scholarly journals Improved Dialysis Removal of Protein-Bound Uraemic Toxins with a Combined Displacement and Adsorption Technique

2021 ◽  
pp. 1-11
Author(s):  
Yuanyuan Shi ◽  
Huajun Tian ◽  
Yifeng Wang ◽  
Yue Shen ◽  
Qiuyu Zhu ◽  
...  
Keyword(s):  
End Stage Renal Disease ◽  
Lipid Emulsion ◽  
Hippuric Acid ◽  
High Plasma ◽  
Displacement Based ◽  
Stage Renal Disease ◽  
End Stage ◽  
Indole 3 Acetic Acid

<b><i>Introduction:</i></b> Protein-bound uraemic toxins (PBUTs) are poorly removed by conventional dialytic techniques, given their high plasma protein binding, and thus low, free (dialysable) plasma concentration. Here, we evaluated and compared PBUTs removal among conventional haemodialysis (HD), adsorption-based HD, displacement-based HD, and their 2 combinations both in vitro and in vivo. <b><i>Methods:</i></b> The removal of PBUTs, including 3-carboxy-4-methyl-5-propyl-2-furan-propanoic acid (CMPF), p-cresyl sulphate (PCS), indoxyl sulphate (IS), indole-3-acetic acid (3-IAA), and hippuric acid, was first evaluated in an in vitro single-pass HD model. Adsorption consisted of adding 40 g/L bovine serum albumin (Alb) to the dialysate and displacement involved infusing fatty acid (FA) mixtures predialyser. Then, uraemic rats were treated with either conventional HD, Alb-based HD, lipid emulsion infusion-based HD or their combination to calculate the reduction ratio (RR), and the total solute removal (TSR) of solutes after 4 h of therapy. <b><i>Results:</i></b> In vitro dialysis revealed that FAs infusion prefilter increased the removal of PCS, IS, and 3-IAA 3.23-fold, 3.01-fold, and 2.24-fold, respectively, compared with baseline and increased the fractional removal of CMPF from undetectable at baseline to 14.33 ± 0.24%, with a dialysis efficacy markedly superior to Alb dialysis. In vivo dialysis showed that ω-6 soybean oil-based lipid emulsion administration resulted in higher RRs and more TSRs for PCS, IS, and 3-IAA after 4-h HD than the control, and the corresponding TSR values for PCS and IS were also significantly increased compared to that of Alb dialysis. Finally, the highest dialysis efficacy for highly bound solute removal was always observed with their combination both in vitro and in vivo. <b><i>Conclusions:</i></b> The concept of combined displacement- and adsorption-based dialysis may open up new avenues and possibilities in the field of dialysis to further enhance PBUTs removal in end-stage renal disease.

Differences between KT/V Measured during Dialysis and KT/V Predicted from Manufacturer Clearance Data

1992 ◽  
Vol 15 (8) ◽  
pp. 465-469 ◽  
Author(s):  
L.K. Saha ◽  
J.C. Van Stone
Keyword(s):  
Renal Disease ◽  
End Stage Renal Disease ◽  
Urea Clearance ◽  
Blood Flows ◽  
The Mean ◽  
Stage Renal Disease ◽  
End Stage

We retrospectively analyzed data from 3,863 dialysis treatments in 329 end-stage renal disease patients over a period of 33 months to evaluate the accuracy of in vitro KT/V estimated by manufacturer's urea clearance data in relation to in vivo measured KT/V. In 1,087 urea clearances measured, mean actual clearance was 87% of predicted. At all blood flows, actual clearances were significantly lower than predicted (8-16% lower than predicted). In 2,807 KT/V measurements, predicted KT/V was 1.238 ± 0.005 whereas the mean of actual measured KT/V was 16% lower or 1.024 ± 0.005 (P < 0.0001). At different blood flows and with different dialyzers, predicted KT/V overestimated actual values. With increasing numbers of reuse, actual/predicted clearance ratios and actual/predicted KT/V ratios progressively dropped. Prescribing dialysis treatments using manufacturer's in vitro generated clearance data can lead to marked underdialysis of patients.

Vimentin cleavage in end-stage renal disease is not related to apoptosis

Open Medicine ◽  
2013 ◽  
Vol 8 (3) ◽  
pp. 297-301 ◽  
Author(s):  
Felix Liebscher ◽  
Tobias Arnold ◽  
Ying Liang ◽  
Thomas Reiter ◽  
Georg Böhmig ◽  
...  
Keyword(s):  
Renal Disease ◽  
Healthy Volunteers ◽  
End Stage Renal Disease ◽  
Caspase 3 ◽  
Vimentin Expression ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients

AbstractAnti-vimentin auto-antibodies contribute to chronic allograft nephropathy. They exist in sera of end-stage renal disease patients on hemodialysis (ESRD) already before renal transplantation. We found recently that a 49 kDa vimentin fragment is increased in lymphocytes of ESRD patients which is presented on the cell surface. In vitro studies showed that such a fragment is formed during apoptosis by active caspase-3. We hypothesized that vimentin degradation in leukocytes of ESRD patients correlates to caspase-3 activation in vivo. Lymphocytes and monocytes were isolated from ESRD patients and from healthy volunteers and analyzed for vimentin expression and caspase-3 activation. In addition, apoptosis was induced in vitro and quantified by flow cytometry. ESRD monocytes have shown only the full length 60 kDa vimentin isoform. ESRD lymphocytes, however, showed in addition a strongly increased expression of the 49 kDa vimentin in all samples. Caspase-3 activation was found in 60% of ESRD lymphocytes and 66% of ESRD monocytes but not in healthy volunteers. UV-mediated induction of apoptosis was not associated with vimentin degradation. These experiments could confirm increased vimentin degradation in ESRD lymphocytes. However, we could not validate any correlation to apoptosis.

scholarly journals A therapeutic vascular conduit to support in vivo cell-secreted therapy

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Edward X. Han ◽  
Hong Qian ◽  
Bo Jiang ◽  
Maria Figetakis ◽  
Natalia Kosyakova ◽  
...  
Keyword(s):  
Vascular Graft ◽  
Large Scale ◽  
Biological Effects ◽  
Therapeutic Protein ◽  
Close Proximity ◽  
Delivery Platform ◽  
Stage Renal Disease ◽  
End Stage

AbstractA significant barrier to implementation of cell-based therapies is providing adequate vascularization to provide oxygen and nutrients. Here we describe an approach for cell transplantation termed the Therapeutic Vascular Conduit (TVC), which uses an acellular vessel as a scaffold for a hydrogel sheath containing cells designed to secrete a therapeutic protein. The TVC can be directly anastomosed as a vascular graft. Modeling supports the concept that the TVC allows oxygenated blood to flow in close proximity to the transplanted cells to prevent hypoxia. As a proof-of-principle study, we used erythropoietin (EPO) as a model therapeutic protein. If implanted as an arteriovenous vascular graft, such a construct could serve a dual role as an EPO delivery platform and hemodialysis access for patients with end-stage renal disease. When implanted into nude rats, TVCs containing EPO-secreting fibroblasts were able to increase serum EPO and hemoglobin levels for up to 4 weeks. However, constitutive EPO expression resulted in macrophage infiltration and luminal obstruction of the TVC, thus limiting longer-term efficacy. Follow-up in vitro studies support the hypothesis that EPO also functions to recruit macrophages. The TVC is a promising approach to cell-based therapeutic delivery that has the potential to overcome the oxygenation barrier to large-scale cellular implantation and could thus be used for a myriad of clinical disorders. However, a complete understanding of the biological effects of the selected therapeutic is absolutely essential.

scholarly journals Uremic Toxins and Their Relation with Oxidative Stress Induced in Patients with CKD

2021 ◽  
Vol 22 (12) ◽  
pp. 6196
Author(s):  
Anna Pieniazek ◽  
Joanna Bernasinska-Slomczewska ◽  
Lukasz Gwozdzinski
Keyword(s):  
Oxidative Stress ◽  
Uremic Toxins ◽  
Water Medium ◽  
Induce Insulin Resistance ◽  
Risk Of Mortality ◽  
Increased Risk ◽  
Stage Renal Disease ◽  
End Stage

The presence of toxins is believed to be a major factor in the development of uremia in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Uremic toxins have been divided into 3 groups: small substances dissolved in water, medium molecules: peptides and low molecular weight proteins, and protein-bound toxins. One of the earliest known toxins is urea, the concentration of which was considered negligible in CKD patients. However, subsequent studies have shown that it can lead to increased production of reactive oxygen species (ROS), and induce insulin resistance in vitro and in vivo, as well as cause carbamylation of proteins, peptides, and amino acids. Other uremic toxins and their participation in the damage caused by oxidative stress to biological material are also presented. Macromolecules and molecules modified as a result of carbamylation, oxidative stress, and their adducts with uremic toxins, may lead to cardiovascular diseases, and increased risk of mortality in patients with CKD.

scholarly journals An Overview of In Vivo and In Vitro Models for Autosomal Dominant Polycystic Kidney Disease: A Journey from 3D-Cysts to Mini-Pigs

2020 ◽  
Vol 21 (12) ◽  
pp. 4537
Author(s):  
Svenja Koslowski ◽  
Camille Latapy ◽  
Pierrïck Auvray ◽  
Marc Blondel ◽  
Laurent Meijer
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
In Vitro Models ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney ◽  
Stage Renal Disease ◽  
End Stage

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inheritable cause of end stage renal disease and, as of today, only a single moderately effective treatment is available for patients. Even though ADPKD research has made huge progress over the last decades, the precise disease mechanisms remain elusive. However, a wide variety of cellular and animal models have been developed to decipher the pathophysiological mechanisms and related pathways underlying the disease. As none of these models perfectly recapitulates the complexity of the human disease, the aim of this review is to give an overview of the main tools currently available to ADPKD researchers, as well as their main advantages and limitations.

scholarly journals In Vivo Shear Stress Determines Circulating Levels of Endothelial Microparticles in End-Stage Renal Disease

Hypertension ◽  
2007 ◽  
Vol 49 (4) ◽  
pp. 902-908 ◽  
Author(s):  
Chantal M. Boulanger ◽  
Nicolas Amabile ◽  
Alain P. Guérin ◽  
Bruno Pannier ◽  
Aurélie S. Leroyer ◽  
...  
Keyword(s):  
Shear Stress ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Endothelial Microparticles ◽  
Stage Renal Disease ◽  
End Stage ◽  
Circulating Levels
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