scholarly journals Scaffolds from Surgically Removed Kidneys as a Potential Source of Organ Transplantation

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Marek Karczewski ◽  
Tomasz Malkiewicz
Keyword(s):  
Cell Attachment ◽  
Kidney Tissue ◽  
Point Of View ◽  
Common Disease ◽  
Kidney Graft ◽  
Binding Domains ◽  
Ecm Architecture ◽  
Stage Renal Disease ◽  
End Stage

End stage renal disease (ESRD) is a common disease, which relates to nearly 600 million people in the total population. What is more, it seems to be a crucial problem from the epidemiological point of view. These facts lead to a further necessity of renal replacement therapy development connected with rising expenditures for the health care system. The aim of kidney tissue engineering is to develop and innovate methods of obtaining renal extracellular matrix (ECM) scaffolds derived from kidney decellularization. Recently, progress has been made towards developing a functional kidney graftin vitroon demand. In fact, decellularized tissues constitute ideal natural scaffolds, due to the preservation of native ECM architecture, as well as of cell-ECM binding domains critical in promoting cell attachment, migration, and proliferation. One of the potential sources of the natural scaffolds is the kidney, which cannot be transplanted immediately after excision.

scholarly journals Silencing of miR-150-5p Ameliorates Diabetic Nephropathy by Targeting SIRT1/p53/AMPK Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Wenmin Dong ◽  
Huiqian Zhang ◽  
Cheng Zhao ◽  
Yun Luo ◽  
Ying Chen
Keyword(s):  
Diabetic Nephropathy ◽  
Kidney Tissue ◽  
Protective Role ◽  
Sirtuin 1 ◽  
Podocyte Injury ◽  
Stage Renal Disease ◽  
End Stage ◽  
Amp Activated Protein Kinase

Diabetic nephropathy (DN) is a common complication of diabetes and an important cause of end-stage renal disease. Increasing evidence suggests that microRNAs (miRNAs) regulate the development of DN. In a preliminary study, high levels of miR-150-5p were detected in the serum and urine of patients with DN. Consequently, we investigated the effect and mechanism of action of miR-150-5p in DN in vitro and in vivo. Our results showed that inhibition of miR-150-5p reversed high glucose-induced podocyte injury and Streptozocin (STZ)-induced diabetic nephropathy in mice. Further analysis revealed that miR-150-5p targeted the 3′ untranslated region (UTR) of sirtuin 1 (SIRT1), consequently decreasing SIRT1 levels in podocytes. Importantly, we found that the silencing of miR-150-5p promoted the interaction between SIRT1 and p53, causing the suppression of p53 acetylation in podocytes and kidney tissue. This resulted in the stimulation of AMP-activated protein kinase (AMPK)-dependent autophagy. In conclusion, our study demonstrated that the silencing of miR-150-5p played a reno-protective role in DN mice through targeting SIRT1.

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 Exosomal Urinary miRNA Signature for Early Diagnosis of Renal Fibrosis in Lupus Nephritis

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 773 ◽  
Author(s):  
Solé ◽  
Moliné ◽  
Vidal ◽  
Ordi-Ros ◽  
Cortés-Hernández
Keyword(s):  
Lupus Nephritis ◽  
Renal Fibrosis ◽  
Target Genes ◽  
Early Stage ◽  
High Sensitivity ◽  
Increased Risk ◽  
Chronicity Index ◽  
Stage Renal Disease ◽  
End Stage

For lupus nephritis (LN) management, it is very important to detect fibrosis at an early stage. Urinary exosomal miRNAs profiling can be used as a potential multi-marker phenotyping tool to identify early fibrosis. We isolated and characterised urinary exosomes and cellular pellets from patients with biopsy-proven LN (n = 45) and healthy controls (n = 20). LN chronicity index (CI) correlated with urinary exosomal miR-21, miR-150, and miR-29c (r = 0.565, 0.840, −0.559, respectively). This miRNA profile distinguished low CI from moderate-high CI in LN patients with a high sensitivity and specificity (94.4% and 99.8%). Furthermore, this multimarker panel predicted an increased risk of progression to end-stage renal disease (ESRD). Pathway analysis identified VEGFA and SP1 as common target genes for the three miRNAs. Immunohistochemistry in LN renal biopsies revealed a significant increase of COL1A1 and COL4A1 correlated with renal chronicity. SP1 decreased significantly in the high-CI group (p = 0.002). VEGFA levels showed no differences. In vitro experiments suggest that these miRNA combinations promote renal fibrosis by increasing profibrotic molecules through SP1 and Smad3/TGFβ pathways. In conclusion, a urinary exosomal multimarker panel composed of miR-21, miR-150, and miR-29c provides a non-invasive method to detect early renal fibrosis and predict disease progression in LN.

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.

In-Vitro Evaluation of an UL TRA Violet Germicidal Connection System for CAPD

1984 ◽  
Vol 4 (4) ◽  
pp. 215-218 ◽  
Author(s):  
Clifford J. Holmes ◽  
Cynthia Miyake ◽  
Winnie Kubey
Keyword(s):  
Microbial Population ◽  
Uv Light ◽  
Second Phase ◽  
Membrane Filters ◽  
Connection System ◽  
Fluid Transfer ◽  
Stage Renal Disease ◽  
End Stage ◽  
Welding Technique

We have evaluated UV irradiation of the setlbag connection as a method of eliminating organisms causing peritonitis among CAPD patients. In the first phase of the study, spike lumens of CAPD transfer sets were inoculated with C. albicans, which are known to be relatively resistant to UV light. After irradiation, results showed a 61og 10 reduction in microbial population. In the second phase, the spikes were contaminated by touch. Following irradiation, 100% of the contaminated spikes were disinfected. These data indicate that UV germicidal systems can achieve a significant reduction of contaminating microbial population on a CAPD transfer-set spike. Continuous ambulatory peritoneal dialysis (CAPD) is now a well-accepted therapy for end-stage renal disease (I). However, peritonitis remains a potential complication of this therapy. Several methods have been proposed for preventing microorganisms from entering the peritoneum via the primary (set-to-bag) connection. Such approaches have included placement of membrane filters in the fluid transfer set (2), use of disinfectant solutions (3), and recently the “sterile welding” technique (4). A gennicidal system, which uses ultraviolet (UV) light as the disinfecting source, has recently become available. Ultraviolet light has beeen utilized in industry and medicine for a number of years and for a number of applications, e.g., disinfecting operating rooms (5) and sterilizing water and packaging materials (6). The present paper describes the evaluation of ultraviolet irradiation as a means of disinfecting the CAPD transfer set-to-bag connection.

Blood Glucose and Cholesterol Control Improved by Continuous Ambulatory Peritoneal Dialysis in Patients with End-Stage Renal Disease and Diabetes Mellitus

1993 ◽  
Vol 13 (2_suppl) ◽  
pp. 239-241 ◽  
Author(s):  
Ann-Marie Wikdahl ◽  
Lena Granbom ◽  
Jens G. Sörensen ◽  
Bernd G. Stegmayr
Keyword(s):  
Peritoneal Dialysis ◽  
Serum Albumin ◽  
Total Cholesterol ◽  
End Stage Renal Disease ◽  
Kidney Graft ◽  
Group 2 ◽  
Cholesterol Control ◽  
Stage Renal Disease ◽  
End Stage ◽  
Group 1

This longitudinal study was performed to evaluate the change of total cholestererol, triglycerides, and glucose control in patients with insulin-dependent diabetes mellitus (IDDM) and end-stage renal disease (ESRD) during predialysis (PreD), on continuous ambulatory peritoneal dialysis (CAPD) and after kidney graft. A total of 20 consecutive patients (7 women, 13 men, mean age 42 years) with IDDM and ESRD were studied retrospectively in 1991 during PreD and during CAPD. Twelve were also investigated after obtaining a kidney graft. Insulin was administered Intraperitoneally (CAPD period) and subcutaneously (PreD and transplant). The mean values of weight, serum albumin, glycosylated hemoglobin (HbA1c), total cholesterol, and triglycerldes were calculated during each period. Patients were age and sex-matched with a group of healthy controls (Group 1) and with a group of patients with IDDM without nephropathy (Group 2). T-test statistics were used. During CAPD, there were significant decreases in HbA1c (mean 8.1 mmol/L vs 12.1, p=0.003) and cholesterol (mean 6.1 mmol/L vs 7.1, p=0.025) compared to PreD. No differences were found between PreD and CAPD stages with regard to weight, serum albumin, or triglycerides. After transplantation an improvement was found In serum albumin compared to PreD and CAPD (mean value 40 g/L.vsvs 34 and 35, p<0.03), and HbA1c compared to PreD (9.6 mmol/L vs 12.1, p=0.014), if the pancreas transplanted were included. Patients compared to Group 1 or 2 showed no differences in total cholesterol or triglycerldes. HbA1c was higher in patients during PreD than in Group 2. Peritoneal dialysis may not be a poor alternative for glucose and total cholesterol control in diabetic patients with ESRD. Transplantation further Improves serum albumin.

Distribution of cyclosporine in blood of a renal-transplant recipient with type V hyperlipoproteinemia.

1987 ◽  
Vol 33 (3) ◽  
pp. 423-428 ◽  
Author(s):  
H L Verrill ◽  
R E Girgis ◽  
R E Easterling ◽  
B S Malhi ◽  
W F Mueller
Keyword(s):  
Renal Transplant ◽  
Plasma Lipids ◽  
Kidney Tissue ◽  
Therapeutic Drug ◽  
Type V Hyperlipoproteinemia ◽  
High Concentrations ◽  
Stage Renal Disease ◽  
End Stage ◽  
Type V ◽  
Severe Type

Abstract A patient with severe type V hyperlipoproteinemia and chronic end-stage renal disease received a renal transplant and therapy with cyclosporine. Concentrations of the drug in plasma as determined by liquid chromatography appeared extraordinarily high for the dose ingested. When we measured the drug in the plasma, plasma cleared by ultracentrifugation, leukocytes, erythrocytes, and whole blood, we found that the high concentrations of cyclosporine were associated with the chylomicrons that always were present in this patient's blood. Cyclosporine added directly to this patient's plasma was less associated with the plasma lipids. Isolated lymphocytes and kidney slices incubated with plasma from this patient bound no more drug than when incubated with nonhyperlipemic plasma containing cyclosporine at a normal therapeutic concentration. We conclude that the cyclosporine associated with the chylomicrons in this patient was not biologically available to either lymphocytes or kidney tissue. We strongly recommend the use of chylomicron-cleared plasma for therapeutic drug monitoring of cyclosporine in type V hyperlipoproteinemic patients.

scholarly journals Soluble Urokinase Receptors in Focal Segmental Glomerulosclerosis: A Review on the Scientific Point of View

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Andreas Kronbichler ◽  
Moin A. Saleem ◽  
Björn Meijers ◽  
Jae Il Shin
Keyword(s):  
Focal Segmental Glomerulosclerosis ◽  
Point Of View ◽  
Soluble Form ◽  
Glomerular Diseases ◽  
Segmental Glomerulosclerosis ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
End Stage

Focal segmental glomerulosclerosis (FSGS) is one of the primary glomerular disorders in both children and adults which can progress to end-stage renal failure. Although there are genetic and secondary causes, circulating factors have also been regarded as an important factor in the pathogenesis of FSGS, because about 40% of the patients with FSGS have recurrence after renal transplantation. Soluble urokinase-type plasminogen activator receptor (suPAR) is a soluble form of uPAR, which is a membrane-bound protein linked to GPI in various immunologically active cells, including podocytes. It has recently been suggested as a potential circulating factor in FSGS by in vitro podocyte experiments, in vivo mice models, and human studies. However, there have also been controversies on this issue, because subsequent studies showed conflicting results. suPAR levels were also increased in patients with other glomerular diseases and were inversely correlated with estimated glomerular filtration rate. Nevertheless, there has been no balanced review on this issue. In this review, we compare the conflicting data on the involvement of suPAR in the pathogenesis of FSGS and shed light on interpretation by taking into account many points and the potential variables and confounders influencing serum suPAR levels.

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