

PubMed

Kakani, Sravan; Yardeni, Tal; Poling, Justin; Ciccone, Carla; Niethamer, Terren; Klootwijk, Enriko D; Manoli, Irini; Darvish, Daniel; Hoogstraten-Miller, Shelley; Zerfas, Patricia; Tian, E; Ten Hagen, Kelly G; Kopp, Jeffrey B; Gahl, William A; Huizing, Marjan

2012-04-01

Pathological glomerular hyposialylation has been implicated in certain unexplained glomerulopathies, including minimal change nephrosis, membranous glomerulonephritis, and IgA nephropathy. We studied our previously established mouse model carrying a homozygous mutation in the key enzyme of sialic acid biosynthesis, N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase. Mutant mice died before postnatal day 3 (P3) from severe glomerulopathy with podocyte effacement and segmental glomerular basement membrane splitting due to hyposialylation. Administration of the sialic acid precursor N-acetylmannosamine (ManNAc) led to improved sialylation and survival of mutant pups beyond P3. We determined the onset of the glomerulopathy in the embryonic stage. A lectin panel, distinguishing normally sialylated from hyposialylated glycans, used WGA, SNA, PNA, Jacalin, HPA, and VVA, indicating glomerular hyposialylation of predominantly O-linked glycoproteins in mutant mice. The glomerular glycoproteins nephrin and podocalyxin were hyposialylated in this unique murine model. ManNAc treatment appeared to ameliorate the hyposialylation status of mutant mice, indicated by a lectin histochemistry pattern similar to that of wild-type mice, with improved sialylation of both nephrin and podocalyxin, as well as reduced albuminuria compared with untreated mutant mice. These findings suggest application of our lectin panel for categorizing human kidney specimens based on glomerular sialylation status. Moreover, the partial restoration of glomerular architecture in ManNAc-treated mice highlights ManNAc as a potential treatment for humans affected with disorders of glomerular hyposialylation. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Glomerular hyperfiltration is strongly correlated with age in Congolese children with sickle cell anaemia.

PubMed

Aloni, Michel Ntetani; Ngiyulu, René Makuala; Ekulu, Pépé Mfutu; Mbutiwi, Fiston IkwaNdol; Makulo, Jean Robert; Gini-Ehungu, Jean Lambert; Nseka, Nazaire Mangani; Lepira, François Bompeka

2017-05-01

Glomerular hyperfiltration is an early marker of sickle cell nephropathy and can lead to microalbuminuria and renal failure. Our aim was to identify the associated risk factors, as these could be of preventative importance. We recruited 150 children with sickle cell anaemia (SCA), aged two to 18 years and living in Kinshasa, the Democratic Republic of Congo. Hyperfiltration and microalbuminuria were defined as an estimated glomerular filtration rate of less than 140 mL/min/1.73 m² and an albumin creatinine ratio of between 30 and 299 mg/g, respectively. Independent determinants of hyperfiltration were assessed using logistic regression analysis. Glomerular hyperfiltration was observed in 60 (40%) children, who were significantly older (10.2 ± 4.1 versus 7.9 ± 4.3 years, p = 0.001) and had a lower body mass index level (14.7 ± 2.3 versus 15.0 ± 2.3 kg/m 2 ) than the 60% without. A higher proportion had microalbuminuria (25.0 versus 13.3%), but the difference was not statistically significant (p>0.05). Increased age and decreased body mass index were the main independent factors associated with glomerular hyperfiltration in the multivariate analysis. A quarter (25%) of the 60 children with SCA with glomerular hyperfiltration had microalbuminuria. Glomerular hyperfiltration was a common finding in this study and was significantly associated with age. ©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

α1β1 integrin/Rac1-dependent mesangial invasion of glomerular capillaries in Alport syndrome.

PubMed

Zallocchi, Marisa; Johnson, Brianna M; Meehan, Daniel T; Delimont, Duane; Cosgrove, Dominic

2013-10-01

Alport syndrome, hereditary glomerulonephritis with hearing loss, results from mutations in type IV collagen COL4A3, COL4A4, or COL4A5 genes. The mechanism for delayed glomerular disease onset is unknown. Comparative analysis of Alport mice and CD151 knockout mice revealed progressive accumulation of laminin 211 in the glomerular basement membrane. We show mesangial processes invading the capillary loops of both models as well as in human Alport glomeruli, as the likely source of this laminin. L-NAME salt-induced hypertension accelerated mesangial cell process invasion. Cultured mesangial cells showed reduced migratory potential when treated with either integrin-linked kinase inhibitor or Rac1 inhibitor, or by deletion of integrin α1. Treatment of Alport mice with Rac1 inhibitor or deletion of integrin α1 reduced mesangial cell process invasion of the glomerular capillary tuft. Laminin α2-deficient Alport mice show reduced mesangial process invasion, and cultured laminin α2-null cells showed reduced migratory potential, indicating a functional role for mesangial laminins in progression of Alport glomerular pathogenesis. Collectively, these findings predict a role for biomechanical insult in the induction of integrin α1β1-dependent Rac1-mediated mesangial cell process invasion of the glomerular capillary tuft as an initiation mechanism of Alport glomerular pathology. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Discrepancy between Medical Evidence Form 2728 and Renal Biopsy for Glomerular Diseases

PubMed Central

Hogan, Susan L.; Jennette, Caroline E.; Kenderes, Barbara; Krisher, Jenna; Jennette, J. Charles; McClellan, William M.

2010-01-01

Background and objectives: The United States Renal Data System (USRDS) is a commonly utilized database for epidemiologic research of ESRD patients. USRDS uses Medical Evidence Form 2728 to collect medical information about ESRD patients. The validity of the Form 2728 “primary cause of renal failure” field for glomerular diseases has not been evaluated, although inconsistencies between Form 2728 information and medical records have been documented previously with respect to comorbidities. Design, setting, participants, & measurements: Form 2728 information was linked with renal biopsy results from the Glomerular Disease Collaborative Network (GDCN) for 217 patients with biopsy-confirmed glomerular diseases who had reached ESRD. Biopsy results were compared with the Form 2728 “primary cause of renal failure” field. Diseases were considered individually, and also categorized into commonly used disease groups. Percentage of agreement and disease-specific measures of validity were calculated. Results: Overall agreement between renal biopsy and Form 2728 was low (14.8% overall, 23.0% when categorized). Agreement was better after Form 2728 was revised in 1995 (10.0% before versus 23.2% after overall). The cause of ESRD field was left blank in 57% of the forms submitted for glomerular disease patients. Individual glomerular diseases had very low specificities, but tended to have high positive predictive values. Conclusions: Form 2728 does not accurately reflect the renal pathology diagnosis as captured by biopsy. The large degree of missing data and misclassification should be of concern to those performing epidemiologic research using Form 2728 information on glomerular diseases. PMID:20688886

Plasma Gelsolin Induced Glomerular Fibrosis via the TGF-β1/Smads Signal Transduction Pathway in IgA Nephropathy

PubMed Central

Zhang, Lei; Han, Changsong; Ye, Fei; He, Yan; Jin, Yinji; Wang, Tianzhen; Wu, Yiqi; Jiang, Yang; Zhang, Fengmin; Jin, Xiaoming

2017-01-01

Glomerular fibrosis has been shown to be closely related to the progression and prognosis of IgA nephropathy (IgAN). However, mechanism underlying IgAN glomerular fibrosis remains unclear. Recently, our study showed that plasma gelsolin (pGSN) was decreased in the serum of an IgAN mouse model and that pGSN deposition was found in the glomeruli. Another cytokine, TGF-β1, which is closely related to glomerular fibrosis, was also found to be highly expressed in the glomeruli. In the present study, we report that pGSN induces glomerular fibrosis through the TGF-β1/Smads signal transduction pathway. This is supported by the following findings: human mesangial cells (HMCs) show remarkable morphological changes and proliferation in response to co-stimulation with pGSN and polymeric IgA1 (pIgA1) from IgAN patients compared to other controls. Moreover, ELISA assays showed that more TGF-β1 secretion was found in HMCs supernatants in the co-stimulation group. Further experiments showed increased TGF-β1, Smad3, p-Smad2/3, Smad4, and collagen 1 and decreased Smad7 expression in the co-stimulation group. Our present study implied that the synergistic effect of pGSN and pIgA induced glomerular fibrosis via the TGF-β1/Smads signal transduction pathway. This might be a potential mechanism for the glomerular fibrosis observed in IgAN patients. PMID:28208683

A Review of Podocyte Biology.

PubMed

Garg, Puneet

2018-05-31

Podocyte biology is a developing science that promises to help improve understanding of the mechanistic nature of multiple diseases associated with proteinuria. Proteinuria in nephrotic syndrome has been linked to mechanistic dysfunctions in the renal glomerulus involving the function of podocyte epithelial cells, including podocyte foot process effacement. Developments in imaging technology are improving knowledge of the detailed structure of the human renal glomerulus and cortex. Podocyte foot processes attach themselves to the glomerular capillaries at the glomerular basement membrane (GBM) forming intercellular junctions that form slit diaphragm filtration barriers that help maintain normal renal function. Damage in this area has been implicated in glomerular disease. Injured podocytes undergo effacement whereby they lose their structure and spread out, leading to a reduction in filtration barrier function. Effacement is typically associated with the presence of proteinuria in focal segmental glomerulosclerosis, minimal change disease, and diabetes. It is thought to be due to a breakdown in the actin cytoskeleton of the foot processes, complex contractile apparatuses that allow podocytes to dynamically reorganize according to changes in filtration requirements. The process of podocyte depletion correlates with the development of glomerular sclerosis and chronic kidney disease. Focal adhesion complexes that interact with the underlying GBM bind the podocytes within the glomerular structure and prevent their detachment. Key Messages: Knowledge of glomerular podocyte biology is helping to advance our understanding of the science and mechanics of the glomerular filtering process, opening the way to a variety of new potential applications for clinical targeting. © 2018 S. Karger AG, Basel.

Glomerular anionic site distribution in nonproteinuric rats. A computer-assisted morphometric analysis.

PubMed

Pilia, P A; Swain, R P; Williams, A V; Loadholt, C B; Ainsworth, S K

1985-12-01

The cationic ultrastructural tracer polyethyleneimine (PEI: pI approximately equal to 11.0), binds electrophysically to uniformly spaced discrete electron-dense anionic sites present in the laminae rarae of the rat glomerular basement membrane (GBM), mesangial reflections of the GBM, Bowman's capsule, and tubular basement membranes when administered intravenously. Computer-assisted morphometric analysis of glomerular anionic sites reveals that the maximum concentration of stainable lamina rara externa (lre) sites (21/10,000 A GBM) occurs 60 minutes after PEI injection with a site-site interspacing of 460 A. Lamina rara interna (lri) sites similarly demonstrate a maximum concentration (20/10,000 A GBM) at 60 minutes with a periodicity of 497 A. The concentration and distribution of anionic sites within the lri was irregular in pattern and markedly decreased in number, while the lre possesses an electrical field that is highly regular at all time intervals analyzed (15, 30, 60, 120, 180, 240, and 300 minutes). Immersion and perfusion of renal tissue with PEI reveals additional heavy staining of the epithelial and endothelial cell sialoprotein coatings. PEI appears to bind to glomerular anionic sites reversibly: ie, between 60 and 180 minutes the concentration of stained sites decreases. At 300 minutes, the interspacing once again approaches the 60-minute concentration. This suggests a dynamic turnover or dissociation followed by a reassociation of glomerular negatively charged PEI binding sites. In contrast, morphometric analysis of anionic sites stained with lysozyme and protamine sulfate reveals interspacings of 642 A and 585 A, respectively; in addition, these tracers produce major glomerular ultrastructural alterations and induce transient proteinuria. PEI does not induce proteinuria in rats, nor does it produce glomerular morphologic alterations when ten times the tracer dosage is administered intravenously. These findings indicate that the choice of ultrastructural charge tracer, the method of administering the tracer, and the time selected for analysis of tissue after administration of tracer significantly influences results. Morphometric analysis of the distribution of glomerular anionic sites in nonproteinuric rats provides a method of evaluating quantitative alterations of the glomerular charge barrier in renal disease models.

Associations of estimated glomerular filtration rate and albuminuria with mortality and renal failure by sex: a meta-analysis.

PubMed

Nitsch, Dorothea; Grams, Morgan; Sang, Yingying; Black, Corri; Cirillo, Massimo; Djurdjev, Ognjenka; Iseki, Kunitoshi; Jassal, Simerjot K; Kimm, Heejin; Kronenberg, Florian; Oien, Cecilia M; Levey, Andrew S; Levin, Adeera; Woodward, Mark; Hemmelgarn, Brenda R

2013-01-29

To assess for the presence of a sex interaction in the associations of estimated glomerular filtration rate and albuminuria with all-cause mortality, cardiovascular mortality, and end stage renal disease. Random effects meta-analysis using pooled individual participant data. 46 cohorts from Europe, North and South America, Asia, and Australasia. 2,051,158 participants (54% women) from general population cohorts (n=1,861,052), high risk cohorts (n=151,494), and chronic kidney disease cohorts (n=38,612). Eligible cohorts (except chronic kidney disease cohorts) had at least 1000 participants, outcomes of either mortality or end stage renal disease of ≥ 50 events, and baseline measurements of estimated glomerular filtration rate according to the Chronic Kidney Disease Epidemiology Collaboration equation (mL/min/1.73 m(2)) and urinary albumin-creatinine ratio (mg/g). Risks of all-cause mortality and cardiovascular mortality were higher in men at all levels of estimated glomerular filtration rate and albumin-creatinine ratio. While higher risk was associated with lower estimated glomerular filtration rate and higher albumin-creatinine ratio in both sexes, the slope of the risk relationship for all-cause mortality and for cardiovascular mortality were steeper in women than in men. Compared with an estimated glomerular filtration rate of 95, the adjusted hazard ratio for all-cause mortality at estimated glomerular filtration rate 45 was 1.32 (95% CI 1.08 to 1.61) in women and 1.22 (1.00 to 1.48) in men (P(interaction)<0.01). Compared with a urinary albumin-creatinine ratio of 5, the adjusted hazard ratio for all-cause mortality at urinary albumin-creatinine ratio 30 was 1.69 (1.54 to 1.84) in women and 1.43 (1.31 to 1.57) in men (P(interaction)<0.01). Conversely, there was no evidence of a sex difference in associations of estimated glomerular filtration rate and urinary albumin-creatinine ratio with end stage renal disease risk. Both sexes face increased risk of all-cause mortality, cardiovascular mortality, and end stage renal disease with lower estimated glomerular filtration rates and higher albuminuria. These findings were robust across a large global consortium.

Temporary renal ischemia during nephron sparing surgery is associated with short-term but not long-term impairment in renal function.

PubMed

Yossepowitch, Ofer; Eggener, Scott E; Serio, Angel; Huang, William C; Snyder, Mark E; Vickers, Andrew J; Russo, Paul

2006-10-01

The emergence of laparoscopic nephron sparing surgery has rekindled interest in the impact of warm renal ischemia on renal function. To provide data with which warm renal ischemia can be compared we analyzed short-term and long-term changes in the glomerular filtration rate after temporary cold renal ischemia. In patients undergoing open nephron sparing surgery the estimated glomerular filtration rate was assessed preoperatively, early in the postoperative hospital stay, and 1 and 12 months after surgery using the abbreviated Modification of Diet in Renal Disease Study equation. We separately analyzed 70 patients with a solitary kidney and 592 with 2 functioning kidneys. The end point was the percent change from the baseline glomerular filtration rate. A linear regression model was used to test the association between the glomerular filtration rate change, and ischemia time, patient age, tumor size, estimated blood loss and intraoperative fluid administration. Median cold ischemia time was 31 minutes in patients with a solitary kidney and 35 minutes in those with 2 kidneys. Compared to patients with 2 kidneys those with a solitary kidney had a significantly lower preoperative estimated glomerular filtration rate (p < 0.001), which decreased a median of 30% during the early postoperative period, and 15% and 32% 1 and 12 months after surgery, respectively. In patients with 2 kidneys the corresponding glomerular filtration rate decreases were 16%, 13% and 14%, respectively. On multivariate analyses in each group cold ischemia duration and intraoperative blood loss were significantly associated with early glomerular filtration rate changes. However, 12 months after surgery age was the only independent predictor of a glomerular filtration rate decrease in patients with 2 kidneys. Cold renal ischemia during nephron sparing surgery is a significant determinant of the short-term postoperative glomerular filtration rate. Longer clamping time is particularly detrimental in patients with a solitary kidney but it does not appear to influence long-term renal function. Patients of advanced age may be less likely to recover from acute ischemic renal injury.

Association of haemodynamic changes measured by serial central venous saturation during ultrafiltration for acutely decompensated heart failure with diuretic resistance and change in renal function.

PubMed

Vazir, Ali; Simpkin, Victoria L; Marino, Philip; Ludman, Andrew; Banya, Winston; Tavazzi, Guido; Bastin, Anthony J; Trenfield, Sarah; Ghori, Arshad; Alexander, Peter D; Griffiths, Mark; Price, Susanna; Sharma, Rakesh; Cowie, Martin R

2016-10-01

Patients with acute decompensated heart failure with diuretic resistance (ADHF-DR) have a poor prognosis. The aim of this study was to assess in patients with ADHF-DR, whether haemodynamic changes during ultrafiltration (UF) are associated with changes in renal function (Δcreatinine) and whether Δcreatinine post UF is associated with mortality. Seventeen patients with ADHF-DR underwent 20 treatments with UF. Serial bloods (4-6 hourly) from the onset of UF treatment were measured for renal function, electrolytes and central venous saturation (CVO2). Univariate and multivariate analysis were performed to assess the relationship between changes in markers of haemodynamics [heart rate (HR), systolic blood pressure (SBP), packed cell volume (PCV) and CVO2] and Δcreatinine. Patients were followed up and mortality recorded. Cox-regression survival analysis was performed to determine covariates associated with mortality. Renal function worsened after UF in 17 of the 20 UF treatments (baseline vs. post UF creatinine: 164±58 vs. 185±69μmol/l, P<0.01). ΔCVO2 was significantly associated with Δcreatinine [β-coefficient of -1.3 95%CI (-1.8 to -0.7), P<0.001] and remained significantly associated with Δcreatinine after considering changes in SBP, HR and PCV [P<0.001]. Ten (59%) patients died at 1-year and 15(88%) by 2-years. Δcreatinine was independently associated with mortality (adjusted-hazard ratio 1.03 (1.01 to 1.07) per 1μmol/l increase in creatinine; P=0.02). Haemodynamic changes during UF as measured by the surrogate of cardiac output was associated with Δcreatinine. Worsening renal function at end of UF treatment occurred in the majority of patients and was associated with mortality. Copyright © 2016. Published by Elsevier Ireland Ltd.

PACSIN2 accelerates nephrin trafficking and is up-regulated in diabetic kidney disease

PubMed Central

Dumont, Vincent; Tolvanen, Tuomas A.; Kuusela, Sara; Wang, Hong; Nyman, Tuula A.; Lindfors, Sonja; Tienari, Jukka; Nisen, Harry; Suetsugu, Shiro; Plomann, Markus; Kawachi, Hiroshi; Lehtonen, Sanna

2017-01-01

Nephrin is a core component of podocyte (glomerular epithelial cell) slit diaphragm and is required for kidney ultrafiltration. Down-regulation or mislocalization of nephrin has been observed in diabetic kidney disease (DKD), characterized by albuminuria. Here, we investigate the role of protein kinase C and casein kinase 2 substrate in neurons 2 (PACSIN2), a regulator of endocytosis and recycling, in the trafficking of nephrin and development of DKD. We observe that PACSIN2 is up-regulated and nephrin mislocalized in podocytes of obese Zucker diabetic fatty (ZDF) rats that have altered renal function. In cultured podocytes, PACSIN2 and nephrin colocalize and interact. We show that nephrin is endocytosed in PACSIN2-positive membrane regions and that PACSIN2 overexpression increases both nephrin endocytosis and recycling. We identify rabenosyn-5, which is involved in early endosome maturation and endosomal sorting, as a novel interaction partner of PACSIN2. Interestingly, rabenosyn-5 expression is increased in podocytes in obese ZDF rats, and, in vitro, its overexpression enhances the association of PACSIN2 and nephrin. We also show that palmitate, which is elevated in diabetes, enhances this association. Collectively, PACSIN2 is up-regulated and nephrin is abnormally localized in podocytes of diabetic ZDF rats. In vitro, PACSIN2 enhances nephrin turnover apparently via a mechanism involving rabenosyn-5. The data suggest that elevated PACSIN2 expression accelerates nephrin trafficking and associates with albuminuria.—Dumont, V., Tolvanen, T. A., Kuusela, S., Wang, H., Nyman, T. A., Lindfors, S., Tienari, J., Nisen, H., Suetsugu, S., Plomann, M., Kawachi, H., Lehtonen, S. PACSIN2 accelerates nephrin trafficking and is up-regulated in diabetic kidney disease. PMID:28550045

The insect nephrocyte is a podocyte-like cell with a filtration slit diaphragm

PubMed Central

Weavers, Helen; Prieto-Sánchez, Silvia; Grawe, Ferdinand; Garcia-López, Amparo; Artero, Ruben; Wilsch-Braeuninger, Michaela; Ruiz-Gómez, Mar; Skaer, Helen; Denholm, Barry

2009-01-01

The nephron is the basic structural and functional unit of the vertebrate kidney. It is composed of a glomerulus, the site of ultrafiltration, and a renal tubule, along which the filtrate is modified. Although widely regarded as a vertebrate adaptation1 ‘nephron-like’ features can be found in the excretory systems of many invertebrates, raising the possibility that components of the vertebrate excretory system were inherited from their invertebrate ancestors2. Here we show that the insect nephrocyte has remarkable anatomical, molecular and functional similarity with the glomerular podocyte, a cell in the vertebrate kidney that forms the main size-selective barrier as blood is ultrafiltered to make urine. In particular, both cell types possess a specialised filtration diaphragm, known as the slit diaphragm in podocytes or the nephrocyte diaphragm in nephrocytes. We find that fly orthologues of the major constituents of the slit diaphragm, including nephrin, neph1, CD2AP, ZO-1 and podocin are expressed in the nephrocyte and form a complex of interacting proteins that closely mirrors the vertebrate slit diaphragm complex. Furthermore, we find the nephrocyte diaphragm is completely lost in flies mutant for nephrin or neph1 orthologues, a phenotype resembling loss of the slit diaphragm in the absence of either nephrin (as in the human kidney disease NPHS1) or neph1. These changes drastically impair filtration function in the nephrocyte. The similarities we describe between invertebrate nephrocytes and vertebrate podocytes provide evidence suggesting the two cell types are evolutionarily related and establish the nephrocyte as a simple model in which to study podocyte biology and podocyte-associated diseases. PMID:18971929

Cryo-EM structure of the cytoplasmic domain of murine transient receptor potential cation channel subfamily C member 6 (TRPC6).

PubMed

Azumaya, Caleigh M; Sierra-Valdez, Francisco; Cordero-Morales, Julio F; Nakagawa, Terunaga

2018-05-11

The kidney maintains the internal milieu by regulating the retention and excretion of proteins, ions, and small molecules. The glomerular podocyte forms the slit diaphragm of the ultrafiltration filter, whose damage leads to progressive kidney failure and focal segmental glomerulosclerosis (FSGS). The canonical transient receptor potential 6 (TRPC6) ion channel is expressed in the podocyte and mutations in its cytoplasmic domain cause FSGS in humans. In vitro evaluation of disease-causing mutations in TRPC6 has revealed that these genetic alterations result in abnormal ion channel gating. However, the mechanism whereby the cytoplasmic domain modulates TRPC6 function is largely unknown. Here we report a cryoEM structure of the cytoplasmic domain of murine TRPC6 at 3.8Å resolution. The cytoplasmic fold of TRPC6 is characterized by an inverted dome-like chamber pierced by four radial horizontal helices that converge into a vertical coiled-coil at the central axis. Unlike in other TRP channels, TRPC6 displays a unique domain swap that occurs at the junction of the horizontal helices and coiled-coil. Multiple FSGS mutations converge at the buried interface between the vertical coiled-coil and the ankyrin repeats, which form the dome, suggesting these regions are critical for allosteric gating modulation. This functionally critical interface is a potential target for drug design. Importantly, dysfunction in other family members leads to learning deficits (TRPC1/4/5) and ataxia (TRPC3). Our data provide a structural framework for the mechanistic investigation of the TRPC family. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Luminal angiotensin II stimulates rat medullary thick ascending limb chloride transport in the presence of basolateral norepinephrine.

PubMed

Baum, Michel

2016-02-15

Angiotensin II (ANG II) is secreted by the proximal tubule resulting in a luminal concentration that is 100- to 1,000-fold greater than that in the blood. Luminal ANG II has been shown to stimulate sodium transport in the proximal tubule and distal nephron. Surprisingly, luminal ANG II inhibits NaCl transport in the medullary thick ascending limb (mTAL), a nephron segment responsible for a significant amount of NaCl absorption from the glomerular ultrafiltrate. We confirmed that addition of 10(-8) M ANG II to the lumen inhibited mTAL chloride transport (220 ± 19 to 165 ± 25 pmol·mm(-1)·min(-1), P < 0.01) and examined whether an interaction with basolateral norepinephrine existed to simulate the in vivo condition of an innervated tubule. We found that in the presence of a 10(-6) M norepinephrine bath, luminal ANG II stimulated mTAL chloride transport from 298 ± 18 to 364 ± 42 pmol·mm(-1)·min(-1) (P < 0.05). Stimulation of chloride transport by luminal ANG II was also observed with 10(-3) M bath dibutyryl cAMP in the bathing solution and bath isoproterenol. A bath of 10(-5) H-89 blocked the stimulation of chloride transport by norepinephrine and prevented the effect of luminal ANG II to either stimulate or inhibit chloride transport. Bath phentolamine, an α-adrenergic agonist, also prevented the decrease in mTAL chloride transport by luminal ANG II. Thus luminal ANG II increases chloride transport with basolateral norepinephrine; an effect likely mediated by stimulation of cAMP. Alpha-1 adrenergic stimulation prevents the inhibition of chloride transport by luminal ANG II. Copyright © 2016 the American Physiological Society.

Effect of Icodextrin Solution on the Preservation of Residual Renal Function in Peritoneal Dialysis Patients: A Randomized Controlled Study.

PubMed

Chang, Tae Ik; Ryu, Dong-Ryeol; Yoo, Tae-Hyun; Kim, Hyung Jong; Kang, Ea Wha; Kim, Hyunwook; Chang, Jae Hyun; Kim, Dong Ki; Moon, Sung Jin; Yoon, Soo Young; Han, Seung Hyeok

2016-03-01

Although icodextrin solution has been highlighted in the fluid management compared to glucose-based solutions, proof of a beneficial effect of icodextrin solution on residual renal function (RRF) is lacking. We conducted a multicenter prospective randomized controlled open-label trial to investigate whether icodextrin solution can preserve RRF.One hundred patients with urine volume ≥750 mL/day from 8 centers in Korea were randomly assigned to receive 1 exchange of icodextrin solution for a ≥8 hour-dwell time and 2 exchanges of 1.5% glucose-based biocompatible neutral pH solution or 1 exchange of ≥2.5% and 2 exchanges of 1.5% glucose-based biocompatible solutions. Using mixed-effects general linear models, we analyzed changes in residual glomerular filtration rate (GFR) and daily urine volume at 1 year.Forty-nine patients were assigned to the icodextrin group and 51 to the glucose solution group. During follow-up, the slope of the decline in residual GFR was -0.170 mL/min/month/1.73 m² in the icodextrin group, while it was -0.155 mL/min/month/1.73 m² in the glucose solution group (95% confidence interval [CI], -0.06 to 0.10; P = 0.701). Daily urine volume decreased faster in the glucose solution group than in the icodextrin group (-31.02 vs -11.88 mL per month; 95% CI, -35.85 to -2.44; P = 0.025). Results were consistent when we analyzed using intention-to-treat and per protocol principles. There were no differences in fluid status, peritoneal ultrafiltration, and peritoneal transport between groups during follow-up.This study clearly showed that icodextrin solution preserves residual urine volume better than glucose solution.

In vivo imaging of leukocyte recruitment to glomeruli in mice using intravital microscopy.

PubMed

Kitching, A Richard; Kuligowski, Michael P; Hickey, Michael J

2009-01-01

Leukocytes mediate some forms of glomerulonephritis, particularly severe proliferative and crescentic forms. The renal glomerulus is one of the few sites within the microvasculature in which leukocyte recruitment occurs in capillaries. However, due to the difficulty of directly visualising the glomerulus, the mechanisms of leukocyte recruitment to glomerular capillaries are poorly understood. To overcome this, a murine kidney can be rendered hydronephrotic, by ligating one ureter, and allowing the mouse to rest for 12 weeks. This allows the visualisation of the glomerular microvasculature during inflammatory responses. In inflammation, in this example induced by anti-glomerular basement membrane (GBM) antibody, leukocytes can be observed undergoing adhesion in glomerular capillaries using intravital microscopy. Leukocyte adhesion can be quantitated using this approach. An observation protocol involving few, limited periods of epifluorescence avoids phototoxicity-induced leukocyte recruitment. The process of hydronephrosis does not alter the ability of anti-GBM-antibody to induce a glomerular inflammatory response. This approach allows detailed investigation of the mechanisms of leukocyte recruitment within glomeruli.

Collagen IV Diseases: A Focus on the Glomerular Basement Membrane in Alport Syndrome

PubMed Central

Cosgrove, Dominic; Liu, Shiguang

2016-01-01

Alport syndrome is the result of mutations in any of three type IV collagen genes, COL4A3, COL4A4, or COL4A5. Because the three collagen chains form heterotrimers, there is an absence of all three proteins in the basement membranes where they are expressed. In the glomerulus, the mature glomerular basement membrane type IV collagen network, normally comprised of two separate networks, α3(IV)/α4(IV)/α5(IV) and α1(IV)/α2(IV), is comprised entirely of collagen α1(IV)/α2. This review addresses the current state of our knowledge regarding the consequence of this change in basement membrane composition, including both the direct, via collagen receptor binding, and indirect, regarding influences on glomerular biomechanics. The state of our current understanding regarding mechanisms of glomerular disease initiation and progression will be examined, as will the current state of the art regarding emergent therapeutic approaches to slow or arrest glomerular disease in Alport patients. PMID:27576055

aPKCλ/ι and aPKCζ Contribute to Podocyte Differentiation and Glomerular Maturation

PubMed Central

Hartleben, Björn; Widmeier, Eugen; Suhm, Martina; Worthmann, Kirstin; Schell, Christoph; Helmstädter, Martin; Wiech, Thorsten; Walz, Gerd; Leitges, Michael; Schiffer, Mario

2013-01-01

Precise positioning of the highly complex interdigitating podocyte foot processes is critical to form the normal glomerular filtration barrier, but the molecular programs driving this process are unknown. The protein atypical protein kinase C (aPKC)—a component of the Par complex, which localizes to tight junctions and interacts with slit diaphragm proteins—may play a role. Here, we found that the combined deletion of the aPKCλ/ι and aPKCζ isoforms in podocytes associated with incorrectly positioned centrosomes and Golgi apparatus and mislocalized molecules of the slit diaphragm. Furthermore, aPKC-deficient podocytes failed to form the normal network of foot processes, leading to defective glomerular maturation with incomplete capillary formation and mesangiolysis. Our results suggest that aPKC isoforms orchestrate the formation of the podocyte processes essential for normal glomerular development and kidney function. Defective aPKC signaling results in a dramatically simplified glomerular architecture, causing severe proteinuria and perinatal death. PMID:23334392

[Why? How? What for? We must measure the glomerular filtration].

PubMed

Treviño-Becerra, Alejandro

2010-01-01

The measurement of the glomerular filtration shows the degree of the functional qualities and the proficiency of the renal system. Despite new technologies, at present the best accepted technique for measuring the glomerular filtration in most countries is the clearance of creatinine in 24 hour urine. The clearance of creatinine has the advantage that it is confident, easy to reproduce, without technical limitations and low cost.

Podocyte-associated talin1 is critical for glomerular filtration barrier maintenance

PubMed Central

Tian, Xuefei; Kim, Jin Ju; Monkley, Susan M.; Gotoh, Nanami; Nandez, Ramiro; Soda, Keita; Inoue, Kazunori; Balkin, Daniel M.; Hassan, Hossam; Son, Sung Hyun; Lee, Yashang; Moeckel, Gilbert; Calderwood, David A.; Holzman, Lawrence B.; Critchley, David R.; Zent, Roy; Reiser, Jochen; Ishibe, Shuta

2014-01-01

Podocytes are specialized actin-rich epithelial cells that line the kidney glomerular filtration barrier. The interface between the podocyte and the glomerular basement membrane requires integrins, and defects in either α3 or β1 integrin, or the α3β1 ligand laminin result in nephrotic syndrome in murine models. The large cytoskeletal protein talin1 is not only pivotal for integrin activation, but also directly links integrins to the actin cytoskeleton. Here, we found that mice lacking talin1 specifically in podocytes display severe proteinuria, foot process effacement, and kidney failure. Loss of talin1 in podocytes caused only a modest reduction in β1 integrin activation, podocyte cell adhesion, and cell spreading; however, the actin cytoskeleton of podocytes was profoundly altered by the loss of talin1. Evaluation of murine models of glomerular injury and patients with nephrotic syndrome revealed that calpain-induced talin1 cleavage in podocytes might promote pathogenesis of nephrotic syndrome. Furthermore, pharmacologic inhibition of calpain activity following glomerular injury substantially reduced talin1 cleavage, albuminuria, and foot process effacement. Collectively, these findings indicate that podocyte talin1 is critical for maintaining the integrity of the glomerular filtration barrier and provide insight into the pathogenesis of nephrotic syndrome. PMID:24531545

Creatinine Clearance Is Not Equal to Glomerular Filtration Rate and Cockcroft-Gault Equation Is Not Equal to CKD-EPI Collaboration Equation.

PubMed

Fernandez-Prado, Raul; Castillo-Rodriguez, Esmeralda; Velez-Arribas, Fernando Javier; Gracia-Iguacel, Carolina; Ortiz, Alberto

2016-12-01

Direct oral anticoagulants (DOACs) may require dose reduction or avoidance when glomerular filtration rate is low. However, glomerular filtration rate is not usually measured in routine clinical practice. Rather, equations that incorporate different variables use serum creatinine to estimate either creatinine clearance in mL/min or glomerular filtration rate in mL/min/1.73 m 2 . The Cockcroft-Gault equation estimates creatinine clearance and incorporates weight into the equation. By contrast, the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations estimate glomerular filtration rate and incorporate ethnicity but not weight. As a result, an individual patient may have very different renal function estimates, depending on the equation used. We now highlight these differences and discuss the impact on routine clinical care for anticoagulation to prevent embolization in atrial fibrillation. Pivotal DOAC clinical trials used creatinine clearance as a criterion for patient enrollment, and dose adjustment and Federal Drug Administration recommendations are based on creatinine clearance. However, clinical biochemistry laboratories provide CKD-EPI glomerular filtration rate estimations, resulting in discrepancies between clinical trial and routine use of the drugs. Copyright © 2016 Elsevier Inc. All rights reserved.

Ultrastructural Characterization of the Glomerulopathy in Alport Mice by Helium Ion Scanning Microscopy (HIM).

PubMed

Tsuji, Kenji; Suleiman, Hani; Miner, Jeffrey H; Daley, James M; Capen, Diane E; Păunescu, Teodor G; Lu, Hua A Jenny

2017-09-15

The glomerulus exercises its filtration barrier function by establishing a complex filtration apparatus consisting of podocyte foot processes, glomerular basement membrane and endothelial cells. Disruption of any component of the glomerular filtration barrier leads to glomerular dysfunction, frequently manifested as proteinuria. Ultrastructural studies of the glomerulus by transmission electron microscopy (TEM) and conventional scanning electron microscopy (SEM) have been routinely used to identify and classify various glomerular diseases. Here we report the application of newly developed helium ion scanning microscopy (HIM) to examine the glomerulopathy in a Col4a3 mutant/Alport syndrome mouse model. Our study revealed unprecedented details of glomerular abnormalities in Col4a3 mutants including distorted podocyte cell bodies and disorganized primary processes. Strikingly, we observed abundant filamentous microprojections arising from podocyte cell bodies and processes, and presence of unique bridging processes that connect the primary processes and foot processes in Alport mice. Furthermore, we detected an altered glomerular endothelium with disrupted sub-endothelial integrity. More importantly, we were able to clearly visualize the complex, three-dimensional podocyte and endothelial interface by HIM. Our study demonstrates that HIM provides nanometer resolution to uncover and rediscover critical ultrastructural characteristics of the glomerulopathy in Col4a3 mutant mice.

The relationship between renal warm ischemia time and glomerular loss. An experimental study in a pig model.

PubMed

Damasceno-Ferreira, José Aurelino; Bechara, Gustavo Ruschi; Costa, Waldemar Silva; Pereira-Sampaio, Marco Aurélio; Sampaio, Francisco José Barcellos; Souza, Diogo Benchimol De

2017-05-01

To investigate the glomerular number after different warm ischemia times. Thirty two pigs were assigned into four groups. Three groups (G10, G20, and G30) were treated with 10, 20, and 30 minutes of left renal warm ischemia. The sham group underwent the same surgery without renal ischemia. The animals were euthanized after 3 weeks, and the kidneys were collected. Right kidneys were used as controls. The kidney weight, volume, cortical-medullar ratio, glomerular volumetric density, volume-weighted mean glomerular volume, and the total number of glomeruli per kidney were obtained. Serum creatinine levels were assessed pre and postoperatively. Serum creatinine levels did not differ among the groups. All parameters were similar for the sham, G10, and G20 groups upon comparison of the right and left organs. The G30 group pigs' left kidneys had lower weight, volume, and cortical-medullar ratio and 24.6% less glomeruli compared to the right kidney. A negative correlation was found between warm ischemia time and glomerular number. About one quarter of glomeruli was lost after 30 minutes of renal warm ischemia. No glomeruli loss was detected before 20 minutes of warm ischemia. However, progressive glomerular loss was associated with increasing warm ischemia time.

Podometrics as a Potential Clinical Tool for Glomerular Disease Management.

PubMed

Kikuchi, Masao; Wickman, Larysa; Hodgin, Jeffrey B; Wiggins, Roger C

2015-05-01

Chronic kidney disease culminating in end-stage kidney disease is a major public health problem costing in excess of $40 billion per year with high morbidity and mortality. Current tools for glomerular disease monitoring lack precision and contribute to poor outcome. The podocyte depletion hypothesis describes the major mechanisms underlying the progression of glomerular diseases, which are responsible for more than 80% of cases of end-stage kidney disease. The question arises of whether this new knowledge can be used to improve outcomes and reduce costs. Podocytes have unique characteristics that make them an attractive monitoring tool. Methodologies for estimating podocyte number, size, density, glomerular volume and other parameters in routine kidney biopsies, and the rate of podocyte detachment from glomeruli into urine (podometrics) now have been developed and validated. They potentially fill important gaps in the glomerular disease monitoring toolbox. The application of these tools to glomerular disease groups shows good correlation with outcome, although data validating their use for individual decision making is not yet available. Given the urgency of the clinical problem, we argue that the time has come to focus on testing these tools for application to individualized clinical decision making toward more effective progression prevention. Copyright © 2015 Elsevier Inc. All rights reserved.

Glomerular loss after arteriovenous and arterial clamping for renal warm ischemia in a swine model.

PubMed

Bechara, Gustavo Ruschi; Damasceno-Ferreira, José Aurelino; Abreu, Leonardo Albuquerque Dos Santos; Costa, Waldemar Silva; Sampaio, Francisco José Barcellos; Pereira-Sampaio, Marco Aurélio; Souza, Diogo Benchimol De

2016-11-01

To evaluate the glomerular loss after arteriovenous or arterial warm ischemia in a swine model. Twenty four pigs were divided into Group Sham (submitted to all surgical steps except the renal ischemia), Group AV (submitted to 30 minutes of warm ischemia by arteriovenous clamping of left kidney vessels), and Group A (submitted to 30 minutes of ischemia by arterial clamping). Right kidneys were used as controls. Weigh, volume, cortical volume, glomerular volumetric density (Vv[Glom]), volume-weighted glomerular volume (VWGV), and the total number of glomeruli were measured for each organ. Group AV showed a 24.5% reduction in its left kidney Vv[Glom] and a 25.4% reduction in the VWGV, when compared to the right kidney. Reductions were also observed when compared to kidneys of sham group. There was a reduction of 19.2% in the total number of glomeruli in AV kidneys. No difference was observed in any parameters analyzed on the left kidneys from group A. Renal warm ischemia of 30 minutes by arterial clamping did not caused significant glomerular damage, but arteriovenous clamping caused significant glomerular loss in a swine model. Clamping only the renal artery should be considered to minimize renal injury after partial nephrectomies.

The mTOR-inhibitor rapamycin mediates proteinuria in nephrotoxic serum nephritis by activating the innate immune response.

PubMed

Kirsch, A H; Riegelbauer, V; Tagwerker, A; Rudnicki, M; Rosenkranz, A R; Eller, K

2012-08-15

Rapamycin (Rapa) is an immunosuppressant used to prevent rejection in recipients of renal transplants. Its clinical use is limited by de novo onset or exacerbation of preexisting proteinuria. In the present study, Rapa administration was started 14 days after induction of murine nephrotoxic serum nephritis (NTS) to study glomerular effects of this mammalian target of rapamycin (mTOR) inhibitor. Glomeruli were laser-microdissected, and real-time PCR was performed to assess effects on glomerular cells and the expression of inflammatory cytokines. Immunohistochemical stainings were performed to confirm mRNA data on the protein level. Compared with nephritic control animals, Rapa-treated mice developed significantly increased albuminuria. This was accompanied by a more prominent glomerular infiltration by CD4(+) T cells and macrophages. Glomerular mRNA expression profiling revealed increased levels of the proinflammatory cytokines interleukin-6 and tumor necrosis factor-α, and the chemokines monocyte chemoattractant protein-1 and macrophage inflammatory protein-1β and their cognate macrophage-associated receptors CCR2 and CCR5 in the Rapa-treated animals. Furthermore, there were elevated glomerular transcription levels of the regulatory T cell phenotype transcription factor Foxp3. No differences in the glomerular expression of the podocyte marker nephrin or the endothelial cell marker CD31 were observed on the mRNA or protein level. In conclusion, our data indicate that Rapa-induced proteinuria in NTS is a result of the activation of the innate immune system rather than a direct toxicity to podocytes or glomerular endothelial cells.

Macrophage Migration Inhibitory Factor Mediates Proliferative GN via CD74

PubMed Central

Djudjaj, Sonja; Lue, Hongqi; Rong, Song; Papasotiriou, Marios; Klinkhammer, Barbara M.; Zok, Stephanie; Klaener, Ole; Braun, Gerald S.; Lindenmeyer, Maja T.; Cohen, Clemens D.; Bucala, Richard; Tittel, Andre P.; Kurts, Christian; Moeller, Marcus J.; Floege, Juergen; Ostendorf, Tammo

2016-01-01

Pathologic proliferation of mesangial and parietal epithelial cells (PECs) is a hallmark of various glomerulonephritides. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that mediates inflammation by engagement of a receptor complex involving the components CD74, CD44, CXCR2, and CXCR4. The proliferative effects of MIF may involve CD74 together with the coreceptor and PEC activation marker CD44. Herein, we analyzed the effects of local glomerular MIF/CD74/CD44 signaling in proliferative glomerulonephritides. MIF, CD74, and CD44 were upregulated in the glomeruli of patients and mice with proliferative glomerulonephritides. During disease, CD74 and CD44 were expressed de novo in PECs and colocalized in both PECs and mesangial cells. Stress stimuli induced MIF secretion from glomerular cells in vitro and in vivo, in particular from podocytes, and MIF stimulation induced proliferation of PECs and mesangial cells via CD74. In murine crescentic GN, Mif-deficient mice were almost completely protected from glomerular injury, the development of cellular crescents, and the activation and proliferation of PECs and mesangial cells, whereas wild-type mice were not. Bone marrow reconstitution studies showed that deficiency of both nonmyeloid and bone marrow–derived Mif reduced glomerular cell proliferation and injury. In contrast to wild-type mice, Cd74-deficient mice also were protected from glomerular injury and ensuing activation and proliferation of PECs and mesangial cells. Our data suggest a novel molecular mechanism and glomerular cell crosstalk by which local upregulation of MIF and its receptor complex CD74/CD44 mediate glomerular injury and pathologic proliferation in GN. PMID:26453615

Expression of agrin, dystroglycan, and utrophin in normal renal tissue and in experimental glomerulopathies.

PubMed

Raats, C J; van den Born, J; Bakker, M A; Oppers-Walgreen, B; Pisa, B J; Dijkman, H B; Assmann, K J; Berden, J H

2000-05-01

The dystrophin-glycoprotein complex, which comprises alpha- and beta-dystroglycan, sarcoglycans, and utrophin/dystrophin, links the cytoskeleton to agrin and laminin in the basal lamina in muscle and epithelial cells. Recently, agrin was identified as a major heparan sulfate proteoglycan in the glomerular basement membrane. In the present study, we found mRNA expression for agrin, dystroglycan, and utrophin in kidney cortex, isolated glomeruli, and cultured podocytes and mesangial cells. In immunofluorescence, agrin was found in the glomerular basement membrane. The antibodies against alpha- and beta-dystroglycan and utrophin revealed a granular podocyte-like staining pattern along the glomerular capillary wall. With immunoelectron microscopy, agrin was found in the glomerular basement membrane, dystroglycan was diffusely found over the entire cell surface of the podocytes, and utrophin was localized in the cytoplasm of the podocyte foot processes. In adriamycin nephropathy, a decrease in the glomerular capillary wall staining for dystroglycan was observed probably secondary to the extensive fusion of foot processes. Immunoelectron microscopy showed a different distribution pattern as compared to the normal kidney, with segmentally enhanced expression of dystroglycan at the basal side of the extensively fused podocyte foot processes. In passive Heymann nephritis we observed no changes in the staining intensity and distribution of the dystrophin-glycoprotein complex by immunofluorescence and immunoelectron microscopy. From these data, we conclude that agrin, dystroglycan, and utrophin are present in the glomerular capillary wall and their ultrastructural localization supports the concept that these molecules are involved in linking the podocyte cytoskeleton to the glomerular basement membrane.

Expression of Agrin, Dystroglycan, and Utrophin in Normal Renal Tissue and in Experimental Glomerulopathies

PubMed Central

Raats, C. J. Ilse; van den Born, Jacob; Bakker, Marinka A. H.; Oppers-Walgreen, Birgitte; Pisa, Brenda J. M.; Dijkman, Henry B. P. M.; Assmann, Karel J. M.; Berden, Jo H. M.

2000-01-01

The dystrophin-glycoprotein complex, which comprises α- and β-dystroglycan, sarcoglycans, and utrophin/dystrophin, links the cytoskeleton to agrin and laminin in the basal lamina in muscle and epithelial cells. Recently, agrin was identified as a major heparan sulfate proteoglycan in the glomerular basement membrane. In the present study, we found mRNA expression for agrin, dystroglycan, and utrophin in kidney cortex, isolated glomeruli, and cultured podocytes and mesangial cells. In immunofluorescence, agrin was found in the glomerular basement membrane. The antibodies against α- and β-dystroglycan and utrophin revealed a granular podocyte-like staining pattern along the glomerular capillary wall. With immunoelectron microscopy, agrin was found in the glomerular basement membrane, dystroglycan was diffusely found over the entire cell surface of the podocytes, and utrophin was localized in the cytoplasm of the podocyte foot processes. In adriamycin nephropathy, a decrease in the glomerular capillary wall staining for dystroglycan was observed probably secondary to the extensive fusion of foot processes. Immunoelectron microscopy showed a different distribution pattern as compared to the normal kidney, with segmentally enhanced expression of dystroglycan at the basal side of the extensively fused podocyte foot processes. In passive Heymann nephritis we observed no changes in the staining intensity and distribution of the dystrophin-glycoprotein complex by immunofluorescence and immunoelectron microscopy. From these data, we conclude that agrin, dystroglycan, and utrophin are present in the glomerular capillary wall and their ultrastructural localization supports the concept that these molecules are involved in linking the podocyte cytoskeleton to the glomerular basement membrane. PMID:10793086

Nocturnal polyuria is related to absent circadian rhythm of glomerular filtration rate.

PubMed

De Guchtenaere, A; Vande Walle, C; Van Sintjan, P; Raes, A; Donckerwolcke, R; Van Laecke, E; Hoebeke, P; Vande Walle, J

2007-12-01

Monosymptomatic nocturnal enuresis is frequently associated with nocturnal polyuria and low urinary osmolality during the night. Initial studies found decreased vasopressin levels associated with low urinary osmolality overnight. Together with the documented desmopressin response, this was suggestive of a primary role for vasopressin in the pathogenesis of enuresis in the absence of bladder dysfunction. Recent studies no longer confirm this primary role of vasopressin. Other pathogenetic factors such as disordered renal sodium handling, hypercalciuria, increased prostaglandins and/or osmotic excretion might have a role. So far, little attention has been given to abnormalities in the circadian rhythm of glomerular filtration rate. We evaluated the circadian rhythm of glomerular filtration rate and diuresis in children with desmopressin resistant monosymptomatic nocturnal enuresis and nocturnal polyuria. We evaluated 15 children (9 boys) 9 to 14 years old with monosymptomatic nocturnal enuresis and nocturnal polyuria resistant to desmopressin treatment. The control group consisted of 25 children (12 boys) 9 to 16 years old with monosymptomatic nocturnal enuresis without nocturnal polyuria. Compared to the control population, children with nocturnal polyuria lost their circadian rhythm not only for diuresis and sodium excretion but also for glomerular filtration rate. Patients with monosymptomatic nocturnal enuresis and nocturnal polyuria lack a normal circadian rhythm for diuresis and sodium excretion, and the circadian rhythm of glomerular filtration rate is absent. This absence of circadian rhythm of glomerular filtration rate and/or sodium handling cannot be explained by a primary role of vasopressin, but rather by a disorder in circadian rhythm of renal glomerular and/or tubular functions.

World Small Animal Veterinary Association Renal Pathology Initiative: Classification of Glomerular Diseases in Dogs.

PubMed

Cianciolo, R E; Mohr, F C; Aresu, L; Brown, C A; James, C; Jansen, J H; Spangler, W L; van der Lugt, J J; Kass, P H; Brovida, C; Cowgill, L D; Heiene, R; Polzin, D J; Syme, H; Vaden, S L; van Dongen, A M; Lees, G E

2016-01-01

Evaluation of canine renal biopsy tissue has generally relied on light microscopic (LM) evaluation of hematoxylin and eosin-stained sections ranging in thickness from 3 to 5 µm. Advanced modalities, such as transmission electron microscopy (TEM) and immunofluorescence (IF), have been used sporadically or retrospectively. Diagnostic algorithms of glomerular diseases have been extrapolated from the World Health Organization classification scheme for human glomerular disease. With the recent establishment of 2 veterinary nephropathology services that evaluate 3-µm sections with a panel of histochemical stains and routinely perform TEM and IF, a standardized objective species-specific approach for the diagnosis of canine glomerular disease was needed. Eight veterinary pathologists evaluated 114 parameters (lesions) in renal biopsy specimens from 89 dogs. Hierarchical cluster analysis of the data revealed 2 large categories of glomerular disease based on the presence or absence of immune complex deposition: The immune complex-mediated glomerulonephritis (ICGN) category included cases with histologic lesions of membranoproliferative or membranous patterns. The second category included control dogs and dogs with non-ICGN (glomerular amyloidosis or focal segmental glomerulosclerosis). Cluster analysis performed on only the LM parameters led to misdiagnosis of 22 of the 89 cases-that is, ICGN cases moved to the non-ICGN branch of the dendrogram or vice versa, thereby emphasizing the importance of advanced diagnostic modalities in the evaluation of canine glomerular disease. Salient LM, TEM, and IF features for each pattern of disease were identified, and a preliminary investigation of related clinicopathologic data was performed. © The Author(s) 2015.

Urine podocyte mRNAs mark disease activity in IgA nephropathy

PubMed Central

Fukuda, Akihiro; Sato, Yuji; Iwakiri, Takashi; Komatsu, Hiroyuki; Kikuchi, Masao; Kitamura, Kazuo; Wiggins, Roger C.; Fujimoto, Shouichi

2015-01-01

Background Podocyte depletion is a major mechanism driving glomerulosclerosis. We and others have previously projected from model systems that podocyte-specific mRNAs in the urine pellet might serve as glomerular disease markers. We evaluated IgA nephropathy (IgAN) to test this concept. Methods From 2009 to 2013, early morning voided urine samples and kidney biopsies from IgAN patients (n = 67) were evaluated in comparison with urine samples from healthy age-matched volunteers (n = 28). Urine podocyte (podocin) mRNA expressed in relation to either urine creatinine concentration or a kidney tubular marker (aquaporin 2) was tested as markers. Results Urine podocyte mRNAs were correlated with the severity of active glomerular lesions (segmental glomerulosclerosis and acute extracapillary proliferation), but not with non-glomerular lesions (tubular atrophy/interstitial fibrosis) or with clinical parameters of kidney injury (serum creatinine and estimated glomerular filtration rate), or with degree of accumulated podocyte loss at the time of biopsy. In contrast, proteinuria correlated with all histological and clinical markers. Glomerular tuft podocyte nuclear density (a measure of cumulative podocyte loss) correlated with tubular atrophy/interstitial fibrosis, estimated-glomerular filtration rate and proteinuria, but not with urine podocyte markers. In a subset of the IgA cohort (n = 19, median follow-up period = 37 months), urine podocyte mRNAs were significantly decreased after treatment, in contrast to proteinuria which was not significantly changed. Conclusions Urine podocyte mRNAs reflect active glomerular injury at a given point in time, and therefore provide both different and additional clinical information that can complement proteinuria in the IgAN decision-making paradigm. PMID:25956757

Association between obesity and glomerular hyperfiltration: the confounding effect of smoking and sodium and protein intakes.

PubMed

Ogna, Adam; Forni Ogna, Valentina; Bochud, Murielle; Guessous, Idris; Paccaud, Fred; Burnier, Michel; Wuerzner, Gregoire

2016-04-01

Glomerular hyperfiltration has been suggested as a possible mechanism linking obesity and chronic kidney disease (CKD), independently of classical risk factors. We explored the association of overweight and obesity with glomerular hyperfiltration in a large sample of the Swiss adult population, accounting for several confounders including dietary factors. Data from a 2010 to 2012 cross-sectional population-based survey in Switzerland were used. Creatinine clearance (CrCl) was determined from 24-h urine collection; CrCl > 140 ml/min was used to define glomerular hyperfiltration. Participants were categorized into lean (<25 kg/m(2)), overweight (25-29.9 kg/m(2)) and obese (≥30 kg/m(2)) according to body mass index (BMI). A total of 1339 participants were included in the analysis [median (IQR) age 49.4 (34.3-63.5) years, 48.9 % men]. The prevalences of overweight and obesity were 32.2 and 14.2 %, respectively. Median CrCl was 102[84-121] ml/min in lean, 110 [87-136] ml/min in overweight and 124 [97-150] ml/min in obese participants (p < 0.001). The prevalence of glomerular hyperfiltration increased across BMI categories (10.4, 20.8 and 34.7 %, respectively; p < 0.001). This positive association remained significant after adjusting for age, sex, hypertension, diabetes, smoking and dietary factors (sodium and protein intakes): odds ratio [95 %CI] 2.39 [1.52-3.76] (p < 0.001) for overweight versus lean and 4.10[2.31-7.27] (p < 0.001) for obesity versus lean. BMI categories and glomerular hyperfiltration are positively associated, independently of other known CKD risk factors and dietary confounders, suggesting that glomerular hyperfiltration may represent an early renal phenotype in obesity. Our observations confirm the significant association of glomerular hyperfiltration with sodium and protein intakes and identify sodium intake as an important modifying factor of the association between hyperfiltration and obesity.

Clinicopathological Analysis of Glomerular Disease of Adult Onset Nephrotic Syndrome in an Indian Cohort- A Retrospective Study

PubMed Central

Suryawanshi, Mayur; Karnik, Swapnil

2017-01-01

Introduction Primary glomerular disease presenting with adult onset nephrotic syndrome are a major cause of chronic renal failure worldwide. The spectrum of renal disease presenting with nephrotic syndrome has undergone a gradual change globally over the course of time. However, there still exist regional differences in the incidence of primary glomerular diseases causing adult onset nephrotic syndrome. Aim To observe the spectrum of renal diseases presenting with adult onset nephrotic syndrome with comparative analysis of changing trends over the last five decades with regards to Western and Indian literature. Materials and Methods Subjects included patients with age of 18-80 years presenting with nephrotic syndrome. Renal biopsies with immunofluoroscence studies were performed in all patients. Baseline clinical parameters of serum urea, creatinine, albumin, globulin, cholesterol, 24 hour urine protein and urine microscopy were recorded. Descriptive statistics was used and results were expressed as frequencies, percentages, and mean±standard deviation. Results A total of 227 patients (72% males) were included for the study. Primary glomerular diseases formed 74.01% of total cases and majority of patients included males in the 4th decade. Minimal Change Disease (MCD) (15.8%) including its variants was the most common primary glomerular disease for adult onset of nephrotic syndrome followed by Mesangial proliferative Glomerulonephritis (MSGN) (13.2%). Membranous nephropathy and Type I Membranoproliferative Glomerulonephritis (MPGN) individually accounted for 12.3% of patients. Focal and Segmental Glomerulosclerosis (FSGS) accounted for only 11% of patients. Although, increased incidence of FSGS has been observed worldwide, there exist important regional differences in primary glomerular diseases in Indian population. MCD remains a major glomerular disease for adult onset nephrotic syndrome in different parts of India. Conclusion Our study over three years represents important data of regional variations of primary glomerular diseases presenting with adult onset nephrotic syndrome. PMID:28658768

Validation of serum free light chain reference ranges in primary care.

PubMed

Galvani, Luca; Flanagan, Jane; Sargazi, Mansour; Neithercut, William D

2016-05-01

The demand for measurement of serum immunoglobulin free kappa (κ) and lambda (λ) light chains has increased. The κ:λ ratio is used to assist in diagnosis/monitoring of plasma cell disorders. The binding site reference range for serum-free light chain κ:λ ratios of 0.26-1.65 was derived from healthy volunteers. Subsequently, a reference range of 0.37-3.1 for patients with chronic kidney disease has been proposed. Elevated free light chain concentrations and borderline raised free light chain ratios also may be found in polyclonal gammopathies and with other non-renal illnesses. This assessment was conducted to validate the established free light chain reference ranges in individuals from primary care. A total of 130 samples were identified from routine blood samples collected in primary care for routine biochemistry testing and estimated glomerular filtration rate calculation. The median and range of κ:λ ratios found in each estimated glomerular filtration rate group used for chronic kidney disease classification were higher than previously described. This was the case for individuals with normal or essentially normal renal function with estimated glomerular filtration rates>90, (0.58-1.76) and estimated glomerular filtration rate of 60-90 mL/min/1.73 m(2), (0.71-1.93). Individuals with estimated glomerular filtration rate 15-30, (0.72-4.50) and estimated glomerular filtration rate <15 ml/min/1.73 m(2) (0.71-4.95) also had higher values when compared to the current renal reference range of 0.37-3.10. Elevation of free light chain-κ:λ ratios may occur in the absence of a reduced renal function shown by a normal estimated glomerular filtration rate and in the presence of reduced renal function by estimated glomerular filtration rate when comparing results with the established reference ranges. Explanations include choice of analytical systems or the presence of other concurrent non-plasma cell illness. © The Author(s) 2016.

Application of ultrafiltration and stable isotopic amendments to field studies of mercury partitioning to filterable carbon in lake water and overland runoff.

PubMed

Babiarz, Christopher L; Hurley, James P; Krabbenhoft, David P; Gilmour, Cynthia; Branfireun, Brian A

2003-03-20

Results from pilot studies on colloidal phase transport of newly deposited mercury in lake water and overland runoff demonstrate that the combination of ultrafiltration, and stable isotope amendment techniques is a viable tool for the study of mercury partitioning to filterable carbon. Ultrafiltration mass balance calculations were generally excellent, averaging 97.3, 96.1 and 99.8% for dissolved organic carbon (DOC), total mercury (Hg(T)), and methylmercury (MeHg), respectively. Sub nanogram per liter quantities of isotope were measurable, and the observed phase distribution from replicate ultrafiltration separations on lake water agreed within 20%. We believe the data presented here are the first published colloidal phase mercury data on lake water and overland runoff from uncontaminated sites. Initial results from pilot-scale lake amendment experiments indicate that the choice of matrix used to dissolve the isotope did not affect the initial phase distribution of the added mercury in the lake. In addition there was anecdotal evidence that native MeHg was either recently produced in the system, or at a minimum, that this 'old' MeHg partitions to the same subset of DOC that binds the amended mercury. Initial results from pilot-scale overland runoff experiments indicate that less than 20% of newly deposited mercury was transported in the filterable fraction (<0.7 microm). There is some indication of colloidal phase enrichment of mercury in runoff compared to the phase distribution of organic carbon, but the mechanism of this enrichment is unclear. The phase distribution of newly deposited mercury can differ from that of organic carbon and native mercury, suggesting that the quality of the carbon (available ligands), not the quantity of carbon, regulates partitioning. Further characterization of DOC is needed to clarify the underlying mechanisms.

Efficient ultrafiltration-based protocol to deplete extracellular vesicles from fetal bovine serum

PubMed Central

Kornilov, Roman; Puhka, Maija; Mannerström, Bettina; Hiidenmaa, Hanna; Peltoniemi, Hilkka; Siljander, Pia; Seppänen-Kaijansinkko, Riitta; Kaur, Sippy

2018-01-01

ABSTRACT Fetal bovine serum (FBS) is the most commonly used supplement in studies involving cell-culture experiments. However, FBS contains large numbers of bovine extracellular vesicles (EVs), which hamper the analyses of secreted EVs from the cell type of preference and, thus, also the downstream analyses. Therefore, a prior elimination of EVs from FBS is crucial. However, the current methods of EV depletion by ultracentrifugation are cumbersome and the commercial alternatives expensive. In this study, our aim was to develop a protocol to completely deplete EVs from FBS, which may have wide applicability in cell-culture applications. We investigated different EV-depleted FBS prepared by our novel ultrafiltration-based protocol, by conventionally used overnight ultracentrifugation, or commercially available depleted FBS, and compared them with regular FBS. All sera were characterized by nanoparticle tracking analysis, electron microscopy, Western blotting and RNA quantification. Next, adipose-tissue mesenchymal stem cells (AT-MSCs) and cancer cells were grown in the media supplemented with the three different EV-depleted FBS and compared with cells grown in regular FBS media to assess the effects on cell proliferation, stress, differentiation and EV production. The novel ultrafiltration-based protocol depleted EVs from FBS clearly more efficiently than ultracentrifugation and commercial methods. Cell proliferation, stress, differentiation and EV production of AT-MSCs and cancer cell lines were similarly maintained in all three EV-depleted FBS media up to 96 h. In summary, our ultrafiltration protocol efficiently depletes EVs, is easy to use and maintains cell growth and metabolism. Since the method is also cost-effective and easy to standardize, it could be used in a wide range of cell-culture applications helping to increase comparability of EV research results between laboratories. PMID:29410778

Ozonation and ultrafiltration for the treatment of olive mill wastewaters: effect of key operating conditions and integration schemes.

PubMed

Martins, Rui C; Ferreira, Ana M; Gando-Ferreira, Licínio M; Quinta-Ferreira, Rosa M

2015-10-01

With the objective of reaching suitable techniques for olive mill wastewater treatment, ozonation and ultrafiltration were studied individually and combined. A continuous reactor was run for the treatment of a phenolic mixture mimicking an actual olive mill wastewater (OMW) by ozonation. The effect of the main operating parameters was analysed (pH, liquid flow rate and ozone inlet concentration). The increase of pH and ozone dose improved ozonation efficiency. As expected, the highest residence time led to higher steady-state degradation (35 % of chemical oxygen demand (COD) abatement). Even if the rise on ozone inlet gas concentration was able to remove COD in a higher extent, it should be taken into consideration that with the lowest oxidant load (15 g O3/m(3)), the maximum steady-state biochemical oxygen demand (BOD5)/COD ratio was reached which would reduce the process costs. These operating conditions (pH 9, 1 mL/min of liquid flow rate and 15 g O3/m(3)) were applied to an actual OMW leading to 80 % of phenolic content abatement and 12 % of COD removal at the steady state. Regarding ultrafiltration, it was concluded that the best total phenolic content (TPh) and COD abatement results (55 and 15 %) are attained for pH 9 and using a transmembrane pressure drop of 1 bar. Among the integration schemes that were tested, ultrafiltration followed by ozonation was able to reach 93 and 20 % of TPh and COD depletion, respectively. Moreover, this sequence led to an effluent with a BOD5/COD ratio of about 0.55 which means that it likely can be posteriorly refined in a municipal wastewater treatment plant.

Carprofen pharmacokinetics in plasma and in control and inflamed canine tissue fluid using in vivo ultrafiltration.

PubMed

Messenger, K M; Wofford, J A; Papich, M G

2016-02-01

Measurement of unbound drug concentrations at their sites of action is necessary for accurate PK/PD modeling. The objective of this study was to determine the unbound concentration of carprofen in canine interstitial fluid (ISF) using in vivo ultrafiltration and to compare pharmacokinetic parameters of free carprofen concentrations between inflamed and control tissue sites. We hypothesized that active concentrations of carprofen would exhibit different dispositions in ISF between inflamed vs. normal tissues. Bilateral ultrafiltration probes were placed subcutaneously in six healthy Beagle dogs 12 h prior to induction of inflammation. Two milliliters of either 2% carrageenan or saline control was injected subcutaneously at each probe site, 12 h prior to intravenous carprofen (4 mg/kg) administration. Plasma and ISF samples were collected at regular intervals for 72 h, and carprofen concentrations were determined using HPLC. Prostaglandin E2 (PGE2 ) concentrations were quantified in ISF using ELISA. Unbound carprofen concentrations were higher in ISF compared with predicted unbound plasma drug concentrations. Concentrations were not significantly higher in inflamed ISF compared with control ISF. Compartmental modeling was used to generate pharmacokinetic parameter estimates, which were not significantly different between sites. Terminal half-life (T½) was longer in the ISF compared with plasma. PGE2 in ISF decreased following administration of carprofen. In vivo ultrafiltration is a reliable method to determine unbound carprofen in ISF, and that disposition of unbound drug into tissue is much higher than predicted from unbound drug concentration in plasma. However, concentrations and pharmacokinetic parameter estimates are not significantly different in inflamed vs. un-inflamed tissues. © 2015 John Wiley & Sons Ltd.

The Effect of Neutral Peritoneal Dialysis Solution with Low Glucose-Degradation-Product on the Fluid Status and Body Composition – A Randomized Control Trial

PubMed Central

Szeto, Cheuk-Chun; Kwan, Bonnie C. H.; Chow, Kai-Ming; Cheng, Phyllis M. S.; Kwong, Vickie W. K.; Choy, Agnes S. M.; Law, Man-Ching; Leung, Chi-Bon; Li, Philip K. T.

2015-01-01

Background Previous studies report conflicting results on the benefit of peritoneal dialysis (PD) patients treated with low glucose degradation product (GDP) solution. The effects of low GDP solution on body fluid status and arterial pulse wave velocity (PWV) have not been studied. Methods We randomly assigned 68 incident PD patients to low GDP (Intervention Group) or conventional solutions (Control Group); 4 dropped off before they received the assigned treatment. Patients were followed for 52 weeks for changes in ultrafiltration, residual renal function, body fluid status and arterial PWV. Result After 52 weeks, Intervention Group had higher overhydration (3.1 ± 2.6 vs 1.9 ± 2.2 L, p = 0.045) and extracellular water volume (17.7 ± 3.9 vs 15.8 ± 3.1 L, p = 0.034) than Control Group. There was no significant difference in PWV between groups. There was no significant difference in residual renal function between the Groups. Intervention Group had lower ultrafiltration volume than Control Group at 4 weeks (0.45 ± .0.61 vs 0.90 ± 0.79 L/day, p = 0.013), but the difference became insignificant at later time points. Intervention Group had lower serum CRP levels than Control Group (4.17 ± 0.77 vs 4.91 ± 0.95 mg/dL, p < 0.0001). Conclusion Incident PD patients treated with low GDP solution have less severe systemic inflammation but trends of less ultrafiltration, and more fluid accumulation. However, the effects on ultrafiltration and fluid accumulation disappear with time. The long term effect of low GDP solution requires further study. Trial Registration ClinicalTrials.gov NCT00966615 PMID:26510186

Assessment of glomerular filtration rate and effective renal plasma flow in cystic fibrosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spino, M.; Chai, R.P.; Isles, A.F.

1985-07-01

A study was conducted to examine renal function in 10 healthy control subjects and eight patients with cystic fibrosis in stable condition. Sequential bolus injections of /sup 99m/Tc-DTPA and /sup 125/I-OIH were administered to assess glomerular filtration rate and effective renal plasma flow, respectively. Blood was subsequently collected for 3 hours, and urine for 24 hours. Renal clearances of both radioisotope markers were virtually identical in patients and controls. Inasmuch as neither glomerular filtration rate nor effective renal plasma flow was enhanced in patients with cystic fibrosis, increased clearance of drugs in these patients is unlikely to be the resultmore » of enhanced glomerular filtration or tubular secretion.« less

Dipping your feet in the water: podocytes in urine.

PubMed

Sir Elkhatim, Rashid; Li, Jordan Y Z; Yong, Tuck Y; Gleadle, Jonathan M

2014-05-01

Podocyte injury and loss plays an important role in the pathogenesis and progression of many kidney diseases. Studies have shown that podocyte-related markers and products can be detected in the urine of patients with glomerular diseases such as focal segmental glomerulosclerosis, IgA nephropathy, lupus nephritis, diabetic nephropathy and pre-eclampsia. Therefore, detecting the loss of podocytes in the urine provides a useful noninvasive technique of gathering information about the disease type and/or activity of glomerular diseases. Currently, urine podocyte-related protein markers, mRNA, microRNA and exosomes have been used with varying degrees of success to study glomerular diseases. The determination of urinary podocyte loss may become an important noninvasive tool in the evaluation of glomerular diseases.

Estimation of residual glomerular filtration rate in peritoneal dialysis patients using cystatin C: comparison with 51Cr-EDTA clearance.

PubMed

Carter, Joanne L; Lane, Catherine E; Fan, Stanley L; Lamb, Edmund J

2011-11-01

Measuring glomerular filtration rate (GFR) is an important assessment in peritoneal dialysis patients. In clinical practice, it is commonly measured by calculating the mean of the urinary clearance of urea and creatinine (GFR(UrCl)) but this process is time consuming and unreliable. We wished to compare several estimates of GFR including residual GFR estimated from cystatin C (GFR(CysC)) using a published equation (Hoek), GFR(UrCl) and (51)Cr-ethylenediaminetetraacetic acid (EDTA) clearance, in peritoneal dialysis patients. GFR(CysC), GFR(UrCl) and (51)Cr-EDTA clearance were measured in 28 patients undergoing peritoneal dialysis in a single dialysis unit. GFR(CysC) was related to GFR(UrCl) (Spearman's rank correlation coefficient r(s) = 0.44; P = 0.0185) and to (51)Cr-EDTA clearance (r(s) = 0.48; P = 0.0099). GFR(CysC) values were significantly (P = 0.0077) lower than (51)Cr-EDTA clearance results (mean bias -19.7%). However, GFR(CysC) did not differ significantly (P > 0.05) from GFR(UrCl). GFR(CysC) is related to GFR(UrCl) but has a significant negative bias against (51)Cr-EDTA. Given the known limitations of (51)Cr-EDTA in estimating GFR in renal failure, this study provides additional validation suggesting that cystatin C-estimated rGFR (GFR(CysC)) gives a reasonable estimation of GFR without the clinical problems associated with 24 h urine collections.

Serum and plasma for total and free anticonvulsant drug analyses: effects on EMIT assays and ultrafiltration devices.

PubMed

Godolphin, W; Trepanier, J; Farrell, K

1983-01-01

The suitability of serum and plasma anticoagulated with heparin, EDTA, citrate, or oxalate was assessed for analysis of free and total phenytoin, carbamazepine, and valproic acid. The free fraction was isolated by ultrafiltration through FreeLevel devices (Syva, Palo Alto, CA). Serum, heparin, and EDTA plasma were satisfactory for both free and total phenytoin and carbamazepine. EDTA could not be used for EMIT (Syva) analysis of valproate. Citrate and, to a lesser degree, oxalate cause a significant negative interference in the concentration of these three drugs as measured both by EMIT and gas-liquid chromatography.

Pre-treatment for ultrafiltration: effect of pre-chlorination on membrane fouling

PubMed Central

Yu, Wenzheng; Xu, Lei; Graham, Nigel; Qu, Jiuhui

2014-01-01

Microbial effects are believed to be a major contributor to membrane fouling in drinking water treatment. Sodium hypochlorite (NaClO) is commonly applied in membrane cleaning, but its potential use as a pretreatment for controlling operational fouling has received little attention. In this study, the effect of adding a continuous low dose of NaClO (1 mg/l as active Cl) in combination with alum, before ultrafiltration, was compared with only alum as pretreatment. The results showed that the addition of NaClO substantially reduced membrane fouling both in terms of the rate of TMP development and the properties of the membrane cake layer. Although the size of nano-scale primary coagulant flocs changed little by the addition of NaClO, the cake layer on the membrane had a greater porosity and a substantially reduced thickness. NaClO was found to inactivate bacteria in the influent flow, which reduced both microbial proliferation and the production of proteins and polysaccharides in the cake layer and contributed significantly to improving the overall ultrafiltration performance. NaClO dosing had no adverse impact on the formation of currently regulated disinfection by-product compounds (THMs and HAAs). PMID:25269375

Pre-treatment for ultrafiltration: effect of pre-chlorination on membrane fouling

NASA Astrophysics Data System (ADS)

Yu, Wenzheng; Xu, Lei; Graham, Nigel; Qu, Jiuhui

2014-10-01

Microbial effects are believed to be a major contributor to membrane fouling in drinking water treatment. Sodium hypochlorite (NaClO) is commonly applied in membrane cleaning, but its potential use as a pretreatment for controlling operational fouling has received little attention. In this study, the effect of adding a continuous low dose of NaClO (1 mg/l as active Cl) in combination with alum, before ultrafiltration, was compared with only alum as pretreatment. The results showed that the addition of NaClO substantially reduced membrane fouling both in terms of the rate of TMP development and the properties of the membrane cake layer. Although the size of nano-scale primary coagulant flocs changed little by the addition of NaClO, the cake layer on the membrane had a greater porosity and a substantially reduced thickness. NaClO was found to inactivate bacteria in the influent flow, which reduced both microbial proliferation and the production of proteins and polysaccharides in the cake layer and contributed significantly to improving the overall ultrafiltration performance. NaClO dosing had no adverse impact on the formation of currently regulated disinfection by-product compounds (THMs and HAAs).

Enrichment and Purification of Casein Glycomacropeptide from Whey Protein Isolate Using Supercritical Carbon Dioxide Processing and Membrane Ultrafiltration

PubMed Central

Bonnaillie, Laetitia M.; Qi, Phoebe; Wickham, Edward; Tomasula, Peggy M.

2014-01-01

Whey protein concentrates (WPC) and isolates (WPI), comprised mainly of β-lactoglobulin (β-LG), α-lactalbumin (α-LA) and casein glycomacropeptide (GMP), are added to foods to boost nutritional and functional properties. Supercritical carbon dioxide (SCO2) has been shown to effectively fractionate WPC and WPI to obtain enriched fractions of α-LA and β-LG, thus creating new whey ingredients that exploit the properties of the individual component proteins. In this study, we used SCO2 to further fractionate WPI via acid precipitation of α-LA, β-LG and the minor whey proteins to obtain GMP-enriched solutions. The process was optimized and α-LA precipitation maximized at low pH and a temperature (T) ≥65 °C, where β-LG with 84% purity and GMP with 58% purity were obtained, after ultrafiltration and diafiltration to separate β-LG from the GMP solution. At 70 °C, β-LG also precipitated with α-LA, leaving a GMP-rich solution with up to 94% purity after ultrafiltration. The different protein fractions produced with the SCO2 process will permit the design of new foods and beverages to target specific nutritional needs. PMID:28234306

Stabilization of flux during dead-end ultra-low pressure ultrafiltration.

PubMed

Peter-Varbanets, Maryna; Hammes, Frederik; Vital, Marius; Pronk, Wouter

2010-06-01

Gravity driven ultrafiltration was operated in dead-end mode without any flushing or cleaning. In contrary to general expectations, the flux value stabilized after about one week of operation and remained constant during an extended period of time (several months). Different surface water types and diluted wastewater were used as feed water and, depending on the feed water composition, stable flux values were in the range of 4-10 L h(-1) m(-2). When sodium azide was added to the feed water to diminish the biological activity, no stabilization of flux occurred, indicating that biological processes play an important role in the flux stabilization process. Confocal laser scanning microscopy revealed the presence of a biofouling layer, of which the structure changed over time, leading to relatively heterogeneous structures. It is assumed that the stabilization of flux is related to the development of heterogeneous structures in the fouling layer, due to biological processes in the layer. The phenomenon of flux stabilization opens interesting possibilities for application, for instance in simple and low-cost ultrafiltration systems for decentralized drinking water treatment in developing and transition countries, independent of energy supply, chemicals, or complex process control. 2010 Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Josephson, Gary B.; Geeting, John GH; Bredt, Ofelia P.

Pacific Northwest National Laboratory (PNNL) has been tasked by Bechtel National Inc. (BNI) on the River Protection Project-Waste Treatment Plant (RPP-WTP) project to perform research and development activities to resolve technical issues identified for the Pretreatment Facility (PTF). The Pretreatment Engineering Platform (PEP) was designed, constructed, and operated as part of a plan to respond to issue M12, "Undemonstrated Leaching Processes." The PEP is a 1/4.5-scale test platform designed to simulate the WTP pretreatment caustic leaching, oxidative leaching, ultrafiltration solids concentration, and slurry washing processes. The PEP replicates the WTP leaching processes using prototypic equipment and control strategies. The PEPmore » also includes non-prototypic ancillary equipment to support the core processing. Two operating scenarios are currently being evaluated for the ultrafiltration process (UFP) and leaching operations. The first scenario has caustic leaching performed in the UFP-2 ultrafiltration feed vessels (i.e., vessel UFP-VSL-T02A in the PEP; and vessels UFP-VSL-00002A and B in the WTP PTF). The second scenario has caustic leaching conducted in the UFP-1 ultrafiltration feed preparation vessels (i.e., vessels UFP-VSL-T01A and B in the PEP; vessels UFP-VSL-00001A and B in the WTP PTF). In both scenarios, 19-M sodium hydroxide solution (NaOH, caustic) is added to the waste slurry in the vessels to leach solid aluminum compounds (e.g., gibbsite, boehmite). Caustic addition is followed by a heating step that uses direct injection of steam to accelerate the leach process. Following the caustic leach, the vessel contents are cooled using vessel cooling jackets and/or external heat exchangers. The main difference between the two scenarios is that for leaching in UFP-1, the 19-M NaOH is added to un-concentrated waste slurry (3-8 wt% solids), while for leaching in UFP-2, the slurry is concentrated to nominally 20 wt% solids using cross-flow ultrafiltration before the addition of caustic. In both scenarios, following the caustic leach, the slurry was then concentrated to 17 wt% and washed with inhibited water to remove NaOH and other soluble salts. Next, the slurry was oxidatively leached using sodium permanganate to solubilize chrome. The slurry was then washed to remove the dissolved chrome and concentrated.« less

Pathways to nephron loss starting from glomerular diseases-insights from animal models.

PubMed

Kriz, Wilhelm; LeHir, Michel

2005-02-01

Studies of glomerular diseases in animal models show that progression toward nephron loss starts with extracapillary lesions, whereby podocytes play the central role. If injuries remain bound within the endocapillary compartment, they will undergo recovery or be repaired by scaring. Degenerative, inflammatory and dysregulative mechanisms leading to nephron loss are distinguished. In addition to several other unique features, the dysregulative mechanisms leading to collapsing glomerulopathy are particular in that glomeruli and tubules are affected in parallel. In contrast, in degenerative and inflammatory diseases, tubular injury is secondary to glomerular lesions. In both of the latter groups of diseases, the progression starts in the glomerulus with the loss of the separation between the tuft and Bowman's capsule by forming cell bridges (parietal cells and/or podocytes) between the glomerular and the parietal basement membranes. Cell bridges develop into tuft adhesions to Bowman's capsule, which initiate the formation of crescents, either by misdirected filtration (proteinaceous crescents) or by epithelial cell proliferation (cellular crescents). Crescents may spread over the entire circumference of the glomerulus and, via the glomerulotubular junction, may extend onto the tubule. Two mechanisms concerning the transfer of a glomerular injury onto the tubulointerstitium are discussed: (1) direct encroachment of extracapillary lesions and (2) protein leakage into tubular urine, resulting in injury to the tubule and the interstitium. There is evidence that direct encroachment is the crucial mechanism. Progression of chronic renal disease is underlain by a vicious cycle which passes on the damage from lost and/or damaged nephrons to so far healthy nephrons. Presently, two mechanisms are discussed: (1) the loss of nephrons leads to compensatory mechanisms in the remaining nephrons (glomerular hypertension, hyperfiltration, hypertrophy) which increase their vulnerability to any further challenge (overload hypothesis); and (2) a proteinuric glomerular disease leads, by some way or another, to tubulointerstitial inflammation and fibrosis, accounting for the further deterioration of renal function (fibrosis hypothesis). So far, no convincing evidence has been published that in primary glomerular diseases fibrosis is harmful to healthy nephrons. The potential of glomerular injuries to regenerate or to be repaired by scaring is limited. The only option for extracapillary injuries with tuft adhesion is repair by formation of a segmental adherent scar (i.e., segmental glomerulosclerosis).

Associations of estimated glomerular filtration rate and albuminuria with mortality and renal failure by sex: a meta-analysis

PubMed Central

Nitsch, Dorothea; Grams, Morgan; Sang, Yingying; Black, Corri; Cirillo, Massimo; Djurdjev, Ognjenka; Iseki, Kunitoshi; Jassal, Simerjot K; Kimm, Heejin; Kronenberg, Florian; Øien, Cecilia M; Levin, Adeera; Woodward, Mark; Hemmelgarn, Brenda R

2013-01-01

Objective To assess for the presence of a sex interaction in the associations of estimated glomerular filtration rate and albuminuria with all-cause mortality, cardiovascular mortality, and end stage renal disease. Design Random effects meta-analysis using pooled individual participant data. Setting 46 cohorts from Europe, North and South America, Asia, and Australasia. Participants 2 051 158 participants (54% women) from general population cohorts (n=1 861 052), high risk cohorts (n=151 494), and chronic kidney disease cohorts (n=38 612). Eligible cohorts (except chronic kidney disease cohorts) had at least 1000 participants, outcomes of either mortality or end stage renal disease of ≥50 events, and baseline measurements of estimated glomerular filtration rate according to the Chronic Kidney Disease Epidemiology Collaboration equation (mL/min/1.73 m2) and urinary albumin-creatinine ratio (mg/g). Results Risks of all-cause mortality and cardiovascular mortality were higher in men at all levels of estimated glomerular filtration rate and albumin-creatinine ratio. While higher risk was associated with lower estimated glomerular filtration rate and higher albumin-creatinine ratio in both sexes, the slope of the risk relationship for all-cause mortality and for cardiovascular mortality were steeper in women than in men. Compared with an estimated glomerular filtration rate of 95, the adjusted hazard ratio for all-cause mortality at estimated glomerular filtration rate 45 was 1.32 (95% CI 1.08 to 1.61) in women and 1.22 (1.00 to 1.48) in men (Pinteraction<0.01). Compared with a urinary albumin-creatinine ratio of 5, the adjusted hazard ratio for all-cause mortality at urinary albumin-creatinine ratio 30 was 1.69 (1.54 to 1.84) in women and 1.43 (1.31 to 1.57) in men (Pinteraction<0.01). Conversely, there was no evidence of a sex difference in associations of estimated glomerular filtration rate and urinary albumin-creatinine ratio with end stage renal disease risk. Conclusions Both sexes face increased risk of all-cause mortality, cardiovascular mortality, and end stage renal disease with lower estimated glomerular filtration rates and higher albuminuria. These findings were robust across a large global consortium. PMID:23360717

Association of the cystatin C/creatinine ratio with the renally cleared hormones parathyroid hormone (PTH) and brain natriuretic peptide (BNP) in primary care patients: a cross-sectional study.

PubMed

Risch, Martin; Risch, Lorenz; Purde, Mette-Triin; Renz, Harald; Ambühl, Patrice; Szucs, Thomas; Tomonaga, Yuki

2016-09-01

The ratio of cystatin C to creatinine (cysC/crea) is regarded as a marker of glomerular filtration quality and predicts mortality. It has been hypothesized that increased mortality may be mediated by the retention of biologically active substances due to shrinking glomerular pores. The present study investigated whether cysC/crea is independently associated with the levels of two renally cleared hormones, which have been linked to increased mortality. We conducted a multicenter, cross-sectional study with a random selection of general practitioners (GPs) from all GP offices in seven Swiss cantons. Markers of glomerular filtration quality were investigated together with estimated glomerular filtration rate (eGFR), albuminuria and urinary neutrophil gelatinase associated lipocalin (uNGAL) as well as two renally cleared low-molecular-weight protein hormones (i.e. BNP and PTH), Morbidity was assessed with the Charlson Comorbidity Index (CCI). A total of 1000 patients (433 males; mean age 57 ± 17 years) were included. There was a significant univariate association of BNP (r = 0.36, p < 0.001) and PTH (r = 0.18, p < 0.001) with cysC/crea. An adjusted model that accounted for kidney function (eGFR), altered glomerular structure (albuminuria), renal stress (uNGAL), and CCI showed that BNP and PTH were independently associated with cysC/crea as well as with the ratio of cystatin C-based to creatinine-based eGFR. In conclusion, in primary care patients, BNP and PTH are independently associated both with markers of glomerular filtration quality and eGFR regardless of structural kidney damage or renal stress. These findings offer an explanation, how altered glomerular filtration quality could contribute to increased mortality.

A kidney-disease gene panel allows a comprehensive genetic diagnosis of cystic and glomerular inherited kidney diseases.

PubMed

Bullich, Gemma; Domingo-Gallego, Andrea; Vargas, Iván; Ruiz, Patricia; Lorente-Grandoso, Laura; Furlano, Mónica; Fraga, Gloria; Madrid, Álvaro; Ariceta, Gema; Borregán, Mar; Piñero-Fernández, Juan Alberto; Rodríguez-Peña, Lidia; Ballesta-Martínez, Maria Juliana; Llano-Rivas, Isabel; Meñica, Mireia Aguirre; Ballarín, José; Torrents, David; Torra, Roser; Ars, Elisabet

2018-05-22

Molecular diagnosis of inherited kidney diseases remains a challenge due to their expanding phenotypic spectra as well as the constantly growing list of disease-causing genes. Here we develop a comprehensive approach for genetic diagnosis of inherited cystic and glomerular nephropathies. Targeted next generation sequencing of 140 genes causative of or associated with cystic or glomerular nephropathies was performed in 421 patients, a validation cohort of 116 patients with previously known mutations, and a diagnostic cohort of 207 patients with suspected inherited cystic disease and 98 patients with glomerular disease. In the validation cohort, a sensitivity of 99% was achieved. In the diagnostic cohort, causative mutations were found in 78% of patients with cystic disease and 62% of patients with glomerular disease, mostly familial cases, including copy number variants. Results depict the distribution of different cystic and glomerular inherited diseases showing the most likely diagnosis according to perinatal, pediatric and adult disease onset. Of all the genetically diagnosed patients, 15% were referred with an unspecified clinical diagnosis and in 2% genetic testing changed the clinical diagnosis. Therefore, in 17% of cases our genetic analysis was crucial to establish the correct diagnosis. Complex inheritance patterns in autosomal dominant polycystic kidney disease and Alport syndrome were suspected in seven and six patients, respectively. Thus, our kidney-disease gene panel is a comprehensive, noninvasive, and cost-effective tool for genetic diagnosis of cystic and glomerular inherited kidney diseases. This allows etiologic diagnosis in three-quarters of patients and is especially valuable in patients with unspecific or atypical phenotypes. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Podocyte Number in Children and Adults: Associations with Glomerular Size and Numbers of Other Glomerular Resident Cells

PubMed Central

Puelles, Victor G.; Douglas-Denton, Rebecca N.; Cullen-McEwen, Luise A.; Li, Jinhua; Hughson, Michael D.; Hoy, Wendy E.; Kerr, Peter G.

2015-01-01

Increases in glomerular size occur with normal body growth and in many pathologic conditions. In this study, we determined associations between glomerular size and numbers of glomerular resident cells, with a particular focus on podocytes. Kidneys from 16 male Caucasian-Americans without overt renal disease, including 4 children (≤3 years old) to define baseline values of early life and 12 adults (≥18 years old), were collected at autopsy in Jackson, Mississippi. We used a combination of immunohistochemistry, confocal microscopy, and design-based stereology to estimate individual glomerular volume (IGV) and numbers of podocytes, nonepithelial cells (NECs; tuft cells other than podocytes), and parietal epithelial cells (PECs). Podocyte density was calculated. Data are reported as medians and interquartile ranges (IQRs). Glomeruli from children were small and contained 452 podocytes (IQR=335–502), 389 NECs (IQR=265–498), and 146 PECs (IQR=111–206). Adult glomeruli contained significantly more cells than glomeruli from children, including 558 podocytes (IQR=431–746; P<0.01), 1383 NECs (IQR=998–2042; P<0.001), and 367 PECs (IQR=309–673; P<0.001). However, large adult glomeruli showed markedly lower podocyte density (183 podocytes per 106 µm3) than small glomeruli from adults and children (932 podocytes per 106 µm3; P<0.001). In conclusion, large adult glomeruli contained more podocytes than small glomeruli from children and adults, raising questions about the origin of these podocytes. The increased number of podocytes in large glomeruli does not match the increase in glomerular size observed in adults, resulting in relative podocyte depletion. This may render hypertrophic glomeruli susceptible to pathology. PMID:25568174

Partial rescue of glomerular laminin alpha5 mutations by wild-type endothelia produce hybrid glomeruli.

PubMed

Abrahamson, Dale R; St John, Patricia L; Isom, Kathryn; Robert, Barry; Miner, Jeffrey H

2007-08-01

Both endothelial cells and podocytes are sources for laminin alpha1 at the inception of glomerulogenesis and then for laminin alpha5 during glomerular maturation. Why glomerular basement membranes (GBM) undergo laminin transitions is unknown, but this may dictate glomerular morphogenesis. In mice that genetically lack laminin alpha5, laminin alpha5beta2gamma1 is not assembled, vascularized glomeruli fail to form, and animals die at midgestation with neural tube closure and placental deficits. It was previously shown that renal cortices of newborn mice contain endothelial progenitors (angioblasts) and that when embryonic day 12 kidneys are transplanted into newborn kidney, hybrid glomeruli (host-derived endothelium and donor-derived podocytes) result. Reasoning that host endothelium may correct the glomerular phenotype that is seen in laminin alpha5 mutants, alpha5 null embryonic day 12 metanephroi were grafted into wild-type newborn kidney. Hybrid glomeruli were identified in grafts by expression of a host-specific LacZ lineage marker. Labeling of glomerular hybrid GBM with chain-specific antibodies showed a markedly stratified distribution of laminins: alpha5 was found only on the inner endothelial half of GBM, whereas alpha1 located to outer layers beneath mutant podocytes. For measurement of the contribution of host endothelium to hybrid GBM, immunofluorescent signals for laminin alpha5 were quantified: Hybrid GBM contained approximately 50% the normal alpha5 complement as wild-type GBM. Electron microscopy of glomerular hybrids showed vascularization, but podocyte foot processes were absent. It was concluded that (1) endothelial and podocyte-derived laminins remain tethered to their cellular origin, (2) developing endothelial cells contribute large amounts of GBM laminins, and (3) podocyte foot process differentiation may require direct exposure to laminin alpha5.

Effects of CTLA4-Fc on glomerular injury in humorally-mediated glomerulonephritis in BALB/c mice

PubMed Central

Kitching, A R; Huang, X R; Ruth, A-J; Tipping, P G; Holdsworth, S R

2002-01-01

The effect of cytotoxic T-lymphocyte-associated molecule 4-immunoglobulin fusion protein (CTLA4-Fc) on humorally-mediated glomerulonephritis was studied in accelerated anti-glomerular basement membrane (anti-GBM) glomerulonephritis induced in BALB/c mice. This strain of mice develops antibody and complement dependent glomerulonephritis under this protocol. Sensitized BALB/c mice developed high levels of circulating autologous antibody titres, intense glomerular deposition of mouse immunoglobulin and complement, significant proteinuria, renal impairment, significant glomerular necrosis and a minor component of crescent formation 10 days after challenge with a nephritogenic antigen (sheep anti-GBM globulin). Early treatment during the primary immune response, or continuous treatment throughout the disease with CTLA4-Fc, significantly suppressed mouse anti-sheep globulin antibody titres in serum, and immunoglobulin and complement deposition in glomeruli. The degree of glomerular necrosis was improved and proteinuria was reduced, particularly in the earlier stages of disease. Late treatment by CTLA4-Fc starting one day after challenge with sheep anti-mouse GBM did not affect antibody production and did not attenuate glomerulonephritis. The low level of crescent formation found in BALB/c mice developing glomerulonephritis was not prevented by the administration of CTLA4-Fc. These results demonstrate that CTLA4-Fc is of benefit in this model of glomerulonephritis by its capacity to attenuate antibody production, without affecting the minor degree of cell-mediated glomerular injury. PMID:12067297

Integrin beta1-mediated matrix assembly and signaling are critical for the normal development and function of the kidney glomerulus.

PubMed

Kanasaki, Keizo; Kanda, Yoshiko; Palmsten, Kristin; Tanjore, Harikrishna; Lee, Soo Bong; Lebleu, Valerie S; Gattone, Vincent H; Kalluri, Raghu

2008-01-15

The human kidneys filter 180 l of blood every day via about 2.5 million glomeruli. The three layers of the glomerular filtration apparatus consist of fenestrated endothelium, specialized extracellular matrix known as the glomerular basement membrane (GBM) and the podocyte foot processes with their modified adherens junctions known as the slit diaphragm (SD). In this study we explored the contribution of podocyte beta1 integrin signaling for normal glomerular function. Mice with podocyte specific deletion of integrin beta1 (podocin-Cre beta1-fl/fl mice) are born normal but cannot complete postnatal renal development. They exhibit detectable proteinuria on day 1 and die within a week. The kidneys of podocin-Cre beta1-fl/fl mice exhibit normal glomerular endothelium but show severe GBM defects with multilaminations and splitting including podocyte foot process effacement. The integrin linked kinase (ILK) is a downstream mediator of integrin beta1 activity in epithelial cells. To further explore whether integrin beta1-mediated signaling facilitates proper glomerular filtration, we generated mice deficient of ILK in the podocytes (podocin-Cre ILK-fl/fl mice). These mice develop normally but exhibit postnatal proteinuria at birth and die within 15 weeks of age due to renal failure. Collectively, our studies demonstrate that podocyte beta1 integrin and ILK signaling is critical for postnatal development and function of the glomerular filtration apparatus.

Pathophysiologic Implications of Reduced Podocyte Number in a Rat Model of Progressive Glomerular Injury

PubMed Central

Macconi, Daniela; Bonomelli, Maria; Benigni, Ariela; Plati, Tiziana; Sangalli, Fabio; Longaretti, Lorena; Conti, Sara; Kawachi, Hiroshi; Hill, Prue; Remuzzi, Giuseppe; Remuzzi, Andrea

2006-01-01

Changes in podocyte number or density have been suggested to play an important role in renal disease progression. Here, we investigated the temporal relationship between glomerular podocyte number and development of proteinuria and glomerulosclerosis in the male Munich Wistar Fromter (MWF) rat. We also assessed whether changes in podocyte number affect podocyte function and focused specifically on the slit diaphragm-associated protein nephrin. Age-matched Wistar rats were used as controls. Estimation of podocyte number per glomerulus was determined by digital morphometry of WT1-positive cells. MWF rats developed moderate hypertension, massive proteinuria, and glomerulosclerosis with age. Glomerular hypertrophy was already observed at 10 weeks of age and progressively increased thereafter. By contrast, mean podocyte number per glomerulus was lower than normal in young animals and further decreased with time. As a consequence, the capillary tuft volume per podocyte was more than threefold increased in older rats. Electron microscopy showed important changes in podocyte structure of MWF rats, with expansion of podocyte bodies surrounding glomerular filtration membrane. Glomerular nephrin expression was markedly altered in MWF rats and inversely correlated with both podocyte loss and proteinuria. Our findings suggest that reduction in podocyte number is an important determinant of podocyte dysfunction and progressive impairment of the glomerular permselectivity that lead to the development of massive proteinuria and ultimately to renal scarring. PMID:16400008

Measuring glomerular number from kidney MRI images

NASA Astrophysics Data System (ADS)

Thiagarajan, Jayaraman J.; Natesan Ramamurthy, Karthikeyan; Kanberoglu, Berkay; Frakes, David; Bennett, Kevin; Spanias, Andreas

2016-03-01

Measuring the glomerular number in the entire, intact kidney using non-destructive techniques is of immense importance in studying several renal and systemic diseases. Commonly used approaches either require destruction of the entire kidney or perform extrapolation from measurements obtained from a few isolated sections. A recent magnetic resonance imaging (MRI) method, based on the injection of a contrast agent (cationic ferritin), has been used to effectively identify glomerular regions in the kidney. In this work, we propose a robust, accurate, and low-complexity method for estimating the number of glomeruli from such kidney MRI images. The proposed technique has a training phase and a low-complexity testing phase. In the training phase, organ segmentation is performed on a few expert-marked training images, and glomerular and non-glomerular image patches are extracted. Using non-local sparse coding to compute similarity and dissimilarity graphs between the patches, the subspace in which the glomerular regions can be discriminated from the rest are estimated. For novel test images, the image patches extracted after pre-processing are embedded using the discriminative subspace projections. The testing phase is of low computational complexity since it involves only matrix multiplications, clustering, and simple morphological operations. Preliminary results with MRI data obtained from five kidneys of rats show that the proposed non-invasive, low-complexity approach performs comparably to conventional approaches such as acid maceration and stereology.

Effects of CTLA4-Fc on glomerular injury in humorally-mediated glomerulonephritis in BALB/c mice.

PubMed

Kitching, A R; Huang, X R; Ruth, A-J; Tipping, P G; Holdsworth, S R

2002-06-01

The effect of cytotoxic T-lymphocyte-associated molecule 4-immunoglobulin fusion protein (CTLA4-Fc) on humorally-mediated glomerulonephritis was studied in accelerated anti-glomerular basement membrane (anti-GBM) glomerulonephritis induced in BALB/c mice. This strain of mice develops antibody and complement dependent glomerulonephritis under this protocol. Sensitized BALB/c mice developed high levels of circulating autologous antibody titres, intense glomerular deposition of mouse immunoglobulin and complement, significant proteinuria, renal impairment, significant glomerular necrosis and a minor component of crescent formation 10 days after challenge with a nephritogenic antigen (sheep anti-GBM globulin). Early treatment during the primary immune response, or continuous treatment throughout the disease with CTLA4-Fc, significantly suppressed mouse anti-sheep globulin antibody titres in serum, and immunoglobulin and complement deposition in glomeruli. The degree of glomerular necrosis was improved and proteinuria was reduced, particularly in the earlier stages of disease. Late treatment by CTLA4-Fc starting one day after challenge with sheep anti-mouse GBM did not affect antibody production and did not attenuate glomerulonephritis. The low level of crescent formation found in BALB/c mice developing glomerulonephritis was not prevented by the administration of CTLA4-Fc. These results demonstrate that CTLA4-Fc is of benefit in this model of glomerulonephritis by its capacity to attenuate antibody production, without affecting the minor degree of cell-mediated glomerular injury.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miyamori, I.; Yasuhara, S.; Takeda, Y.

The effects of captopril on effective renal plasma flow and glomerular filtration rate were studied using a noninvasive radioisotopic method on individual kidneys in eight patients with renovascular hypertension and 12 patients with essential hypertension with various renin levels. Four patients with renovascular hypertension had unilateral while three had bilateral renal artery stenosis. The effective renal plasma flow and glomerular filtration rate were determined by using /sup 131/I-iodohippurate sodium and /sup 99m/Tc-diethylenetriamine pentaacetic acid, respectively. Glomerular filtration rate and effective renal plasma flow were significantly reduced in the stenotic kidneys of patients with renovascular hypertension compared with values in nonstenoticmore » kidneys (p less than 0.01). Treatment with captopril, 37.5 to 75 mg/day for 1 to 48 weeks, further reduced the glomerular filtration rate only in stenotic kidneys, and effective renal plasma flow increased in both kidney types. In two of the three renal hypertensive patients with bilateral renal artery stenosis, captopril produced a reversible azotemia that was unrelated to the fall in blood pressure, as evidenced by the lack of azotemia seen after a moderate blood pressure reduction induced by other antihypertensive medications. These results indicate that endogenous angiotensin II is essential in maintaining the glomerular filtration rate in stenotic kidneys and suggest that a reduction in glomerular filtration rate during captopril administration could indicate the presence of renal artery stenosis.« less

Outcome of the acute glomerular injury in proliferative lupus nephritis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chagnac, A.; Kiberd, B.A.; Farinas, M.C.

1989-09-01

Treatment with total lymphoid irradiation (TLI) and corticosteroids markedly reduced activity of systemic lupus erythematosis in 10 patients with diffuse proliferative lupus nephritis (DPLN) complicated by a nephrotic syndrome. Physiologic and morphometric techniques were used serially before, and 12 and 36 mo post-TLI to characterize the course of glomerular injury. Judged by a progressive reduction in the density of glomerular cells and immune deposits, glomerular inflammation subsided. A sustained reduction in the fractional clearance of albumin, IgG and uncharged dextrans of radius greater than 50 A, pointed to a parallel improvement in glomerular barrier size-selectivity. Corresponding changes in GFR weremore » modest, however. A trend towards higher GFR at 12 mo was associated with a marked increase in the fraction of glomerular tuft area occupied by patent capillary loops as inflammatory changes receded. A late trend toward declining GFR beyond 12 mo was associated with progressive glomerulosclerosis, which affected 57% of all glomeruli globally by 36 mo post-TLI. Judged by a parallel increase in volume by 59%, remaining, patent glomeruli had undergone a process of adaptive enlargement. We propose that an increasing fraction of glomeruli continues to undergo progressive sclerosis after DPLN has become quiescent, and that the prevailing GFR depends on the extent to which hypertrophied remnant glomeruli can compensate for the ensuing loss of filtration surface area.« less

Chronic kidney disease: Pathological and functional evaluation with intravoxel incoherent motion diffusion-weighted imaging.

PubMed

Mao, Wei; Zhou, Jianjun; Zeng, Mengsu; Ding, Yuqin; Qu, Lijie; Chen, Caizhong; Ding, Xiaoqiang; Wang, Yaqiong; Fu, Caixia

2018-05-01

Because chronic kidney disease (CKD) is a worldwide problem, accurate pathological and functional evaluation is required for planning treatment and follow-up. Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) can assess both capillary perfusion and tissue diffusion and may be helpful in evaluating renal function and pathology. To evaluate functional and pathological alterations in CKD by applying IVIM-DWI. Prospective study. In all, 72 CKD patients who required renal biopsy and 20 healthy volunteers. 1.5T. All subjects underwent IVIM-DWI of the kidneys, and image analysis was performed by two radiologists. The mean values of true diffusion coefficient (D), pseudo diffusion coefficient (D*), and perfusion fraction (f) were acquired from renal parenchyma. Correlation between IVIM-DWI parameters and estimated glomerular filtration rate (eGFR), as well as pathological damage, were assessed. One-way analysis of variance (ANOVA), paired sample t-test and Spearman correlation analysis. The paired sample t-test revealed that IVIM-DWI parameters were significantly lower in medulla than cortex for both patients and controls (P < 0.01). Regardless of whether eGFR was reduced, ANOVA revealed that f values of renal parenchyma were significantly lower in patients than controls (P < 0.05). Spearman correlation analysis revealed that there were positive correlations between eGFR and D (cortex, r = 0.466, P < 0.001; medulla, r = 0.491, P < 0.001), and between eGFR and f (cortex, r = 0.713, P < 0.001; medulla, r = 0.512, P < 0.001). Negative correlations were found between f and glomerular injury (cortex, r = -0.773, P < 0.001; medulla, r = -0.629, P < 0.001), and between f and tubulointerstitial lesion (cortex, r = -0.728, P < 0.001; medulla, r = -0.547, P < 0.001). IVIM-DWI might be feasible for noninvasive evaluation of renal function and pathology of CKD, especially in detection of renal insufficiency at an early stage. 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1251-1259. © 2017 International Society for Magnetic Resonance in Medicine.

Glomerular Lesions in Proteinuric Miniature Schnauzer Dogs.

PubMed

Furrow, E; Lees, G E; Brown, C A; Cianciolo, R E

2017-05-01

Miniature Schnauzer dogs are predisposed to idiopathic hypertriglyerceridemia, which increases risk for diseases such as pancreatitis and gallbladder mucocele. Recently, elevated triglyceride concentrations have been associated with proteinuria in this breed, although it is difficult to determine which abnormality is primary. Retrospective review of renal tissue from 27 proteinuric Miniature Schnauzers revealed that 20 dogs had ultrastructural evidence of osmophilic globules consistent with lipid in glomerular tufts. Seven of these dogs had lipid thromboemboli in glomerular capillary loops that distorted their shape and compressed circulating erythrocytes. Triglyceride concentrations were reported in 6 of these 7 dogs, and all were hypertriglyceridemic. In addition, glomerular lipidosis (defined as accumulation of foam cells within peripheral capillary loops) was identified in a single dog. The remaining 12 dogs had smaller amounts of lipid that could only be identified ultrastructurally. Neither signalment data nor clinicopathologic parameters (serum albumin, serum creatinine, urine protein-to-creatinine ratio, and blood pressure) differed among the various types of lipid lesions. During the time course of this study, all dogs diagnosed with glomerular lipid thromboemboli were Miniature Schnauzers, underscoring the importance of recognizing these clear spaces within capillary loops as lipid.

The Epidermal Growth Factor Receptor Promotes Glomerular Injury and Renal Failure in Rapidly Progressive Crescentic Glomerulonephritis; the Identification of Possible Therapy

PubMed Central

Bollée, Guillaume; Flamant, Martin; Schordan, Sandra; Fligny, Cécile; Rumpel, Elisabeth; Milon, Marine; Schordan, Eric; Sabaa, Nathalie; Vandermeersch, Sophie; Galaup, Ariane; Rodenas, Anita; Casal, Ibrahim; Sunnarborg, Susan W; Salant, David J; Kopp, Jeffrey B.; Threadgill, David W; Quaggin, Susan E; Dussaule, Jean-Claude; Germain, Stéphane; Mesnard, Laurent; Endlich, Karlhans; Boucheix, Claude; Belenfant, Xavier; Callard, Patrice; Endlich, Nicole; Tharaux, Pierre-Louis

2011-01-01

Rapidly progressive glomerulonephritis (RPGN) is a clinical a morphological expression of severe glomerular injury. Glomerular injury manifests as a proliferative histological pattern (“crescents”) with accumulation of T cells and macrophages, and proliferation of intrinsic glomerular cells. We show de novo induction of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in intrinsic glomerular epithelial cells (podocytes) from both mice and humans with RPGN. HB-EGF induction increases phosphorylation of the EGFR/ErbB1 receptor in mice with RPGN. In HB-EGF-deficient mice, EGFR activation in glomeruli is absent and the course of RPGN is improved. Autocrine HB-EGF induces a phenotypic switch in podocytes in vitro. Conditional deletion of the Egfr gene from podocytes of mice alleviates the severity of RPGN. Pharmacological blockade of EGFR also improves the course of RPGN, even when started 4 days after the induction of experimental RPGN. This suggests that targeting the HB-EGF/EGFR pathway could also be beneficial for treatment of human RPGN. PMID:21946538

Glomerular disease: why is there a dearth of high quality clinical trials?

PubMed

Leaf, David E; Appel, Gerald B; Radhakrishnan, Jai

2010-08-01

There is a paucity of high quality clinical trials in glomerular disease, particularly in non-diabetic kidney disease. The aims of this review include quantifying the extent of this problem and exploring reasons for the scarcity of such trials in primary glomerular disease, with an emphasis on immunoglobulin A nephropathy, minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy in comparison with the more common diseases of diabetic nephropathy and lupus nephritis. Reasons for the dearth of high quality clinical trials in primary glomerular disease include (1) low prevalence of disease; (2) variability in clinical presentation; (3) variability in treatment response; (4) lack of consensus in definitions; (5) difficulty in recruiting patients; (6) high costs of randomized controlled trials; and (7) lack of collaborative efforts. To facilitate greater numbers of high quality clinical trials in glomerular disease, practice guidelines should establish common classification systems of disease and common clinical end points, industry and non-industry sponsored research should find common ground and work together toward advancing science, and national registries should be created to encourage collaborations across institutions and across nations.

Cluster Analysis of Rat Olfactory Bulb Responses to Diverse Odorants

PubMed Central

Falasconi, Matteo; Leon, Michael; Johnson, Brett A.; Marco, Santiago

2012-01-01

In an effort to deepen our understanding of mammalian olfactory coding, we have used an objective method to analyze a large set of odorant-evoked activity maps collected systematically across the rat olfactory bulb to determine whether such an approach could identify specific glomerular regions that are activated by related odorants. To that end, we combined fuzzy c-means clustering methods with a novel validity approach based on cluster stability to evaluate the significance of the fuzzy partitions on a data set of glomerular layer responses to a large diverse group of odorants. Our results confirm the existence of glomerular response clusters to similar odorants. They further indicate a partial hierarchical chemotopic organization wherein larger glomerular regions can be subdivided into smaller areas that are rather specific in their responses to particular functional groups of odorants. These clusters bear many similarities to, as well as some differences from, response domains previously proposed for the glomerular layer of the bulb. These data also provide additional support for the concept of an identity code in the mammalian olfactory system. PMID:22459165

[Current insights about recurrence of glomerular diseases after renal transplantation].

PubMed

Kofman, Tomek; Oniszczuk, Julie; Lang, Philippe; Grimbert, Philippe; Audard, Vincent

2018-05-01

Recurrence of glomerular disease after renal transplantation is a frequent cause of graft loss. Incidence, risk factors and outcome of recurrence are widely due to the underlying glomerular disease. Graft biopsy analysis is required to confirm the definitive diagnosis of recurrence and to start an appropriate therapy that, in some cases, remains challenging to prevent graft failure. Increased use of protocol biopsy and recent advances in our understanding of the pathogenesis of some glomerular diseases with the identification of some relevant biomarkers provide a unique opportunity to initiate kidney-protective therapy at early stages of recurrence on the graft. This review summarizes our current knowledge on the management of many recurrent primary and secondary glomerulonephritis after kidney transplantation. Copyright © 2018 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.

Glomerular diseases outcome at one year in a tertiary care centre

PubMed Central

Mahmud, Huma Mamun; Kumar, Darshan; Irum, Humera; Farman Ali, Syed

2015-01-01

Objectives: To determine outcome in primary and secondary glomerular diseases at one year follow up. Methods: Study design is observational cohort, done in out-patient department, Dow Iinternational Medical College, DUHS. All information gathered on a proforma. All patients with dipstick positive proteinuria and clinical glomerular disease were included in study. Patients with no proteinuria were excluded so were patients with stage 5 CKD. Patients were followed for proteinuria and renal insufficiency at completion of one year follow up. Statistical analysis was done on SPSS version 16. Result: Total number of patients who completed one year follow up was 173. Mean age of patients was 51.67+ 10.16 (range 15 to 75 years). Ninety two (53.2%), were males and 81(46.8%) were females, ratio being 1.1: 1.0. Mean weight of our patients was 67.43+ 14.13 Kg, (35 to 107 kg). Commonest cause of glomerular disease in our patient was diabetic nephropathy which was seen in 94.2% patients. Commonest associated problem with glomerular disease was hypertension seen in 66.5% of patients. Four out of 173 patients had stage 5 CKD at end of follow up at one year while quantitativ proteinuria remained same at one year follow up. Conclusion: One year follow up is critical for patients with glomerular disease associated with stage 4 CKD as progression to end stage renal failure may be seen within one year in these patients. PMID:26101512

Basement Membrane Defects in Genetic Kidney Diseases

PubMed Central

Chew, Christine; Lennon, Rachel

2018-01-01

The glomerular basement membrane (GBM) is a specialized structure with a significant role in maintaining the glomerular filtration barrier. This GBM is formed from the fusion of two basement membranes during development and its function in the filtration barrier is achieved by key extracellular matrix components including type IV collagen, laminins, nidogens, and heparan sulfate proteoglycans. The characteristics of specific matrix isoforms such as laminin-521 (α5β2γ1) and the α3α4α5 chain of type IV collagen are essential for the formation of a mature GBM and the restricted tissue distribution of these isoforms makes the GBM a unique structure. Detailed investigation of the GBM has been driven by the identification of inherited abnormalities in matrix proteins and the need to understand pathogenic mechanisms causing severe glomerular disease. A well-described hereditary GBM disease is Alport syndrome, associated with a progressive glomerular disease, hearing loss, and lens defects due to mutations in the genes COL4A3, COL4A4, or COL4A5. Other proteins associated with inherited diseases of the GBM include laminin β2 in Pierson syndrome and LMX1B in nail patella syndrome. The knowledge of these genetic mutations associated with GBM defects has enhanced our understanding of cell–matrix signaling pathways affected in glomerular disease. This review will address current knowledge of GBM-associated abnormalities and related signaling pathways, as well as discussing the advances toward disease-targeted therapies for patients with glomerular disease. PMID:29435440

GEC-targeted HO-1 expression reduces proteinuria in glomerular immune injury.

PubMed

Duann, Pu; Lianos, Elias A

2009-09-01

Induction of heme oxygenase (HO)-1 is a key defense mechanism against oxidative stress. Compared with tubules, glomeruli are refractory to HO-1 upregulation in response to injury. This can be a disadvantage as it may be associated with insufficient production of cytoprotective heme-degradation metabolites. We, therefore, explored whether 1) targeted HO-1 expression can be achieved in glomeruli without altering their physiological integrity and 2) this expression reduces proteinuria in immune injury induced by an anti-glomerular basement membrane (GBM) antibody (Ab). We employed a 4.125-kb fragment of a mouse nephrin promoter downstream to which a FLAG-tagged hHO-1 cDNA sequence was inserted and subsequently generated transgenic mice from the FVB/N parental strain. There was a 16-fold higher transgene expression in the kidney than nonspecific background (liver) while the transprotein immunolocalized in glomerular epithelial cells (GEC). There was no change in urinary protein excretion, indicating that GEC-targeted HO-1 expression had no effect on glomerular protein permeability. Urinary protein excretion in transgenic mice with anti-GBM Ab injury (days 3 and 6) was significantly lower compared with wild-type controls. There was no significant change in renal expression levels of profibrotic (TGF-beta1) or anti-inflammatory (IL-10) cytokines in transgenic mice with anti-GBM Ab injury. These observations indicate that GEC-targeted HO-1 expression does not alter glomerular physiological integrity and reduces proteinuria in glomerular immune injury.

GEC-targeted HO-1 expression reduces proteinuria in glomerular immune injury

PubMed Central

Duann, Pu; Lianos, Elias A.

2009-01-01

Induction of heme oxygenase (HO)-1 is a key defense mechanism against oxidative stress. Compared with tubules, glomeruli are refractory to HO-1 upregulation in response to injury. This can be a disadvantage as it may be associated with insufficient production of cytoprotective heme-degradation metabolites. We, therefore, explored whether 1) targeted HO-1 expression can be achieved in glomeruli without altering their physiological integrity and 2) this expression reduces proteinuria in immune injury induced by an anti-glomerular basement membrane (GBM) antibody (Ab). We employed a 4.125-kb fragment of a mouse nephrin promoter downstream to which a FLAG-tagged hHO-1 cDNA sequence was inserted and subsequently generated transgenic mice from the FVB/N parental strain. There was a 16-fold higher transgene expression in the kidney than nonspecific background (liver) while the transprotein immunolocalized in glomerular epithelial cells (GEC). There was no change in urinary protein excretion, indicating that GEC-targeted HO-1 expression had no effect on glomerular protein permeability. Urinary protein excretion in transgenic mice with anti-GBM Ab injury (days 3 and 6) was significantly lower compared with wild-type controls. There was no significant change in renal expression levels of profibrotic (TGF-β1) or anti-inflammatory (IL-10) cytokines in transgenic mice with anti-GBM Ab injury. These observations indicate that GEC-targeted HO-1 expression does not alter glomerular physiological integrity and reduces proteinuria in glomerular immune injury. PMID:19587144

Acute glomerular upregulation of ornithine decarboxylase is not essential for mesangial cell proliferation and matrix expansion in anti-Thy-1-nephritis.

PubMed

Ketteler, M; Westenfeld, R; Gawlik, A; de Heer, E; Distler, A

2000-01-01

Pathways of L-arginine metabolism including nitric oxide, agmatine and polyamine synthesis are upregulated during glomerular inflammation in experimental glomerulonephritis. In anti-Thy-1-glomerulonephritis L-arginine-deficient diets ameliorate the disease course in this model. However, it is unclear which metabolic pathway is affected by this substrate depletion. Since polyamines are important proproliferative molecules, we studied the effect of specific polyamine synthesis blockade in vivo on mesangial cell proliferation and glomerular fibrosis in this model. Anti-Thy-1-glomerulonephritis was induced in male Sprague-Dawley rats by single-bolus injection of monoclonal ER4-antibodies. Rats were treated with difluoromethylornithine (0.5-2% in the drinking water), a selective inhibitor of the rate-limiting enzyme of polyamine synthesis, ornithine decarboxylase (ODC). Mesangial cell proliferation and matrix expansion were evaluated in PAS-stained kidney tissues. Glomerular TGF-beta and biglycan-mRNA-expression were determined by Northern blot analysis and albuminuria was measured using a competitive ELISA. Data were compared to untreated controls. Though complete inhibition of ODC activity was achieved at any time point, difluoromethlornithine treatment had no significant effect on albuminuria, glomerular matrix protein expression and mesangial cell count in this model. The acute upregulation of glomerular ODC activity above baseline in anti-Thy1-glomerulonephritis is not pathophysiologically important for disease development however, biological effects of available polyamine pools cannot be excluded by our study.

Do Anesthetic Techniques Influence the Threshold for Glomerular Capillary Hemorrhage Induced in Rats by Contrast-Enhanced Diagnostic Ultrasound?

PubMed

Miller, Douglas L; Lu, Xiaofang; Fabiilli, Mario; Dou, Chunyan

2016-02-01

Glomerular capillary hemorrhage can be induced by ultrasonic cavitation during contrast-enhanced diagnostic ultrasound (US) exposure, an important nonthermal US bioeffect. Recent studies of pulmonary US exposure have shown that thresholds for another nonthermal bioeffect of US, pulmonary capillary hemorrhage, is strongly influenced by whether xylazine is included in the specific anesthetic technique. The objective of this study was to determine the influence of xylazine on contrast-enhanced diagnostic US-induced glomerular capillary hemorrhage. In this study, anesthesia with ketamine only was compared to ketamine plus xylazine for induction of glomerular capillary hemorrhage in rats by 1.6-MHz intermittent diagnostic US with a microsphere contrast agent (similar to Definity; Lantheus Medical Imaging, Inc, North Billerica, MA). Glomerular capillary hemorrhage was measured as a percentage of glomeruli with hemorrhage found in histologic sections for groups of rats scanned at different peak rarefactional pressure amplitudes. There was a significant difference between the magnitude of the glomerular capillary hemorrhage between the anesthetics at 2.3 MPa, with 45.6% hemorrhage for ketamine only, increasing to 63.2% hemorrhage for ketamine plus xylazine (P < .001). However, the thresholds for the two anesthetic methods were virtually identical at 1.0 MPa, based on linear regression of the exposure response data. Thresholds for contrast-enhanced diagnostic US-induced injury of the microvasculature appear to be minimally affected by anesthetic methods. © 2016 by the American Institute of Ultrasound in Medicine.

Vitamin E-coated membrane dialyzer and beta2-microglobulin removal.

PubMed

Mandolfo, S; Bucci, R; Imbasciati, E

2003-12-01

This study was designed to test the removal of beta2-microglobulin (beta2M) in a vitamin E-modified membrane. We investigated in vivo the dialyzer (Excebrane, series EE, 1.8 m2) with respect to hydraulic permeability (Kuf), maximum ultrafiltration rate (UF max), sieving coefficient (Sc), and solute clearances in hemodialysis (HD) and in soft hemodiafiltration (HDF). Kuf was 18.4 ml/h/mmHg, UF max was 75 ml/min, and Sc for beta2M was 0.45. Clearance values at 400 ml/min of Qb in HD were 258 ml/min for urea, 201 ml/min for creatinine, and 135 ml/min for phosphate. In soft HDF, clearances were slightly higher. beta2M clearance was 26 ml/min in HD and 43 ml/min in soft HDF. In conclusion, Excebrane (series EE) procures a soft HDF with an amount of substitution fluid in post dilution mode of over 60 ml/min. Remarkable small solute clearances were obtained when the blood flow was raised to 400 ml/min. A significant reduction of beta2M is demonstrated by HDF.

Ethanol at low concentrations protects glomerular podocytes through alcohol dehydrogenase and 20-HETE.

PubMed

McCarthy, Ellen T; Zhou, Jianping; Eckert, Ryan; Genochio, David; Sharma, Rishi; Oni, Olurinde; De, Alok; Srivastava, Tarak; Sharma, Ram; Savin, Virginia J; Sharma, Mukut

2015-01-01

Clinical studies suggest cardiovascular and renal benefits of ingesting small amounts of ethanol. Effects of ethanol, role of alcohol dehydrogenase (ADH) or of 20-hydroxyeicosatetraenoic acid (20-HETE) in podocytes of the glomerular filtration barrier have not been reported. We found that mouse podocytes at baseline generate 20-HETE and express ADH but not CYP2e1. Ethanol at high concentrations altered the actin cytoskeleton, induced CYP2e1, increased superoxide production and inhibited ADH gene expression. Ethanol at low concentrations upregulated the expression of ADH and CYP4a12a. 20-HETE, an arachidonic acid metabolite generated by CYP4a12a, blocked the ethanol-induced cytoskeletal derangement and superoxide generation. Ethanol at high concentration or ADH inhibitor increased glomerular albumin permeability in vitro. 20-HETE and its metabolite produced by ADH activity, 20-carboxy-arachidonic acid, protected the glomerular permeability barrier against an ADH inhibitor, puromycin or FSGS permeability factor. We conclude that ADH activity is required for glomerular function, 20-HETE is a physiological substrate of ADH in podocytes and that podocytes are useful biosensors to understand glomeruloprotective effects of ethanol. Published by Elsevier Inc.

Glomerular Lesions in Proteinuric Miniature Schnauzer Dogs

PubMed Central

Furrow, E.; Lees, G. E.; Brown, C. A.; Cianciolo, R. E.

2017-01-01

Miniature Schnauzer dogs are predisposed to idiopathic hypertriglyerceridemia, which increases risk for diseases such as pancreatitis and gallbladder mucocele. Recently, elevated triglyceride concentrations have been associated with proteinuria in this breed, although it is difficult to determine which abnormality is primary. Retrospective review of renal tissue from 27 proteinuric Miniature Schnauzers revealed that 20 dogs had ultrastructural evidence of osmophilic globules consistent with lipid in glomerular tufts. Seven of these dogs had lipid thromboemboli in glomerular capillary loops that distorted their shape and compressed circulating erythrocytes. Triglyceride concentrations were reported in 6 of these 7 dogs, and all were hypertriglyceridemic. In addition, glomerular lipidosis (defined as accumulation of foam cells within peripheral capillary loops) was identified in a single dog. The remaining 12 dogs had smaller amounts of lipid that could only be identified ultrastructurally. Neither signalment data nor clinicopathologic parameters (serum albumin, serum creatinine, urine protein-to-creatinine ratio, and blood pressure) differed among the various types of lipid lesions. During the time course of this study, all dogs diagnosed with glomerular lipid thromboemboli were Miniature Schnauzers, underscoring the importance of recognizing these clear spaces within capillary loops as lipid. PMID:28005494

Glomerular and Mitral-Granule Cell Microcircuits Coordinate Temporal and Spatial Information Processing in the Olfactory Bulb.

PubMed

Cavarretta, Francesco; Marasco, Addolorata; Hines, Michael L; Shepherd, Gordon M; Migliore, Michele

2016-01-01

The olfactory bulb processes inputs from olfactory receptor neurons (ORNs) through two levels: the glomerular layer at the site of input, and the granule cell level at the site of output to the olfactory cortex. The sequence of action of these two levels has not yet been examined. We analyze this issue using a novel computational framework that is scaled up, in three-dimensions (3D), with realistic representations of the interactions between layers, activated by simulated natural odors, and constrained by experimental and theoretical analyses. We suggest that the postulated functions of glomerular circuits have as their primary role transforming a complex and disorganized input into a contrast-enhanced and normalized representation, but cannot provide for synchronization of the distributed glomerular outputs. By contrast, at the granule cell layer, the dendrodendritic interactions mediate temporal decorrelation, which we show is dependent on the preceding contrast enhancement by the glomerular layer. The results provide the first insights into the successive operations in the olfactory bulb, and demonstrate the significance of the modular organization around glomeruli. This layered organization is especially important for natural odor inputs, because they activate many overlapping glomeruli.

Glomerular function in sickle cell disease patients during crisis.

PubMed

Aderibigbe, A; Arije, A; Akinkugbe, O O

1994-06-01

An 8 month prospective study was carried out in 20 adult sickle cell disease (SCD) patients 16 sickle cell anaemia (Hbss) and 4 sickle cell Hbc disease (Hbsc); who had vaso-occlusive crises within the study period to determine the extent of the effect of sickle cell crisis on glomerular function in SCD patients during crisis. The male: female ratio was 1:57 and their mean age was 21.1 +/- 7.9 years. Creatinine clearance (CCr), as an index of glomerular function, was determined at the pre-crisis, crisis, 2 and 4 weeks post-crisis and at the end of the study period. The mean values of their CCr dropped from 113.37 +/- 33.80mls/min at pre-crisis stage to 96.39 +/- 30.13mls/min during crisis (p < 0.001) indicating glomerular dysfunction. It improved significantly to 107.75 +/- 30.20mls/min at 4 weeks post-crisis (p < 0.001). There was no significant differences in the mean values of CCr at the end of the study (116.20 +/- 31.43mls/min) compared to the pre-crisis stage (p > 0.05). It is concluded that glomerular dysfunction in SCD patients during crisis is potentially reversible.

Ethanol at Low Concentrations Protects Glomerular Podocytes through Alcohol Dehydrogenase and 20-HETE

PubMed Central

McCarthy, Ellen T.; Zhou, Jianping; Eckert, Ryan; Genochio, David; Sharma, Rishi; Oni, Olurinde; De, Alok; Srivastava, Tarak; Sharma, Ram; Savin, Virginia J.; Sharma, Mukut

2014-01-01

Clinical studies suggest cardiovascular and renal benefits of ingesting small amounts of ethanol. Effects of ethanol, role of alcohol dehydrogenase (ADH) or of 20-hydroxyeicosatetraenoic acid (20-HETE) in podocytes of the glomerular filtration barrier have not been reported. We found that mouse podocytes at baseline generate 20-HETE and express ADH but not CYP2e1. Ethanol at high concentrations altered the actin cytoskeleton, induced CYP2e1, increased superoxide production and inhibited ADH gene expression. Ethanol at low concentrations upregulated the expression of ADH and CYP4a12a. 20-HETE, an arachidonic acid metabolite generated by CYP4a12a, blocked the ethanol-induced cytoskeletal derangement and superoxide generation. Ethanol at high concentration or ADH inhibitor increased glomerular albumin permeability in vitro. 20-HETE and its metabolite produced by ADH activity, 20-carboxy-arachidonic acid, protected the glomerular permeability barrier against an ADH inhibitor, puromycin or FSGS permeability factor. We conclude that ADH activity is required for glomerular function, 20-HETE is a physiological substrate of ADH in podocytes and that podocytes are useful biosensors to understand glomeruloprotective effects of ethanol. PMID:25447342

Neuronal proteins are novel components of podocyte major processes and their expression in glomerular crescents supports their role in crescent formation.

PubMed

Sistani, Laleh; Rodriguez, Patricia Q; Hultenby, Kjell; Uhlen, Mathias; Betsholtz, Christer; Jalanko, Hannu; Tryggvason, Karl; Wernerson, Annika; Patrakka, Jaakko

2013-01-01

The podocyte has a central role in the glomerular filtration barrier typified by a sophisticated morphology of highly organized primary (major) and secondary (foot) processes. The molecular makeup of foot processes is well characterized, but that of major processes is poorly known. Previously, we profiled the glomerular transcriptome through large-scale sequencing and microarray profiling. Unexpectedly, the survey found expression of three neuronal proteins (Huntingtin interacting protein 1 (Hip1), neurofascin (Nfasc), and olfactomedin-like 2a (Olfml2a)), all enriched in the glomerulus. These proteins were expressed exclusively by podocytes, wherein they localized to major processes as verified by RT-PCR, western blotting, immunofluorescence, and immunoelectron microscopy. During podocyte development, these proteins colocalized with vimentin, confirming their association with major processes. Using immunohistochemistry, we found coexpression of Hip1 and Olfml2a along with the recognized podocyte markers synaptopodin and Pdlim2 in glomerular crescents of human kidneys, indicating the presence of podocytes in these lesions. Thus, three neuronal proteins are highly expressed in podocyte major process. Using these new markers we found that podocytes contribute to the formation of glomerular crescents.

Determination of glomerular function in advanced renal failure.

PubMed Central

Manz, F; Alatas, H; Kochen, W; Lutz, P; Rebien, W; Schärer, K

1977-01-01

In 15 children with advanced chronic renal failure, glomerular filtration rate was determined by different methods. Inulin clearance correlated well with the mean of creatinine and urea clearance, and also with 51-chromium edetic acid (EDTA) clearance measured over 24 hours. The absolute values of creatinine clearance and of 51Cr-EDTA clearance measured up to 8 hours were higher than inulin clearance. In advanced renal failure both the 51Cr-EDTA clearance measured over 24 hours, and the mean of creatinine and urea clearance, provide acceptable estimates of true glomerular filtration rate. PMID:411426

[Could isolated mesangial deposits of C3 be responsible of glomerular hematuric nephropathies (author's transl)].

PubMed

Saint-Andre, J P; Touzard, D; Houssin, A; Simard, C

1982-01-01

This communication presents three cases of prolonged macroscopic hematuria in young subjects. Complementary explorations eliminated urologic or vascular causes. Renal biopsies showed minimal glomerular lesions with light microscopy, normal basement membranes in electron microscopy and mesangial deposits of C3 and properdine in immunofluorescence. Although the mesangial deposits of C3 lack specificity and the number of observations is small, it appears useful to report such cases so as to indicate their frequency and perhaps their autonomy, in glomerular hematuric nephropathies.

Preparation of hydrophilic and antifouling polysulfone ultrafiltration membrane derived from phenolphthalin by copolymerization method

NASA Astrophysics Data System (ADS)

Liu, Zhixiao; Mi, Zhiming; Chen, Chunhai; Zhou, Hongwei; Zhao, Xiaogang; Wang, Daming

2017-04-01

In this task, carboxylated polysulfone (PSF-COOH) was achieved by introducing the monomer of phenolphthalin (PPL) containing carboxyl to the molecule backbone of polysulfone (PSF). And a series of PSF-COOH copolymers with different carboxylation degree was synthesized by adjusting the molar (%) of bisphenol A (BPA) and PPL in direct copolymerization method and was prepared as PSF-COOH ultrafiltration membranes via phase separation method. The effect of PPL molar (%) in copolymers on the morphology, hydrophilicity, permeation flux, antifouling and mechanical properties of membranes was investigated by scanning electron microscope (SEM), atomic force microscope (AFM), water contact angle, ultrafiltration experiments and universal testing machine, respectively. The results showed that with the increased carboxyl content in membranes, the hydrophilicity, permeation fluxes and antifouling properties of membranes gradually increased. When the molar (%) of PPL to BPA was 100:0, the membrane exhibited the highest pure water flux (329.6 L/m2 h) and the maximum flux recovery rate (92.5%). When the content of carboxyl in the membrane was 80% or more, after three cycles of BSA solution (1 g/L) filtration, the flux recovery rate was basically constant or showed a slightly increase. Thus, it can achieve the goal of long term usage without compromising flux.

Evaluation of Membrane Ultrafiltration and Residual Chlorination as a Decentralized Water Treatment Strategy for Ten Rural Healthcare Facilities in Rwanda

PubMed Central

Huttinger, Alexandra; Dreibelbis, Robert; Roha, Kristin; Ngabo, Fidel; Kayigamba, Felix; Mfura, Leodomir; Moe, Christine

2015-01-01

There is a critical need for safe water in healthcare facilities (HCF) in low-income countries. HCF rely on water supplies that may require additional on-site treatment, and need sustainable technologies that can deliver sufficient quantities of water. Water treatment systems (WTS) that utilize ultrafiltration membranes for water treatment can be a useful technology in low-income countries, but studies have not systematically examined the feasibility of this technology in low-income settings. We monitored 22 months of operation of 10 WTS, including pre-filtration, membrane ultrafiltration, and chlorine residual disinfection that were donated to and operated by rural HCF in Rwanda. The systems were fully operational for 74% of the observation period. The most frequent reasons for interruption were water shortage (8%) and failure of the chlorination mechanism (7%). When systems were operational, 98% of water samples collected from the HCF taps met World Health Organization (WHO) guidelines for microbiological water quality. Water quality deteriorated during treatment interruptions and when water was stored in containers. Sustained performance of the systems depended primarily on organizational factors: the ability of the HCF technician to perform routine servicing and repairs, and environmental factors: water and power availability and procurement of materials, including chlorine and replacement parts in Rwanda. PMID:26516883

Ultrafiltration by a compacted clay membrane. I - Oxygen and hydrogen isotopic fractionation. II - Sodium ion exclusion at various ionic strengths.

NASA Technical Reports Server (NTRS)

Coplen, T. B.; Hanshaw, B. B.

1973-01-01

Laboratory experiments were carried out to determine the magnitude of the isotopic fractionation of distilled water and of 0.01N NaCl forced to flow at ambient temperature under a hydraulic pressure drop of 100 bars across a montmorillonite disk compacted to a porosity of 35% by a pressure of 330 bars. The ultrafiltrates in both experiments were depleted in D by 2.5% and in O-18 by 0.8% relative to the residual solution. No additional isotopic fractionation due to a salt-filtering mechanism was observed at NaCl concentrations up to 0.01N. Adsorption is most likely the principal mechanism which produces isotopic fractionation, but molecular diffusion may play a minor role. The results suggest that oxygen and hydrogen isotopic fractionation of ground water during passage through compacted clayey sediments should be a common occurrence, in accord with published interpretations of isotopic data from the Illinois and Alberta basins. It is shown how it is possible to proceed from the ion exchange capacity of clay minerals and, by means of the Donnan membrane equilibrium concept and the Teorell-Meyer-Siever theory, develop a theory to explain why and to what extent ultrafiltration occurs when solutions of known concentration are forced to flow through a clay membrane.

Quickly Screening for Potential α-Glucosidase Inhibitors from Guava Leaves Tea by Bioaffinity Ultrafiltration Coupled with HPLC-ESI-TOF/MS Method.

PubMed

Wang, Lu; Liu, Yufeng; Luo, You; Huang, Kuiying; Wu, Zhenqiang

2018-02-14

Guava leaves tea (GLT) has a potential antihyperglycemic effect. Nevertheless, it is unclear which compound plays a key role in reducing blood sugar. In this study, GLT extract (IC 50 = 19.37 ± 0.21 μg/mL) exhibited a stronger inhibitory potency against α-glucosidase than did acarbose (positive control) at IC 50 = 178.52 ± 1.37 μg/mL. To rapidly identify the specific α-glucosidase inhibitor components from GLT, an approach based on bioaffinity ultrafiltration combined with high performance liquid chromatography coupled to electrospray ionization-time-of-flight-mass spectrometry (BAUF-HPLC-ESI-TOF/MS) was developed. Under the optimal bioaffinity ultrafiltration conditions, 11 corresponding potential α-glucosidase inhibitors with high affinity degrees (ADs) were screened and identified from the GLT extract. Quercetin (IC 50 = 4.51 ± 0.71 μg/mL) and procyanidin B3 (IC 50 = 28.67 ± 5.81 μg/mL) were determined to be primarily responsible for the antihyperglycemic effect, which further verified the established screening method. Moreover, structure-activity relationships were discussed. In conclusion, the BAUF-HPLC-ESI-TOF/MS method could be applied to determine the potential α-glucosidase inhibitors from complex natural products quickly.

Detection of Macromolecular Fractions in HCN Polymers Using Electrophoretic and Ultrafiltration Techniques.

PubMed

Marín-Yaseli, Margarita R; Cid, Cristina; Yagüe, Ana I; Ruiz-Bermejo, Marta

2017-02-01

Elucidating the origin of life involves synthetic as well as analytical challenges. Herein, for the first time, we describe the use of gel electrophoresis and ultrafiltration to fractionate HCN polymers. Since the first prebiotic synthesis of adenine by Oró, HCN polymers have gained much interest in studies on the origins of life due to the identification of biomonomers and related compounds within them. Here, we demonstrate that macromolecular fractions with electrophoretic mobility can also be detected within HCN polymers. The migration of polymers under the influence of an electric field depends not only on their sizes (one-dimensional electrophoresis) but also their different isoelectric points (two-dimensional electrophoresis, 2-DE). The same behaviour was observed for several macromolecular fractions detected in HCN polymers. Macromolecular fractions with apparent molecular weights as high as 250 kDa were detected by tricine-SDS gel electrophoresis. Cationic macromolecular fractions with apparent molecular weights as high as 140 kDa were also detected by 2-DE. The HCN polymers synthesized were fractionated by ultrafiltration. As a result, the molecular weight distributions of the macromolecular fractions detected in the HCN polymers directly depended on the synthetic conditions used to produce these polymers. The implications of these results for prebiotic chemistry will be discussed. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

Use of Enterococcus faecalis and Bacillus atrophaeus as surrogates to establish and maintain laboratory proficiency for concentration of water samples using ultrafiltration.

PubMed

Mapp, Latisha; Klonicki, Patricia; Takundwa, Prisca; Hill, Vincent R; Schneeberger, Chandra; Knee, Jackie; Raynor, Malik; Hwang, Nina; Chambers, Yildiz; Miller, Kenneth; Pope, Misty

2015-11-01

The U.S. Environmental Protection Agency's (EPA) Water Laboratory Alliance (WLA) currently uses ultrafiltration (UF) for concentration of biosafety level 3 (BSL-3) agents from large volumes (up to 100-L) of drinking water prior to analysis. Most UF procedures require comprehensive training and practice to achieve and maintain proficiency. As a result, there was a critical need to develop quality control (QC) criteria. Because select agents are difficult to work with and pose a significant safety hazard, QC criteria were developed using surrogates, including Enterococcus faecalis and Bacillus atrophaeus. This article presents the results from the QC criteria development study and results from a subsequent demonstration exercise in which E. faecalis was used to evaluate proficiency using UF to concentrate large volume drinking water samples. Based on preliminary testing EPA Method 1600 and Standard Methods 9218, for E. faecalis and B. atrophaeus respectively, were selected for use during the QC criteria development study. The QC criteria established for Method 1600 were used to assess laboratory performance during the demonstration exercise. Based on the results of the QC criteria study E. faecalis and B. atrophaeus can be used effectively to demonstrate and maintain proficiency using ultrafiltration. Published by Elsevier B.V.

Influence of Surface Properties of Filtration-Layer Metal Oxide on Ceramic Membrane Fouling during Ultrafiltration of Oil/Water Emulsion.

PubMed

Lu, Dongwei; Zhang, Tao; Gutierrez, Leo; Ma, Jun; Croué, Jean-Philippe

2016-05-03

In this work, ceramic ultrafiltration membranes deposited with different metal oxides (i.e., TiO2, Fe2O3, MnO2, CuO, and CeO2) of around 10 nm in thickness and similar roughness were tested for O/W emulsion treatment. A distinct membrane fouling tendency was observed, which closely correlated to the properties of the filtration-layer metal oxides (i.e., surface hydroxyl groups, hydrophilicity, surface charge, and adhesion energy for oil droplets). Consistent with the distinct bond strength of the surface hydroxyl groups, hydrophilicity of these common metal oxides is quite different. The differences in hydrophilicity consequently lead to different adhesion of these metal oxides toward oil droplets, consistent with the irreversible membrane fouling tendency. In addition, the surface charge of the metal oxide opposite to that of emulsion can help to alleviate irreversible membrane fouling in ultrafiltration. Highly hydrophilic Fe2O3 with the lowest fouling tendency could be a potential filtration-layer material for the fabrication/modification of ceramic membranes for O/W emulsion treatment. To the best of our knowledge, this is the first study clearly showing the correlations between surface properties of filtration-layer metal oxides and ceramic membrane fouling tendency by O/W emulsion.

Performance of ceramic ultrafiltration membranes and fouling behavior of a dye-polysaccharide binary system.

PubMed

Zuriaga-Agustí, E; Alventosa-deLara, E; Barredo-Damas, S; Alcaina-Miranda, M I; Iborra-Clar, M I; Mendoza-Roca, J A

2014-05-01

Ultrafiltration membrane processes have become an established technology in the treatment and reuse of secondary effluents. Nevertheless, membrane fouling arises as a major obstacle in the efficient operation of these systems. In the current study, the performance of tubular ultrafiltration ceramic membranes was evaluated according to the roles exerted by membrane pore size, transmembrane pressure and feed concentration on a binary foulant system simulating textile wastewater. For that purpose, carboxymethyl cellulose sodium salt (CMC) and an azo dye were used as colloidal and organic foulants, respectively. Results showed that a larger pore size enabled more solutes to get adsorbed into the pores, producing a sharp permeate flux decline attributed to the rapid pore blockage. Besides, an increase in CMC concentration enhanced severe fouling in the case of the tighter membrane. Concerning separation efficiency, organic matter was almost completely removed with removal efficiency above 98.5%. Regarding the dye, 93% of rejection was achieved. Comparable removal efficiencies were attributed to the dynamic membrane formed by the cake layer, which governed process performance in terms of rejection and selectivity. As a result, none of the evaluated parameters showed significant influence on separation efficiency, supporting the significant role of cake layer on filtration process. Copyright © 2014 Elsevier Ltd. All rights reserved.

Evaluation of Membrane Ultrafiltration and Residual Chlorination as a Decentralized Water Treatment Strategy for Ten Rural Healthcare Facilities in Rwanda.

PubMed

Huttinger, Alexandra; Dreibelbis, Robert; Roha, Kristin; Ngabo, Fidel; Kayigamba, Felix; Mfura, Leodomir; Moe, Christine

2015-10-27

There is a critical need for safe water in healthcare facilities (HCF) in low-income countries. HCF rely on water supplies that may require additional on-site treatment, and need sustainable technologies that can deliver sufficient quantities of water. Water treatment systems (WTS) that utilize ultrafiltration membranes for water treatment can be a useful technology in low-income countries, but studies have not systematically examined the feasibility of this technology in low-income settings. We monitored 22 months of operation of 10 WTS, including pre-filtration, membrane ultrafiltration, and chlorine residual disinfection that were donated to and operated by rural HCF in Rwanda. The systems were fully operational for 74% of the observation period. The most frequent reasons for interruption were water shortage (8%) and failure of the chlorination mechanism (7%). When systems were operational, 98% of water samples collected from the HCF taps met World Health Organization (WHO) guidelines for microbiological water quality. Water quality deteriorated during treatment interruptions and when water was stored in containers. Sustained performance of the systems depended primarily on organizational factors: the ability of the HCF technician to perform routine servicing and repairs, and environmental factors: water and power availability and procurement of materials, including chlorine and replacement parts in Rwanda.

Establishment of conditionally immortalized human glomerular mesangial cells in culture, with unique migratory properties.

PubMed

Sarrab, Ramadan M; Lennon, Rachel; Ni, Lan; Wherlock, Matthew D; Welsh, Gavin I; Saleem, Moin A

2011-11-01

The aim of this study was to establish an immortalized human mesangial cell line similar to mesangial cells in vivo for use as a tool for understanding glomerular cell function. Mesangial cells were isolated from glomerular outgrowths from a normal human kidney, then retrovirally transfected with a temperature-sensitive SV40T antigen+human telomerase (hTERT). Mesangial cells exhibited features of compact cells with small bodies in a confluent monolayer at 33°C, but the cell shape changed to flat and stellate after 5 days in growth-restrictive conditions (37°C). Western blot and immunofluorescence analysis showed that podocyte markers (nephrin, CD2AP, podocin, Wilms' tumor-1) and an endothelial-specific molecule (VE-cadherin) were not detectable in this cell line, whereas markers characteristic of mesangial cells (α-SMA, fibronectin, and PDGFβ-R) were strongly expressed. In migration assays, a significant reduction in wound surface was observed in podocyte and endothelial cells as soon as 12 h (75 and 62%, respectively) and complete wound closure after 24 h. In contrast, no significant change was observed in mesangial cells after 12 h, and even after 48 h the wounds were not completely closed. Until now, conditionally immortalized podocyte and endothelial cell lines derived from mice and humans have been described, and this has greatly boosted research on glomerular physiology and pathology. We have established the first conditionally immortalized human glomerular mesangial cell line, which will be an important adjunct in studies of representative glomerular cells, as well as in coculture studies. Unexpectedly, mesangial cells' ability to migrate seems to be slower than for other glomerular cells, suggesting this line will demonstrate functional properties distinct from previously available mesangial cell cultures. This conditionally immortalized human mesangial cell line represents a new tool for the study of human mesangial cell biology in vitro.

De novo glomerular diseases after renal transplantation: How is it different from recurrent glomerular diseases?

PubMed Central

Abbas, Fedaey; El Kossi, Mohsen; Jin, Jon Kim; Sharma, Ajay; Halawa, Ahmed

2017-01-01

The glomerular diseases after renal transplantation can occur de novo, i.e., with no relation to the native kidney disease, or more frequently occur as a recurrence of the original disease in the native kidney. There may not be any difference in clinical features and histological pattern between de novo glomerular disease and recurrence of original glomerular disease. However, structural alterations in transplanted kidney add to dilemma in diagnosis. These changes in architecture of histopathology can happen due to: (1) exposure to the immunosuppression specifically the calcineurin inhibitors (CNI); (2) in vascular and tubulointerstitial alterations as a result of antibody mediated or cell-mediated immunological onslaught; (3) post-transplant viral infections; (4) ischemia-reperfusion injury; and (5) hyperfiltration injury. The pathogenesis of the de novo glomerular diseases differs with each type. Stimulation of B-cell clones with subsequent production of the monoclonal IgG, particularly IgG3 subtype that has higher affinity to the negatively charged glomerular tissue, is suggested to be included in PGNMID pathogenesis. De novo membranous nephropathy can be seen after exposure to the cryptogenic podocyte antigens. The role of the toxic effects of CNI including tissue fibrosis and the hemodynamic alterations may be involved in the de novo FSGS pathophysiology. The well-known deleterious effects of HCV infection and its relation to MPGN disease are frequently reported. The new concepts have emerged that demonstrate the role of dysregulation of alternative complement pathway in evolution of MPGN that led to classifying into two subgroups, immune complex mediated MPGN and complement-mediated MPGN. The latter comprises of the dense deposit disease and the C3 GN disease. De novo C3 disease is rather rare. Prognosis of de novo diseases varies with each type and their management continues to be empirical to a large extent. PMID:29312858

Pattern of glomerular disease in the Saudi population: a single-center, five-year retrospective study.

PubMed

Nawaz, Z; Mushtaq, F; Mousa, D; Rehman, E; Sulaiman, M; Aslam, N; Khawaja, N

2013-11-01

Glomerular diseases continue to be the leading cause of end-stage renal disease (ESRD) globally. Hence, it is important to recognize the pattern of glomerular diseases in different geographical areas in order to understand the patho-biology, incidence and progression of the disorder. Published studies from different centers in Saudi Arabia have reported contradicting results. In this retrospective study, we report our experience at the Armed Forces Hospital, Riyadh, Saudi Arabia. A total of 348 native renal biopsies performed at our center on patients with proteinuria >1 g, hematuria and/or renal impairment during a period of 5 years (between January 2005 and December 2009) were studied by a histopathologist using light microscopy, immunofluorescence and electron microscopy, and were categorized. Results showed that primary glomerular disease accounted for 55.1% of all renal biopsies. The most common histological lesion was focal and segmental glomerulosclerosis (FSGS) (27.6%), followed by minimal change disease (MCD) (17.7%) and membrano-proliferative glomerulonephritis (MPGN) (13.0%). Secondary glomerular disease accounted for 37.9% of the glomerular diseases, with lupus nephritis (LN) being the most common lesion (54.5%), followed by hypertensive nephrosclerosis (22%), post-infectious glomerulonephritis (7.5%), diabetic nephropathy (DN) (6.8%) and vasculitides (4.5%). Four percent of all biopsies turned out to be ESRD while biopsy was inadequate in 2.8% of the cases. In conclusion, our study showed that FSGS was the most common primary GN encountered, while LN was the most common secondary GN. We encountered 14 cases of crescentic glomerulonephritis. Also, the prevalence of MPGN, MCD, IgA nephropathy and membranous GN was many folds higher in males when compared with the Western data. We believe that it is mandatory to maintain a Saudi Arabian Renal Biopsy Registry to understand better the pattern of glomerular disease in the Saudi population and to follow any change in trend.

Chronic Kidney Disease Epidemiology Collaboration versus Modification of Diet in Renal Disease equations for renal function evaluation in patients undergoing partial nephrectomy.

PubMed

Shikanov, Sergey; Clark, Melanie A; Raman, Jay D; Smith, Benjamin; Kaag, Matthew; Russo, Paul; Wheat, Jeffrey C; Wolf, J Stuart; Huang, William C; Shalhav, Arieh L; Eggener, Scott E

2010-11-01

A novel equation, the Chronic Kidney Disease Epidemiology Collaboration, has been proposed to replace the Modification of Diet in Renal Disease for estimated glomerular filtration rate due to higher accuracy, particularly in the setting of normal renal function. We compared these equations in patients with 2 functioning kidneys undergoing partial nephrectomy. We assembled a cohort of 1,158 patients from 5 institutions who underwent partial nephrectomy between 1991 and 2009. Only subjects with 2 functioning kidneys were included in the study. The end points were baseline estimated glomerular filtration rate, last followup estimated glomerular filtration rate (3 to 18 months), absolute and percent change estimated glomerular filtration rate ([absolute change/baseline] × 100%), and proportion of newly developed chronic kidney disease stage III. The agreement between the equations was evaluated using Bland-Altman plots and the McNemar test for paired observations. Mean baseline estimated glomerular filtration rate derived from the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration equations were 73 and 77 ml/minute/1.73 m(2), respectively, and following surgery were 63 and 67 ml/minute/1.73 m(2), respectively. Mean percent change estimated glomerular filtration rate was -12% for both equations (p = 0.2). The proportion of patients with newly developed chronic kidney disease stage III following surgery was 32% and 25%, according to the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration equations, respectively (p = 0.001). For patients with 2 functioning kidneys undergoing partial nephrectomy the Chronic Kidney Disease Epidemiology Collaboration equation provides slightly higher glomerular filtration rate estimates compared to the Modification of Diet in Renal Disease equation, with 7% fewer patients categorized as having chronic kidney disease stage III or worse. Copyright © 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Viral-Associated GN: Hepatitis C and HIV.

PubMed

Kupin, Warren L

2017-08-07

Viruses are capable of inducing a wide spectrum of glomerular disorders that can be categorized on the basis of the duration of active viremia: acute, subacute, or chronic. The variable responses of the adaptive immune system to each time period of viral infection results mechanistically in different histologic forms of glomerular injury. The unique presence of a chronic viremic carrier state with either hepatitis C (HCV) or HIV has led to the opportunity to study in detail various pathogenic mechanisms of viral-induced glomerular injury, including direct viral infection of renal tissue and the development of circulating immune complexes composed of viral antigens that deposit along the glomerular basement membrane. Epidemiologic data show that approximately 25%-30% of all HIV patients are coinfected with HCV and 5%-10% of all HCV patients are coinfected with HIV. This situation can often lead to a challenging differential diagnosis when glomerular disease occurs in this dual-infected population and requires the clinician to be familiar with the clinical presentation, laboratory workup, and pathophysiology behind the development of renal disease for both HCV and HIV. Both of these viruses can be categorized under the new classification of infection-associated GN as opposed to being listed as causes of postinfectious GN as has previously been applied to them. Neither of these viruses lead to renal injury after a latent period of controlled and inactive viremia. The geneses of HCV- and HIV-associated glomerular diseases share a total dependence on the presence of active viral replication to sustain renal injury so the renal disease cannot be listed under "postinfectious" GN. With the new availability of direct-acting antivirals for HCV and more effective combined antiretroviral therapy for HIV, successful remission and even regression of glomerular lesions can be achieved if initiated at an early stage. Copyright © 2017 by the American Society of Nephrology.

Podocytes from the diagnostic and therapeutic point of view.

PubMed

Müller-Deile, Janina; Schiffer, Mario

2017-08-01

The central role of podocytes in glomerular diseases makes this cell type an interesting diagnostic tool as well as a therapeutic target. In this review, we discuss the current literature on the use of podocytes and podocyte-specific markers as non-invasive diagnostic tools in different glomerulopathies. Furthermore, we highlight the direct effects of drugs currently used to treat primary glomerular diseases and describe their direct cellular effects on podocytes. A new therapeutic potential is seen in drugs targeting the podocytic actin cytoskeleton which is essential for podocyte foot process structure and function. Incubation of cultured human podocyte cell lines with sera from patients with active glomerular diseases is currently also used to identify novel circulating factors with pathophysiological relevance for the glomerular filtration barrier. In addition, treatment of detached urinary podocytes from patients with substances that restore their cytoskeleton might serve as a novel personalized tool to estimate their potential for podocyte recovery ex vivo.

Application of ultrafiltration and stable isotopic amendments to field studies of mercury partitioning to filterable carbon in lake water and overland runoff

USGS Publications Warehouse

Babiarz, Christopher L.; Hurley, J.P.; Krabbenhoft, D.P.; Gilmour, C.; Branfireun, B.A.

2003-01-01

Results from pilot studies on colloidal phase transport of newly deposited mercury in lake water and overland runoff demonstrate that the combination of ultrafiltration, and stable isotope amendment techniques is a viable tool for the study of mercury partitioning to filterable carbon. Ultrafiltration mass balance calculations were generally excellent, averaging 97.3, 96.1 and 99.8% for dissolved organic carbon (DOC), total mercury (HgT), and methylmercury (MeHg), respectively. Sub nanogram per liter quantities of isotope were measurable, and the observed phase distribution from replicate ultrafiltration separations on lake water agreed within 20%. We believe the data presented here are the first published colloidal phase mercury data on lake water and overland runoff from uncontaminated sites. Initial results from pilot-scale lake amendment experiments indicate that the choice of matrix used to dissolve the isotope did not affect the initial phase distribution of the added mercury in the lake. In addition there was anecdotal evidence that native MeHg was either recently produced in the system, or at a minimum, that this 'old' MeHg partitions to the same subset of DOC that binds the amended mercury. Initial results from pilot-scale overland runoff experiments indicate that less than 20% of newly deposited mercury was transported in the filterable fraction (<0.7 ??m). There is some indication of colloidal phase enrichment of mercury in runoff compared to the phase distribution of organic carbon, but the mechanism of this enrichment is unclear. The phase distribution of newly deposited mercury can differ from that of organic carbon and native mercury, suggesting that the quality of the carbon (available ligands), not the quantity of carbon, regulates partitioning. Further characterization of DOC is needed to clarify the underlying mechanisms. ?? 2002 Elsevier Science B.V. All rights reserved.

Competitive binding experiments can reduce the false positive results of affinity-based ultrafiltration-HPLC: A case study for identification of potent xanthine oxidase inhibitors from Perilla frutescens extract.

PubMed

Wang, Zhiqiang; Kwon, Shin Hwa; Hwang, Seung Hwan; Kang, Young-Hee; Lee, Jae-Yong; Lim, Soon Sung

2017-03-24

The purpose of this study was to assess the possibility of using competitive binding experiments with ultrafiltration-HPLC analysis to identify potent xanthine oxidase (XO) inhibitors from the Perilla frutescens extract as an attempt to reduce the number of false positive results. To isolate the enzyme-ligand complex from unbound compounds, the P. frutescens extract was either incubated in the absence of XO, in the presence of XO, or with the active site blocked XO before the ultrafiltration was performed. Allopurinaol was used as the XO active site blocker. The unbound compounds were subjected to HPLC analysis. The degree of total binding (TBD) and degree of specific binding (SBD) of each compound were calculated using the peak areas. TBD represents the binding affinities of compounds from the P. frutescens extract for the XO binding site. SBD represents the XO competitive binding between allopurinol and ligands from the extract samples. Two criteria were applied to select putative targets that could help avoid false positives. These include TBD>30% and SBD>10%. Using that approach, kaempferol-3-O-rutinoside, rosmarinic acid, methyl-rosmarinic acid, apigenin, and 4',5,7-trimethoxyflavone were identified, from total 11 compounds, as potent XO inhibitors. Finally, apigenin, 4',5,7-trimethoxyflavone, and luteolin were XO inhibitors verified through an XO inhibition assay and structural simulation of the complex. These results showed that the newly developed strategy has the advantage that the number of targets identified via ultrafiltration-HPLC can be narrowed from many false positives. However, not all false positives can be eliminated with this approach. Some potent inhibitors might also be excluded with the use of this method. The limitations of this method are also discussed herein. Copyright © 2017 Elsevier B.V. All rights reserved.

Validation of a highly sensitive ICP-MS method for the determination of platinum in biofluids: application to clinical pharmacokinetic studies with oxaliplatin.

PubMed

Morrison, J G; White, P; McDougall, S; Firth, J W; Woolfrey, S G; Graham, M A; Greenslade, D

2000-12-01

ELOXATIN (Oxaliplatin) is a novel platinum containing anti-cancer agent with a diaminocyclohexane carrier ligand which has been approved in several major European countries. Clinical studies have demonstrated that the compound exhibits marked activity against colorectal cancers in combination with 5-fluorouracil (5-FU). The aim of this work was to develop and validate a highly sensitive inductively coupled plasma mass spectrometry assay for the determination of oxaliplatin-derived platinum in plasma ultrafiltrate, plasma and whole blood and to apply this technique to clinical pharmacokinetic studies with oxaliplatin. Ultratrace detection of platinum in plasma ultrafiltrate was achieved using ultrasonic nebulisation combined with ICP-MS. This technique allows detection of platinum at the 0.001 microg Pt/ml level in only 100 microl of matrix. Assays in blood and plasma utilised a standard Meinhardt nebuliser and spray chamber, achieving detection limits of 0.1 microg Pt/ml in 100 and 200 microl of matrix, respectively. The assays were validated (accuracy and precision within +/- 15%) over the concentration ranges: 0.001-0.250 microg Pt/ml in plasma ultrafiltrate and 0.1-10 microg Pt/ml for plasma and whole blood. The effect of sample digestion. dilution, long term frozen storage and quantitation in the presence of 5-FU were also investigated and validated. The method was used to monitor platinum exposure following oxaliplatin administration (130 mg/m2) to cancer patients. Following a 2 h i.v. infusion, peak platinum levels declined in a triphasic manner in all blood compartments. Free platinum was detected in plasma ultrafiltrate at low levels (0.001 0.010 microg Pt/ml) for up to 3 weeks. In conclusion, a highly sensitive and specific assay has been developed for the determination of platinum in biofluids. This method enabled characterisation of the long term exposure to platinum in patients following oxaliplatin treatment.

Association of calcium with colloidal particles and speciation of calcium in the Kalix and Amazon rivers

NASA Astrophysics Data System (ADS)

Dahlqvist, Ralf; Benedetti, Marc F.; Andersson, Karen; Turner, David; Larsson, Tobias; Stolpe, Björn; Ingri, Johan

2004-10-01

A considerable amount of colloidally bound Ca has been detected in water samples from Amazonian rivers and the Kalix River, a sub-arctic boreal river. Fractionation experiments using several analytical techniques and processing tools were conducted in order to elucidate the matter. Results show that on average 84% of the total Ca concentration is present as free Ca. Particulate, colloidal and complexed Ca constitute the remaining 16%, of which the colloidal fraction is significant. Ultrafiltration experiments show that the colloidal fraction in the sampled Amazonian rivers and the Kalix River range between 1% and 25%. In both the Amazonian and the Kalix rivers the technique of cross-flow ultrafiltration was used to isolate particles and colloids. The difference in concentration measured with ICP-AES and a Ca ion-selective electrode in identical samples was used to define the free Ca concentration and thus indirectly the magnitude of the particulate, colloidal and complexed fractions. Results from the Kalix and Amazonian rivers are in excellent agreement. Furthermore, the results show that the colloidal concentrations of Ca can be greatly overestimated (up to 227%) when conventional analysis and calculation of ultrafiltration data is used due to retention of free Ca ions during the ultrafiltration process. Calculation methods for colloidal matter are presented in this work, using complementary data from ISE analysis. In the Kalix River temporal changes in the fractionation of Ca were studied before, during and after a spring-flood event. Changes in the size distribution of colloidally associated Ca was studied using FlFFF (Flow Field-Flow Fractionation) coupled on-line to a HR ICP-MS. The FlFFF-HR ICP-MS fractograms clearly show the colloidal component of Ca, supporting the ultrafiltration findings. During winter conditions the size distribution of colloidally associated Ca has a concentration maximum at ˜5 to 10 nm in diameter, shifting to smaller sizes (<5 nm) during and after the spring flood. This shift in size distribution follows a change in the river during this period from ironoxyhydroxy colloids being the most important colloidal carrier phase to humic substances during and after the spring flood. WHAM and NICA-Donnan models were used to calculate the amount of colloidally bound Ca. The results similar for both models, show that on average 16% of the Ca may be associated to a colloidal phase, which is in broad agreement with the measurements.

Correlation between cystatin C-based formulas, Schwartz formula and urinary creatinine clearance for glomerular filtration rate estimation in children with kidney disease.

PubMed

Safaei-Asl, Afshin; Enshaei, Mercede; Heydarzadeh, Abtin; Maleknejad, Shohreh

2016-01-01

Assessment of glomerular filtration rate (GFR) is an important tool for monitoring renal function. Regarding to limitations in available methods, we intended to calculate GFR by cystatin C (Cys C) based formulas and determine correlation rate of them with current methods. We studied 72 children (38 boys and 34 girls) with renal disorders. The 24 hour urinary creatinine (Cr) clearance was the gold standard method. GFR was measured with Schwartz formula and Cys C-based formulas (Grubb, Hoek, Larsson and Simple). Then correlation rates of these formulas were determined. Using Pearson correlation coefficient, a significant positive correlation between all formulas and the standard method was seen (R(2) for Schwartz, Hoek, Larsson, Grubb and Simple formula was 0.639, 0.722, 0.705, 0.712, 0.722, respectively) (P<0.001). Cys C-based formulas could predict the variance of standard method results with high power. These formulas had correlation with Schwarz formula by R(2) 0.62-0.65 (intermediate correlation). Using linear regression and constant (y-intercept), it revealed that Larsson, Hoek and Grubb formulas can estimate GFR amounts with no statistical difference compared with standard method; but Schwartz and Simple formulas overestimate GFR. This study shows that Cys C-based formulas have strong relationship with 24 hour urinary Cr clearance. Hence, they can determine GFR in children with kidney injury, easier and with enough accuracy. It helps the physician to diagnosis of renal disease in early stages and improves the prognosis.

Using Mathematical Algorithms to Modify Glomerular Filtration Rate Estimation Equations

PubMed Central

Zhu, Bei; Wu, Jianqing; Zhu, Jin; Zhao, Weihong

2013-01-01

Background The equations provide a rapid and low-cost method of evaluating glomerular filtration rate (GFR). Previous studies indicated that the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease-Epidemiology (CKD-EPI) and MacIsaac equations need further modification for application in Chinese population. Thus, this study was designed to modify the three equations, and compare the diagnostic accuracy of the equations modified before and after. Methodology With the use of 99 mTc-DTPA renal dynamic imaging as the reference GFR (rGFR), the MDRD, CKD-EPI and MacIsaac equations were modified by two mathematical algorithms: the hill-climbing and the simulated-annealing algorithms. Results A total of 703 Chinese subjects were recruited, with the average rGFR 77.14±25.93 ml/min. The entire modification process was based on a random sample of 80% of subjects in each GFR level as a training sample set, the rest of 20% of subjects as a validation sample set. After modification, the three equations performed significant improvement in slop, intercept, correlated coefficient, root mean square error (RMSE), total deviation index (TDI), and the proportion of estimated GFR (eGFR) within 10% and 30% deviation of rGFR (P10 and P30). Of the three modified equations, the modified CKD-EPI equation showed the best accuracy. Conclusions Mathematical algorithms could be a considerable tool to modify the GFR equations. Accuracy of all the three modified equations was significantly improved in which the modified CKD-EPI equation could be the optimal one. PMID:23472113

The Natural Time Course of Membrane Alterations During Peritoneal Dialysis Is Partly Altered by Peritonitis.

PubMed

van Esch, Sadie; Struijk, Dirk G; Krediet, Raymond T

2016-01-01

♦ The quality of the peritoneal membrane can deteriorate over time. Exposure to glucose-based dialysis solutions is the most likely culprit. Because peritonitis is a common complication of peritoneal dialysis (PD), distinguishing between the effect of glucose exposure and a possible additive effect of peritonitis is difficult. The aim of the present study was to compare the time-course of peritoneal transport characteristics in patients without a single episode of peritonitis-representing the natural course-and in patients who experienced 1 or more episodes of peritonitis during long-term follow-up. ♦ This prospective, single-center cohort study enrolled incident adult PD patients who started PD during 1990-2010. A standard peritoneal permeability analysis was performed in the first year of PD treatment and was repeated every year. The results in patients without a single episode of peritonitis ("no-peritonitis group") were compared with the results obtained in patients who experienced 1 or more peritonitis episodes ("peritonitis group") during a follow-up of 4 years. ♦ The 124 patients analyzed included 54 in the no-peritonitis group and 70 in the peritonitis group. The time-course of small-solute transport was different in the groups, with the peritonitis group showing an earlier and more pronounced increase in the mass transfer area coefficient for creatinine (p = 0.07) and in glucose absorption (p = 0.048). In the no-peritonitis group, the net ultrafiltration rate (NUFR) and the transcapillary ultrafiltration rate (TCUFR) both showed a steep increase from the 1st to the 2nd year of PD that was absent in the peritonitis group. Both groups showed a decrease in the NUFR after year 3. A decrease in the TCUFR occurred only in the peritonitis group. That decrease was already present after the year 1 in patients with severe peritonitis. The time-course of free water transport showed a continuous increase in the patients without peritonitis, but a decrease in the patients who experienced peritonitis (p < 0.01). No difference was observed in the time-course of the effective lymphatic absorption rate. The time-courses of immunoglobulin G and α2-macroglobulin clearances showed a decrease in both patient groups, with a concomitant increase of the restriction coefficient. Those changes were not evidently influenced by peritonitis. The two groups showed a similar decrease in the mesothelial cell mass marker cancer antigen 125 during follow-up. ♦ On top of the natural course of peritoneal function, peritonitis episodes to some extent influence the time-course of small-solute and fluid transport-especially the transport of solute-free water. Those modifications increase the risk for overhydration. Copyright © 2016 International Society for Peritoneal Dialysis.

Sodium Chloride and Water Transport in the Medullary Thick Ascending Limb of Henle. EVIDENCE FOR ACTIVE CHLORIDE TRANSPORT

PubMed Central

Rocha, Antonino S.; Kokko, Juha P.

1973-01-01

Transport of NaCl and water was examined in the rabbit medullary thick ascending limb of Henle (ALH) by perfusing isolated segments of these nephrons in vitro. Osmotic water permeability was evaluated by perfusing tubules against imposed osmotic gradients. In these experiments the net transport of fluid remained at zero when segments of thick ALH were perfused with isotonic ultrafiltrate in a bath of rabbit serum in which the serum osmolality was increased by the addition of either 239±8 mosmol/liter of raffinose or 232±17 mosmol of NaCl indicating that the thick ascending limb of Henle is impermeant to osmotic flow of water. When these tubules were perfused at slow rates with isosmolal ultrafiltrate of same rabbit serum as used for the bath, the effluent osmolality was consistently lowered to concentrations less than the perfusate and the bath. That this decrease in collected fluid osmolality represented salt transport was demonstrated in a separate set of experiments in which it was shown that the sodium and chloride concentrations decreased to 0.79±0.02 and 0.77±0.02 respectively when compared with the perfusion fluid concentrations. In each instance the simultaneously determined transtubular potential difference (PD) revealed the lumen to be positive with the magnitude dependent on the perfusion rate. At flow rates above 2 nl·min-1, the mean transtubular PD was stable and equal to 6.70±0.34 mv. At stop-flow conditions this PD became more positive. Ouabain and cooling reversibly decreased the magnitude of this PD. The transtubular PD remained positive, 3.3±0.2 mV, when complete substitution of Na by choline was carried out in both the perfusion fluid and the bathing media. These results are interpreted to indicate that the active transport process is primarily an electrogenic chloride mechanism. The isotopic permeability coefficient for Na was 6.27±0.38 × 10-5 cm·s-1 indicating that the thick ALH is approximately as permeable to Na as the proximal convoluted tubule. The chloride permeability coefficient for the thick ALH was 1.06±0.12 × 10-5 cm·s-1 which is significantly less than the chloride permeability of the proximal tubule. These data demonstrate that the medullary thick ascending limb of Henle is water impermeable while having the capacity for active outward solute transport as a consequence of an electrogenic chloride pump. The combination of these characteristics allows this segment to generate a dilute tubular fluid and participate as the principal energy source for the overall operation of the countercurrent multiplication system. Images PMID:4685086

Automatic computational labeling of glomerular textural boundaries

NASA Astrophysics Data System (ADS)

Ginley, Brandon; Tomaszewski, John E.; Sarder, Pinaki

2017-03-01

The glomerulus, a specialized bundle of capillaries, is the blood filtering unit of the kidney. Each human kidney contains about 1 million glomeruli. Structural damages in the glomerular micro-compartments give rise to several renal conditions; most severe of which is proteinuria, where excessive blood proteins flow freely to the urine. The sole way to confirm glomerular structural damage in renal pathology is by examining histopathological or immunofluorescence stained needle biopsies under a light microscope. However, this method is extremely tedious and time consuming, and requires manual scoring on the number and volume of structures. Computational quantification of equivalent features promises to greatly ease this manual burden. The largest obstacle to computational quantification of renal tissue is the ability to recognize complex glomerular textural boundaries automatically. Here we present a computational pipeline to accurately identify glomerular boundaries with high precision and accuracy. The computational pipeline employs an integrated approach composed of Gabor filtering, Gaussian blurring, statistical F-testing, and distance transform, and performs significantly better than standard Gabor based textural segmentation method. Our integrated approach provides mean accuracy/precision of 0.89/0.97 on n = 200Hematoxylin and Eosin (HE) glomerulus images, and mean 0.88/0.94 accuracy/precision on n = 200 Periodic Acid Schiff (PAS) glomerulus images. Respective accuracy/precision of the Gabor filter bank based method is 0.83/0.84 for HE and 0.78/0.8 for PAS. Our method will simplify computational partitioning of glomerular micro-compartments hidden within dense textural boundaries. Automatic quantification of glomeruli will streamline structural analysis in clinic, and can help realize real time diagnoses and interventions.

Extracellular purines' action on glomerular albumin permeability in isolated rat glomeruli: insights into the pathogenesis of albuminuria.

PubMed

Kasztan, Małgorzata; Piwkowska, Agnieszka; Kreft, Ewelina; Rogacka, Dorota; Audzeyenka, Irena; Szczepanska-Konkel, Mirosława; Jankowski, Maciej

2016-07-01

Purinoceptors (adrengeric receptors and P2 receptors) are expressed on the cellular components of the glomerular filtration barrier, and their activation may affect glomerular permeability to albumin, which may ultimately lead to albuminuria, a well-established risk factor for the progression of chronic kidney disease and development of cardiovascular diseases. We investigated the mechanisms underlying the in vitro and in vivo purinergic actions on glomerular filter permeability to albumin by measuring convectional albumin permeability (Palb) in a single isolated rat glomerulus based on the video microscopy method. Primary cultured rat podocytes were used for the analysis of Palb, cGMP accumulation, PKG-Iα dimerization, and immunofluorescence. In vitro, natural nucleotides (ATP, ADP, UTP, and UDP) and nonmetabolized ATP analogs (2-meSATP and ATP-γ-S) increased Palb in a time- and concentration-dependent manner. The effects were dependent on P2 receptor activation, nitric oxide synthase, and cytoplasmic guanylate cyclase. ATP analogs significantly increased Palb, cGMP accumulation, and subcortical actin reorganization in a PKG-dependent but nondimer-mediated route in cultured podocytes. In vivo, 2-meSATP and ATP-γ-S increased Palb but did not significantly affect urinary albumin excretion. Both agonists enhanced the clathrin-mediated endocytosis of albumin in podocytes. A product of adenine nucleotides hydrolysis, adenosine, increased the permeability of the glomerular barrier via adrenergic receptors in a dependent and independent manner. Our results suggest that the extracellular nucleotides that stimulate an increase of glomerular Palb involve nitric oxide synthase and cytoplasmic guanylate cyclase with actin reorganization in podocytes. Copyright © 2016 the American Physiological Society.

Shifts in podocyte histone H3K27me3 regulate mouse and human glomerular disease

PubMed Central

Majumder, Syamantak; Thieme, Karina; Batchu, Sri N.; Alghamdi, Tamadher A.; Bowskill, Bridgit B.; Kabir, M. Golam; Liu, Youan; Advani, Suzanne L.; White, Kathryn E.; Geldenhuys, Laurette; Tennankore, Karthik K.; Poyah, Penelope; Siddiqi, Ferhan S.

2017-01-01

Histone protein modifications control fate determination during normal development and dedifferentiation during disease. Here, we set out to determine the extent to which dynamic changes to histones affect the differentiated phenotype of ordinarily quiescent adult glomerular podocytes. To do this, we examined the consequences of shifting the balance of the repressive histone H3 lysine 27 trimethylation (H3K27me3) mark in podocytes. Adriamycin nephrotoxicity and subtotal nephrectomy (SNx) studies indicated that deletion of the histone methylating enzyme EZH2 from podocytes decreased H3K27me3 levels and sensitized mice to glomerular disease. H3K27me3 was enriched at the promoter region of the Notch ligand Jag1 in podocytes, and derepression of Jag1 by EZH2 inhibition or knockdown facilitated podocyte dedifferentiation. Conversely, inhibition of the Jumonji C domain–containing demethylases Jmjd3 and UTX increased the H3K27me3 content of podocytes and attenuated glomerular disease in adriamycin nephrotoxicity, SNx, and diabetes. Podocytes in glomeruli from humans with focal segmental glomerulosclerosis or diabetic nephropathy exhibited diminished H3K27me3 and heightened UTX content. Analogous to human disease, inhibition of Jmjd3 and UTX abated nephropathy progression in mice with established glomerular injury and reduced H3K27me3 levels. Together, these findings indicate that ostensibly stable chromatin modifications can be dynamically regulated in quiescent cells and that epigenetic reprogramming can improve outcomes in glomerular disease by repressing the reactivation of developmental pathways. PMID:29227285

Laminin α2-Mediated Focal Adhesion Kinase Activation Triggers Alport Glomerular Pathogenesis

PubMed Central

Delimont, Duane; Dufek, Brianna M.; Meehan, Daniel T.; Zallocchi, Marisa; Gratton, Michael Anne; Phillips, Grady; Cosgrove, Dominic

2014-01-01

It has been known for some time that laminins containing α1 and α2 chains, which are normally restricted to the mesangial matrix, accumulate in the glomerular basement membranes (GBM) of Alport mice, dogs, and humans. We show that laminins containing the α2 chain, but not those containing the α1 chain activates focal adhesion kinase (FAK) on glomerular podocytes in vitro and in vivo. CD151-null mice, which have weakened podocyte adhesion to the GBM rendering these mice more susceptible to biomechanical strain in the glomerulus, also show progressive accumulation of α2 laminins in the GBM, and podocyte FAK activation. Analysis of glomerular mRNA from both models demonstrates significant induction of MMP-9, MMP-10, MMP-12, MMPs linked to GBM destruction in Alport disease models, as well as the pro-inflammatory cytokine IL-6. SiRNA knockdown of FAK in cultured podocytes significantly reduced expression of MMP-9, MMP-10 and IL-6, but not MMP-12. Treatment of Alport mice with TAE226, a small molecule inhibitor of FAK activation, ameliorated fibrosis and glomerulosclerosis, significantly reduced proteinuria and blood urea nitrogen levels, and partially restored GBM ultrastructure. Glomerular expression of MMP-9, MMP-10 and MMP-12 mRNAs was significantly reduced in TAE226 treated animals. Collectively, this work identifies laminin α2-mediated FAK activation in podocytes as an important early event in Alport glomerular pathogenesis and suggests that FAK inhibitors, if safe formulations can be developed, might be employed as a novel therapeutic approach for treating Alport renal disease in its early stages. PMID:24915008

Anti-C1q autoantibodies deposit in glomeruli but are only pathogenic in combination with glomerular C1q-containing immune complexes

PubMed Central

Trouw, Leendert A.; Groeneveld, Tom W.L.; Seelen, Marc A.; Duijs, Jacques M.G.J.; Bajema, Ingeborg M.; Prins, Frans A.; Kishore, Uday; Salant, David J.; Verbeek, J. Sjef; Kooten, Cees van; Daha, Mohamed R.

2004-01-01

Anti-C1q autoantibodies are present in sera of patients with several autoimmune diseases, including systemic lupus erythematosus (SLE). Strikingly, in SLE the presence of anti-C1q is associated with the occurrence of nephritis. We have generated mouse anti–mouse C1q mAb’s and used murine models to investigate whether anti-C1q autoantibodies actually contribute to renal pathology in glomerular immune complex disease. Administration of anti-C1q mAb JL-1, which recognizes the collagen-like region of C1q, resulted in glomerular deposition of C1q and anti-C1q autoantibodies and mild granulocyte influx, but no overt renal damage. However, combination of JL-1 with a subnephritogenic dose of C1q-fixing anti–glomerular basement membrane (anti-GBM) antibodies enhanced renal damage characterized by persistently increased levels of infiltrating granulocytes, major histological changes, and increased albuminuria. This was not observed when a non–C1q-fixing anti-GBM preparation was used. Experiments with different knockout mice showed that renal damage was dependent not only on glomerular C1q and complement activation but also on Fcγ receptors. In conclusion, anti-C1q autoantibodies deposit in glomeruli together with C1q but induce overt renal disease only in the context of glomerular immune complex disease. This provides an explanation why anti-C1q antibodies are especially pathogenic in patients with SLE. PMID:15343386

Glomerular Immune Deposits Are Predictive of Poor Long-Term Outcome in Patients with Adult Biopsy-Proven Minimal Change Disease: A Cohort Study in Korea.

PubMed

Lee, Sung Woo; Yu, Mi-Yeon; Baek, Seon Ha; Ahn, Shin-Young; Kim, Sejoong; Na, Ki Young; Chae, Dong-Wan; Chin, Ho Jun

2016-01-01

There has been little published information on risk factors for poor long-term outcome in adult biopsy-proven minimal change disease (MCD). Data from sixty-three adult, biopsy-proven primary MCD patients treated at a tertiary university hospital between 2003 and 2013 were analyzed. Baseline clinical and pathologic factors were assessed for the associations with composite outcome of creatinine doubling, end stage renal disease, or all-cause mortality. During a median (interquartile) 5.0 (2.8-5.0) years, the composite outcome occurred in 11.1% (7/63) of patients. The rate of glomerular immune deposits was 23.8% (15/63). Patients with glomerular immune deposits showed a significantly lower urine protein creatinine ratio than those without deposits (P = 0.033). The rate of non-responders was significantly higher in patients with glomerular immune deposits than in those without deposits (P = 0.033). In patients with deposits, 26.7% (4/15) developed the composite outcome, while only 6.3% (3/48) developed the composite outcome among those without deposits (P = 0.049). In multivariate Cox proportional hazards regression analysis, the presence of glomerular immune deposits was the only factor associated with development of the composite outcome (hazard ratio: 2.310, 95% confidence interval: 1.031-98.579, P = 0.047). Glomerular immune deposits were associated with increased risk of a composite outcome in adult MCD patients. The higher rate of non-responders in patients with deposits might be related to the poor outcome. Future study is needed.

Biophysical properties of normal and diseased renal glomeruli.

PubMed

Wyss, Hans M; Henderson, Joel M; Byfield, Fitzroy J; Bruggeman, Leslie A; Ding, Yaxian; Huang, Chunfa; Suh, Jung Hee; Franke, Thomas; Mele, Elisa; Pollak, Martin R; Miner, Jeffrey H; Janmey, Paul A; Weitz, David A; Miller, R Tyler

2011-03-01

The mechanical properties of tissues and cells including renal glomeruli are important determinants of their differentiated state, function, and responses to injury but are not well characterized or understood. Understanding glomerular mechanics is important for understanding renal diseases attributable to abnormal expression or assembly of structural proteins and abnormal hemodynamics. We use atomic force microscopy (AFM) and a new technique, capillary micromechanics, to measure the elastic properties of rat glomeruli. The Young's modulus of glomeruli was 2,500 Pa, and it was reduced to 1,100 Pa by cytochalasin and latunculin, and to 1,400 Pa by blebbistatin. Cytochalasin or latrunculin reduced the F/G actin ratios of glomeruli but did not disrupt their architecture. To assess glomerular biomechanics in disease, we measured the Young's moduli of glomeruli from two mouse models of primary glomerular disease, Col4a3(-/-) mice (Alport model) and Tg26(HIV/nl) mice (HIV-associated nephropathy model), at stages where glomerular injury was minimal by histopathology. Col4a3(-/-) mice express abnormal glomerular basement membrane proteins, and Tg26(HIV/nl) mouse podocytes have multiple abnormalities in morphology, adhesion, and cytoskeletal structure. In both models, the Young's modulus of the glomeruli was reduced by 30%. We find that glomeruli have specific and quantifiable biomechanical properties that are dependent on the state of the actin cytoskeleton and nonmuscle myosins. These properties may be altered early in disease and represent an important early component of disease. This increased deformability of glomeruli could directly contribute to disease by permitting increased distension with hemodynamic force or represent a mechanically inhospitable environment for glomerular cells.

Epidermal growth factor receptor inhibition with erlotinib ameliorates anti-Thy 1.1-induced experimental glomerulonephritis.

PubMed

Rintala, Jukka M; Savikko, Johanna; Rintala, Sini E; Palin, Niina; Koskinen, Petri K

2016-06-01

Mesangial proliferative glomerulonephritis is a common glomerular disorder that may lead to end-stage renal disease. Epidermal growth factor (EGF) plays an important role in the regulation of cell growth, proliferation, and differentiation and in the pathology of various renal diseases. Erlotinib is a novel, oral, highly selective tyrosine kinase inhibitor of the EGF receptor. It is clinically used to treat non-small cell lung and pancreatic cancers. Here, we investigated the effect of erlotinib on the progression of mesangioproliferative glomerulonephritis in an experimental model. Mesangial glomerulonephritis was induced with anti-rat Thy-1.1 antibody in male Wistar rats weighing 150-160 g. Rats were treated with erlotinib (10 mg/kg/day p.o.) or vehicle only (polyethylene glycol). Native Wistar rat kidneys were used as histological controls. Serum creatinine levels were measured at day 7. Kidneys were harvested 7 days after antibody administration for histology. Native controls showed no histological signs of glomerular pathology. In the vehicle group, intense glomerular inflammation developed after 7 days and prominent mesangial cell proliferation and glomerular matrix accumulation was seen. Erlotinib was well tolerated and there were no adverse effects during the follow-up period. Erlotinib significantly prevented progression of the glomerular inflammatory response and glomerular mesangial cell proliferation as well as matrix accumulation when compared with the vehicle group. Erlotinib also preserved renal function. These results indicate that erlotinib prevents the early events of experimental mesangial proliferative glomerulonephritis. Therefore, inhibition of the EGF receptor with erlotinib could prevent the progression of glomerulonephritis also in clinical nephrology.

Anti-glomerular basement membrane blood test

MedlinePlus

... the part of the kidney that helps filter waste and extra fluid from the blood. Anti-glomerular basement membrane antibodies are antibodies against this membrane. They can lead to kidney damage. This article describes the blood test to detect these antibodies.

Secondary wastewater polishing with ultrafiltration membranes for unrestricted reuse: fouling and flushing modeling.

PubMed

Gillerman, Leonid; Bick, Amos; Buriakovsky, Nisan; Oron, Gideon

2006-11-01

The effects of operating parameters such astransmembrane pressure, retentate, and recirculation volumetric flow rates on the productivity of an ultrafiltration membrane were studied using field data and development of a management model. Correlation equations for predicting the volumetric permeate flow rates were derived from general membrane blocking laws and experimental data. The experimental data were obtained from a pilot study carried out in the Arad wastewater treatment system (a pilot plant operating in feed and bleed operation mode) located several kilometers west of the City of Arad, Israel. Correlation predictions were confirmed with the independent experimental results. The results enabled us to develop a mathematical expression accurately describing the decline in flux due to fouling.

Concentration and separation of biological organisms by ultrafiltration and dielectrophoresis

DOEpatents

Simmons, Blake A.; Hill, Vincent R.; Fintschenko, Yolanda; Cummings, Eric B.

2010-10-12

Disclosed is a method for monitoring sources of public water supply for a variety of pathogens by using a combination of ultrafiltration techniques together dielectrophoretic separation techniques. Because water-borne pathogens, whether present due to "natural" contamination or intentional introduction, would likely be present in drinking water at low concentrations when samples are collected for monitoring or outbreak investigations, an approach is needed to quickly and efficiently concentrate and separate particles such as viruses, bacteria, and parasites in large volumes of water (e.g., 100 L or more) while simultaneously reducing the sample volume to levels sufficient for detecting low concentrations of microbes (e.g., <10 mL). The technique is also designed to screen the separated microbes based on specific conductivity and size.

Effect of membrane properties on the performance of a hybrid GAC and ultrafiltration process for water treatment.

PubMed

Qiao, Tiejun; Wu, Guangxue; Zhang, Xihui; Au, Doris W T; Zhang, Jinsong

2012-06-01

The performance of a hybrid granular activated carbon (GAC) and ultrafiltration (UF) process for water treatment was investigated using five types of UF membranes. The removal percentages for chemical oxygen demand (COD(Mn)), particles (> or = 2 microm) and total bacteria by the hybrid process were 30-40%, 98-99% and 76-92%, respectively. No invertebrates were detected in the hybrid process effluent. Transmembrane pressure and specific permeate flux (SPF) of the five types of membranes varied. With decreasing membrane pore sizes, removal of COD(Mn) and particles increased, whereas SPF firstly decreased and then increased. Hydrophilic membranes had a relatively high COD(Mn) removal potential, but did not obviously affect particle removal or SPF.

Clinical dehydration and glomerular filtration rate in acute paediatric gastroenteritis.

PubMed

Milani, Gregorio P; Fossali, Emilio F; Perri, Alessandra; Vettori, Arianna; Grillo, Paolo; Agostoni, Carlo

2013-08-01

To evaluate changes in glomerular filtration rate in acute gastroenteritis. The correlation between two clinical diagnostic scales and glomerular filtration rate has been investigated in 113 children with acute gastroenteritis in a paediatric emergency setting. A significant reduction of GFR was found in 10% children less than, and 5% children higher than, 2 years of age with acute gastroenteritis. The differences observed as for risk of renal hypoperfusion suggests to consider the age of children as an important determinant to consider the dehydration status in acute gastroenteritis. ©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Podocytes populate cellular crescents in a murine model of inflammatory glomerulonephritis.

PubMed

Moeller, Marcus J; Soofi, Abdulsalaam; Hartmann, Inge; Le Hir, Michel; Wiggins, Roger; Kriz, Wilhelm; Holzman, Lawrence B

2004-01-01

Cellular crescents are a defining histologic finding in many forms of inflammatory glomerulonephritis. Despite numerous studies, the origin of glomerular crescents remains unresolved. A genetic cell lineage-mapping study with a novel transgenic mouse model was performed to investigate whether visceral glomerular epithelial cells, termed podocytes, are precursors of cells that populate cellular crescents. The podocyte-specific 2.5P-Cre mouse line was crossed with the ROSA26 reporter line, resulting in irreversible constitutive expression of beta-galactosidase in doubly transgenic 2.5P-Cre/ROSA26 mice. In these mice, crescentic glomerulonephritis was induced with a previously described rabbit anti-glomerular basement membrane antiserum nephritis approach. Interestingly, beta-galactosidase-positive cells derived from podocytes adhered to the parietal basement membrane and populated glomerular crescents during the early phases of cellular crescent formation, accounting for at least one-fourth of the total cell mass. In cellular crescents, the proliferation marker Ki-67 was expressed in beta-galactosidase-positive and beta-galactosidase-negative cells, indicating that both cell types contributed to the formation of cellular crescents through proliferation in situ. Podocyte-specific antigens, including WT-1, synaptopodin, nephrin, and podocin, were not expressed by any cells in glomerular crescents, suggesting that podocytes underwent profound phenotypic changes in this nephritis model.

Metal accumulation and nephron heterogeneity in mercuric chloride-induced acute renal failure.

PubMed

Wilks, M F; Gregg, N J; Bach, P H

1994-01-01

The present study was designed to assess the effects of mercury on glomerular integrity during the early phase of acute renal failure. The silver amplification method showed distribution of mercury in midcortical and juxtamedullary glomeruli and on the brush border of the S2 segment of the proximal tubule 15 min after treatment. At 30 min, there was a decrease in glomerular staining and increased mercury in the proximal tubule. After 3 hr, mercury was no longer detectable in glomeruli but was widespread in the lumen of the proximal tubule. By 24 hr, mercury was prominent in all proximal tubular segments throughout the cortex. The presence of mercury in glomeruli was not related to hemodynamic changes, as there was no evidence for blood redistribution toward juxtamedullary glomeruli as assessed by the filling of the microvascular system with Monastral Blue B. The reduced activity of horseradish peroxidase (administered i.v. 90 sec and 10 min before sacrifice) in juxtamedullary glomeruli 30 min after mercury administration suggests a decreased uptake of horseradish peroxidase or an increased glomerular protein filtration. These data support glomerular filtration as the predominant excretory route for mercury, highlight the marked nephron heterogeneity in the distribution of this metal, and show that impairment of glomerular integrity occurs before necrosis of the proximal tubules and acute renal failure.

Prevalence of glomerular hyperfiltration and nephromegaly in normo- and microalbuminuric type 2 diabetic patients.

PubMed

Gragnoli, G; Signorini, A M; Tanganelli, I; Fondelli, C; Borgogni, P; Borgogni, L; Vattimo, A; Ferrari, F; Guercia, M

1993-01-01

Glomerular hyperfiltration, correlated with nephromegaly, is a frequent finding in type 1 (insulin-dependent) diabetes. In type 2 (non-insulin-dependent) diabetes, very few studies have been performed, and the results have been inconclusive. Glomerular filtration rate (GFR) and kidney volume, using 99mTc-DTPA scintigraphy and ultrasonography, respectively, were evaluated in 58 control subjects and 163 type 2 diabetic patients; 79 of whom were normoalbuminuric and 84 microalbuminuric. In the two groups of patients, these parameters did not differ significantly from those of controls, even when hypertensive subjects were excluded. Glomerular hyperfiltration was observed in 10 cases; all were normotensive (9.8%), of whom 7 were normoalbuminuric and 3 microalbuminuric. Nephromegaly was observed in 3 other normotensive microalbuminuric diabetic patients. Hypertensive subjects showed a lower GFR than normotensive patients and control subjects. Multivariate analysis showed a negative correlation between glomerular filtrate and systolic blood pressure (BP) in the overall population of patients and in normo- and microalbuminuric patients taken separately. It is concluded that the relationship between these variables forms a continuum in our type 2 diabetic patients; it may also be important in determining the low prevalence of hyperfiltration and nephromegaly found in our patients, who had BP levels higher than those of controls.

Citral is renoprotective for focal segmental glomerulosclerosis by inhibiting oxidative stress and apoptosis and activating Nrf2 pathway in mice.

PubMed

Yang, Shun-Min; Hua, Kuo-Feng; Lin, Yu-Chuan; Chen, Ann; Chang, Jia-Ming; Kuoping Chao, Louis; Ho, Chen-Lung; Ka, Shuk-Man

2013-01-01

The pathogenesis of focal segmental glomerulosclerosis (FSGS) is considered to be associated with oxidative stress, mononuclear leukocyte recruitment and infiltration, and matrix production and/or matrix degradation, although the exact etiology and pathogenic pathways remain to be determined. Establishment of a pathogenesis-based therapeutic strategy for the disease is clinically warranted. Citral (3,7-dimethyl-2,6-octadienal), a major active compound in Litseacubeba, a traditional Chinese herbal medicine, can inhibit oxidant activity, macrophage and NF-κB activation. In the present study, first, we used a mouse model of FSGS with the features of glomerular epithelial hyperplasia lesions (EPHLs), a key histopathology index of progression of FSGS, peri-glomerular inflammation, and progressive glomerular hyalinosis/sclerosis. When treated with citral for 28 consecutive days at a daily dose of 200 mg/kg of body weight by gavage, the FSGS mice showed greatly reduced EPHLs, glomerular hyalinosis/sclerosis and peri-glomerular mononuclear leukocyte infiltration, suggesting that citral may be renoprotective for FSGS and act by inhibiting oxidative stress and apoptosis and early activating the Nrf2 pathway. Meanwhile, a macrophage model involved in anti-oxidative and anti-inflammatory activities was employed and confirmed the beneficial effects of citral on the FSGS model.

Citral Is Renoprotective for Focal Segmental Glomerulosclerosis by Inhibiting Oxidative Stress and Apoptosis and Activating Nrf2 Pathway in Mice

PubMed Central

Yang, Shun-Min; Hua, Kuo-Feng; Lin, Yu-Chuan; Chen, Ann; Chang, Jia-Ming; Kuoping Chao, Louis; Ho, Chen-Lung; Ka, Shuk-Man

2013-01-01

The pathogenesis of focal segmental glomerulosclerosis (FSGS) is considered to be associated with oxidative stress, mononuclear leukocyte recruitment and infiltration, and matrix production and/or matrix degradation, although the exact etiology and pathogenic pathways remain to be determined. Establishment of a pathogenesis-based therapeutic strategy for the disease is clinically warranted. Citral (3,7-dimethyl-2,6-octadienal), a major active compound in Litsea cubeba , a traditional Chinese herbal medicine, can inhibit oxidant activity, macrophage and NF-κB activation. In the present study, first, we used a mouse model of FSGS with the features of glomerular epithelial hyperplasia lesions (EPHLs), a key histopathology index of progression of FSGS, peri-glomerular inflammation, and progressive glomerular hyalinosis/sclerosis. When treated with citral for 28 consecutive days at a daily dose of 200 mg/kg of body weight by gavage, the FSGS mice showed greatly reduced EPHLs, glomerular hyalinosis/sclerosis and peri-glomerular mononuclear leukocyte infiltration, suggesting that citral may be renoprotective for FSGS and act by inhibiting oxidative stress and apoptosis and early activating the Nrf2 pathway. Meanwhile, a macrophage model involved in anti-oxidative and anti-inflammatory activities was employed and confirmed the beneficial effects of citral on the FSGS model. PMID:24069362

Glomerular latency coding in artificial olfaction.

PubMed

Yamani, Jaber Al; Boussaid, Farid; Bermak, Amine; Martinez, Dominique

2011-01-01

Sensory perception results from the way sensory information is subsequently transformed in the brain. Olfaction is a typical example in which odor representations undergo considerable changes as they pass from olfactory receptor neurons (ORNs) to second-order neurons. First, many ORNs expressing the same receptor protein yet presenting heterogeneous dose-response properties converge onto individually identifiable glomeruli. Second, onset latency of glomerular activation is believed to play a role in encoding odor quality and quantity in the context of fast information processing. Taking inspiration from the olfactory pathway, we designed a simple yet robust glomerular latency coding scheme for processing gas sensor data. The proposed bio-inspired approach was evaluated using an in-house SnO(2) sensor array. Glomerular convergence was achieved by noting the possible analogy between receptor protein expressed in ORNs and metal catalyst used across the fabricated gas sensor array. Ion implantation was another technique used to account both for sensor heterogeneity and enhanced sensitivity. The response of the gas sensor array was mapped into glomerular latency patterns, whose rank order is concentration-invariant. Gas recognition was achieved by simply looking for a "match" within a library of spatio-temporal spike fingerprints. Because of its simplicity, this approach enables the integration of sensing and processing onto a single-chip.

Coexistent findings of renal glomerular disease with Hashimoto's thyroiditis.

PubMed

Koçak, Gülay; Huddam, Bülent; Azak, Alper; Ortabozkoyun, Levent; Duranay, Murat

2012-05-01

Hashimoto's thyroiditis (HT) is a common autoimmune thyroid disease with a female preponderance. Renal involvement in HT is not uncommon. In the present study, we aimed to define the frequency and characteristics of the glomerular diseases associated with HT and further the understanding of any common pathogenesis between HT and glomerular disease. We reviewed retrospectively 28 patients with HT who were referred to our Department because of unexplained haematuria, proteinuria or renal impairment from 2007 to 2011. Routine laboratory investigations including blood count, serum biochemistry, urinalysis and 24-h urinary protein excretion were performed on all patients. Renal biopsy was performed in 20 patients with HT, and the specimens were examined by light microscopy and immunofluorescence staining. We detected four cases of focal segmental glomerulosclerosis (FSGS), four membranous glomerulonephritis (MGN), two minimal-change disease (MCD), three immunoglobulin A nephritis (IgAN), three chronic glomerulonephritis (CGN) and one amyloidosis. In three patients, the renal biopsy findings were nonspecific. Daily urinary protein excretion and glomerular filtration rates were found to be independent of the level of thyroid hormone and thyroid-specific autoantibodies. Glomerular pathologies associated with HT are similar to those in the general population, the most common lesions being MGN, FSGS and IgA nephritis. © 2012 Blackwell Publishing Ltd.

Post-infectious acute glomerulonephritis with podocytopathy induced by parvovirus B19 infection.

PubMed

Hara, Satoshi; Hirata, Masayoshi; Ito, Kiyoaki; Mizushima, Ichiro; Fujii, Hiroshi; Yamada, Kazunori; Nagata, Michio; Kawano, Mitsuhiro

2018-03-01

Human parvovirus B19 infection causes a variety of glomerular diseases such as post-infectious acute glomerulonephritis and collapsing glomerulopathy. Although each of these appears independently, it has not been fully determined why parvovirus B19 provokes such a variety of different glomerular phenotypes. Here, we report a 68-year-old Japanese man who showed endocapillary proliferative glomerulonephritis admixed with podocytopathy in association with parvovirus B19 infection. The patient showed acute onset of heavy proteinuria, microscopic hematuria and kidney dysfunction with arthralgia and oliguria after close contact with a person suffering from erythema infectiosum. In the kidney biopsy specimen, glomeruli revealed diffuse and global endocapillary infiltration of inflammatory cells, with some also showing tuft collapse with aberrant vacuolation, swelling, and hyperplasia of glomerular epithelial cells. Immunofluorescence revealed dense granular C3 deposition that resembled the "starry sky pattern". Intravenous glucocorticoid pulse therapy followed by oral prednisolone and cyclosporine combination therapy resulted in considerable amelioration of the kidney dysfunction and urinary abnormalities. The present case reveals that parvovirus B19 infection can induce different glomerular phenotypes even in the same kidney structure. This finding may provide hints useful for the further elucidation of the pathogenesis of parvovirus B19-induced glomerular lesions. © 2018 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

Intraglomerular pressure and mesangial stretching stimulate extracellular matrix formation in the rat.

PubMed Central

Riser, B L; Cortes, P; Zhao, X; Bernstein, J; Dumler, F; Narins, R G

1992-01-01

To define the interplay of glomerular hypertension and hypertrophy with mesangial extracellular matrix (ECM) deposition, we examined the effects of glomerular capillary distention and mesangial cell stretching on ECM synthesis. The volume of microdissected rat glomeruli (Vg), perfused ex vivo at increasing flows, was quantified and related to the proximal intraglomerular pressure (PIP). Glomerular compliance, expressed as the slope of the positive linear relationship between PIP and Vg was 7.68 x 10(3) microns 3/mmHg. Total Vg increment (PIP 0-150 mmHg) was 1.162 x 10(6) microns 3 or 61% (n = 13). A 16% increase in Vg was obtained over the PIP range equivalent to the pathophysiological limits of mean transcapillary pressure difference. A similar effect of renal perfusion on Vg was also noted histologically in tissue from kidneys perfused/fixed in vivo. Cultured mesangial cells undergoing cyclic stretching increased their synthesis of protein, total collagen, and key components of ECM (collagen IV, collagen I, laminin, fibronectin). Synthetic rates were stimulated by cell growth and the degree of stretching. These results suggest that capillary expansion and stretching of mesangial cells by glomerular hypertension provokes increased ECM production which is accentuated by cell growth and glomerular hypertrophy. Mesangial expansion and glomerulosclerosis might result from this interplay of mechanical and metabolic forces. Images PMID:1430216

Podocyte-Specific VEGF-A Gain of Function Induces Nodular Glomerulosclerosis in eNOS Null Mice

PubMed Central

Veron, Delma; Aggarwal, Pardeep K.; Velazquez, Heino; Kashgarian, Michael; Moeckel, Gilbert

2014-01-01

VEGF-A and nitric oxide are essential for glomerular filtration barrier homeostasis and are dysregulated in diabetic nephropathy. Here, we examined the effect of excess podocyte VEGF-A on the renal phenotype of endothelial nitric oxide synthase (eNOS) knockout mice. Podocyte-specific VEGF164 gain of function in eNOS−/− mice resulted in nodular glomerulosclerosis, mesangiolysis, microaneurysms, and arteriolar hyalinosis associated with massive proteinuria and renal failure in the absence of diabetic milieu or hypertension. In contrast, podocyte-specific VEGF164 gain of function in wild-type mice resulted in less pronounced albuminuria and increased creatinine clearance. Transmission electron microscopy revealed glomerular basement membrane thickening and podocyte effacement in eNOS−/− mice with podocyte-specific VEGF164 gain of function. Furthermore, glomerular nodules overexpressed collagen IV and laminin extensively. Biotin-switch and proximity ligation assays demonstrated that podocyte-specific VEGF164 gain of function decreased glomerular S-nitrosylation of laminin in eNOS−/− mice. In addition, treatment with VEGF-A decreased S-nitrosylated laminin in cultured podocytes. Collectively, these data indicate that excess glomerular VEGF-A and eNOS deficiency is necessary and sufficient to induce Kimmelstiel-Wilson–like nodular glomerulosclerosis in mice through a process that involves deposition of laminin and collagen IV and de-nitrosylation of laminin. PMID:24578128

Serum level of vascular endothelial growth factor is influenced by erythropoietin treatment in peritoneal dialysis patients. (Grupo de Estudios Peritoneales de Madrid).

PubMed

del Peso, G; Selgas, R; Bajo, M A; Fernández de Castro, M; Aguilera, A; Cirugeda, A; Jiménez, C

2000-01-01

Some patients on long-term peritoneal dialysis (PD) develop a hyperpermeability state, owing to peritoneal neoangiogenesis. Vascular endothelial growth factor (VEGF), a potent mitogen for endothelial cells, has been implicated in most diseases characterized by microvascular neoformation. Erythropoietin (EPO) is able to induce endothelial proliferation in vitro. Our aim was to elucidate whether VEGF serum levels are influenced by EPO treatment, and whether VEGF serum level maintains a relationship with peritoneal transport data. We analyzed serum levels of VEGF in 35 PD patients (18 males, 17 females). Mean age was 58 years, with a mean time on PD of 98 +/- 75 months. Of the 35 patients, 19 were on automated peritoneal dialysis, and 16 were on continuous ambulatory peritoneal dialysis. Seven patients had diabetes. Peritoneal transport parameters were: urea mass transfer coefficient (MTC), 19.5 +/- 6.6 mL/min; creatinine MTC, 9.9 +/- 4.7 mL/min; net ultrafiltration, 491 +/- 166 mL per 4-hour dwell. Twenty seven patients were under therapy with recombinant human erythropoietin (rHuEPO). Mean serum VEGF levels were 347 +/- 203 pg/mL (range 66-857 pg/mL), with most patients in the normal range (60-700 pg/mL). VEGF levels did not correlate with age, sex, primary renal disease, diabetes, type of PD, time on PD, peritonitis, and cumulative glucose load. We found no correlation with urea MTC, creatinine MTC, ultrafiltration rate, or protein effluent levels. However, a significant negative correlation with residual renal function was seen (r = -0.39, p < 0.05). Patients treated with rHuEPO showed significantly higher serum levels of VEGF than non treated patients (375 +/- 220 pg/mL vs 251 +/- 75 pg/mL, p < 0.05), although they had similar residual renal function. We conclude that increased serum VEGF levels are associated with EPO treatment. Consequently, VEGF might have a role in the EPO effects found in PD patients. Whether both agents are related to peritoneal neoangiogenesis requires further research.

Ceramic ultrafiltration membranes with photocatalytic properties

NASA Astrophysics Data System (ADS)

Bell, Deborah Wildman

The photocatalytic properties of ceramic ultrafilters have been utilized in the development of a novel in-situ membrane cleaning process for ultrafiltration membranes fabricated from titania. The use of the photoactive membrane layer mitigates the effects of foulants in the system, thereby yielding an increase in the observed overall flux without sacrificing rejection of the solute by the membrane. Photocatalytic membranes of titania supported on porous tubes of alpha-alumina were fabricated using sol-gel techniques. These membranes were developed on the basis of the results of two-level factorial experimental designs. Electron microscopy and x-ray spectrometry were employed to evaluate coverage of the support by the membrane, the thickness of the membrane, and the presence of defects in the membrane. The photocatalytic membrane system was characterized to determine both morphological and performance parameters. Morphological parameters included the pore diameters, Darcy coefficients, and the individual resistances associated with each of the porous layers comprising the composite photocatalytic membrane. Performance parameters included the nominal molecular weight cutoff values of the ceramic membranes, the rate of permeation of pure solvent in the presence and the absence of UV illumination through the porous layers of interest, and the ability of the photocatalytic membrane to resist fouling and maintain permselectivity in the presence of UV illumination. The photocatalytic membranes were used to ultrafilter aqueous solutions of polymeric organic foulants present at an initial concentration of 1 x 10-3 M. Formation of a gel layer of foulant on the surface of the membrane was observed in the presence and in the absence of UV radiation; however, the results of permeability experiments indicated that formation of this foulant layer was significantly retarded (by a factor of two) in the presence of UV radiation. Improvement in the flow rate of permeate through the membrane was attributed to photocatalytic degradation of solute molecules comprising the indicated gel layer. This hypothesis was confirmed by mass spectrometry measurements. In both the presence and the absence of illumination, rejection of solutes by the membrane was greater than 97%, as determined by total organic carbon analyses of the permeate.

Power generation using different cation, anion, and ultrafiltration membranes in microbial fuel cells.

PubMed

Kim, Jung Rae; Cheng, Shaoan; Oh, Sang-Eun; Logan, Bruce E

2007-02-01

Proton exchange membranes (PEMs) are often used in microbial fuel cells (MFCs) to separate the liquid in the anode and cathode chambers while allowing protons to pass between the chambers. However, negatively or positively charged species present at high concentrations in the medium can also be used to maintain charge balance during power generation. An anion exchange membrane (AEM) produced the largest power density (up to 610 mW/m2) and Coulombic efficiency (72%) in MFCs relative to values achieved with a commonly used PEM (Nafion), a cation exchange membrane (CEM), or three different ultrafiltration (UF) membranes with molecular weight cut offs of 0.5K, 1K, and 3K Daltons in different types of MFCs. The increased performance of the AEM was due to proton charge-transfer facilitated by phosphate anions and low internal resistance. The type of membrane affected maximum power densities in two-chamber, air-cathode cube MFCs (C-MFCs) with low internal resistance (84-91 omega for all membranes except UF-0.5K) but not in two-chamber aqueous-cathode bottle MFCs (B-MFCs) due to their higher internal resistances (1230-1272 omega except UF-0.5K). The UF-0.5K membrane produced very high internal resistances (6009 omega, B-MFC; 1814omega, C-MFC) and was the least permeable to both oxygen (mass transfer coefficient of k(O) = 0.19 x 10(-4) cm/s) and acetate (k(A) = 0.89 x 10(-8) cm/s). Nafion was the most permeable membrane to oxygen (k(O) = 1.3 x 10(-4) cm/s), and the UF-3K membrane was the most permeable to acetate (k(A) = 7.2 x 10(-8) cm/s). Only a small percent of substrate was unaccounted for based on measured Coulombic efficiencies and estimates of biomass production and substrate losses using Nafion, CEM, and AEM membranes (4-8%), while a substantial portion of substrate was lost to unidentified processes for the UF membranes (40-89%). These results show that many types of membranes can be used in two-chambered MFCs, even membranes that transfer negatively charged species.

Finding the bottom and using it

PubMed Central

Sandoval, Ruben M.; Wang, Exing; Molitoris, Bruce A.

2014-01-01

Maximizing 2-photon parameters used in acquiring images for quantitative intravital microscopy, especially when high sensitivity is required, remains an open area of investigation. Here we present data on correctly setting the black level of the photomultiplier tube amplifier by adjusting the offset to allow for accurate quantitation of low intensity processes. When the black level is set too high some low intensity pixel values become zero and a nonlinear degradation in sensitivity occurs rendering otherwise quantifiable low intensity values virtually undetectable. Initial studies using a series of increasing offsets for a sequence of concentrations of fluorescent albumin in vitro revealed a loss of sensitivity for higher offsets at lower albumin concentrations. A similar decrease in sensitivity, and therefore the ability to correctly determine the glomerular permeability coefficient of albumin, occurred in vivo at higher offset. Finding the offset that yields accurate and linear data are essential for quantitative analysis when high sensitivity is required. PMID:25313346

[Analysis of elderly outpatients in relation to nutritional status, sarcopenia, renal function, and bone density].

PubMed

Salmaso, Franciany Viana; Vigário, Patrícia dos Santos; Mendonça, Laura Maria Carvalho de; Madeira, Miguel; Vieira Netto, Leonardo; Guimarães, Marcela Rodrigues Moreira; Farias, Maria Lucia Fleiuss de

2014-04-01

To evaluate relationships between nutritional status, sarcopenia and osteoporosis in older women. We studied 44 women, 67-94 years, by mini-nutritional assessment (MAN), glomerular filtration corr. 1.73 m(2), body mass index (BMI), arm circumference and calf (CP and CB), bone mineral density and body composition, DXA (fat mass MG; lean MM). We gauge sarcopenia: IMM MM = MSS + MIS/height(2). We used the Pearson correlation coefficient, p < 0.05 as significant. MNA and IMM were positively correlated with BMI, CP, CB and MG. Age influenced negatively FG corr., BMI, FM, IMM and CP. Fourteen had a history of osteoporotic fractures. The lowest T-score was directly related to MAN and MG. CONCLUSIONS The aging caused the decline of FG, fat mass and muscle; the calf circumference, and brachial reflected nutritional status and body composition; and major influences on BMD were nutritional status and fat mass.

Decreased Nephrin and GLEPP-1, But Increased VEGF, Flt-1, and Nitrotyrosine, Expressions in Kidney Tissue Sections From Women With Preeclampsia

PubMed Central

Zhao, Shuang; Gu, Xin; Groome, Lynn J.; Wang, Yuping

2011-01-01

Renal injury is a common pathophysiological feature in women with preeclampsia as evidenced by increased protein leakage (proteinuria) and glomerular injury (glomerular endotheliosis). Recently, podocyturia was found in preeclampsia, suggesting podocyte shedding occurs in this pregnancy disorder. However, podocyte function in preeclampsia is poorly understood. In this study, the authors have examined podocyte-specific protein expressions for nephrin, glomerular epithelial protein 1 (GLEPP-1), and ezrin in kidney biopsy tissue sections from women with preeclampsia. Expressions for vascular endothelial growth factor (VEGF) and its receptor Flt-1 and oxidative stress marker nitrotyrosine and antioxidant CuZn-superoxide dismutase (CuZn-SOD) were also examined. Kidney tissue sections from nonhypertensive and chronic hypertensive participants were stained as controls. The findings were (1) nephrin and GLEPP-1 were mainly expressed in glomerular podocytes; (2) ezrin was expressed in both glomerular podocytes and tubular epithelial cells; (3) compared to tissue sections from nonhypertensive and chronic hypertensive participants, nephrin and GLEPP-1 expressions were much reduced in tissue sections from preeclampsia and ezrin expression was reduced in podocytes; (4) enhanced VEGF, Flt-1, and nitrotyrosine, but reduced CuZn-SOD, expressions were observed in both glomerular podocytes and endothelial cells in tissue sections from preeclampsia; and (5) the expression pattern for nephrin, GLEPP-1, ezrin, VEGF, Flt-1, and CuZn-SOD were similar between tissue sections from nonhypertensive and chronic hypertensive participants. Although the authors could not conclude from this biopsy study whether the podocyte injury is the cause or effect of the preeclampsia phenotype, the data provide compelling evidence that podocyte injury accompanied by altered angiogenesis process and increased oxidative stress occurs in kidney of patients with preeclampsia. PMID:19528353

Physiologic regulation of atrial natriuretic peptide receptors in rat renal glomeruli.

PubMed Central

Ballermann, B J; Hoover, R L; Karnovsky, M J; Brenner, B M

1985-01-01

Isolated rat renal glomeruli and cultured glomerular mesangial and epithelial cells were examined for atrial natriuretic peptide (ANP) receptors, and for ANP-stimulated cyclic guanosine monophosphate (cGMP) generation. In glomeruli from normal rats, human (1-28) 125I-ANP bound to a single population of high affinity receptors with a mean equilibrium dissociation constant of 0.46 nM. Human (1-28) ANP markedly stimulated cGMP generation, but not cAMP generation in normal rat glomeruli. Analogues of ANP that bound to the glomerular ANP receptor with high affinity stimulated cGMP accumulation, whereas the (13-28) ANP fragment, which failed to bind to the receptor, was devoid of functional activity. Cell surface receptors for ANP were expressed on cultured glomerular mesangial but not epithelial cells, and appreciable ANP-stimulated cGMP accumulation was elicited only in mesangial cells. Approximately 12,000 ANP receptor sites were present per mesangial cell, with an average value for the equilibrium dissociation constant of 0.22 nM. Feeding of a low-salt diet to rats for 2 wk resulted in marked up regulation of the glomerular ANP receptor density to a mean of 426 fmol/mg protein, compared with 116 fmol/mg in rats given a high-salt diet. A modest reduction in the affinity of glomerular ANP receptors was also observed in rats fed the low-salt diet. ANP-stimulated cGMP generation in glomeruli did not change with alterations in salt intake. We conclude that high salt feeding in the rat results in reduced glomerular ANP receptor density relative to values in salt restricted rats. Furthermore, the mesangial cell is a principal target for ANP binding in the glomerulus. Images PMID:3001139

Associations between age, body size and nephron number with individual glomerular volumes in urban West African males.

PubMed

McNamara, Bridgette J; Diouf, Boucar; Hughson, Michael D; Hoy, Wendy E; Bertram, John F

2009-05-01

Glomerulomegaly has been associated with an increased risk of renal disease. Few reports have investigated the heterogeneity of glomerular size within kidneys and associated risk factors. This study measured the individual glomerular volume (IGV) of 720 non-sclerotic glomeruli in kidneys of adult West African males, and investigated associations of IGV with age, total glomerular (nephron) number and body surface area (BSA). IGVs were determined in the kidneys of 24 Senegalese males from two age groups (12 subjects aged 20- 30 years and 12 subjects aged 50-70 years). Subjects were randomly chosen at autopsies performed at Le Dantec Hospital in Dakar. Volumes of 30 glomeruli per subject were determined using the disector/Cavalieri stereological method. IGVs ranged from 1.31 x 10(6) microm3 to 12.40 x 10(6) microm3 (a 9.4-fold variation). IGV varied up to 5.3-fold within single kidneys. The trimmed range of IGV within subjects (10th to 90th percentile of IGV) was directly correlated with median glomerular size. The mean and standard deviation (SD) of IGV did not differ significantly between age groups or between subjects with higher (> or =1.78 m2) and lower BSA (<1.78 m2). In older subjects the SD of IGV was significantly and directly correlated with BSA. Kidneys with less than 1 million nephrons had significantly larger mean IGV than kidneys with more than 1 million nephrons, and the trimmed range of IGVs within subjects was inversely correlated with total glomerular number. There was a considerable variation in IGV within kidneys of Senegalese males at autopsy. The heterogeneity of IGV was increased in association with low nephron number and increased BSA, with more pronounced effects in older subjects.

Glomerular filtration rate and kidney size in type 2 (non-insulin-dependent) diabetes mellitus.

PubMed

Wirta, O R; Pasternack, A I

1995-07-01

The objective of the present study was to estimate glomerular filtration rate and kidney size in recently diagnosed and long-term type 2 (non-insulin-dependent) diabetic subjects. The study design comprised of a population-based controlled cross-sectional survey of middle-aged type 2 diabetic subjects in the City of Tampere, Southwest Finland. One hundred and fifty consecutive recently diagnosed and 146 long-term middle-aged type 2 diabetic subjects with a disease duration of at least five years and one hundred and fifty age- and sex-matched (to recent diabetic subjects) non-diabetic control subjects were recruited. The glomerular filtration rate by single-shot 51Cr-EDTA clearance and kidney size by native X-ray tomography were measured. The glomerular filtration rate (ml/min/1.73 m2) was increased in both recently diagnosed (males 121 [27] and females 112 [27]) and long-term (males 123 [24] and females 102 [36]) diabetic subjects (corrected for age) compared to control subjects (males 111 [26] and females 93 [17]). The kidney areas (cm2) were greater in both recent diabetic (males 116.6 [15.4] and females 99.1 [15.3] and long-term diabetic (males 118.3 [15.8] and females 100.4 [15.2]) subjects than in the control group (males 104.3 [12.0] and females 88.6 [12.0]). All differences between diabetic subjects and non-diabetic subjects were statistically significant (p < 0.05), except that between long-term diabetic and non-diabetic females for glomerular filtration rate (p = 0.07). Analyzed by linear regression glomerular filtration rate was related to kidney area in all study groups and to hemoglobin A1c in long-term diabetic males.(ABSTRACT TRUNCATED AT 250 WORDS)

Glomerular Immune Deposits Are Predictive of Poor Long-Term Outcome in Patients with Adult Biopsy-Proven Minimal Change Disease: A Cohort Study in Korea

PubMed Central

Lee, Sung Woo; YU, Mi-Yeon; Baek, Seon Ha; Ahn, Shin-Young; Kim, Sejoong; Na, Ki Young; Chae, Dong-Wan; Chin, Ho Jun

2016-01-01

Background and Objectives There has been little published information on risk factors for poor long-term outcome in adult biopsy-proven minimal change disease (MCD). Methods Data from sixty-three adult, biopsy-proven primary MCD patients treated at a tertiary university hospital between 2003 and 2013 were analyzed. Baseline clinical and pathologic factors were assessed for the associations with composite outcome of creatinine doubling, end stage renal disease, or all-cause mortality. Results During a median (interquartile) 5.0 (2.8–5.0) years, the composite outcome occurred in 11.1% (7/63) of patients. The rate of glomerular immune deposits was 23.8% (15/63). Patients with glomerular immune deposits showed a significantly lower urine protein creatinine ratio than those without deposits (P = 0.033). The rate of non-responders was significantly higher in patients with glomerular immune deposits than in those without deposits (P = 0.033). In patients with deposits, 26.7% (4/15) developed the composite outcome, while only 6.3% (3/48) developed the composite outcome among those without deposits (P = 0.049). In multivariate Cox proportional hazards regression analysis, the presence of glomerular immune deposits was the only factor associated with development of the composite outcome (hazard ratio: 2.310, 95% confidence interval: 1.031–98.579, P = 0.047). Conclusion Glomerular immune deposits were associated with increased risk of a composite outcome in adult MCD patients. The higher rate of non-responders in patients with deposits might be related to the poor outcome. Future study is needed. PMID:26799663

Comparison of glomerular activity patterns by fMRI and wide-field calcium imaging: implications for principles underlying odor mapping

PubMed Central

Sanganahalli, Basavaraju G.; Rebello, Michelle R.; Herman, Peter; Papademetris, Xenophon; Shepherd, Gordon M.; Verhagen, Justus V.; Hyder, Fahmeed

2015-01-01

Functional imaging signals arise from distinct metabolic and hemodynamic events at the neuropil, but how these processes are influenced by pre- and post-synaptic activities need to be understood for quantitative interpretation of stimulus-evoked mapping data. The olfactory bulb (OB) glomeruli, spherical neuropil regions with well-defined neuronal circuitry, can provide insights into this issue. Optical calcium-sensitive fluorescent dye imaging (OICa2+) reflects dynamics of pre-synaptic input to glomeruli, whereas high-resolution functional magnetic resonance imaging (fMRI) using deoxyhemoglobin contrast reveals neuropil function within the glomerular layer where both pre- and post-synaptic activities contribute. We imaged odor-specific activity patterns of the dorsal OB in the same anesthetized rats with fMRI and OICa2+ and then co-registered the respective maps to compare patterns in the same space. Maps by each modality were very reproducible as trial-to-trial patterns for a given odor, overlapping by ~80%. Maps evoked by ethyl butyrate and methyl valerate for a given modality overlapped by ~80%, suggesting activation of similar dorsal glomerular networks by these odors. Comparison of maps generated by both methods for a given odor showed ~70% overlap, indicating similar odor-specific maps by each method. These results suggest that odor-specific glomerular patterns by high-resolution fMRI primarily tracks pre-synaptic input to the OB. Thus combining OICa2+ and fMRI lays the framework for studies of OB processing over a range of spatiotemporal scales, where OICa2+ can feature the fast dynamics of dorsal glomerular clusters and fMRI can map the entire glomerular sheet in the OB. PMID:26631819

Coexistence of Anti-Glomerular Basement Membrane Glomerulonephritis and Membranous Nephropathy in a Female Patient with Preserved Renal Function.

PubMed

Ogawara, Aoi; Harada, Makoto; Ichikawa, Tohru; Fujii, Kazuaki; Ehara, Takashi; Kobayashi, Mamoru

2017-12-01

Renal prognosis for anti-glomerular basement membrane (GBM) glomerulonephritis is poor. The greater the amount of anti-GBM antibody binding the antigen (type IV collagen of the glomerular basement membrane), the greater the number of crescents that develop in glomeruli, resulting in progression of renal impairment. Immunofluorescence staining reveals linear IgG depositions on glomerular capillary walls. Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in middle-aged to elderly patients. Immune complex is deposited in the sub-epithelial space of the glomerulus resulting in the development of a membranous lesion. Immunofluorescence staining reveals granular IgG depositions on glomerular capillary walls. Coexisting anti-GBM glomerulonephritis and MN are rare and, here we report a case of coexisting anti-GBM glomerulonephritis and MN with preserved renal function. There are some cases of coexisting anti-GBM glomerulonephritis and MN do not show severely decreased renal function. A 76-year-old Japanese woman presented with nephrotic syndrome, microscopic hematuria, and was positive for anti-GBM antibody. Kidney biopsy revealed linear and granular IgG depositions in glomerular capillary walls, crescent formations, and electron-dense deposits in the sub-epithelial space. She was diagnosed with anti-GBM glomerulonephritis and MN. Steroid and cyclosporine therapy achieved complete remission, and kidney function was preserved. In conclusion, coexisting anti-GBM glomerulonephritis and MN can have preserved renal function. IgG subclass of deposited anti-GBM antibody may be associated with the severity of anti-GBM glomerulonephritis. In addition, in the case of nephrotic syndrome with hematuria, we should consider the possibility of coexisting anti-GBM glomerulonephritis and MN.

Glomerular Epithelial Cells-Targeted Heme Oxygenase-1 Over Expression in the Rat: Attenuation of Proteinuria in Secondary But Not Primary Injury.

PubMed

Atsaves, Vassilios; Makri, Panagiota; Detsika, Maria G; Tsirogianni, Alexandra; Lianos, Elias A

2016-01-01

Induction of heme oxygenase 1 (HO-1) in glomerular epithelial cells (GEC) in response to injury is poor and this may be a disadvantage. We, therefore, explored whether HO-1 overexpression in GEC can reduce proteinuria induced by puromycin aminonucleoside (PAN) or in anti-glomerular basement membrane (GBM) antibody (Ab)-mediated glomerulonephritis (GN). HO-1 overexpression in GEC (GECHO-1) of Sprague-Dawley rats was achieved by targeting a FLAG-human (h) HO-1 using transposon-mediated transgenesis. Direct GEC injury was induced by a single injection of PAN. GN was induced by administration of an anti-rat GBM Ab and macrophage infiltration in glomeruli was assessed by immunohistochemistry and western blot analysis, which was also used to assess glomerular nephrin expression. In GECHO-1 rats, FLAG-hHO-1 transprotein was co-immunolocalized with nephrin. Baseline glomerular HO-1 protein levels were higher in GECHO-1 compared to wild type (WT) rats. Administration of either PAN or anti-GBM Ab to WT rats increased glomerular HO-1 levels. Nephrin expression markedly decreased in glomeruli of WT or GECHO-1 rats treated with PAN. In anti-GBM Ab-treated WT rats, nephrin expression also decreased. In contrast, it was preserved in anti-GBM Ab-treated GECHO-1 rats. In these, macrophage infiltration in glomeruli and the ratio of urine albumin to urine creatinine (Ualb/Ucreat) were markedly reduced. There was no difference in Ualb/Ucreat between WT and GECHO-1 rats treated with PAN. Depending on the type of injury, HO-1 overexpression in GEC may or may not reduce proteinuria. Reduced macrophage infiltration and preservation of nephrin expression are putative mechanisms underlying the protective effect of HO-1 overexpression following immune injury. © 2016 S. Karger AG, Basel.

HANAC Syndrome Col4a1 Mutation Causes Neonate Glomerular Hyperpermeability and Adult Glomerulocystic Kidney Disease

PubMed Central

Chen, Zhiyong; Migeon, Tiffany; Verpont, Marie-Christine; Zaidan, Mohamad; Sado, Yoshikazu; Kerjaschki, Dontscho; Ronco, Pierre

2016-01-01

Hereditary angiopathy, nephropathy, aneurysms, and muscle cramps (HANAC) syndrome is an autosomal dominant syndrome caused by mutations in COL4A1 that encodes the α1 chain of collagen IV, a major component of basement membranes. Patients present with cerebral small vessel disease, retinal tortuosity, muscle cramps, and kidney disease consisting of multiple renal cysts, chronic kidney failure, and sometimes hematuria. Mutations producing HANAC syndrome localize within the integrin binding site containing CB3[IV] fragment of the COL4A1 protein. To investigate the pathophysiology of HANAC syndrome, we generated mice harboring the Col4a1 p.Gly498Val mutation identified in a family with the syndrome. Col4a1 G498V mutation resulted in delayed glomerulogenesis and podocyte differentiation without reduction of nephron number, causing albuminuria and hematuria in newborns. The glomerular defects resolved within the first month, but glomerular cysts developed in 3-month-old mutant mice. Abnormal structure of Bowman’s capsule was associated with metalloproteinase induction and activation of the glomerular parietal epithelial cells that abnormally expressed CD44, α-SMA, ILK, and DDR1. Inflammatory infiltrates were observed around glomeruli and arterioles. Homozygous Col4a1 G498V mutant mice additionally showed dysmorphic papillae and urinary concentration defects. These results reveal a developmental role for the α1α1α2 collagen IV molecule in the embryonic glomerular basement membrane, affecting podocyte differentiation. The observed association between molecular alteration of the collagenous network in Bowman’s capsule of the mature kidney and activation of parietal epithelial cells, matrix remodeling, and inflammation may account for glomerular cyst development and CKD in patients with COL4A1-related disorders. PMID:26260163

HANAC Syndrome Col4a1 Mutation Causes Neonate Glomerular Hyperpermeability and Adult Glomerulocystic Kidney Disease.

PubMed

Chen, Zhiyong; Migeon, Tiffany; Verpont, Marie-Christine; Zaidan, Mohamad; Sado, Yoshikazu; Kerjaschki, Dontscho; Ronco, Pierre; Plaisier, Emmanuelle

2016-04-01

Hereditary angiopathy, nephropathy, aneurysms, and muscle cramps (HANAC) syndrome is an autosomal dominant syndrome caused by mutations in COL4A1 that encodes the α1 chain of collagen IV, a major component of basement membranes. Patients present with cerebral small vessel disease, retinal tortuosity, muscle cramps, and kidney disease consisting of multiple renal cysts, chronic kidney failure, and sometimes hematuria. Mutations producing HANAC syndrome localize within the integrin binding site containing CB3[IV] fragment of the COL4A1 protein. To investigate the pathophysiology of HANAC syndrome, we generated mice harboring the Col4a1 p.Gly498Val mutation identified in a family with the syndrome. Col4a1 G498V mutation resulted in delayed glomerulogenesis and podocyte differentiation without reduction of nephron number, causing albuminuria and hematuria in newborns. The glomerular defects resolved within the first month, but glomerular cysts developed in 3-month-old mutant mice. Abnormal structure of Bowman's capsule was associated with metalloproteinase induction and activation of the glomerular parietal epithelial cells that abnormally expressed CD44,α-SMA, ILK, and DDR1. Inflammatory infiltrates were observed around glomeruli and arterioles. Homozygous Col4a1 G498V mutant mice additionally showed dysmorphic papillae and urinary concentration defects. These results reveal a developmental role for the α1α1α2 collagen IV molecule in the embryonic glomerular basement membrane, affecting podocyte differentiation. The observed association between molecular alteration of the collagenous network in Bowman's capsule of the mature kidney and activation of parietal epithelial cells, matrix remodeling, and inflammation may account for glomerular cyst development and CKD in patients with COL4A1-related disorders. Copyright © 2016 by the American Society of Nephrology.

BAMBI Elimination Enhances Alternative TGF-β Signaling and Glomerular Dysfunction in Diabetic Mice

PubMed Central

Fan, Ying; Li, Xuezhu; Xiao, Wenzhen; Fu, Jia; Harris, Ray C.; Lindenmeyer, Maja; Cohen, Clemens D.; Guillot, Nicolas; Baron, Margaret H.; Wang, Niansong; Lee, Kyung; He, John C.; Chuang, Peter Y.

2015-01-01

BMP, activin, membrane-bound inhibitor (BAMBI) acts as a pseudo-receptor for the transforming growth factor (TGF)-β type I receptor family and a negative modulator of TGF-β kinase signaling, and BAMBI−/− mice show mild endothelial dysfunction. Because diabetic glomerular disease is associated with TGF-β overexpression and microvascular alterations, we examined the effect of diabetes on glomerular BAMBI mRNA levels. In isolated glomeruli from biopsies of patients with diabetic nephropathy and in glomeruli from mice with type 2 diabetes, BAMBI was downregulated. We then examined the effects of BAMBI deletion on streptozotocin-induced diabetic glomerulopathy in mice. BAMBI−/− mice developed more albuminuria, with a widening of foot processes, than BAMBI+/+ mice, along with increased activation of alternative TGF-β pathways such as extracellular signal–related kinase (ERK)1/2 and Smad1/5 in glomeruli and cortices of BAMBI−/− mice. Vegfr2 and Angpt1, genes controlling glomerular endothelial stability, were downmodulated in glomeruli from BAMBI−/− mice with diabetes. Incubation of glomeruli from nondiabetic BAMBI+/+ or BAMBI−/− mice with TGF-β resulted in the downregulation of Vegfr2 and Angpt1, effects that were more pronounced in BAMBI−/− mice and were prevented by a MEK inhibitor. The downregulation of Vegfr2 in diabetes was localized to glomerular endothelial cells using a histone yellow reporter under the Vegfr2 promoter. Thus, BAMBI modulates the effects of diabetes on glomerular permselectivity in association with altered ERK1/2 and Smad1/5 signaling. Future therapeutic interventions with inhibitors of alternative TGF-β signaling may therefore be of interest in diabetic nephropathy. PMID:25576053

ET-1 increases reactive oxygen species following hypoxia and high-salt diet in the mouse glomerulus.

PubMed

Heimlich, J B; Speed, J S; Bloom, C J; O'Connor, P M; Pollock, J S; Pollock, D M

2015-03-01

This study was designed to determine whether ET-1 derived from endothelial cells contributes to oxidative stress in the glomerulus of mice subjected to a high-salt diet and/or hypoxia. C57BL6/J control mice or vascular endothelial cell ET-1 knockout (VEET KO) mice were subjected to 3-h exposure to hypoxia (8% O₂) and/or 2 weeks of high-salt diet (4% NaCl) prior to metabolic cage assessment of renal function and isolation of glomeruli for the determination of reactive oxygen species (ROS). In control mice, hypoxia significantly increased urinary protein excretion during the initial 24 h, but only in animals on a high-salt diet. Hypoxia increased glomerular ET-1 mRNA expression in control, but not in vascular endothelial cell ET-1 knockout (VEET KO) mice. Under normoxic conditions, mice on a high-salt diet had approx. 150% higher glomerular ET-1 mRNA expression compared with a normal-salt diet (P < 0.05). High-salt diet administration significantly increased glomerular ROS production in flox control, but not in glomeruli isolated from VEET KO mice. In C57BL6/J mice, the ETA receptor-selective antagonist, ABT-627, significantly attenuated the increase in glomerular ROS production produced by high-salt diet. In addition, chronic infusion of C57BL6/J mice with a subpressor dose of ET-1 (osmotic pumps) significantly increased the levels of glomerular ROS that were prevented by ETA antagonist treatment. These data suggest that both hypoxia and a high-salt diet increase glomerular ROS production via endothelial-derived ET-1-ETA receptor activation and provide a potential mechanism for ET-1-induced nephropathy. © 2014 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Wavelet-based segmentation of renal compartments in DCE-MRI of human kidney: initial results in patients and healthy volunteers.

PubMed

Li, Sheng; Zöllner, Frank G; Merrem, Andreas D; Peng, Yinghong; Roervik, Jarle; Lundervold, Arvid; Schad, Lothar R

2012-03-01

Renal diseases can lead to kidney failure that requires life-long dialysis or renal transplantation. Early detection and treatment can prevent progression towards end stage renal disease. MRI has evolved into a standard examination for the assessment of the renal morphology and function. We propose a wavelet-based clustering to group the voxel time courses and thereby, to segment the renal compartments. This approach comprises (1) a nonparametric, discrete wavelet transform of the voxel time course, (2) thresholding of the wavelet coefficients using Stein's Unbiased Risk estimator, and (3) k-means clustering of the wavelet coefficients to segment the kidneys. Our method was applied to 3D dynamic contrast enhanced (DCE-) MRI data sets of human kidney in four healthy volunteers and three patients. On average, the renal cortex in the healthy volunteers could be segmented at 88%, the medulla at 91%, and the pelvis at 98% accuracy. In the patient data, with aberrant voxel time courses, the segmentation was also feasible with good results for the kidney compartments. In conclusion wavelet based clustering of DCE-MRI of kidney is feasible and a valuable tool towards automated perfusion and glomerular filtration rate quantification. Copyright © 2011 Elsevier Ltd. All rights reserved.

Molecular genetic analysis of podocyte genes in focal segmental glomerulosclerosis--a review.

PubMed

Löwik, M M; Groenen, P J; Levtchenko, E N; Monnens, L A; van den Heuvel, L P

2009-11-01

This review deals with podocyte proteins that play a significant role in the structure and function of the glomerular filter. Genetic linkage studies has identified several genes involved in the development of nephrotic syndrome and contributed to the understanding of the pathophysiology of glomerular proteinuria and/or focal segmental glomerulosclerosis. Here, we describe already well-characterized genetic diseases due to mutations in nephrin, podocin, CD2AP, alpha-actinin-4, WT1, and laminin beta2 chain, as well as more recently identified genetic abnormalities in TRPC6, phospholipase C epsilon, and the proteins encoded by the mitochondrial genome. In addition, the role of the proteins which have shown to be important for the structure and functions by gene knockout studies in mice, are also discussed. Furthermore, some rare syndromes with glomerular involvement, in which molecular defects have been recently identified, are briefly described. In summary, this review updates the current knowledge of genetic causes of congenital and childhood nephrotic syndrome and provides new insights into mechanisms of glomerular dysfunction.

In vivo imaging of kidney glomeruli transplanted into the anterior chamber of the mouse eye

PubMed Central

Kistler, Andreas D.; Caicedo, Alejandro; Abdulreda, Midhat H.; Faul, Christian; Kerjaschki, Dontscho; Berggren, Per-Olof; Reiser, Jochen; Fornoni, Alessia

2014-01-01

Multiphoton microscopy enables live imaging of the renal glomerulus. However, repeated in vivo imaging of the same glomerulus over extended periods of time and the study of glomerular function independent of parietal epithelial and proximal tubular cell effects has not been possible so far. Here, we report a novel approach for non-invasive imaging of acapsular glomeruli transplanted into the anterior chamber of the mouse eye. After microinjection, glomeruli were capable of engrafting on the highly vascularized iris. Glomerular structure was preserved, as demonstrated by podocyte specific expression of cyan fluorescent protein and by electron microscopy. Injection of fluorescence-labeled dextrans of various molecular weights allowed visualization of glomerular filtration and revealed leakage of 70 kDa dextran in an inducible model of proteinuria. Our findings demonstrate functionality and long-term survival of glomeruli devoid of Bowman's capsule and provide a novel approach for non-invasive longitudinal in vivo study of glomerular physiology and pathophysiology. PMID:24464028

Quantitative indexes of aminonucleoside-induced nephrotic syndrome.

PubMed Central

Nevins, T. E.; Gaston, T.; Basgen, J. M.

1984-01-01

Aminonucleoside of puromycin (PAN) is known to cause altered glomerular permeability, resulting in a nephrotic syndrome in rats. The early sequence of this lesion was studied quantitatively, with the application of a new morphometric technique for determining epithelial foot process widths and a sensitive assay for quantifying urinary albumin excretion. Twenty-four hours following a single intraperitoneal injection of PAN, significant widening of foot processes was documented. Within 36 hours significant increases in urinary albumin excretion were observed. When control rats were examined, there was no clear correlation between epithelial foot process width and quantitative albumin excretion. However, in the PAN-treated animals, abnormal albuminuria only appeared in association with appreciable foot process expansion. These studies indicate that quantitative alterations occur in the rat glomerular capillary wall as early as 24 hours after PAN. Further studies of altered glomerular permeability may use these sensitive measures to more precisely define the temporal sequence and elucidate possible subgroups of experimental glomerular injury. Images Figure 1 Figure 2 PMID:6486243

Screening and identification of α-glucosidase inhibitors from Shenqi Jiangtang Granule by ultrafiltration liquid chromatography and mass spectrometry.

PubMed

Zhang, Hui; Zhang, Xiaojing; Jiang, Huijie; Xu, Cong; Tong, Shengqiang; Yan, Jizhong

2018-02-01

Shenqi Jiangtang Granule, a well-known traditional Chinese herbal preparation, has been widely used for the treatment of type II diabetes mellitus. In this work, an ultrafiltration liquid chromatography with quadrupole time-of-flight mass spectrometry method was proposed for the rapid identification of bioactive ingredients from Shenqi Jiangtang Granule using α-glucosidase as an example. First, the chemical profile of this preparation was clarified, including 37 saponins, 17 flavonoids, 37 lignans, and seven other compounds. After incubation with α-glucosidase in vitro, the methanol extract with an IC 50 value of 0.19 mg/mL exhibited significant inhibitory activity. Then, 18 specific binding peaks were screened, and 15 peaks were identified. Among these, ten compounds were reported to have potential α-glucosidase inhibitory activity for the first time. Subsequently, the inhibitory activities of these active compounds were evaluated by ultraviolet spectrophotometry with p-nitrophenyl α-d-glucopyranoside as a substrate. As a result, gomisin J and gomisin D exhibited stronger α-glucosidase inhibitory activities than other active compounds with IC 50 values of 77.69 and 133.85 μM, respectively. The results demonstrated that the integrated ultrafiltration liquid chromatography with mass spectrometry method was an effective and powerful tool for the discovery of active ingredients in Shenqi Jiangtang Granule. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fluid removal in acute heart failure: diuretics versus devices.

PubMed

Krishnamoorthy, Arun; Felker, G Michael

2014-10-01

Fluid removal and relief of congestion are central to treatment of acute heart failure. Diuretics have been the decongestive mainstay but their known limitations have led to the exploration of alternative strategies. This review compares diuretics with ultrafiltration and examines the recent evidence evaluating their use. Relevant recent studies are the Diuretic Optimization Strategies Evaluation trial (of diuretics) and the Cardiorenal Rescue Study in Acute Decompensated Heart Failure (of ultrafiltration). The Diuretic Optimization Strategies Evaluation study evaluated strategies of loop diuretic use during acute heart failure (continuous infusion versus intermittent bolus and high dose versus low dose). After 72  h, there was no significant difference with either comparison for the coprimary end points. Patients treated with a high-dose strategy tended to have greater diuresis and more decongestion compared with low-dose therapy, at the cost of transient changes in renal function. The Cardiorenal Rescue Study in Acute Decompensated Heart Failure study showed that in acute heart failure patients with persistent congestion and worsening renal function, ultrafiltration, as compared with a medical therapy, was associated with similar weight loss but greater increase in serum creatinine and more adverse events. Decongestion remains a major challenge in acute heart failure. Although recent studies provide useful data to guide practice, the relatively poor outcomes point to the continued need to identify better strategies for safe and effective decongestion.

Ultrafiltration-LC-MS combined with semi-preparative HPLC for the simultaneous screening and isolation of lactate dehydrogenase inhibitors from Belamcanda chinensis.

PubMed

Li, Senlin; Li, Sainan; Tang, Ying; Liu, Chunming; Chen, Lina; Zhang, Yuchi

2016-12-01

Stroke represents the fourth leading cause of death in the USA and the second leading cause of death worldwide. Lactate dehydrogenase inhibitors are widely used in the treatment of ischemic stroke and natural products are considered a promising source of novel lactate dehydrogenase inhibitors. In this study, we used PC12 cells to determine the protective effect of extracts from the herb Belamcanda chinensis following toxic challenge. Using ultrafiltration high-performance liquid chromatography coupled with photo-diode array detection and electrospray ionization mass spectrometry, we screened and identified isoflavonoids from Belamcanda chinensis extracts. Semi-preparative high-performance liquid chromatography was then applied to separate and isolate the active constituents. Using these methods, we identified six major compounds in Belamcanda chinensis as lactate dehydrogenase inhibitors: tectoridin, iristectorin A, iridin, tectorigenin, irigenin, and irisflorentin, which were then isolated to >92% purity. This is the first report that Belamcanda chinensis extracts contain potent lactate dehydrogenase inhibitors. Our results demonstrate that the systematic isolation of bioactive components from Belamcanda chinensis guided by ultrafiltration high-performance liquid chromatography coupled with photo-diode array detection and electrospray ionization mass spectrometry represents a feasible and efficient technique that could be extended for the identification and isolation of other enzyme inhibitors. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Interstitial matrix proteins determine hyaluronan reflection and fluid retention in rabbit joints: effect of protease

PubMed Central

Sabaratnam, S; Coleman, P J; Mason, R M; Levick, J R

2007-01-01

Hyaluronan (HA) retention inside the synovial cavity of joints serves diverse protective roles. We tested the hypothesis that HA retention is mediated by the network of extracellular matrix proteins in the synovial lining. Cannulated rabbit knee joints were infused with HA solution with or without pretreatment by chymopapain, a collagen-sparing protease. Trans-synovial fluid escape rate was measured and, after a period of trans-synovial filtration, samples of intra-articular fluid and subsynovial fluid were analysed for HA to assess its trans-synovial ultrafiltration. In control joints, HA ultrafiltration was confirmed by postfiltration increases in intra-articular HA concentration (259 ± 17% of infused concentration) and reduced subsynovial concentration (30 ± 8%; n = 11). The proportion of HA molecules reflected by the synovium was 57–75%. Chymopapain treatment increased the hydraulic permeability of the synovial lining ∼13-fold, almost abolished the trans-synovial difference in HA concentration and reduced the HA reflected fraction to 3–7% (n = 6; P < 0.001, ANOVA). Structural studies confirmed that chymopapain treatment depleted the matrix of proteoglycans but preserved its collagen. The findings thus demonstrate that HA ultrafiltration and synovial hydraulic permeability are determined by the network of non-collagen, extracellular matrix proteins. This may be important clinically, since protease activity is raised in rheumatoid arthritis, as are HA and fluid escape. PMID:17008373

Influence of gas-liquid two-phase flow on angiotensin-I converting enzyme inhibitory peptides separation by ultra-filtration.

PubMed

Charoenphun, Narin; Youravong, Wirote

2017-01-01

Membrane fouling is a major problem in ultra-filtration systems and two-phase flow is a promising technique for permeate flux enhancement. The objective of this research was to study the use of an ultra-filtration (UF) system to enrich angiotensin-I converting enzyme (ACE) inhibitory peptides from tilapia protein hydrolysate. To select the most appropriate membrane and operating condition, the effects of membrane molecular weight cut-off (MWCO), transmembrane pressure (TMP) and cross-flow velocity (CFV) on permeate flux and ACE inhibitory peptide separation were studied. Additionally, the gas-liquid two-phase flow technique was applied to investigate its effect on the process capability. The results showed that the highest ACE inhibitory activity was obtained from permeate of the 1 kDa membrane. In terms of TMP and CFV, the permeate flux tended to increase with TMP and CFV. The use of gas-liquid two-phase flow as indicated by shear stress number could reduce membrane fouling and increase the permeate flux up to 42%, depending on shear stress number. Moreover, the use of a shear stress number of 0.039 led to an augmentation in ACE inhibitory activity of permeates. Operating conditions using a shear stress number of 0.039 were recommended for enrichment of ACE inhibitory peptides. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Removal of Surrogate Bacteriophages and Enteric Viruses from Seeded Environmental Waters Using a Semi-technical Ultrafiltration Unit.

PubMed

Frohnert, Anne; Kreißel, Katja; Lipp, Pia; Dizer, Halim; Hambsch, Beate; Szewzyk, Regine; Selinka, Hans-Christoph

2015-03-19

Experiments to determine the removal of viruses in different types of water (surface water from two reservoirs for drinking water treatment, treated groundwater and groundwater contaminated with either 5 or 30 % of wastewater) by ultrafiltration were performed with a semi-technical ultrafiltration unit. Concentrations of human adenoviruses (HAdVs), murine norovirus (MNV), and the bacteriophages MS2, ΦX174 and PRD1 were measured in the feed water and the filtrate, and log removal values were calculated. Bacteria added to the feed water were not detected in the filtrates. In contrast, in most cases viruses and bacteriophages were still present in the filtrates: log removal values were in the range of 1.4-6.3 depending on virus sizes and water qualities. Best removals were observed with bacteriophage PRD1 and HAdVs, followed by MNV and phages MS2 and ΦX174. Virus size, however, was not the only criterion for efficient removal. In diluted wastewater as compared to drinking water and uncontaminated environmental waters, virus removal was clearly higher for all viruses, most likely due to higher membrane fouling. For quality assessment purposes of membrane filtration efficiencies with regard to the elimination of human viruses the small bacteriophages MS2 and ΦX174 should be used as conservative viral indicators.

Block copolymer self-assembly derived ultrafiltration membranes: From science to start-up

NASA Astrophysics Data System (ADS)

Wiesner, Ulrich

In the last ten years a novel method to generate asymmetric ultrafiltration membranes has been established. It is based on the combination of block copolymer self-assembly with non-solvent induced phase separation (NIPS) and is now referred to as SNIPS. NIPS as an industry proven method for the formation of phase inversion membranes opening a pathway to scale up and commercialization of these membranes. The combination of NIPS with block copolymer self-assembly leads to asymmetric membranes with narrow pore size distributions in the top surface layer (so called isoporous membranes) as well as high pore densities, thereby potentially combining high resolution with high flux in membrane separation processes. Such membranes have potential applications in the biopharmaceutical industry where a large fraction of the costs are currently associated with time-consuming non-membrane based separation processes. This talk will describe a family of isoporous ultrafiltration membranes based on the self-assembly behavior of an ABC triblock terpolymer which has led to the formation of a start-up company out of Cornell University. After introduction of the SNIPS process in general, and its application to such ABC triblock terpolymers in particular, open scientific questions associated with the formation mechanisms of the top surface separation layer in such membranes is discussed, which is at the heart of enabling high performance separation behavior. Furthermore, challenges translating scientific work into industrial settings are highlighted.

Peritoneum: a noble membrane in long-term dialysis treatment.

PubMed

Barone, Roberto J; Campora, María I; Gimenez, Nélida S; Ramirez, Liliana; Santopietro, Mónica; Grbavac, Drago; Pattin, Mauricio; Panese, Sergio A

2009-01-01

The durability of the peritoneum as a dialysis membrane is as yet an unanswered question. Peritonitis episodes have an important effect in long-term treatment. To evaluate survival of the peritoneum for dialysis, we analyzed peritoneal failure related to technique dropout because of peritonitis, inadequate dialysis, and ultrafiltration disorders. We retrospectively analyzed data for 89 peritoneal dialysis patients who had been treated for at least 3 months [52 women, 37 men; mean age: 50.91 +/- 13.72 years (range: 22 - 81 years)] from August 4, 1993, to July 1, 2008. The Kaplan-Meier method was used to measure peritoneum survival, with only a definitive switch to hemodialysis or death from peritonitis, ultrafiltration failure, or inadequate dialysis as endpoints. Total treatment time was 5008 patient-months (mean: 55 +/- 44 patient-months), and the historical annual rate of peritonitis was 0.37 per year at risk (1 episode in 32.52 patient-months). Of the 89 patients, 19 dropped treatment because of peritonitis and 1 because of ultrafiltration failure. Peritoneum survival was 98.8%, 93.7%, 87.6%, 66.9%, 46.4%, and 33.8% at 1, 3, 5, 8, 10, and 14 years. In the 15 years of our program, peritoneum failure represented less than 1.5% of drop-out causes annually. The peritoneum is a reliable membrane to reach dialysis targets in long-term therapy.

Study and optimization of the ultrasound-enhanced cleaning of an ultrafiltration ceramic membrane through a combined experimental-statistical approach.

PubMed

Alventosa-deLara, E; Barredo-Damas, S; Alcaina-Miranda, M I; Iborra-Clar, M I

2014-05-01

Membrane fouling is one of the main drawbacks of ultrafiltration technology during the treatment of dye-containing effluents. Therefore, the optimization of the membrane cleaning procedure is essential to improve the overall efficiency. In this work, a study of the factors affecting the ultrasound-assisted cleaning of an ultrafiltration ceramic membrane fouled by dye particles was carried out. The effect of transmembrane pressure (0.5, 1.5, 2.5 bar), cross-flow velocity (1, 2, 3 ms(-1)), ultrasound power level (40%, 70%, 100%) and ultrasound frequency mode (37, 80 kHz and mixed wave) on the cleaning efficiency was evaluated. The lowest frequency showed better results, although the best cleaning performance was obtained using the mixed wave mode. A Box-Behnken Design was used to find the optimal conditions for the cleaning procedure through a response surface study. The optimal operating conditions leading to the maximum cleaning efficiency predicted (32.19%) were found to be 1.1 bar, 3 ms(-1) and 100% of power level. Finally, the optimized response was compared to the efficiency of a chemical cleaning with NaOH solution, with and without the use of ultrasound. By using NaOH, cleaning efficiency nearly triples, and it improves up to 25% by adding ultrasound. Copyright © 2013 Elsevier B.V. All rights reserved.

Exacerbation of Diabetic Renal Alterations in Mice Lacking Vasohibin-1

PubMed Central

Hinamoto, Norikazu; Maeshima, Yohei; Yamasaki, Hiroko; Nasu, Tatsuyo; Saito, Daisuke; Watatani, Hiroyuki; Ujike, Haruyo; Tanabe, Katsuyuki; Masuda, Kana; Arata, Yuka; Sugiyama, Hitoshi; Sato, Yasufumi; Makino, Hirofumi

2014-01-01

Vasohibin-1 (VASH1) is a unique endogenous inhibitor of angiogenesis that is induced in endothelial cells by pro-angiogenic factors. We previously reported renoprotective effect of adenoviral delivery of VASH1 in diabetic nephropathy model, and herein investigated the potential protective role of endogenous VASH1 by using VASH1-deficient mice. Streptozotocin-induced type 1 diabetic VASH1 heterozygous knockout mice (VASH1+/−) or wild-type diabetic mice were sacrificed 16 weeks after inducing diabetes. In the diabetic VASH1+/− mice, albuminuria were significantly exacerbated compared with the diabetic wild-type littermates, in association with the dysregulated distribution of glomerular slit diaphragm related proteins, nephrin and ZO-1, glomerular basement membrane thickning and reduction of slit diaphragm density. Glomerular monocyte/macrophage infiltration and glomerular nuclear translocation of phosphorylated NF-κB p65 were significantly exacerbated in the diabetic VASH1+/− mice compared with the diabetic wild-type littermates, accompanied by the augmentation of VEGF-A, M1 macrophage-derived MCP-1 and phosphorylation of IκBα, and the decrease of angiopoietin-1/2 ratio and M2 macrophage-derived Arginase-1. The glomerular CD31+ endothelial area was also increased in the diabetic VASH1+/− mice compared with the diabetic-wild type littermates. Furthermore, the renal and glomerular hypertrophy, glomerular accumulation of mesangial matrix and type IV collagen and activation of renal TGF-β1/Smad3 signaling, a key mediator of renal fibrosis, were exacerbated in the diabetic VASH1+/− mice compared with the diabetic wild-type littermates. In conditionally immortalized mouse podocytes cultured under high glucose condition, transfection of VASH1 small interfering RNA (siRNA) resulted in the reduction of nephrin, angiopoietin-1 and ZO-1, and the augmentation of VEGF-A compared with control siRNA. These results suggest that endogenous VASH1 may regulate the development of diabetic renal alterations, partly via direct effects on podocytes, and thus, a strategy to recover VASH1 might potentially lead to the development of a novel therapeutic approach for diabetic nephropathy. PMID:25255225

Deletion of pro-angiogenic factor vasohibin-2 ameliorates glomerular alterations in a mouse diabetic nephropathy model

PubMed Central

Masuda, Kana; Ujike, Haruyo; Hinamoto, Norikazu; Miyake, Hiromasa; Tanimura, Satoshi; Sugiyama, Hitoshi; Sato, Yasufumi; Maeshima, Yohei; Wada, Jun

2018-01-01

Angiogenesis has been implicated in glomerular alterations in the early stage of diabetic nephropathy. We previously reported the renoprotective effects of vasohibin-1 (VASH1), which is a novel angiogenesis inhibitor derived from endothelial cells, on diabetic nephropathy progression. Vasohibin-2 (VASH2) was originally identified as a VASH1 homolog and possesses pro-angiogenic activity in contrast to VASH1. In addition, VASH2 was recently shown to promote epithelial-to-mesenchymal transition via enhanced transforming growth factor (TGF)-β signaling in cancer cells. Herein, we investigated the pathogenic roles of VASH2 in diabetic nephropathy using VAHS2-deficient mice. The type 1 diabetes model was induced by intraperitoneal injections of streptozotocin in VASH2 homozygous knockout (VASH2LacZ/LacZ) or wild-type mice. These mice were euthanized 16 weeks after inducing hyperglycemia. Increased urine albumin excretion and creatinine clearance observed in diabetic wild-type mice were significantly prevented in diabetic VASH2-deficient mice. Accordingly, diabetes-induced increase in glomerular volume and reduction in glomerular slit-diaphragm density were significantly improved in VASH2 knockout mice. Increased glomerular endothelial area was also suppressed in VASH2-deficient mice, in association with inhibition of enhanced vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2), but not VEGF level. Furthermore, glomerular accumulation of mesangial matrix, including type IV collagen, and increased expression of TGF-β were improved in diabetic VASH2 knockout mice compared with diabetic wild-type mice. Based on the immunofluorescence findings, endogenous VASH2 localization in glomeruli was consistent with mesangial cells. Human mesangial cells (HMCs) were cultured under high glucose condition in in vitro experiments. Transfection of VASH2 small interfering RNA (siRNA) into the HMCs resulted in the suppression of type IV collagen production induced by high glucose compared with control siRNA. These results indicate that VASH2 may be involved in diabetes-induced glomerular alterations, particularly impaired filtration barrier and mesangial expansion. Therefore, VASH2 is likely to represent a promising therapeutic target for diabetic nephropathy. PMID:29641565

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prof. P. Somasundaran

The aim of the project is to develop and evaluate efficient novel surfactant mixtures for enhanced oil recovery. Preliminary ultra-filtration tests suggest that two kinds of micelles may exist in binary surfactant mixtures at different concentrations. Due to the important role played in interfacial processes by micelles as determined by their structures, focus of the current work is on the delineation of the relationship between such aggregate structures and chemical compositions of the surfactants. A novel analytical centrifuge application is explored to generate information on structures of different surfactants aggregates. In this report, optical systems, typical output of the analyticalmore » ultracentrifuge results and four basic experiments are discussed. Initial sedimentation velocity investigations were conducted using nonyl phenol ethoxylated decyl ether (NP-10) to choose the best analytical protocol, calculate the partial specific volume and obtain information on sedimentation coefficient, aggregation mass of micelles. The partial specific volume was calculated to be 0.920. Four softwares: Optima{trademark} XL-A/XL-I data analysis software, DCDT+, Svedberg and SEDFIT, were compared for the analysis of sedimentation velocity experimental data. The sedimentation coefficient and aggregation number of NP-10 micelles obtained using the first three softwares at 25 C are 209, 127, and 111, respectively. The last one is closest to the result from Light Scattering. The reason for the differences in numbers obtained using the three softwares is discussed. Based on these tests, Svedberg and SEDFIT analysis are chosen for further studies. This approach using the analytical ultracentrifugation offers an unprecedented opportunity now to obtain important information on mixed micelles and their role in interfacial processes.« less

Using the Drosophila Nephrocyte to Model Podocyte Function and Disease

PubMed Central

Helmstädter, Martin; Huber, Tobias B.; Hermle, Tobias

2017-01-01

Glomerular disorders are a major cause of end-stage renal disease and effective therapies are often lacking. Nephrocytes are considered to be part of the Drosophila excretory system and form slit diaphragms across cellular membrane invaginations. Nehphrocytes have been shown to share functional, morphological, and molecular features with podocytes, which form the glomerular filter in vertebrates. Here, we report the progress and the evolving tool-set of this model system. Combining a functional, accessible slit diaphragm with the power of the genetic tool-kit in Drosophila, the nephrocyte has the potential to greatly advance our understanding of the glomerular filtration barrier in health and disease. PMID:29270398

Inhibition of Akt/mTOR/p70S6K Signaling Activity With Huangkui Capsule Alleviates the Early Glomerular Pathological Changes in Diabetic Nephropathy.

PubMed

Wu, Wei; Hu, Wei; Han, Wen-Bei; Liu, Ying-Lu; Tu, Yue; Yang, Hai-Ming; Fang, Qi-Jun; Zhou, Mo-Yi; Wan, Zi-Yue; Tang, Ren-Mao; Tang, Hai-Tao; Wan, Yi-Gang

2018-01-01

Huangkui capsule (HKC), a Chinese modern patent medicine extracted from Abelmoschus manihot (L.) medic, has been widely applied to clinical therapy in the early diabetic nephropathy (DN) patients. However, it remains elusive whether HKC can ameliorate the inchoate glomerular injuries in hyperglycemia. Recently the activation of phosphatidylinositol-3-kinase (PI3K)/serine-threonine kinase (Akt)/mammalian target of rapamycin (mTOR) signaling and its downstream regulator, 70-kDa ribosomal protein S6 kinase (p70S6K), play important roles in the early glomerular pathological changes of DN including glomerular hypertrophy, glomerular basement membrane (GBM) thickening and mild mesangial expansion. This study thereby aimed to clarify therapeutic effects of HKC during the initial phase of DN and its underlying mechanisms. Fifteen rats were randomly divided into 3 groups: the normal group, the model group and the HKC group. The early DN model rats were induced by unilateral nephrectomy combined with intraperitoneal injection of streptozotocin, and administered with either HKC suspension or vehicle after modeling and for a period of 4 weeks. Changes in the incipient glomerular lesions-related parameters in urine and blood were analyzed. Kidneys were isolated for histomorphometry, immunohistochemistry, immunofluorescence and Western blotting (WB) at sacrifice. In vitro , murine mesangial cells (MCs) were used to investigate inhibitory actions of hyperoside (HYP), a bioactive component of HKC, on cellular hypertrophy-associated signaling pathway by WB, compared with rapamycin (RAP). For the early DN model rats, HKC ameliorated micro-urinary albumin, body weight and serum albumin, but had no significant effects on renal function and liver enzymes; HKC improved renal shape, kidney weight and kidney hypertrophy index; HKC attenuated glomerular hypertrophy, GBM thickening and mild mesangial expansion; HKC inhibited the phosphorylation of Akt, mTOR and p70S6K, and the protein over-expression of transforming growth factor-β1 in kidneys. In vitro , the phosphorylation of PI3K, Akt, mTOR and p70S6K in MCs induced by high-glucose was abrogated by treatment of HYP or RAP. On the whole, this study further demonstrated HKC safely and efficiently alleviates the early glomerular pathological changes of DN, likely by inhibiting Akt/mTOR/p70S6K signaling activity in vivo and in vitro , and provided the first evidence that HKC directly contributes to the prevention of the early DN.

Neutrophil Extracellular Trap-Related Extracellular Histones Cause Vascular Necrosis in Severe GN.

PubMed

Kumar, Santhosh V R; Kulkarni, Onkar P; Mulay, Shrikant R; Darisipudi, Murthy N; Romoli, Simone; Thomasova, Dana; Scherbaum, Christina R; Hohenstein, Bernd; Hugo, Christian; Müller, Susanna; Liapis, Helen; Anders, Hans-Joachim

2015-10-01

Severe GN involves local neutrophil extracellular trap (NET) formation. We hypothesized a local cytotoxic effect of NET-related histone release in necrotizing GN. In vitro, histones from calf thymus or histones released by neutrophils undergoing NETosis killed glomerular endothelial cells, podocytes, and parietal epithelial cells in a dose-dependent manner. Histone-neutralizing agents such as antihistone IgG, activated protein C, or heparin prevented this effect. Histone toxicity on glomeruli ex vivo was Toll-like receptor 2/4 dependent, and lack of TLR2/4 attenuated histone-induced renal thrombotic microangiopathy and glomerular necrosis in mice. Anti-glomerular basement membrane GN involved NET formation and vascular necrosis, whereas blocking NET formation by peptidylarginine inhibition or preemptive anti-histone IgG injection significantly reduced all aspects of GN (i.e., vascular necrosis, podocyte loss, albuminuria, cytokine induction, recruitment or activation of glomerular leukocytes, and glomerular crescent formation). To evaluate histones as a therapeutic target, mice with established GN were treated with three different histone-neutralizing agents. Anti-histone IgG, recombinant activated protein C, and heparin were equally effective in abrogating severe GN, whereas combination therapy had no additive effects. Together, these results indicate that NET-related histone release during GN elicits cytotoxic and immunostimulatory effects. Furthermore, neutralizing extracellular histones is still therapeutic when initiated in established GN. Copyright © 2015 by the American Society of Nephrology.

Parietal cells-new perspectives in glomerular disease.

PubMed

Miesen, Laura; Steenbergen, Eric; Smeets, Bart

2017-07-01

In normal glomeruli, parietal epithelial cells (PECs) line the inside of Bowman's capsule and form an inconspicuous sheet of flat epithelial cells in continuity with the proximal tubular epithelial cells (PTECs) at the urinary pole and with the podocytes at the vascular pole. PECs, PTECs and podocytes have a common mesenchymal origin and are the result of divergent differentiation during embryogenesis. Podocytes and PTECs are highly differentiated cells with well-established functions pertaining to the maintenance of the filtration barrier and transport, respectively. For PECs, no specific function other than a structural one has been known until recently. Possible important functions for PECs in the fate of the glomerulus in glomerular disease have now become apparent: (1) PECs may be involved in the replacement of lost podocytes; (2) PECs form the basis of extracapillary proliferative lesions and subsequent sclerosis in glomerular disease. In addition to the acknowledgement that PECs are crucial in glomerular disease, knowledge has been gained regarding the molecular processes driving the phenotypic changes and behavior of PECs. Understanding these molecular processes is important for the development of specific therapeutic approaches aimed at either stimulation of the regenerative function of PECs or inhibition of the pro-sclerotic action of PECs. In this review, we discuss recent advances pertaining to the role of PECs in glomerular regeneration and disease and address the major molecular processes involved.

Role for Macrophage Metalloelastase in Glomerular Basement Membrane Damage Associated with Alport Syndrome

PubMed Central

Rao, Velidi H.; Meehan, Daniel T.; Delimont, Duane; Nakajima, Motowo; Wada, Takashi; Ann Gratton, Michael; Cosgrove, Dominic

2006-01-01

Alport syndrome is a glomerular basement membrane (GBM) disease caused by mutations in type IV collagen genes. A unique irregular thickening and thinning of the GBM characterizes the progressive glomerular pathology. The metabolic imbalances responsible for these GBM irregularities are not known. Here we show that macrophage metalloelastase (MMP-12) expression is >40-fold induced in glomeruli from Alport mice and is markedly induced in glomeruli of both humans and dogs with Alport syndrome. Treatment of Alport mice with MMI270 (CGS27023A), a broad spectrum MMP inhibitor that blocks MMP-12 activity, results in largely restored GBM ultrastructure and function. Treatment with BAY-129566, a broad spectrum MMP inhibitor that does not inhibit MMP-12, had no effect. We show that inhibition of CC chemokine receptor 2 (CCR2) receptor signaling with propagermanium blocks induction of MMP-12 mRNA and prevents GBM damage. CCR2 receptor is expressed in glomerular podocytes of Alport mice, suggesting MCP-1 activation of CCR2 on podocytes may underlie induction of MMP-12. These data indicate that the irregular GBM that characterizes Alport syndrome may be mediated, in part, by focal degradation of the GBM due to MMP dysregulation, in particular, MMP-12. Thus, MMP-12/CCR2 inhibitors may provide a novel and effective therapeutic strategy for Alport glomerular disease. PMID:16816359

Existence of a regulatory loop between MCP-1 and TGF-beta in glomerular immune injury.

PubMed

Wolf, Gunter; Jocks, Thomas; Zahner, Gunther; Panzer, Ulf; Stahl, Rolf A K

2002-11-01

Glomerular upregulation of monocyte chemotactic protein-1 (MCP-1), followed by an influx of monocytes resulting eventually in extracellular matrix deposition is a common sequel of many types of glomerulonephritis. However, it is not entirely clear how early expression of MCP-1 is linked to the later development of glomerulosclerosis. Because transforming growth factor-beta (TGF-beta) is a key regulator of extracellular matrix proteins, we hypothesized that there might be a regulatory loop between early glomerular MCP-1 induction and subsequent TGF-beta expression. To avoid interference with other cytokines that may be released from infiltrating monocytes, isolated rat kidneys were perfused with a polyclonal anti-thymocyte-1 antiserum (ATS) and rat serum (RS) as a complement source to induce glomerular injury. Renal TGF-beta protein and mRNA expressions were strongly stimulated after perfusion with ATS-RS. This effect was attenuated by coperfusion with a neutralizing anti-MCP-1 but was partly mimicked by perfusion with recombinant MCP-1 protein. On the other hand, renal MCP-1 expression and production were stimulated by administration of ATS-RS. Additional perfusion with an anti-TGF-beta antibody further aggravated this increase, whereas application of recombinant TGF-beta protein reduced MCP-1 formation. Our data demonstrate an intrinsic regulatory loop in which increased MCP-1 levels stimulate TGF-beta formation in resident glomerular cells in the absence of infiltrating immune competent cells.

Novel routes of albumin passage across the glomerular filtration barrier.

PubMed

Castrop, H; Schießl, I M

2017-03-01

Albuminuria is a hallmark of kidney diseases of various aetiologies and an unambiguous symptom of the compromised integrity of the glomerular filtration barrier. Furthermore, there is increasing evidence that albuminuria per se aggravates the development and progression of chronic kidney disease. This review covers new aspects of the movement of large plasma proteins across the glomerular filtration barrier in health and disease. Specifically, this review focuses on the role of endocytosis and transcytosis of albumin by podocytes, which constitutes a new pathway of plasma proteins across the filtration barrier. Thus, we summarize what is known about the mechanisms of albumin endocytosis by podocytes and address the fate of the endocytosed albumin, which is directed to lysosomal degradation or transcellular movement with subsequent vesicular release into the urinary space. We also address the functional consequences of overt albumin endocytosis by podocytes, such as the formation of pro-inflammatory cytokines, which might eventually result in a deterioration of podocyte function. Finally, we consider the diagnostic potential of podocyte-derived albumin-containing vesicles in the urine as an early marker of a compromised glomerular barrier function. In terms of new technical approaches, the review covers how our knowledge of the movement of albumin across the glomerular filtration barrier has expanded by the use of new intravital imaging techniques. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Influence of operating conditions on ceramic ultrafiltration membrane performance when treating textile effluents.

PubMed

Barredo-Damas, S; Alcaina-Miranda, M I; Gemma, M; Iborra-Clar, M I; Mendoza-Roca, J A

2011-01-01

This work studies the performance of three commercial ceramic ultrafiltration membranes (ZrO(2)-TiO(2)) treating raw effluent from a textile industry. The effect of crossflow velocity at 3, 4 and 5 m s(-1) as well as membrane characteristics, such as molecular weight cut-off (30, 50 and 150 kDa), on process performance were studied. Experiments were carried out in concentration mode in order to observe the effect of volume reduction factor simultaneously. Results showed a combined influence of both crossflow velocity and molecular weight cut-off on flux performance. TOC and COD removals up to 70% and 84% respectively were reached. On the other hand, almost complete color (>97%) and turbidity (>99%) removals were achieved for all the membranes and operating conditions.

Method for concentration and separation of biological organisms by ultrafiltration and dielectrophoresis

DOEpatents

Simmons, Blake A.; Hill, Vincent R.; Fintschenko, Yolanda; Cummings, Eric B.

2012-09-04

Disclosed is a method for monitoring sources of public water supply for a variety of pathogens by using a combination of ultrafiltration techniques together dielectrophoretic separation techniques. Because water-borne pathogens, whether present due to "natural" contamination or intentional introduction, would likely be present in drinking water at low concentrations when samples are collected for monitoring or outbreak investigations, an approach is needed to quickly and efficiently concentrate and separate particles such as viruses, bacteria, and parasites in large volumes of water (e.g., 100 L or more) while simultaneously reducing the sample volume to levels sufficient for detecting low concentrations of microbes (e.g., <10 mL). The technique is also designed to screen the separated microbes based on specific conductivity and size.

Quantification of Free Phenytoin by Liquid Chromatography Tandem Mass Spectrometry (LC/MS/MS).

PubMed

Peat, Judy; Frazee, Clint; Garg, Uttam

2016-01-01

Phenytoin (diphenylhydantoin) is an anticonvulsant drug that has been used for decades for the treatment of many types of seizures. The drug is highly protein bound and measurement of free-active form of the drug is warranted particularly in patients with conditions that can affect drug protein binding. Here, we describe a LC/MS/MS method for the measurement of free phenytoin. Free drug is separated by ultrafiltration of serum or plasma. Ultrafiltrate is treated with acetonitrile containing internal standard phenytoin d-10 to precipitate proteins. The mixture is centrifuged and supernatant is injected onto LC-MS-MS, and analyzed using multiple reaction monitoring. This method is linear from 0.1 to 4.0 μg/mL and does not demonstrate any significant ion suppression or enhancement.

WATER QUALITY

EPA Science Inventory

This manual was develped to provide an overview of microfiltration and ultrafiltration technology for operators, administrators, engineers, scientists, educators, and anyone seeking an introduction to these processes. Chapters on theory, water quality, applications, design, equip...

Insulin Sensitivity Measured With Euglycemic Clamp Is Independently Associated With Glomerular Filtration Rate in a Community-Based Cohort

PubMed Central

Nerpin, Elisabet; Risérus, Ulf; Ingelsson, Erik; Sundström, Johan; Jobs, Magnus; Larsson, Anders; Basu, Samar; Ärnlöv, Johan

2008-01-01

OBJECTIVE—To investigate the association between insulin sensitivity and glomerular filtration rate (GFR) in the community, with prespecified subgroup analyses in normoglycemic individuals with normal GFR. RESEARCH DESIGN AND METHODS—We investigated the cross-sectional association between insulin sensitivity (M/I, assessed using euglycemic clamp) and cystatin C–based GFR in a community-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men [ULSAM], n = 1,070). We also investigated whether insulin sensitivity predicted the incidence of renal dysfunction at a follow-up examination after 7 years. RESULTS—Insulin sensitivity was directly related to GFR (multivariable-adjusted regression coefficient for 1-unit higher M/I 1.19 [95% CI 0.69–1.68]; P < 0.001) after adjusting for age, glucometabolic variables (fasting plasma glucose, fasting plasma insulin, and 2-h glucose after an oral glucose tolerance test), cardiovascular risk factors (hypertension, dyslipidemia, and smoking), and lifestyle factors (BMI, physical activity, and consumption of tea, coffee, and alcohol). The positive multivariable-adjusted association between insulin sensitivity and GFR also remained statistically significant in participants with normal fasting plasma glucose, normal glucose tolerance, and normal GFR (n = 443; P < 0.02). In longitudinal analyses, higher insulin sensitivity at baseline was associated with lower risk of impaired renal function (GFR <50 ml/min per 1.73 m2) during follow-up independently of glucometabolic variables (multivariable-adjusted odds ratio for 1-unit higher of M/I 0.58 [95% CI 0.40–0.84]; P < 0.004). CONCLUSIONS—Our data suggest that impaired insulin sensitivity may be involved in the development of renal dysfunction at an early stage, before the onset of diabetes or prediabetic glucose elevations. Further studies are needed in order to establish causality. PMID:18509205

Effects of childbirth on podocyturia in women with normotensive, uncomplicated pregnancies.

PubMed

Furuta, Itsuko; Zhai, Tianyue; Umazume, Takeshi; Ishikawa, Satoshi; Nakagawa, Kinuko; Kojima, Takashi; Yamada, Takahiro; Morikawa, Mamoru; Minakami, Hisanori

2017-06-01

Changes in hemodynamics and blood pressure occur shortly before and after childbirth regardless of the mode of delivery. This study aimed to test the hypothesis that parturition induces a temporal increase in podocyturia monitored by podocyte-specific protein podocin mRNA expression levels (Pod-mRNA). A total of 105 urine specimens, consisting of 43 and 62 from 18 and 20 otherwise healthy women with vaginal delivery (VD) and elective cesarean delivery (ECS), respectively, were studied. Determination of urine protein and creatinine (Cr) concentrations and quantitative analyses of Pod-mRNA, nephrin mRNA (Nep-mRNA), synaptopodin mRNA (Syn-mRNA), and aquaporin 2 mRNA expression were performed using RT-PCR in pelleted urine samples. Levels of mRNA expression were corrected by urine Cr concentration. Podocyturia increased significantly, concomitant with a significantly decreased Nep:Pod-mRNA ratio (NPR) in the urine, collected immediately before or after childbirth regardless of the delivery mode compared with urine collected before commencement of labor or on postpartum day 3 or later. Podocyturia was significantly negatively correlated with NPR [correlation coefficient ( r ) = -0.614/-0.750 for VD/ECS women, respectively], as well as the Syn:Pod-mRNA ratio. Systolic blood pressure exceeded 140 mmHg during labor in 50% of VD women, and mean arterial pressure was significantly positively correlated with podocyturia during labor in VD women ( r  = 0.733). Thus parturition induces a transient increase in urine podocytes with reduced Nep- and Syn-mRNA expressions. Glomerular podocytes with reduced Nep- and Syn-mRNA levels were suggested to be likely to detach from the glomerular basement membrane around childbirth. Copyright © 2017 the American Physiological Society.

Effects of serum creatinine calibration on estimated renal function in african americans: the Jackson heart study.

PubMed

Wang, Wei; Young, Bessie A; Fülöp, Tibor; de Boer, Ian H; Boulware, L Ebony; Katz, Ronit; Correa, Adolfo; Griswold, Michael E

2015-05-01

The calibration to isotope dilution mass spectrometry-traceable creatinine is essential for valid use of the new Chronic Kidney Disease Epidemiology Collaboration equation to estimate the glomerular filtration rate. For 5,210 participants in the Jackson Heart Study (JHS), serum creatinine was measured with a multipoint enzymatic spectrophotometric assay at the baseline visit (2000-2004) and remeasured using the Roche enzymatic method, traceable to isotope dilution mass spectrometry in a subset of 206 subjects. The 200 eligible samples (6 were excluded, 1 for failure of the remeasurement and 5 for outliers) were divided into 3 disjoint sets-training, validation and test-to select a calibration model, estimate true errors and assess performance of the final calibration equation. The calibration equation was applied to serum creatinine measurements of 5,210 participants to estimate glomerular filtration rate and the prevalence of chronic kidney disease (CKD). The selected Deming regression model provided a slope of 0.968 (95% confidence interval [CI], 0.904-1.053) and intercept of -0.0248 (95% CI, -0.0862 to 0.0366) with R value of 0.9527. Calibrated serum creatinine showed high agreement with actual measurements when applying to the unused test set (concordance correlation coefficient 0.934, 95% CI, 0.894-0.960). The baseline prevalence of CKD in the JHS (2000-2004) was 6.30% using calibrated values compared with 8.29% using noncalibrated serum creatinine with the Chronic Kidney Disease Epidemiology Collaboration equation (P < 0.001). A Deming regression model was chosen to optimally calibrate baseline serum creatinine measurements in the JHS, and the calibrated values provide a lower CKD prevalence estimate.

[Diagnostic ability of Chronic Kidney Disease Epidemiology Collaboration and Modification of Diet in Renal Disease-4 equations to estimate glomerular filtration rate in with multimorbidity patients].

PubMed

Cabrerizo-García, José Luis; Díez-Manglano, Jesús; García-Arilla, Ernesto; Revillo-Pinilla, Paz; Ramón-Puertas, José; Sebastián-Royo, Mariano

2015-01-06

The Modification of Diet in Renal Disease (MDRD) equation is recommended by most scientific societies to calculate the estimated glomerular filtration rate (GFR). Recently the group Chronic Kidney Disease Epidemiology Collaboration (CKP-EPI) has published a new, more precise and accurate equation. We have analyzed its behavior in a group of polypathological patients (PP) and compared it with the classic MDRD-4.version Multicenter, observational, descriptive and transversal study. We calculated GFR by MDRD-4 and CKD-EPI in 425 PP. Each stage was assigned according to the GFR: 1:>90; 2: 60-89; 3: 30-59; 4: 15-29; and 5 < 15 ml/min/1.73m(2). We analyzed the correlation between both and the patients reclassified by CKD-EPI. Mean age was (mean [SD]) 81.7 (7.9) years. 55.3% were women. The mean estimated GFR was 58.6 (26.3) ml/min/1,73m(2) by MDRD-4 and 52.7 (23.0) ml/min/1.73m(2) by CKD-EPI (P<.001; Spearman's Rho correlation and Lin concordance coefficients: 0.993 and 0.948). The Bland-Altman plots reflected lower values for GFR for CKD-EPI equation. In the stage 2, 21.2% were reclassified by CKD-EPI to the stage 3, with women older than 83 years being the more disadvantaged subgroup with 27.3% or reclassification. CKD-EPI equation applied to PP worsens the results of MDRD-4. In general, it originates low values of GFR and increases the degree of renal insufficiency, especially in older women. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

A pseudo-three-dimensional model for quantification of oxygen diffusion from preglomerular arteries to renal tissue and renal venous blood.

PubMed

Lee, Chang-Joon; Ngo, Jennifer P; Kar, Saptarshi; Gardiner, Bruce S; Evans, Roger G; Smith, David W

2017-08-01

To assess the physiological significance of arterial-to-venous (AV) oxygen shunting, we generated a new pseudo-three-dimensional computational model of oxygen diffusion from intrarenal arteries to cortical tissue and veins. The model combines the 11 branching levels (known as "Strahler" orders) of the preglomerular renal vasculature in the rat, with an analysis of an extensive data set obtained using light microscopy to estimate oxygen mass transfer coefficients for each Strahler order. Furthermore, the AV shunting model is now set within a global oxygen transport model that includes transport from arteries, glomeruli, peritubular capillaries, and veins to tissue. While a number of lines of evidence suggest AV shunting is significant, most importantly, our AV oxygen shunting model predicts AV shunting is small under normal physiological conditions (~0.9% of total renal oxygen delivery; range 0.4-1.4%), but increases during renal ischemia, glomerular hyperfiltration (~2.1% of total renal oxygen delivery; range 0.84-3.36%), and some cardiovascular disease states (~3.0% of total renal oxygen delivery; range 1.2-4.8%). Under normal physiological conditions, blood Po 2 is predicted to fall by ~16 mmHg from the root of the renal artery to glomerular entry, with AV oxygen shunting contributing ~40% and oxygen diffusion from arteries to tissue contributing ~60% of this decline. Arterial Po 2 is predicted to fall most rapidly from Strahler order 4 , under normal physiological conditions. We conclude that AV oxygen shunting normally has only a small impact on renal oxygenation, but may exacerbate renal hypoxia during renal ischemia, hyperfiltration, and some cardiovascular disease states. Copyright © 2017 the American Physiological Society.

Acoustic radiation force impulse elastography of the kidneys: is shear wave velocity affected by tissue fibrosis or renal blood flow?

PubMed

Asano, Kenichiro; Ogata, Ai; Tanaka, Keiko; Ide, Yoko; Sankoda, Akiko; Kawakita, Chieko; Nishikawa, Mana; Ohmori, Kazuyoshi; Kinomura, Masaru; Shimada, Noriaki; Fukushima, Masaki

2014-05-01

The aim of this study was to identify the main influencing factor of the shear wave velocity (SWV) of the kidneys measured by acoustic radiation force impulse elastography. The SWV was measured in the kidneys of 14 healthy volunteers and 319 patients with chronic kidney disease. The estimated glomerular filtration rate was calculated by the serum creatinine concentration and age. As an indicator of arteriosclerosis of large vessels, the brachial-ankle pulse wave velocity was measured in 183 patients. Compared to the degree of interobserver and intraobserver deviation, a large variance of SWV values was observed in the kidneys of the patients with chronic kidney disease. Shear wave velocity values in the right and left kidneys of each patient correlated well, with high correlation coefficients (r = 0.580-0.732). The SWV decreased concurrently with a decline in the estimated glomerular filtration rate. A low SWV was obtained in patients with a high brachial-ankle pulse wave velocity. Despite progression of renal fibrosis in the advanced stages of chronic kidney disease, these results were in contrast to findings for chronic liver disease, in which progression of hepatic fibrosis results in an increase in the SWV. Considering that a high brachial-ankle pulse wave velocity represents the progression of arteriosclerosis in the large vessels, the reduction of elasticity succeeding diminution of blood flow was suspected to be the main influencing factor of the SWV in the kidneys. This study indicates that diminution of blood flow may affect SWV values in the kidneys more than the progression of tissue fibrosis. Future studies for reducing data variance are needed for effective use of acoustic radiation force impulse elastography in patients with chronic kidney disease.

The reliability of glomerular filtration rate measured from plasma clearance: a multi-centre study of 1,878 healthy potential renal transplant donors.

PubMed

Peters, A Michael; Howard, Bethany; Neilly, Mark D J; Seshadri, Nagabhushan; Sobnack, Ravin; Hooker, Claire A; Irwin, Andrew; Snelling, Hayley; Gruning, Thomas; Perry, Laura; Patel, Neva H; Lawson, Richard S; Shabo, Gregory; Williams, Nigel; Dave, Surendra; Barnfield, Mark C

2012-04-01

The objective of the study was to undertake a clinical audit of departmental performance in the measurement of glomerular filtration rate (GFR) using the coefficient of variation (CV) of extracellular fluid volume (ECFV) as the benchmark. ECFV is held within narrow limits in healthy subjects, narrower than GFR, and should therefore have a low CV. Fifteen departments participated in this retrospective study of healthy renal transplant donors. Data were analysed separately for men (n ranged from 28 to 115 per centre; total = 819) and women (n = 28-146; 1,059). All centres used the slope-intercept method with blood sample numbers ranging from two to five. Subjects did not fast prior to GFR measurement. GFR was scaled to body surface area (BSA) and corrected for the single compartment assumption. GFR scaled to ECFV was calculated as the terminal slope rate constant and corrected for the single compartment assumption. ECFV/BSA was calculated as the ratio of GFR/BSA to GFR/ECFV. The departmental CVs of ECFV/BSA and GFR/BSA ranged from 8.3 to 25.8% and 12.8 to 21.9%, respectively, in men, and from 9.6 to 21.1% and 14.8 to 23.7%, respectively, in women. Both CVs correlated strongly between men and women from the same centre, suggesting department-specific systematic errors. GFR/BSA was higher in men in 14 of 15 centres, whereas GFR/ECFV was higher in women in 14 of 15 centres. Both correlated strongly between men and women, suggesting regional variation in GFR. The CV of ECFV/BSA in normal subjects is a useful indicator of the technical robustness with which GFR is measured and, in this study, indicated a wide variation in departmental performance.

Vascular endothelial growth factor receptor-3 is a novel target to improve net ultrafiltration in methylglyoxal-induced peritoneal injury.

PubMed

Terabayashi, Takeshi; Ito, Yasuhiko; Mizuno, Masashi; Suzuki, Yasuhiro; Kinashi, Hiroshi; Sakata, Fumiko; Tomita, Takako; Iguchi, Daiki; Tawada, Mitsuhiro; Nishio, Ryosuke; Maruyama, Shoichi; Imai, Enyu; Matsuo, Seiichi; Takei, Yoshifumi

2015-09-01

Appropriate fluid balance is important for good clinical outcomes and survival in patients on peritoneal dialysis. We recently reported that lymphangiogenesis associated with fibrosis developed in the peritoneal cavity via the transforming growth factor-β1-vascular endothelial growth factor-C (VEGF-C) pathway. We investigated whether VEGF receptor-3 (VEGFR-3), the receptor for VEGF-C and -D, might be a new target to improve net ultrafiltration by using adenovirus-expressing soluble VEGFR-3 (Adeno-sVEGFR-3) in rodent models of peritoneal injury induced by methylglyoxal (MGO). We demonstrated that lymphangiogenesis developed in these MGO models, especially in the diaphragm, indicating that lymphangiogenesis is a common feature in the peritoneal cavity with inflammation and fibrosis. In MGO models, VEGF-D was significantly increased in the diaphragm; however, VEGF-C was not significantly upregulated. Adeno-sVEGFR-3, which was detected on day 50 after administration via tail vein injections, successfully suppressed lymphangiogenesis in the diaphragm and parietal peritoneum in mouse MGO models without significant effects on fibrosis, inflammation, or neoangiogenesis. Drained volume in the peritoneal equilibration test using a 7.5% icodextrin peritoneal dialysis solution (the 7.5% icodextrin peritoneal equilibration test) was improved by Adeno-sVEGFR-3 on day 22 (P<0.05) and day 50 after reduction of inflammation (P<0.01), indicating that the 7.5% icodextrin peritoneal equilibration test identifies changes in lymphangiogenesis. The solute transport rate was not affected by suppression of lymphangiogenesis. In human peritoneal dialysis patients, the dialysate to plasma ratio of creatinine positively correlated with the dialysate VEGF-D concentration (P<0.001). VEGF-D mRNA was significantly higher in the peritoneal membranes of patients with ultrafiltration failure, indicating that VEGF-D is involved in the development of lymphangiogenesis in peritoneal dialysis patients. These results indicate that VEGFR-3 is a new target to improve net ultrafiltration by suppressing lymphatic absorption and that the 7.5% icodextrin peritoneal equilibration test is useful for estimation of lymphatic absorption.

[Effect of priming solution and ultrafiltration on post-operative bleeding and blood transfusion in cardiac surgery. Randomized controlled trial].

PubMed

Olmos Rodríguez, M; Ballester Hernández, J A; Arteta Bárcenas, M T; Rodríguez Cerezo, A; Vidarte Ortiz de Artiñano, M A; Veiga Alameda, C

2015-02-01

Assess the effectiveness of priming the extracorporeal circulation system with albumin-mannitol combined with ultrafiltration during extracorporeal circulation to reduce post-operative bleeding and transfusion requirements in heart surgery, as well as its impact on the fluid balance, coagulation and hematocrit parameters, re-operation for bleeding, ICU, and hospital length of stay. A total of 134 patients scheduled for heart surgery were randomized to receive Ringer's lactate 1,500mL in the priming reservoir (group C), or mannitol 20% 250mL, albumin 20% 150mL and Ringer's lactate 1,100mL combined with ultrafiltration (group T). Bleeding volume, transfusions, fluid balance, coagulation, and hematology parameters were determined until 48h in the post-operative period. There was a reduction of postoperative bleeding in group T, 1,165±789mL vs 992±662mL (P=.17), and red blood cell concentrate transfusions, 694±843mL vs 413±605mL (P=.03). Intra-operative and post-operative fluid balance was significantly less positive in group T, with an overall balance of 2,292±2,152mL vs 5,388±2,834mL (P<.001). There were higher values of hemoglobin and hematocrit, intraoperative (P<.001), on admission to ICU (P=.001), and at 6h (P=.05) in group T, and lower INR at 6h (P=.01) and 24h (P=.02). Re-operation rate and length of stay in ICU were higher in group C, but not statiscally significant. The priming of extracorporeal reservoir with mannitol, albumin, and Ringer's lactate, combined with ultrafiltration, significantly improves intra- and post-operative fluid balance, resulting in a reduction in blood transfusions, with no significant decrease in post-operative bleeding, re-operation bleeding rate, and length of stay in the ICU. Copyright © 2014 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Single Daily Icodextrin Exchange as Initial and Solitary Therapy.

PubMed

Agar, Baris U; Sloand, James A

2018-01-01

Incremental dialysis utilizes gradually increasing dialysis doses in response to declines in residual kidney function, and it is the preferred renal replacement therapy for patients who have just transitioned to end-stage renal disease (ESRD). Incremental peritoneal dialysis (PD) may impose fewer restrictions on patients' lifestyle, help attenuate lifetime peritoneal and systemic exposure to glucose and its degradation products, and minimize connections that could compromise the sterile fluid path. In this study, we utilized a 3-pore kinetic model to assess fluid and solute removal during single daily icodextrin treatments for patients with varying glomerular filtration rates (GFR). Single icodextrin exchanges of 8 to 16 hours using 2- and 2.5-L bag volumes were simulated for different patient transport types (i.e., high to low) to predict daily peritoneal ultrafiltration (UF), daily peritoneal sodium removal, and weekly total (peritoneal + residual kidney) Kt/V (Kt/V Total ) for patients with residual renal GFRs ranging from 0 to 15 mL/min/1.73 m 2 . Daily peritoneal UF varied from 359 to 607 mL, and daily peritoneal Na removal varied from 52 to 87 mEq depending on length of icodextrin exchange and bag volume. Both were effectively independent of patient transport type. All but very large patients (total body water [TBW] > 60 L) were predicted to achieve adequate dialysis (Kt/V Total ≥ 1.7) with a GFR of 10 mL/min/1.73 m 2 , and small patients (TBW: 30 L) were predicted to achieve adequate dialysis with a GFR of 6 mL/min/1.73 m 2 . A single daily icodextrin exchange can be tailored to augment urea, UF, and Na removal in patients with sufficient residual kidney function (RKF). A solitary icodextrin exchange may therefore be reasonable initial therapy for some incident ESRD patients. Copyright © 2018 International Society for Peritoneal Dialysis.

Preparation and Preliminary Dialysis Performance Research of Polyvinylidene Fluoride Hollow Fiber Membranes

PubMed Central

Zhang, Qinglei; Lu, Xiaolong; Liu, Juanjuan; Zhao, Lihua

2015-01-01

In this study, the separation properties of Polyvinylidene fluoride (PVDF) hollow fiber hemodialysis membranes were improved by optimizing membrane morphology and structure. The results showed that the PVDF membrane had better mechanical and separation properties than Fresenius Polysulfone High-Flux (F60S) membrane. The PVDF membrane tensile stress at break, tensile elongation and bursting pressure were 11.3 MPa, 395% and 0.625 MPa, respectively. Ultrafiltration (UF) flux of pure water reached 108.2 L∙h−1∙m−2 and rejection of Albumin from bovine serum was 82.3%. The PVDF dialyzers were prepared by centrifugal casting. The influences of membrane area and simulate fluid flow rate on dialysis performance were investigated. The results showed that the clearance rate of urea and Lysozyme (LZM) were improved with increasing membrane area and fluid flow rate while the rejection of albumin from bovine serum (BSA) had little influence. The high-flux PVDF dialyzer UF coefficient reached 62.6 mL/h/mmHg. The PVDF dialyzer with membrane area 0.69 m2 has the highest clearance rate to LZM and urea. The clearance rate of LZM was 66.8% and urea was 87.7%. PMID:25807890

Removal of low-molecular weight DBPs and inorganic ions for characterization of high-molecular weight DBPs in drinking water.

PubMed

Zhang, Xiangru; Minear, Roger A

2006-03-01

High-molecular weight (MW) halogenated disinfection byproducts (DBPs) may cause adverse health effects. In this work several issues related to the better separation and characterization of the high MW halogenated DBPs (MW>500Da) were studied. Ultra-filtration (UF) coupled with a nominal 500-Da membrane was employed to flush out low MW DBPs and inorganic ions. Two procedures, intermittent UF and continuous UF, were used and compared. The results demonstrate that haloacetic acids, chloride and sodium ions could be effectively flushed out, and most of phosphate ions could be flushed out for a given dilution number or sufficient Milli-Q water. The size exclusion chromatograms indicate that haloacetic acids and trihalomethanes were not bound to Suwannee River fulvic acid (SRFA); 2,4,6-trichlorophenol might form some binding with SRFA, but it appeared to be very weak and readily broken up when passing along the size exclusion column. The octanol-water partition coefficients of low MW DBPs and the properties of humic substances seem to play key roles in determining the formation of possible bindings between low MW DBPs and humic substances.

[Not Available].

PubMed

Fernández Castillo, Rafael; Cañadas de la Fuente, Gustavo R; Cañadas de la Fuente, Guillermo A; De la Fuente Solana, Emilia Inmaculada; Esteban de la Rosa, Rafael José; Bravo Soto, Juan

2016-07-19

Introducción: la obesidad y el sobrepeso presentan efectos adversos sobre la salud, lo que contribuye a la aparición de enfermedades metabólicas y cardiovasculares que ponen en peligro la integridad del injerto.Objetivo: investigar la influencia del IMC pretrasplante renal sobre el funcionamiento del injerto renal al año de trasplante mediante el estudio de cuatro métodos distintos de medir la filtración glomerular.Material y métodos: en este trabajo se ha seguido a 1.336 pacientes de ambos sexos trasplantados renales; se les realizaron mediciones pretrasplante y postrasplante de parámetros bioquímicos, mediciones antropométricas y función renal mediante medidas de filtrado glomerular.Resultados: a mayor índice de masa corporal pretrasplante se produce una disminución del filtrado glomerular medido por cuatro métodos distintos, así como mayor porcentaje de rechazos.Conclusiones: un IMC elevado pretrasplante contribuye a la disfunción del injerto, a una disminución del filtrado glomerular y a complicaciones del injerto en el primer año postrasplante.

Alport syndrome and Pierson syndrome: Diseases of the glomerular basement membrane.

PubMed

Funk, Steven D; Lin, Meei-Hua; Miner, Jeffrey H

2018-04-16

The glomerular basement membrane (GBM) is an important component of the kidney's glomerular filtration barrier. Like all basement membranes, the GBM contains type IV collagen, laminin, nidogen, and heparan sulfate proteoglycan. It is flanked by the podocytes and glomerular endothelial cells that both synthesize it and adhere to it. Mutations that affect the GBM's collagen α3α4α5(IV) components cause Alport syndrome (kidney disease with variable ear and eye defects) and its variants, including thin basement membrane nephropathy. Mutations in LAMB2 that impact the synthesis or function of laminin α5β2γ1 (LM-521) cause Pierson syndrome (congenital nephrotic syndrome with eye and neurological defects) and its less severe variants, including isolated congenital nephrotic syndrome. The very different types of kidney diseases that result from mutations in collagen IV vs. laminin are likely due to very different pathogenic mechanisms. A better understanding of these mechanisms should lead to targeted therapeutic approaches that can help people with these rare but important diseases. Copyright © 2017 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

Pro: 'The usefulness of biomarkers in glomerular diseases'. The problem: moving from syndrome to mechanism--individual patient variability in disease presentation, course and response to therapy.

PubMed

Mariani, Laura H; Kretzler, Matthias

2015-06-01

The diagnosis and treatment decisions in glomerular disease are principally based on renal pathology and nonspecific clinical laboratory measurements such as serum creatinine and urine protein. Using these classification approaches, patients have marked variability in rate of progression and response to therapy, exposing a significant number of patients to toxicity without benefit. Additionally, clinical trials are at risk of not being able to detect an efficacious therapy in relevant subgroups as patients with shared clinical-pathologic diagnoses have heterogeneous underlying pathobiology. To change this treatment paradigm, biomarkers that reflect the molecular mechanisms underlying the clinical-pathologic diagnoses are needed. Recent progress to identify such biomarkers has been aided by advances in molecular profiling, large-scale data generation and multi-scalar data integration, including prospectively collected clinical data. This article reviews the evolving success stories in glomerular disease biomarkers across the genotype-phenotype continuum and highlights opportunities to transition to precision medicine in glomerular disease. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Renin-angiotensin system within the diabetic podocyte.

PubMed

Márquez, Eva; Riera, Marta; Pascual, Julio; Soler, María José

2015-01-01

Diabetic kidney disease is the leading cause of end-stage renal disease. Podocytes are differentiated cells necessary for the development and maintenance of the glomerular basement membrane and the capillary tufts, as well as the function of the glomerular filtration barrier. The epithelial glomerular cells express a local renin-angiotensin system (RAS) that varies in different pathological situations such as hyperglycemia or mechanical stress. RAS components have been shown to be altered in diabetic podocytopathy, and their modulation may modify diabetic nephropathy progression. Podocytes are a direct target for angiotensin II-mediated injury by altered expression and distribution of podocyte proteins. Furthermore, angiotensin II promotes podocyte injury indirectly by inducing cellular hypertrophy, increased apoptosis, and changes in the anionic charge of the glomerular basement membrane, among other effects. RAS blockade has been shown to decrease the level of proteinuria and delay the progression of chronic kidney disease. This review summarizes the local intraglomerular RAS and its imbalance in diabetic podocytopathy. A better understanding of the intrapodocyte RAS might provide a new approach for diabetic kidney disease treatment. Copyright © 2015 the American Physiological Society.

Nomograms for predicting graft function and survival in living donor kidney transplantation based on the UNOS Registry.

PubMed

Tiong, H Y; Goldfarb, D A; Kattan, M W; Alster, J M; Thuita, L; Yu, C; Wee, A; Poggio, E D

2009-03-01

We developed nomograms that predict transplant renal function at 1 year (Modification of Diet in Renal Disease equation [estimated glomerular filtration rate]) and 5-year graft survival after living donor kidney transplantation. Data for living donor renal transplants were obtained from the United Network for Organ Sharing registry for 2000 to 2003. Nomograms were designed using linear or Cox regression models to predict 1-year estimated glomerular filtration rate and 5-year graft survival based on pretransplant information including demographic factors, immunosuppressive therapy, immunological factors and organ procurement technique. A third nomogram was constructed to predict 5-year graft survival using additional information available by 6 months after transplantation. These data included delayed graft function, any treated rejection episodes and the 6-month estimated glomerular filtration rate. The nomograms were internally validated using 10-fold cross-validation. The renal function nomogram had an r-square value of 0.13. It worked best when predicting estimated glomerular filtration rate values between 50 and 70 ml per minute per 1.73 m(2). The 5-year graft survival nomograms had a concordance index of 0.71 for the pretransplant nomogram and 0.78 for the 6-month posttransplant nomogram. Calibration was adequate for all nomograms. Nomograms based on data from the United Network for Organ Sharing registry have been validated to predict the 1-year estimated glomerular filtration rate and 5-year graft survival. These nomograms may facilitate individualized patient care in living donor kidney transplantation.

Glomerular hemodynamic alterations during acute hyperinsulinemia in normal and diabetic rats

NASA Technical Reports Server (NTRS)

Tucker, B. J.; Anderson, C. M.; Thies, R. S.; Collins, R. C.; Blantz, R. C.

1992-01-01

Treatment of insulin dependent diabetes invariably requires exogenous insulin to control blood glucose. Insulin treatment, independent of other factors associated with insulin dependent diabetes, may induce changes that affect glomerular function. Due to exogenous delivery of insulin in insulin dependent diabetes entering systemic circulation prior to the portal vein, plasma levels of insulin are often in excess of that observed in non-diabetics. The specific effects of hyperinsulinemia on glomerular hemodynamics have not been previously examined. Micropuncture studies were performed in control (non-diabetic), untreated diabetic and insulin-treated diabetic rats 7 to 10 days after administration of 65 mg/kg body weight streptozotocin. After the first period micropuncture measurements were obtained, 5 U of regular insulin (Humulin-R) was infused i.v., and glucose clamped at euglycemic values (80 to 120 mg/dl). Blood glucose concentration in non-diabetic controls was 99 +/- 6 mg/dl. In control rats, insulin infusion and glucose clamp increased nephron filtration rate due to decreases in both afferent and efferent arteriolar resistance (afferent greater than efferent) resulting in increased plasma flow and increased glomerular hydrostatic pressure gradient. However, insulin infusion and glucose clamp produced the opposite effect in both untreated and insulin-treated diabetic rats with afferent arteriolar vasoconstriction resulting in decreases in plasma flow, glomerular hydrostatic pressure gradient and nephron filtration rate. Thromboxane A2 (TX) synthetase inhibition partially decreased the vasoconstrictive response due to acute insulin infusion in diabetic rats preventing the decrease in nephron filtration rate.(ABSTRACT TRUNCATED AT 250 WORDS).

Long-Term Renal Function Recovery following Radical Nephrectomy for Kidney Cancer: Results from a Multicenter Confirmatory Study.

PubMed

Zabor, Emily C; Furberg, Helena; Lee, Byron; Campbell, Steven; Lane, Brian R; Thompson, R Houston; Antonio, Elvis Caraballo; Noyes, Sabrina L; Zaid, Harras; Jaimes, Edgar A; Russo, Paul

2018-04-01

We sought to confirm the findings from a previous single institution study of 572 patients from Memorial Sloan Kettering Cancer Center in which we found that 49% of patients recovered to the preoperative estimated glomerular filtration rate within 2 years following radical nephrectomy for renal cell carcinoma. A multicenter retrospective study was performed in 1,928 patients using data contributed from 3 independent centers. The outcome of interest was postoperative recovery to the preoperative estimated glomerular filtration rate. Data were analyzed using cumulative incidence and competing risks regression with death from any cause treated as a competing event. This study demonstrated that 45% of patients had recovered to the preoperative estimated glomerular filtration rate by 2 years following radical nephrectomy. Furthermore, this study confirmed that recovery of renal function differed according to preoperative renal function such that patients with a lower preoperative estimated glomerular filtration rate had an increased chance of recovery. This study also suggested that larger tumor size and female gender were significantly associated with an increased chance of renal function recovery. In this multicenter retrospective study we confirmed that in the long term a large proportion of patients recover to preoperative renal function following radical nephrectomy for kidney tumors. Recovery is more likely among those with a lower preoperative estimated glomerular filtration rate. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Acid Sphingomyelinase Gene Deficiency Ameliorates the Hyperhomocysteinemia-Induced Glomerular Injury in Mice

PubMed Central

Boini, Krishna M.; Xia, Min; Li, Caixia; Zhang, Chun; Payne, Lori P.; Abais, Justine M.; Poklis, Justin L.; Hylemon, Philip B.; Li, Pin-Lan

2011-01-01

Hyperhomocysteinemia (hHcys) enhances ceramide production, leading to the activation of NADPH oxidase and consequent glomerular oxidative stress and sclerosis. The present study was performed to determine whether acid sphingomyelinase (Asm), a ceramide-producing enzyme, is implicated in the development of hHcys-induced glomerular oxidative stress and injury. Uninephrectomized Asm-knockout (Asm−/−) and wild-type (Asm+/+) mice, with or without Asm short hairpin RNA (shRNA) transfection, were fed a folate-free (FF) diet for 8 weeks, which significantly elevated the plasma Hcys level compared with mice fed normal chow. By using in vivo molecular imaging, we found that transfected shRNAs were expressed in the renal cortex starting on day 3 and continued for 24 days. The FF diet significantly increased renal ceramide production, Asm mRNA and activity, urinary total protein and albumin excretion, glomerular damage index, and NADPH-dependent superoxide production in the renal cortex from Asm+/+ mice compared with that from Asm−/− or Asm shRNA-transfected wild-type mice. Immunofluorescence analysis showed that the FF diet decreased the expression of podocin but increased desmin and ceramide levels in glomeruli from Asm+/+ mice but not in those from Asm−/− and Asm shRNA-transfected wild-type mice. In conclusion, our observations reveal that Asm plays a pivotal role in mediating podocyte injury and glomerular sclerosis associated with NADPH oxidase–associated local oxidative stress during hHcys. PMID:21893018

Diabetic Kidney Disease: A Syndrome Rather Than a Single Disease

PubMed Central

Piccoli, Giorgina B.; Grassi, Giorgio; Cabiddu, Gianfranca; Nazha, Marta; Roggero, Simona; Capizzi, Irene; De Pascale, Agostino; Priola, Adriano M.; Di Vico, Cristina; Maxia, Stefania; Loi, Valentina; Asunis, Anna M.; Pani, Antonello; Veltri, Andrea

2015-01-01

The term "diabetic kidney" has recently been proposed to encompass the various lesions, involving all kidney structures that characterize protean kidney damage in patients with diabetes. While glomerular diseases may follow the stepwise progression that was described several decades ago, the tenet that proteinuria identifies diabetic nephropathy is disputed today and should be limited to glomerular lesions. Improvements in glycemic control may have contributed to a decrease in the prevalence of glomerular lesions, initially described as hallmarks of diabetic nephropathy, and revealed other types of renal damage, mainly related to vasculature and interstitium, and these types usually present with little or no proteinuria. Whilst glomerular damage is the hallmark of microvascular lesions, ischemic nephropathies, renal infarction, and cholesterol emboli syndrome are the result of macrovascular involvement, and the presence of underlying renal damage sets the stage for acute infections and drug-induced kidney injuries. Impairment of the phagocytic response can cause severe and unusual forms of acute and chronic pyelonephritis. It is thus concluded that screening for albuminuria, which is useful for detecting "glomerular diabetic nephropathy", does not identify all potential nephropathies in diabetes patients. As diabetes is a risk factor for all forms of kidney disease, diagnosis in diabetic patients should include the same combination of biochemical, clinical, and imaging tests as employed in non-diabetic subjects, but with the specific consideration that chronic kidney disease (CKD) may develop more rapidly and severely in diabetic patients. PMID:26676663

Requirement for Class II Phosphoinositide 3-Kinase C2α in Maintenance of Glomerular Structure and Function▿

PubMed Central

Harris, David P.; Vogel, Peter; Wims, Marie; Moberg, Karen; Humphries, Juliane; Jhaver, Kanchan G.; DaCosta, Christopher M.; Shadoan, Melanie K.; Xu, Nianhua; Hansen, Gwenn M.; Balakrishnan, Sanjeevi; Domin, Jan; Powell, David R.; Oravecz, Tamas

2011-01-01

An early lesion in many kidney diseases is damage to podocytes, which are critical components of the glomerular filtration barrier. A number of proteins are essential for podocyte filtration function, but the signaling events contributing to development of nephrotic syndrome are not well defined. Here we show that class II phosphoinositide 3-kinase C2α (PI3KC2α) is expressed in podocytes and plays a critical role in maintaining normal renal homeostasis. PI3KC2α-deficient mice developed chronic renal failure and exhibited a range of kidney lesions, including glomerular crescent formation and renal tubule defects in early disease, which progressed to diffuse mesangial sclerosis, with reduced podocytes, widespread effacement of foot processes, and modest proteinuria. These findings were associated with altered expression of nephrin, synaptopodin, WT-1, and desmin, indicating that PI3KC2α deficiency specifically impacts podocyte morphology and function. Deposition of glomerular IgA was observed in knockout mice; importantly, however, the development of severe glomerulonephropathy preceded IgA production, indicating that nephropathy was not directly IgA mediated. PI3KC2α deficiency did not affect immune responses, and bone marrow transplantation studies also indicated that the glomerulonephropathy was not the direct consequence of an immune-mediated disease. Thus, PI3KC2α is critical for maintenance of normal glomerular structure and function by supporting normal podocyte function. PMID:20974805

Association between anti-beta2 glycoprotein I antibodies and renal glomerular C4d deposition in lupus nephritis patients with glomerular microthrombosis: a prospective study of 155 cases.

PubMed

Shen, Y; Chen, X-W; Sun, C-Y; Dai, M; Yan, Y-C; Yang, C-D

2010-09-01

Glomerular microthrombosis (GMT) is a common vascular change in patients with lupus nephritis (LN). The mechanism underlying GMT is still unknown. In our previous study, we found that the level of IgG anti-beta2 glycoprotein I (beta2GPI) antibodies was higher in the LN-GMT group than in the LN-non-GMT group, which indicated that anti-beta2GPI antibodies may play a role in GMT formation. Many studies have demonstrated that the activation of the classical complement pathway may play a critical role in fetal loss and aPL-induced thrombosis formation. To investigate whether complement activation plays a role in GMT formation and to evaluate its relationship with aPL, we prospectively investigated deposition of C4d in 155 renal biopsy specimens of LN patients. The results revealed a strong relationship between the intensity of glomerular C4d staining and the presence of microthrombi (p < 0.001). The detection rate of IgG anti-beta2GPI antibodies was higher in the LN-GMT group than in the LN-non-GMT group (p < 0.05). Further, the intensity of glomerular C4d staining was significantly related with IgG anti-beta2GPI antibodies (p < 0.05). The results of our study suggest that anti-beta2GPI antibodies may play a role in GMT formation, and this process might involve complement activation.

Comparison of odor and mating-induced glomerular activation in the main olfactory bulb of estrous female ferrets.

PubMed

Batterton, M N; Robarts, D; Woodley, S K; Baum, M J

2006-06-12

Previously [S.K. Woodley, M.J. Baum, Differential activation of glomeruli in the ferret's main olfactory bulb by anal scent gland odors from males and females: an early step in mate identification, Eur. J. Neurosci. 20 (2004) 1025-1032], the receipt of intromission from a male activated glomeruli (indexed by Fos immunoreactivity in juxtaglomerular cells) in the main olfactory bulb (MOB) of estrous female ferrets which exceeded the activation seen after exposure to male anal scent gland odorants alone. We asked whether centrifugal inputs (e.g., from the locus coeruleus to the MOB) generated by the receipt of vaginal-cervical stimulation influence odor-induced MOB glomerular activation. We compared the activation of MOB glomeruli in estrous female ferrets which received a unilateral naris occlusion prior to exposure to: unscented air, volatile odorants from an anesthetized male, volatile + non-volatile odorants from direct physical contact with an anesthetized male, or mating stimulation. Little glomerular activation was observed in the MOB ipsilateral to an occluded naris, including females which received intromission. An equivalent distribution of activated glomeruli was observed in the ventral MOB of estrous females which either received mating stimulation or had direct physical contact with an anesthetized male. Considerably less glomerular activation occurred in females exposed only to volatile male odors. The MOB of female ferrets responded to body odorants from the opposite sex; however, there was no evidence that mating-induced centrifugal inputs directly activated MOB glomeruli or modified odor-induced glomerular activation.

SITE TECHNOLOGY CAPSULE: ZENOGEM™ WASTEWATER TREATMENT PROCESS

EPA Science Inventory

Zenon Environmental System's ZenoGem™ Wastewater Treatment Process treats aqueous media contaminated with volatile/semi-volatile organic compounds. This technology combines aerobic biological treatment to remove biodegradable organic compounds with ultrafiltration to separate res...

21 CFR 177.2910 - Ultra-filtration membranes.

Code of Federal Regulations, 2012 CFR

2012-04-01

... a microporous poly(vinylidene fluoride) membrane with a hydrophilic surface modifier consisting of... washing with a minimum of 8 gallons of potable water prior to their first use in contact with food. (g...

21 CFR 177.2910 - Ultra-filtration membranes.

Code of Federal Regulations, 2011 CFR

2011-04-01

... a microporous poly(vinylidene fluoride) membrane with a hydrophilic surface modifier consisting of... washing with a minimum of 8 gallons of potable water prior to their first use in contact with food. (g...

21 CFR 177.2910 - Ultra-filtration membranes.

Code of Federal Regulations, 2013 CFR

2013-04-01

... a microporous poly(vinylidene fluoride) membrane with a hydrophilic surface modifier consisting of... washing with a minimum of 8 gallons of potable water prior to their first use in contact with food. (g...

Associations between age, body size and nephron number with individual glomerular volumes in urban West African males

PubMed Central

McNamara, Bridgette J.; Diouf, Boucar; Hughson, Michael D.; Hoy, Wendy E.; Bertram, John F.

2009-01-01

Background. Glomerulomegaly has been associated with an increased risk of renal disease. Few reports have investigated the heterogeneity of glomerular size within kidneys and associated risk factors. This study measured the individual glomerular volume (IGV) of 720 non-sclerotic glomeruli in kidneys of adult West African males, and investigated associations of IGV with age, total glomerular (nephron) number and body surface area (BSA). Methods. IGVs were determined in the kidneys of 24 Senegalese males from two age groups (12 subjects aged 20– 30 years and 12 subjects aged 50–70 years). Subjects were randomly chosen at autopsies performed at Le Dantec Hospital in Dakar. Volumes of 30 glomeruli per subject were determined using the disector/Cavalieri stereological method. Results. IGVs ranged from 1.31 × 106 μm3 to 12.40 × 106 μm3 (a 9.4-fold variation). IGV varied up to 5.3-fold within single kidneys. The trimmed range of IGV within subjects (10th to 90th percentile of IGV) was directly correlated with median glomerular size. The mean and standard deviation (SD) of IGV did not differ significantly between age groups or between subjects with higher (≥1.78 m2) and lower BSA (<1.78 m2). In older subjects the SD of IGV was significantly and directly correlated with BSA. Kidneys with less than 1 million nephrons had significantly larger mean IGV than kidneys with more than 1 million nephrons, and the trimmed range of IGVs within subjects was inversely correlated with total glomerular number. Conclusion. There was a considerable variation in IGV within kidneys of Senegalese males at autopsy. The heterogeneity of IGV was increased in association with low nephron number and increased BSA, with more pronounced effects in older subjects. PMID:19028752

Contribution of stone size to chronic kidney disease in kidney stone formers.

PubMed

Ahmadi, Farrokhlagha; Etemadi, Samira Motedayen; Lessan-Pezeshki, Mahbob; Mahdavi-Mazdeh, Mitra; Ayati, Mohsen; Mir, Alireza; Yazdi, Hadi Rokni

2015-01-01

To determine whether stone burden correlates with the degree of chronic kidney disease in kidney stone formers. A total of 97 extracorporeal shockwave lithotripsy candidates aged 18 years and older were included. Size, number and location of the kidney stones, along with cumulative stone size, defined as the sum of diameters of all stones) were determined. Estimated glomerular filtration rate was determined using the Chronic Kidney Disease Epidemiology Collaboration cystatin C/creatinine equation, and chronic kidney disease was defined as estimated glomerular filtration rate <60 mL/min/1.73 m(2). In individuals with cumulative stone size <20 mm, estimated glomerular filtration rate significantly decreased when moving from the first (estimated glomerular filtration rate 75.5 ± 17.8 mL/min/1.73 m(2)) to the fourth (estimated glomerular filtration rate 56.4 ± 20.44 mL/min/1.73 m(2) ) quartile (P = 0.004). When patients with a cumulative stone size ≥ 20 mm were included, the observed association was rendered non-significant. In individuals with a cumulative stone size < 20 mm, each 1-mm increase in cumulative stone size was associated with a 20% increased risk of having chronic kidney disease. The relationship persisted even after adjustment for age, sex, body mass index, C-reactive protein, fasting plasma glucose, thyroid stimulating hormone, presence of microalbuminuria, history of renal calculi, history of extracorporeal shockwave lithotripsy, number and location of the stones (odds ratio 1.24, 95% confidence interval 1.02-1.52). The same was not observed for individuals with a cumulative stone size ≥ 20 mm. In kidney stone formers with a cumulative stone size up to 20 mm, estimated glomerular filtration rate linearly declines with increasing cumulative stone size. Additionally, cumulative stone size is an independent predictor of chronic kidney disease in this group of patients. © 2014 The Japanese Urological Association.

Progressive glomerular and tubular damage in sickle cell trait and sickle cell anemia mouse models.

PubMed

Saraf, Santosh L; Sysol, Justin R; Susma, Alexandru; Setty, Suman; Zhang, Xu; Gudehithlu, Krishnamurthy P; Arruda, Jose A L; Singh, Ashok K; Machado, Roberto F; Gordeuk, Victor R

2018-02-02

Homozygosity for the hemoglobin (Hb) S mutation (HbSS, sickle cell anemia) results in hemoglobin polymerization under hypoxic conditions leading to vaso-occlusion and hemolysis. Sickle cell anemia affects 1:500 African Americans and is a strong risk factor for kidney disease, although the mechanisms are not well understood. Heterozygous inheritance (HbAS; sickle cell trait) affects 1:10 African Americans and is associated with an increased risk for kidney disease in some reports. Using transgenic sickle mice, we investigated the histopathologic, ultrastructural, and gene expression differences with the HbS mutation. Consistent with progressive glomerular damage, we observed progressively greater urine protein concentrations (P = 0.03), glomerular hypertrophy (P = 0.002), and glomerular cellularity (P = 0.01) in HbAA, HbAS, and HbSS mice, respectively. Ultrastructural studies demonstrated progressive podocyte foot process effacement, glomerular basement membrane thickening with reduplication, and tubular villous atrophy with the HbS mutation. Gene expression studies highlighted the differential expression of several genes involved in prostaglandin metabolism (AKR1C18), heme and iron metabolism (HbA-A2, HMOX1, SCL25A37), electrolyte balance (SLC4A1, AQP6), immunity (RSAD2, C3, UBE2O), fatty acid metabolism (FASN), hypoxia hall-mark genes (GCK, SDC3, VEGFA, ETS1, CP, BCL2), as well as genes implicated in other forms of kidney disease (PODXL, ELMO1, FRMD3, MYH9, APOA1). Pathway analysis highlighted increased gene enrichment in focal adhesion, extracellular matrix-receptor interaction, and axon guidance pathways. In summary, using transgenic sickle mice, we observed that inheritance of the HbS mutation is associated with glomerular and tubular damage and identified several candidate genes and pathways for future investigation in sickle cell trait and sickle cell anemia-related kidney disease. Copyright © 2018 Elsevier Inc. All rights reserved.

Underlying renal insufficiency: the pivotal risk factor for Pneumocystis jirovecii pneumonia in immunosuppressed patients with non-transplant glomerular disease.

PubMed

Ye, Wen-Ling; Tang, Nan; Wen, Yu-Bing; Li, Hang; Li, Min-Xi; Du, Bin; Li, Xue-Mei

2016-11-01

Data on PCP in patients with glomerular disease are rare. The aim of this study was to assess the predictors of PCP development, the risk factors for mortality and the incidence of acute kidney injury (AKI) when high-dose trimethoprim-sulphamethoxazole (TMP-SMX) was used in patients with non-transplant glomerular disease. Forty-seven patients with PCP, as confirmed by positive results for Pneumocystis jirovecii DNA or Pneumocystis jirovecii cysts tested by a methenamine silver stain between January 1, 2003, and December 30, 2012, were retrospectively investigated. The baseline characteristics of glomerular disease, clinical findings of PCP and renal parameters after treatment were collected. Predictors for PCP development and risk factors for mortality were determined using a multivariate logistic regression analysis. All PCP patients exclusively received immunosuppressants. Baseline renal insufficiency [estimated glomerular filtration rate (eGFR) <60 mL/min·1.73 m 2 ] was present in 87.23 % of patients. The overall mortality rate was 29.79 %. A pulmonary coinfection and the need for mechanical ventilation were independently associated with PCP mortality. A lower eGFR, lower serum albumin level and a higher percentage of global glomerulosclerosis were independent predictors of PCP in patients with IgA nephropathy receiving immunosuppressants. AKI occurred in 60.47 % of patients who received TMP-SMX. After treatment cessation, 93.75 % of surviving patients showed a recovery of renal function to baseline values. PCP is a fatal complication in patients with glomerular disease, and the use of immunosuppressants may be a basic risk factor for this infection. Underlying renal insufficiency and high renal pathology chronicity are the key risk factors for PCP in IgA nephropathy. TMP-SMX therapy remains an ideal choice because of high treatment response and frequently reversible kidney injury.

GLUT-1 overexpression: Link between hemodynamic and metabolic factors in glomerular injury?

PubMed

Gnudi, Luigi; Viberti, GianCarlo; Raij, Leopoldo; Rodriguez, Veronica; Burt, Davina; Cortes, Pedro; Hartley, Barry; Thomas, Stephen; Maestrini, Sabrina; Gruden, Gabriella

2003-07-01

Mesangial matrix deposition is the hallmark of hypertensive and diabetic glomerulopathy. At similar levels of systemic hypertension, Dahl salt-sensitive but not spontaneously hypertensive rats (SHR) develop glomerular hypertension, which is accompanied by upregulation of transforming growth factor beta1 (TGF-beta1), mesangial matrix expansion, and sclerosis. GLUT-1 is ubiquitously expressed and is the predominant glucose transporter in mesangial cells. In mesangial cells in vitro, GLUT-1 overexpression increases basal glucose transport, resulting in excess fibronectin and collagen production. TGF-beta1 has been shown to upregulate GLUT-1 expression. We demonstrated that in hypertensive Dahl salt-sensitive (S) rats fed 4% NaCl (systolic blood pressure [SBP]: 236+/-9 mm Hg), but not in similarly hypertensive SHR (SBP: 230+/-10 mm Hg) or their normotensive counterparts (Dahl S fed 0.5% NaCl, SBP: 145+/-5 mm Hg; and Wistar-Kyoto, SBP: 137+/-3 mm Hg), there was an 80% upregulation of glomerular GLUT-1 protein expression (P< or =0.03). This was accompanied by a 2.7-fold upregulation of TGF-beta1 protein expression in glomeruli of DSH compared with DSN rats (P=0.02). TGF-beta1 expression was not upregulated and did not differ in the glomeruli of Wistar-Kyoto and SHR rats. As an in vitro surrogate of the in vivo hemodynamic stress imposed by glomerular hypertension, we used mechanical stretching of human and rat mesangial cells. We found that after 33 hours of stretching, mesangial cells overexpressed GLUT-1 (40%) and showed an increase in basal glucose transport of similar magnitude (both P< or =0.01), which could be blocked with an anti TGF-beta1-neutralizing antibody. These studies suggest a novel link between hemodynamic and metabolic factors that may cooperate in inducing progressive glomerular injury in conditions characterized by glomerular hypertension.

Pretreatment Engineering Platform Phase 1 Final Test Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kurath, Dean E.; Hanson, Brady D.; Minette, Michael J.

2009-12-23

Pacific Northwest National Laboratory (PNNL) was tasked by Bechtel National Inc. (BNI) on the River Protection Project, Hanford Tank Waste Treatment and Immobilization Plant (RPP-WTP) project to conduct testing to demonstrate the performance of the WTP Pretreatment Facility (PTF) leaching and ultrafiltration processes at an engineering-scale. In addition to the demonstration, the testing was to address specific technical issues identified in Issue Response Plan for Implementation of External Flowsheet Review Team (EFRT) Recommendations - M12, Undemonstrated Leaching Processes.( ) Testing was conducted in a 1/4.5-scale mock-up of the PTF ultrafiltration system, the Pretreatment Engineering Platform (PEP). Parallel laboratory testing wasmore » conducted in various PNNL laboratories to allow direct comparison of process performance at an engineering-scale and a laboratory-scale. This report presents and discusses the results of those tests.« less

Effect of acid whey-fortified breads on caecal fermentation processes and blood lipid profile in rats.

PubMed

Wronkowska, Małgorzata; Soral-Śmietana, Maria; Zduńczyk, Zenon; Juśkiewicz, Jerzy; Jadacka, Monika; Majkowska, Anna; Dajnowiec, Fabian J

2017-08-01

Two types of diet - standard and atherogenic - were used to study the effect of wheat or wheat-rye breads supplemented with 20 % acid whey concentrate after ultrafiltration on the physiological response of growing rats. The acid whey concentrate after ultrafiltration used in rat diets caused reduced weight gain (for atherogenic diet with wheat bread); growth of caecum tissue and digesta weight; a decrease in the pH of caecum digesta (for atherogenic diet); reduced activity of bacterial glycolytic enzymes; and a significant increase in total SCFA for both types of diet with wheat-rye breads containing acid whey concentrate. For wheat bread with acid whey, in standard diet, a statistically significant increase was found in the population of bifidobacteria. The results showed that the acid whey concentrates could be used as a valuable food ingredient.

Ultrafiltration for the Determination of Cu Complexed with Dissolved Organic Matters of Different Molecular Weight from a Eutrophic River, China.

PubMed

Li, Anding; Zhang, Yan; Zhou, Beihai; Xin, Kailing; Gu, Yingnan; Xu, Weijie; Tian, Jie

2018-05-21

The molecular weight of dissolved organic matter (DOM) is one of the essential factors controlling the properties of metal complexes. A continuous ultrafiltration experiment was designed to study the properties of Cu complexes with different molecular weights in a river before and after eutrophication. The results showed that the concentration of DOM increased from 26.47 to 38.20 mg/L during the eutrophication process, however, DOM was still dominated by the small molecular weight fraction before and after eutrophication. The amount of Cu-DOM complexes increased with the increasing of molecular weight, however, the amounts of DOM-Cu complexes before eutrophication were higher than those after eutrophication. This is because DOM contained more -COOH and -OH before eutrophication and these functional groups are the active sites complexed with Cu.

Polyethersulfone - barium chloride blend ultrafiltration membranes for dye removal studies

NASA Astrophysics Data System (ADS)

Rambabu, K.; Srivatsan, N.; Gurumoorthy, Anand V. P.

2017-11-01

A series of Polyethersulfone (PES) - barium chloride (BaCl2) blend ultra filtration membrane was developed by varying the BaCl2 concentration in the dope solution. Prepared membranes were subjected to membrane characterization and their performance was studied through dye rejection tests. Morphological studies through SEM and AFM showed that the composite membranes exhibited differences in morphologies, porosities and properties due to the BaCl2 addition as compared with pristine PES membrane. Addition of the inorganic modifier enhanced the hydrophilicity and water permeability of the blend membrane system. Polymer enhanced ultrafiltration of dye solutions showed that the proposed blend system had better performance in terms of flux and rejection efficiency than the pure polymer membrane. The performance of the 2 wt% BaCl2 blend membrane was more promising for application to real time dye wastewater studies.

Synthesis and characterization of composite polysulfone membranes for desalination in nanofiltration technique.

PubMed

Akbari, A; Homayonfal, M; Jabbari, V

2010-01-01

Composite nanofiltration (NF) membrane was developed polyacrylic acid (PAA) in situ UV graft polymerization process using ultrafiltration (UF) polysulfone (PSF) membrane as porous support. FT-IR spectra indicated that grafting was performed and it show peaks at 1,732 cm⁻¹ and 3,396 cm⁻¹ region for CO and OH starching bond of acrylic acid (AA) monomer, respectively. AFM microscopy showed the roughness of surface was reduced by increase of UV irradiation times. Effect of irradiation time on the grafting of acrylic acid (AA) in the same concentration was discussed. The salts rejection increase was accompanied with grafting of polysulfone (PSF) ultrafiltration (UF) membrane. The rejection of Na₂SO₄, MgSO₄, NaCl and CaCl₂ salts by PSF-grafted-PAA nanofiltration (NF) membrane was in 98, 60, 52 and 30% respectively, under 0.3 MPa.

Treatment of the Bleaching Effluent from Sulfite Pulp Production by Ceramic Membrane Filtration

PubMed Central

Ebrahimi, Mehrdad; Busse, Nadine; Kerker, Steffen; Schmitz, Oliver; Hilpert, Markus; Czermak, Peter

2015-01-01

Pulp and paper waste water is one of the major sources of industrial water pollution. This study tested the suitability of ceramic tubular membrane technology as an alternative to conventional waste water treatment in the pulp and paper industry. In this context, in series batch and semi-batch membrane processes comprising microfiltration, ultrafiltration and nanofiltration, ceramic membranes were developed to reduce the chemical oxygen demand (COD) and remove residual lignin from the effluent flow during sulfite pulp production. A comparison of the ceramic membranes in terms of separation efficiency and performance revealed that the two-stage process configuration with microfiltration followed by ultrafiltration was most suitable for the efficient treatment of the alkaline bleaching effluent tested herein, reducing the COD concentration and residual lignin levels by more than 35% and 70%, respectively. PMID:26729180

Treatment of the Bleaching Effluent from Sulfite Pulp Production by Ceramic Membrane Filtration.

PubMed

Ebrahimi, Mehrdad; Busse, Nadine; Kerker, Steffen; Schmitz, Oliver; Hilpert, Markus; Czermak, Peter

2015-12-31

Pulp and paper waste water is one of the major sources of industrial water pollution. This study tested the suitability of ceramic tubular membrane technology as an alternative to conventional waste water treatment in the pulp and paper industry. In this context, in series batch and semi-batch membrane processes comprising microfiltration, ultrafiltration and nanofiltration, ceramic membranes were developed to reduce the chemical oxygen demand (COD) and remove residual lignin from the effluent flow during sulfite pulp production. A comparison of the ceramic membranes in terms of separation efficiency and performance revealed that the two-stage process configuration with microfiltration followed by ultrafiltration was most suitable for the efficient treatment of the alkaline bleaching effluent tested herein, reducing the COD concentration and residual lignin levels by more than 35% and 70%, respectively.

Reduction of disinfection by-product precursors in reservoir water by coagulation and ultrafiltration.

PubMed

Wang, Feng; Gao, Baoyu; Ma, Defang; Yue, Qinyan; Li, Ruihua; Wang, Qianwen

2016-11-01

In this study, reservoir water intended for drinking water supply was treated by (i) ultrafiltration (UF) (ii) coagulation (CW) (iii) coagulation combined with ultrafiltration (CW-UF). To probe the influences of three treatment processes on disinfection byproduct (DBP) precursors in source water, the changes of dissolved organic matter (DOM) amounts and physicochemical properties, and disinfection byproduct (DBP) formation characteristics during chlorine disinfection were investigated. Both carbonaceous DBP (C-DBP) and nitrogenous DBP (N-DBP) formation and speciation were analyzed. The influence of chlorine dose, contact time on DBP formation and speciation were also studied to optimize the disinfection conditions to minimize the DBP formation. Compared with UF and CW alone, CW-UF improved the dissolved organic carbon (DOC) removal from about 20 % to 59 %. The three-dimensional excitation and emission matrix (3DEEM) fluorescence spectroscopy analysis showed that CW-UF had high removal efficiency in microbial products (Region IV), fulvic acid-like (Region III) and humic acid-like (Region V). The total C-DBP was determined by the formation of trihalomethanes and trichloromethane was the most abundant species (40 %). The most abundant N-DBP species was dichloroacetonitrile (32.5 %), followed by trichloroactetonitrile. CW-UF effectively reduced the risk of DBPs in drinking water supply by reducing 30.8 % and 16.9 % DBPs formation potential compared with UF and CW alone. Increasing contact time improved the yields of both C-DBPs and N-DBPs. Chlorine dosage had slight influence on DBP yield in this study.

Selective separation of Eu{sup 3+} using polymer-enhanced ultrafiltration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Norton, M.V.

1994-03-01

A process to selectively remove {sup 241}Am from liquid radioactive waste was investigated as an actinide separation method applicable to Hanford and other waste sites. The experimental procedures involved removal of Eu, a nonradioactive surrogate for Am, from aqueous solutions at pH 5 using organic polymers in conjunction with ultrafiltration. Commercially available polyacrylic acid (60,000 MW) and Pacific Northwest Laboratory`s (PNL) synthesized E3 copolymer ({approximately}10,000 MW) were tested. Test solutions containing 10 {mu}g/mL of Eu were dosed vath each polymer at various concentrations in order to bind Eu (i.e., by complexation and/or cation exchange) for subsequent rejection by an ultrafiltrationmore » coupon. Test solutions were filtered with and without polymer to determine if enhanced Eu separation could be achieved from polymer treatment. Both polymers significantly increased Eu removal. Optimum concentrations were 20 {mu}g/mL of polyacrylic acid and 100 {mu}g/mL of E3 for 100% Eu rejection by the Amicon PM10 membrane at 55 psi. In addition to enhancement of removal, the polymers selectively bound Eu over Na, suggesting that selective separation of Eu was possible. This suggests that polymer-enhanced ultrafiltration is a potential process for separation of {sup 241}Am from Hanford tank waste, further investigation of binding agents and membranes effective under very alkaline and high ionic strength is warranted. This process also has potential applications for selective separation of toxic metals from industrial process streams.« less

Dual-Functional Ultrafiltration Membrane for Simultaneous Removal of Multiple Pollutants with High Performance.

PubMed

Pan, Shunlong; Li, Jiansheng; Noonan, Owen; Fang, Xiaofeng; Wan, Gaojie; Yu, Chengzhong; Wang, Lianjun

2017-05-02

Simultaneous removal of multiple pollutants from aqueous solution with less energy consumption is crucial in water purification. Here, a novel concept of dual-functional ultrafiltration (DFUF) membrane is demonstrated by entrapment of nanostructured adsorbents into the finger-like pores of ultrafiltration (UF) membrane rather than in the membrane matrix in previous reports of blend membranes, resulting in an exceptionally high active content and simultaneous removal of multiple pollutants from water due to the dual functions of rejection and adsorption. As a demonstration, hollow porous Zr(OH) x nanospheres (HPZNs) were immobilized in poly(ether sulfone) (PES) UF membranes through polydopamine coating with a high content of 68.9 wt %. The decontamination capacity of DFUF membranes toward multiple model pollutants (colloidal gold, polyethylene glycol (PEG), Pb(II)) was evaluated against a blend membrane. Compared to the blend membrane, the DFUF membranes showed 2.1-fold increase in the effective treatment volume for the treatment of Pb(II) contaminated water from 100 ppb to below 10 ppb (WHO drinking water standard). Simultaneously, the DFUF membranes effectively removed the colloidal gold and PEG below instrument detection limit, however the blend membrane only achieved 97.6% and 96.8% rejection for colloidal gold and PEG, respectively. Moreover, the DFUF membranes showed negligible leakage of nanoadsorbents during testing; and the membrane can be easily regenerated and reused. This study sheds new light on the design of high performance multifunction membranes for drinking water purification.

Fractionation of canine serum magnesium.

PubMed

Schenck, Patricia A

2005-06-01

Serum total magnesium (tMg) consists of 3 fractions: ionized magnesium (iMg), protein-bound magnesium (pbMg), and complexed magnesium (cMg). Serum iMg may be measured by an ion-selective electrode, but determination of pbMg and cMg has not been attempted in dogs. The objectives of this study were to assess the validity of a micropartition system to fractionate serum tMg and to establish reference intervals for pbMg, cMg, and iMg in clinically normal dogs using this method. Serum samples from 10 clinically healthy dogs were fractionated using a micropartition system (Centrifree YM-30, Amicon Corp, Lexington, MA, USA). Serum tMg and iMg were measured in whole serum, and tMg was also measured in the ultrafiltrate. Concentration of cMg was obtained by the subtraction of iMg from tMg concentrations of the ultrafiltrate. Protein-bound Mg was calculated by subtracting the tMg concentration of the ultrafiltrate from the tMg concentration of whole serum. Results for pbMg and cMg using the micropartition system showed good reproducibility. Determination of tMg and iMg had acceptable inter- and intra-assay precision. Concentrations of iMg, cMg, and pbMg were 0.50 +/- 0.05 mmol/L, 0.05 +/- 0.04 mmol/L, and 0.24 +/- 0.04 mmol/L, representing 63%, 6%, and 31% of the tMg concentration, respectively. The micropartition system was a reproducible means to accurately assess cMg and pbMg concentrations in dogs.

Gold nanoparticle chemiresistors operating in biological fluids.

PubMed

Hubble, Lee J; Chow, Edith; Cooper, James S; Webster, Melissa; Müller, Karl-Heinz; Wieczorek, Lech; Raguse, Burkhard

2012-09-07

Functionalised gold nanoparticle (Au(NP)) chemiresistors are investigated for direct sensing of small organic molecules in biological fluids. The principle reason that Au(NP) chemiresistors, and many other sensing devices, have limited operation in biological fluids is due to protein and lipid fouling deactivating the sensing mechanism. In order to extend the capability of such chemiresistor sensors to operate directly in biofluids, it is essential to minimise undesirable matrix effects due to protein and lipidic components. Ultrafiltration membranes were investigated as semi-permeable size-selective barriers to prevent large biomolecule interactions with Au(NP) chemiresistors operating in protein-loaded biofluids. All of the ultrafiltration membranes protected the Au(NP) chemiresistors from fouling by the globular biomolecules, with the 10 kDa molecular weight cut-off size being optimum for operation in biofluids. Titrations of toluene in different protein-loaded fluids indicated that small molecule detection was possible. A sensor array consisting of six different thiolate-functionalised Au(NP) chemiresistors protected with a size-selective ultrafiltration membrane successfully identified, and discriminated the spoilage of pasteurised bovine milk. This proof-of-principle study demonstrates the on-chip protein separation and small metabolite detection capability, illustrating the potential for this technology in the field of microbial metabolomics. Overall, these results demonstrate that a sensor array can be protected from protein fouling with the use of a membrane, significantly increasing the possible application areas of Au(NP) chemiresistors ranging from the food industry to health services.

Pharmacokinetic analysis of flomoxef in children undergoing cardiopulmonary bypass and modified ultrafiltration.

PubMed

Masuda, Zenichi; Kurosaki, Yuji; Ishino, Kozo; Yamauchi, Keita; Sano, Shunji

2008-04-01

Cardiopulmonary bypass (CPB) induces changes in the pharmacokinetics of drugs. The purpose of this study was to model the pharmacokinetics of flomoxef, a cephalosporin antibiotic, in pediatric cardiac surgery. Each patient received a flomoxef dose of 30 mg/kg as a bolus after the induction of anesthesia and an additional dose (1 g for a child weighing < 10 kg, 2 g for > or = 10 kg) was injected into the CPB prime. Modified ultrafiltration (MUF) was routinely performed. Blood samples, urine, and ultrafiltrate were collected. In seven patients (group I), serum flomoxef concentration-time courses were analyzed by a modified two-compartment model. Utilizing the estimated parameters, serum concentrations were simulated in another eight patients (group II). The initiation of CPB resulted in an abrupt increase in serum flomoxef concentrations in group I; however, concentrations declined biexponentially. The amount of excreted flomoxef in the urine and by MUF was 47% +/- 8% of the total administered dose. In group II, an excellent fit was found between the values calculated by the program and the observed serum concentrations expressed; most of the performance errors were <1.0. There was no difference in any kinetic parameter between group I and groups I + II (n = 15). The pharmacokinetics of flomoxef in children undergoing CPB and MUF were well fitted to a modified two-compartment model. Using the kinetic data from this study, the individualization of dosage regimens for prophylactic use of flomoxef might be possible.

Current advances in screening for bioactive components from medicinal plants by affinity ultrafiltration mass spectrometry.

PubMed

Chen, Guilin; Huang, Bill X; Guo, Mingquan

2018-05-21

Medicinal plants have played an important role in maintaining human health for thousands of years. However, the interactions between the active components in medicinal plants and some certain biological targets during a disease are still unclear in most cases. To conduct the high-throughput screening for small active molecules that can interact with biological targets, which is of great theoretical significance and practical value. The ultrafiltration mass spectrometry (UF-LC/MS) is a powerful bio-analytical method by combining affinity ultrafiltration and liquid chromatography-mass spectrometry (LC/MS), which could rapidly screen and identify small active molecules that bind to biological targets of interest at the same time. Compared with other analytical methods, affinity UF-LC/MS has the characteristics of fast, sensitive and high throughput, and is especially suitable for the complicated extracts of medicinal plants. In this review, the basic principle, characteristics and some most recent challenges in UF-LC/MS have been demonstrated. Meanwhile, the progress and applications of affinity UF-LC/MS in the discovery of the active components from natural medicinal plants and the interactions between small molecules and biological target proteins are also briefly summarised. In addition, the future directions for UF-LC/MS are also prospected. Affinity UF-LC/MS is a powerful tool in studies on the interactions between small active molecules and biological protein targets, especially in the high-throughput screening of active components from the natural medicinal plants. Copyright © 2018 John Wiley & Sons, Ltd.

Production of wheat gluten hydrolysates with reduced antigenicity employing enzymatic hydrolysis combined with downstream unit operations.

PubMed

Merz, Michael; Kettner, Lucas; Langolf, Emma; Appel, Daniel; Blank, Imre; Stressler, Timo; Fischer, Lutz

2016-08-01

Due to allergies or other health disorders a certain segment of the population is not able to safely consume some plant proteins, which are the main protein support in human nutrition. Coeliac disease is a prominent autoimmune disorder and requires a strict adherence to a gluten-free diet. The aim of this study was to identify suitable combinations of enzymatic hydrolysis and common unit operations in food processing (centrifugation, ultra-filtration) to produce gluten-free wheat gluten hydrolysates for food application. To analyse the hydrolysates, a simple and cheap competitive ELISA protocol was designed and validated in this study as well. The competitive ELISA was validated using gliadin spiked skim milk protein hydrolysates, due to the latter application of the assay. The limit of quantification was 4.19 mg kg(-1) , which allowed the identification of gluten-free (<20 mg kg(-1) ) hydrolysates. Enzymatic hydrolysis, including the type of peptidase, and the downstream processing greatly affected the antigenicity of the hydrolysates. Enzymatic hydrolysis and downstream processing operations, such as centrifugation and ultra-filtration, reduced the antigenicity of wheat gluten hydrolysates. Gluten-free hydrolysates were obtained with Flavourzyme after centrifugation (25 g L(-1) substrate) and after 1 kDa ultra-filtration (100 g L(-1) substrate). A multiple peptidase complex, such as Flavourzyme, seems to be required for the production of gluten-free hydrolysates. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

Tangential Flow Ultrafiltration Allows Purification and Concentration of Lauric Acid-/Albumin-Coated Particles for Improved Magnetic Treatment.

PubMed

Zaloga, Jan; Stapf, Marcus; Nowak, Johannes; Pöttler, Marina; Friedrich, Ralf P; Tietze, Rainer; Lyer, Stefan; Lee, Geoffrey; Odenbach, Stefan; Hilger, Ingrid; Alexiou, Christoph

2015-08-14

Superparamagnetic iron oxide nanoparticles (SPIONs) are frequently used for drug targeting, hyperthermia and other biomedical purposes. Recently, we have reported the synthesis of lauric acid-/albumin-coated iron oxide nanoparticles SEON(LA-BSA), which were synthesized using excess albumin. For optimization of magnetic treatment applications, SPION suspensions need to be purified of excess surfactant and concentrated. Conventional methods for the purification and concentration of such ferrofluids often involve high shear stress and low purification rates for macromolecules, like albumin. In this work, removal of albumin by low shear stress tangential ultrafiltration and its influence on SEON(LA-BSA) particles was studied. Hydrodynamic size, surface properties and, consequently, colloidal stability of the nanoparticles remained unchanged by filtration or concentration up to four-fold (v/v). Thereby, the saturation magnetization of the suspension can be increased from 446.5 A/m up to 1667.9 A/m. In vitro analysis revealed that cellular uptake of SEON(LA-BSA) changed only marginally. The specific absorption rate (SAR) was not greatly affected by concentration. In contrast, the maximum temperature Tmax in magnetic hyperthermia is greatly enhanced from 44.4 °C up to 64.9 °C by the concentration of the particles up to 16.9 mg/mL total iron. Taken together, tangential ultrafiltration is feasible for purifying and concentrating complex hybrid coated SPION suspensions without negatively influencing specific particle characteristics. This enhances their potential for magnetic treatment.

21 CFR 177.2910 - Ultra-filtration membranes.

Code of Federal Regulations, 2010 CFR

2010-04-01

... of a sintered carbon support that is coated with zirconium oxide (CAS Reg. No. 1314-23-4) containing... of an aluminum oxide support that is coated with zirconium oxide (CAS Reg. No. 1314-23-4) containing...

Effects of tea consumption on renal function in a metropolitan Chinese population: the Guangzhou biobank cohort study.

PubMed

van Hasselt, Tim J; Pickles, Oliver; Midgley-Hunt, Alex; Jiang, Chao Quiang; Zhang, Wei Sen; Cheng, Kar Keung; Thomas, Graham Neil; Lam, Tai Hing

2014-01-01

Green tea consumption has been associated with many prophylactic health benefits. This study examined for the first time associations between tea consumption and renal function in a Chinese population. Cross-sectional baseline data including demographics, and lifestyle and weekly consumption of green, black, and oolong tea were analyzed from 12,428 ambulatory subjects aged 50 to 85 years (67.3% female) that were randomly selected from the membership list of a community social and welfare association in Guangzhou, China. Associations between tea consumption and renal function were assessed using regression analyses to adjust for potential confounding factors. Renal function was assessed using the estimated glomerular filtration rate (eGFR) and in a subcohort of 1,910 participants using a spot urinary albumin-to-creatinine ratio. Six thousand eight hundred and seventy-two participants drank at least 1 type of tea. Oolong tea consumption was negatively associated with eGFR (β-coefficient -0.019, P = .025), but in a gender-stratified analysis this was not the case. In men, black tea was positively associated with eGFR (β-coefficient 0.037, P = .013), but not in women (β-coefficient -0.002, P = .856). Otherwise, no statistically significant consistent associations between the measures of renal function and consumption of green tea, black tea, or oolong tea individually or total tea consumption were identified. Overall there was no clear evidence to suggest any consistent association between renal function and tea consumption in this large population-based study of older Chinese individuals. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Effects of bisphenol A treatment during pregnancy on kidney development in mice: a stereological and histopathological study.

PubMed

Nuñez, P; Fernandez, T; García-Arévalo, M; Alonso-Magdalena, P; Nadal, A; Perillan, C; Arguelles, J

2018-04-01

Bisphenol A (BPA) is a chemical found in plastics that resembles oestrogen in organisms. Developmental exposure to endocrine-disrupting chemicals, such as BPA, increases the susceptibility to type 2 diabetes (T2DM) and cardiovascular diseases. Animal studies have reported a nephron deficit in offspring exposed to maternal diabetes. The aim of this study was to investigate the prenatal BPA exposure effects on nephrogenesis in a mouse model that was predisposed to T2DM. This study quantitatively evaluated the renal structural changes using stereology and histomorphometry methods. The OF1 pregnant mice were treated with a vehicle or BPA (10 or 100 μg/kg/day) during days 9-16 of gestation (early nephrogenesis). The 30-day-old offspring were sacrificed, and tissue samples were collected and prepared for histopathological and stereology studies. Glomerular abnormalities and reduced glomerular formation were observed in the BPA offspring. The kidneys of the BPA10 and BPA100 female offspring had a significantly lower glomerular number and density than those of the CONTROL female offspring. The glomerular histomorphometry revealed a significant difference between the female and male CONTROL offspring for the analysed glomerular parameters that disappeared in the BPA10 and BPA100 offspring. In addition, the kidney histopathological examination showed typical male cuboidal epithelial cells of the Bowman capsule in the female BPA offspring. Exposure to environmentally relevant doses of BPA during embryonic development altered nephrogenesis. These structural changes could be associated with an increased risk of developing cardiometabolic diseases later in life.

Diabetic kidney lesions of GIPRdn transgenic mice: podocyte hypertrophy and thickening of the GBM precede glomerular hypertrophy and glomerulosclerosis.

PubMed

Herbach, Nadja; Schairer, Irene; Blutke, Andreas; Kautz, Sabine; Siebert, Angela; Göke, Burkhard; Wolf, Eckhard; Wanke, Ruediger

2009-04-01

Diabetic nephropathy is the leading cause of end-stage renal disease and the largest contributor to the total cost of diabetes care. Rodent models are excellent tools to gain more insight into the pathogenesis of diabetic nephropathy. In the present study, we characterize the age-related sequence of diabetes-associated kidney lesions in GIPR(dn) transgenic mice, a novel mouse model of early-onset diabetes mellitus. Clinical-chemical analyses as well as qualitative and quantitative morphological analyses of the kidneys of GIPR(dn) transgenic animals and nontransgenic littermate controls were performed at 3, 8, 20, and 28 wk of age. Early renal changes of transgenic mice consisted of podocyte hypertrophy, reduced numerical volume density of podocytes in glomeruli, and homogenous thickening of the glomerular basement membrane, followed by renal and glomerular hypertrophy as well as mesangial expansion and matrix accumulation. At 28 wk of age, glomerular damage was most prominent, including advanced glomerulosclerosis, tubulointerstitial lesions, and proteinuria. Real-time PCR demonstrated increased glomerular expression of Col4a1, Fn1, and Tgfb1. Immunohistochemistry revealed increased mesangial deposition of collagen type IV, fibronectin, and laminin. The present study shows that GIPR(dn) transgenic mice exhibit renal changes that closely resemble diabetes-associated kidney alterations in humans. Data particularly from male transgenic mice indicate that podocyte hypertrophy is directly linked to hyperglycemia, without the influence of mechanical stress. GIPR(dn) transgenic mice are considered an excellent new tool to study the mechanisms involved in onset and progression of diabetic nephropathy.

Investigation of repeated vaccination as a possible cause of glomerular disease in mink.

PubMed

Newman, Shelley Joy; Johnson, Roger; Sears, William; Wilcock, Brian

2002-07-01

The search for antigens capable of causing immune-complex-mediated glomerulonephritis continues. Modified live-virus vaccines commercially available for veterinary use are a possible source. In this study, repeated vaccination of mink with live-virus vaccines was investigated as a model for vaccine-induced glomerular injury. Three groups of 10-wk-old mink, 15 per group, were vaccinated once with 4-way vaccine against distemper, Pseudomonas aeruginosa infection, botulism and mink viral enteritis. Subsequently, all mink in each group each were vaccinated either with the 4-way vaccine, a monovalent canine distemper vaccine, or saline. Glomerular function was assessed at 2-wk intervals by determining the urinary protein:creatinine (P:C) ratio. Kidney sections taken at necropsy, 20 wk after the 1st vaccination, were examined by light and immunofluorescent microscopy for deposition of immunoglobulin and complement. There was no statistically significant difference between the treated and control groups based on average urinary P:C ratio medians. Light microscopic changes were detected in glomeruli, but Fisher's exact test showed no significant differences between any of the treatment groups. Deposition of immunoglobulin but not complement was significantly more frequent (P < 0.05) in the glomeruli of animals that received multiple injections of the 4-way vaccine than in the glomeruli of those given only the monovalent canine distemper vaccine or saline. These findings suggest that repeated vaccination may increase the glomerular deposition of immunoglobulin. Further studies are required to determine if the increased deposition of immunoglobulin contributes to the development of glomerular damage and to identify the antigens driving production of the deposited immunoglobulin.

Microalbuminuria and plasma aldosterone levels in nondiabetic treatment-naïve patients with hypertension.

PubMed

Catena, Cristiana; Colussi, GianLuca; Martinis, Flavia; Novello, Marileda; Sechi, Leonardo A

2017-12-01

Identification of factors that contribute to urinary albumin losses in hypertensive nephropathy is crucial for prevention of renal deterioration. The aim of this study was to investigate the relationship of low-grade albuminuria with plasma aldosterone levels in treatment-naïve hypertensive patients free of additional comorbidities that might affect renal function. In 242 newly diagnosed patients with uncomplicated primary hypertension, we obtained duplicate 24-h urine collections for measurement of urinary albumin/creatinine ratio (UACR) and measured plasma aldosterone levels. Patients with diabetes, overt proteinuria (>300 mg/day), glomerular filtration rate less than 30 ml/min per 1.73 m, and previous renal diseases were excluded. Increasing UACR was associated with significantly and progressively higher blood pressure (BP), HDL-cholesterol, and plasma aldosterone levels, and with lower glomerular filtration. Microalbuminuria (30-300 mg/day) was detected in 41 (17%) of 242 hypertensive patients, and these patients had significantly higher BP and plasma aldosterone levels (178 ± 113 vs. 128 ± 84 pg/ml; P = 0.001), and lower glomerular filtration than patients without microalbuminuria. UACR was directly and independently correlated with BP and plasma aldosterone levels. In a logistic regression model, presence of microalbuminuria was associated with plasma aldosterone levels independently of glomerular filtration and demographic, anthropometric, and metabolic variables. In nondiabetic, treatment-naïve patients with hypertension, low-grade albuminuria is independently associated with elevated plasma aldosterone. These findings suggest a contribution of aldosterone to the early glomerular changes occurring in hypertensive nephropathy.

Glomerular hypertrophy in subjects with low nephron number: contributions of sex, body size and race

PubMed Central

Puelles, Victor G.; Douglas-Denton, Rebecca N.; Zimanyi, Monika A.; Armitage, James A.; Hughson, Michael D.; Kerr, Peter G.; Bertram, John F.

2014-01-01

Background We have shown that low nephron number (Nglom) is a strong determinant of individual glomerular volume (IGV) in male Americans. However, whether the same pattern is present in female Americans remains unclear. The contributions of body surface area (BSA) and race to IGV in the context of Nglom also require further evaluation. Methods Kidneys without overt renal disease were collected at autopsy in Mississippi, USA. The extremes of female Nglom were used to define high and low Nglom for both sexes. Nglom and IGV were estimated by design-based stereology. A total of 24 African and Caucasian American females (n = 12 per race; 6 per Nglom extreme) were included. These subjects were subsequently matched to 24 comparable males by age and Nglom and to 18 additional males by age, Nglom and BSA. Results IGV average and variance were very similar in female African and Caucasian Americans with high and low Nglom. Males with low Nglom from both races showed greater IGV average and variance than comparable females matched by age and Nglom. These differences in IGV between sexes were not observed in Caucasian Americans with low Nglom that were matched by age, Nglom and BSA. In contrast, glomeruli from African Americans were larger than those from Caucasian Americans, especially in subjects with high Nglom. Conclusions While female Americans with low Nglom did not show glomerular hypertrophy, comparable males with low Nglom showed marked glomerular hypertrophy that was closely associated with high BSA. Glomerular size in African Americans may be confounded by multiple additional factors. PMID:24792374

A SAGE based approach to human glomerular endothelium: defining the transcriptome, finding a novel molecule and highlighting endothelial diversity.

PubMed

Sengoelge, Guerkan; Winnicki, Wolfgang; Kupczok, Anne; von Haeseler, Arndt; Schuster, Michael; Pfaller, Walter; Jennings, Paul; Weltermann, Ansgar; Blake, Sophia; Sunder-Plassmann, Gere

2014-08-27

Large scale transcript analysis of human glomerular microvascular endothelial cells (HGMEC) has never been accomplished. We designed this study to define the transcriptome of HGMEC and facilitate a better characterization of these endothelial cells with unique features. Serial analysis of gene expression (SAGE) was used for its unbiased approach to quantitative acquisition of transcripts. We generated a HGMEC SAGE library consisting of 68,987 transcript tags. Then taking advantage of large public databases and advanced bioinformatics we compared the HGMEC SAGE library with a SAGE library of non-cultured ex vivo human glomeruli (44,334 tags) which contained endothelial cells. The 823 tags common to both which would have the potential to be expressed in vivo were subsequently checked against 822,008 tags from 16 non-glomerular endothelial SAGE libraries. This resulted in 268 transcript tags differentially overexpressed in HGMEC compared to non-glomerular endothelia. These tags were filtered using a set of criteria: never before shown in kidney or any type of endothelial cell, absent in all nephron regions except the glomerulus, more highly expressed than statistically expected in HGMEC. Neurogranin, a direct target of thyroid hormone action which had been thought to be brain specific and never shown in endothelial cells before, fulfilled these criteria. Its expression in glomerular endothelium in vitro and in vivo was then verified by real-time-PCR, sequencing and immunohistochemistry. Our results represent an extensive molecular characterization of HGMEC beyond a mere database, underline the endothelial heterogeneity, and propose neurogranin as a potential link in the kidney-thyroid axis.

Effects of high glucose on the production of heparan sulfate proteoglycan by mesangial and epithelial cells.

PubMed

van Det, N F; van den Born, J; Tamsma, J T; Verhagen, N A; Berden, J H; Bruijn, J A; Daha, M R; van der Woude, F J

1996-04-01

Changes in heparan sulfate metabolism may be important in the pathogenesis of diabetic nephropathy. Recent studies performed on renal biopsies from patients with diabetic nephropathy revealed a decrease in heparan sulfate glycosaminoglycan staining in the glomerular basement membrane without changes in staining for heparan sulfate proteoglycan-core protein. To understand this phenomenon at the cellular level, we investigated the effect of high glucose conditions on the synthesis of heparan sulfate proteoglycan by glomerular cells in vitro. Human adult mesangial and glomerular visceral epithelial cells were cultured under normal (5 mM) and high glucose (25 mM) conditions. Immunofluorescence performed on cells cultured in 25 mM glucose confirmed and extended the in vivo histological observations. Using metabolic labeling we observed an altered proteoglycan production under high glucose conditions, with predominantly a decrease in heparan sulfate compared to dermatan sulfate or chondroitin sulfate proteoglycan. N-sulfation analysis of heparan sulfate proteoglycan produced under high glucose conditions revealed less di- and tetrasaccharides compared to larger oligosaccharides, indicating an altered sulfation pattern. Furthermore, with quantification of glomerular basement membrane heparan sulfate by ELISA, a significant decrease was observed when mesangial and visceral epithelial cells were cultured in high glucose conditions. We conclude that high glucose concentration induces a significant alteration of heparan sulfate production by mesangial cells and visceral epithelial cells. Changes in sulfation and changes in absolute quantities are both observed and may explain the earlier in vivo observations. These changes may be of importance for the altered integrity of the glomerular charge-dependent filtration barrier and growth-factor matrix interactions in diabetic nephropathy.

Preliminary Findings of Serum Creatinine and Estimated Glomerular Filtration Rate (eGFR) in Adolescents with Intellectual Disabilities

ERIC Educational Resources Information Center

Lin, Jin-Ding; Lin, Lan-Ping; Hsieh, Molly; Lin, Pei-Ying

2010-01-01

The present study aimed to describe the kidney function profile--serum creatinine and estimated glomerular filtration rate (eGFR), and to examine the relationships of predisposing factors to abnormal serum creatinine in people with intellectual disabilities (ID). Data were collected by a cross-sectional study of 827 aged 15-18 years adolescents…

Risk factors associated with the deterioration of renal function after kidney transplantation.

PubMed

Serón, Daniel; Fulladosa, Xavier; Moreso, Francesc

2005-12-01

Renal function early after transplantation is associated with a large number of risk factors, including donor age and acute rejection. During the 1990s, donor age increased and the incidence of acute rejection decreased. Renal function between the third and sixth month improved slightly, while renal function deterioration between the third or sixth month and the 12th month improved significantly. This modification coincides with the introduction of mycophenolate mofetil and tacrolimus. The tendency for sustained renal improvement early after transplantation became more evident after the introduction of anti-calcineurin-free regimens. Studies of protocol biopsies have shown that there is an increase of glomerular volume after transplantation and that a larger glomerular volume at 4 months is associated with a better glomerular filtration rate. This adaptation mechanism is impaired in patients with chronic allograft nephropathy or in patients with high cyclosporin levels. Taken together, these data suggest that the steady improvement of renal allograft function may be partly explained by a better glomerular adaptation after transplantation because of the avoidance of the vasoconstrictive effect of anti-calcineurinic agents, and a significant decrease in the prevalence of chronic allograft nephropathy early after transplantation.

New optical probes for the continuous monitoring of renal function

NASA Astrophysics Data System (ADS)

Dorshow, Richard B.; Asmelash, Bethel; Chinen, Lori K.; Debreczeny, Martin P.; Fitch, Richard M.; Freskos, John N.; Galen, Karen P.; Gaston, Kimberly R.; Marzan, Timothy A.; Poreddy, Amruta R.; Rajagopalan, Raghavan; Shieh, Jeng-Jong; Neumann, William L.

2008-02-01

The ability to continuously monitor renal function via the glomerular filtration rate (GFR) in the clinic is currently an unmet medical need. To address this need we have developed a new series of hydrophilic fluorescent probes designed to clear via glomerular filtration for use as real time optical monitoring agents at the bedside. The ideal molecule should be freely filtered via the glomerular filtration barrier and be neither reabsorbed nor secreted by the renal tubule. In addition, we have hypothesized that a low volume of distribution into the interstitial space could also be advantageous. Our primary molecular design strategy employs a very small pyrazine-based fluorophore as the core unit. Modular chemistry for functionalizing these systems for optimal pharmacokinetics (PK) and photophysical properties have been developed. Structure-activity relationship (SAR) and pharmacokinetic (PK) studies involving hydrophilic pyrazine analogues incorporating polyethylene glycol (PEG), carbohydrate, amino acid and peptide functionality have been a focus of this work. Secondary design strategies for minimizing distribution into the interstitium while maintaining glomerular filtration include enhancing molecular volume through PEG substitution. In vivo optical monitoring experiments with advanced candidates have been correlated with plasma PK for measurement of clearance and hence GFR.

Printing-assisted surface modifications of patterned ultrafiltration membranes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wardrip, Nathaniel C.; Dsouza, Melissa; Urgun-Demirtas, Meltem

Understanding and restricting microbial surface attachment will enhance wastewater treatment with membranes. We report a maskless lithographic patterning technique for the generation of patterned polymer coatings on ultrafiltration membranes. Polyethylene glycol, zwitterionic, or negatively charged hydrophilic polymer compositions in parallel- or perpendicular-striped patterns with respect to feed flow were evaluated using wastewater. Membrane fouling was dependent on the orientation and chemical composition of the coatings. Modifications reduced alpha diversity in the attached microbial community (Shannon indices decreased from 2.63 to 1.89) which nevertheless increased with filtration time. Sphingomonas species, which condition membrane surfaces and facilitate cellular adhesion, were depleted inmore » all modified membranes. Microbial community structure was significantly different between control, different patterns, and different chemistries. Lastly, this study broadens the tools for surface modification of membranes with polymer coatings and for understanding and optimization of antifouling surfaces.« less

Performance of ultrafiltration membrane process combined with coagulation/sedimentation.

PubMed

Jang, N Y; Watanabe, Y; Minegishi, S

2005-01-01

Effects of coagulation/sedimentation as a pre-treatment on the dead-end ultrafiltration (UF) membrane process were studied in terms of membrane fouling and removal efficiency of natural dissolved organic matter, using Chitose River water. Two types of experiment were carried out. One was a bench scale membrane filtration with jar-test and the other was membrane filtration pilot plant combined with the Jet Mixed Separator (JMS) as a pre-coagulation/sedimentation unit. In the bench scale experiment, the effects of coagulant dosage, pH and membrane operating pressure on the membrane fouling and removal efficiency of natural dissolved organic matter were investigated. In the pilot plant experiment, we also investigated the effect of pre-coagulation/sedimentation on the membrane fouling and the removal efficiency of natural dissolved organic matter. Coagulation/sedimentation prior to membrane filtration process controlled the membrane fouling and increased the removal efficiency of natural dissolved organic matter.