Restenosis in Hemodialytic Fistulas and Chronic Kidney Disease-Associated Vascular Disease: Two Pathologies Driven by Metakaryotic Stem Cells

2017 ◽  
pp. 96-107 ◽  
Author(s):  
Gianandrea Pasquinelli ◽  
William G. Thilly ◽  
Elena V. Gostjeva ◽  
Paola Todeschini ◽  
Giuseppe Cianciolo ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Stem Cells ◽  
Kidney Disease ◽  
Vascular Disease

scholarly journals Embryonic Stem Cells-loaded Gelatin Microcryogels Slow Progression of Chronic Kidney Disease

2016 ◽  
Vol 129 (4) ◽  
pp. 392-398 ◽  
Author(s):  
Xiao-Dong Geng ◽  
Wei Zheng ◽  
Cong-Mei Wu ◽  
Shu-Qiang Wang ◽  
Quan Hong ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Kidney Disease ◽  
Embryonic Stem ◽  
Slow Progression

Abstract 471: Combination of Allogeneic Mesenchymal and Kidney Stem Cells Ameliorates Chronic Kidney Disease Induced Heart Failure With Preserved Ejection Fraction

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Angela C Castellanos ◽  
Bryon A Tompkins ◽  
Makoto Natsumeda ◽  
Victoria Florea ◽  
Monisha Banerjee ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Kidney Disease ◽  
Stem Cells ◽  
Stem Cell ◽  
Kidney Disease ◽  
Ejection Fraction ◽  
Cell Therapy ◽  
Renal Artery ◽  
Preserved Ejection Fraction ◽  
Kidney Stem Cells

Background: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous condition involving multiple comorbidities. Phenotypic classification of HFpEF associated with chronic kidney disease (CKD) manifests worse outcomes, compared to other HFpEF phenotypes. Few treatments improve morbidity and mortality in HFpEF. Stem cell therapy promotes cardiac repair in ischemic and non-ischemic cardiomyopathies. We hypothesized that allogeneic stem cell treatment ameliorates HFpEF in a large animal model of CKD. Methods: Yorkshire pigs (n=26) underwent 5/6 embolization-mediated nephrectomy and 4-weeks later received either: allogeneic mesenchymal stem cells (MSCs) (10х10 6 ), Kidney stem cells (KSC; 10х10 6 ), combination (ACCT; MSC+KSC; 1:1 ratio [5х10 6 each]), or placebo (n=6-7/ group). Cell therapy was delivered via the patent renal artery of the remnant kidney. RNAsec analysis compared placebo and ACCT groups. Results: Mean arterial pressure increased significantly in the placebo- (21.89±6.05 mmHg, p<0.0001) compared to the ACCT-group (p=0.04) at 12 weeks. Glomerular filtration rate improved significantly in the ACCT group (p=0.002). RNAseq analysis revealed a significant decrease in genes normally increased during kidney transplant rejection (q<10 -6 , NES = -2.32) in ACCT. Consistent with these results, there was a downregulation of canonical drivers of tubular damage and regeneration, including SOX9 (-2.39 fold, p=0.0004) and apoptosis of kidney cell types (-24.89 fold, p=0.004), including podocytes (-2.065 fold, p=0.04) with ACCT. ACCT administration also downregulated genes related to oxidative stress (-4.6 fold, p<0.0001), fibrosis, inflammatory response (-4.760 fold, p=<0.05), and renin-angiotensin signaling (-3.162 fold, p=0.024), which are related to cardiac hypertrophy pathways (-7.23, fold, p<0.0001). EDPVR improved in with ACCT (p=0.003), indicating decreased ventricular stiffness. Ejection fraction, relative wall thickness, and left ventricular mass did not differ between groups at 12 weeks. Conclusion: Intra-renal artery allogeneic cell therapy was safe. Beneficial effects were observed in the ACCT and MSC groups in the kidney and heart. These findings have important implications on the use of cell therapy for HFpEF and cardiorenal syndrome.

scholarly journals Stem cell-based treatment of kidney diseases

2020 ◽  
Vol 245 (10) ◽  
pp. 902-910
Author(s):  
Binbin Pan ◽  
Guoping Fan
Keyword(s):  
Chronic Kidney Disease ◽  
Stem Cells ◽  
Acute Kidney Injury ◽  
Stem Cell ◽  
Kidney Disease ◽  
Cell Therapy ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Great Promise ◽  
Kidney Organoids

Kidney dysfunction, including chronic kidney disease and acute kidney injury, is a globally prevalent health problem. However, treatment regimens are still lacking, especially for conditions involving kidney fibrosis. Stem cells hold great promise in the treatment of chronic kidney disease and acute kidney injury, but success has been hampered by insufficient incorporation of the stem cells in the injured kidney. Thus, new approaches for the restoration of kidney function after acute or chronic injury have been explored. Recently, kidney organoids have emerged as a useful tool in the treatment of kidney diseases. In this review, we discuss the mechanisms and approaches of cell therapy in acute kidney injury and chronic kidney disease, including diabetic kidney disease and lupus nephritis. We also summarize the potential applications of kidney organoids in the treatment of kidney diseases. Impact statement Stem cells hold great promise in regenerative medicine. Pluripotent stem cells have been differentiated into kidney organoids to understand human kidney development and to dissect renal disease mechanisms. Meanwhile, recent studies have explored the treatment of kidney diseases using a variety of cells, including mesenchymal stem cells and renal derivatives. This mini-review discusses the diverse mechanisms underlying current renal disease treatment via stem cell therapy. We postulate that clinical applications of stem cell therapy for kidney diseases can be readily achieved in the near future.

Imaging for detection of vascular disease in chronic kidney disease patients

2015 ◽  
Author(s):  
Paolo Raggi ◽  
Luis D’Marco
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Vascular Disease ◽  
Mineral Metabolism ◽  
Fibrous Tissue ◽  
Inflammatory Cells ◽  
Arterial System ◽  
Arterial Circulation ◽  
Atherosclerosis Risk Factors ◽  
Calcium Crystals

The well-known severity of cardiovascular disease in patients suffering from chronic kidney disease (CKD) requires an accurate risk stratification of these patients in several clinical situations. Imaging has been used successfully for such purpose in the general population and it has demonstrated excellent potential among CKD patients as well. Two main forms of arterial pathology develop in patients with CKD: atherosclerosis, with accumulation of inflammatory cells, lipids, fibrous tissue and calcium in the subintimal space, and arteriosclerosis. The latter is characterized by accumulation of deposits of hydroxyapatite and amorphous calcium crystals in the muscular media of the vessel wall, and is believed to be more closely associated with alterations of mineral metabolism than with traditional atherosclerosis risk factors. The result is the development of what appears to be premature arterial ageing, with loss of elastic properties, increased stiffness, and increased overall fragility of the arterial system. Despite intensifying research and increasing awareness of these issues, the underlying pathophysiology of the aggressive vasculopathy of CKD remains largely unknown. As a consequence, there are currently very limited pathways to prevent progression of vascular damage in CKD. The indications, strengths and weaknesses of several imaging modalities employed to evaluate vascular disease in CKD are described, focusing on coronary arterial circulation and the peripheral arteries, with the exclusion of the intracranial arteries.

scholarly journals Atherosclerotic vascular disease is more prevalent among black ESKD patients on long-term CAPD in South Africa

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
S. O. Oguntola ◽  
M. O. Hassan ◽  
R. Duarte ◽  
A. Vachiat ◽  
P. Manga ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Vascular Disease ◽  
Left Ventricular ◽  
Atherosclerotic Vascular Disease ◽  
Ckd Stage ◽  
Significant Difference ◽  
Echocardiographic Parameters ◽  
Relationship Of ◽  
The Relationship

Abstract Background Occurrence of cardiovascular disease (CVD) in the setting of chronic kidney disease (CKD) can be described as a “cruel alliance”, with CVD responsible for about half of all deaths among CKD patients. Chronic kidney disease patients are more likely to die from CVD than progress to end stage kidney disease (ESKD). Dyslipidaemia, a known traditional risk factor for CVD, is highly prevalent among CKD patients and with an even higher frequency among ESKD patients on dialytic therapies. Prolonged exposure of continuous ambulatory peritoneal dialysis (CAPD) patients to high glucose concentrations in CAPD fluid have been associated with increased risk of cardiovascular events. In this study, we investigated the relationship of atherosclerotic vascular disease (AsVD) to clinical and echocardiographic parameters among black South Africans with CKD (stage 3) and ESKD on CAPD and haemodialysis (HD). Methods This was a cross-sectional study of 40 adult (18–65 years) non-diabetic CKD patients (kidney disease outcome quality initiative [KDOQI] stage 3), 40 ESKD patients on CAPD, 40 ESKD patients on HD and 41 age and sex-matched healthy controls. An interviewer-administered questionnaire was used to obtain information on participants’ sociodemographic and cardiovascular risk factors. Anthropometric parameters were measured. Serum blood samples were analysed for creatinine, albumin and lipid profile; lipoprotein ratios, Framingham’s risk score and the 10-year risk of developing coronary heart disease (CHD) were calculated. Echocardiography was performed on all patients and carotid intima media thickness (CIMT) was measured in both right and left carotid arteries at 1 cm proximal to the carotid bulb. Spearman’s rank correlation and binary logistic regression were conducted to determine the relationship of AsVD to clinical and echocardiographic parameters. Results Atherosclerotic vascular disease was most prevalent among ESKD patients on CAPD (70%, n = 28/40). Chronic kidney disease and HD patients exhibited a similar prevalence (47.5%, n = 19/40), while the prevalence in controls was 17.1% (n = 7/41). Presence of AsVD was associated with significantly older age, higher waist hip ratio (WHR), left ventricular mass index (LVMI) and Framingham’s 10-year risk of developing CHD. Significant differences in clinical and echocardiographic parameters were observed when the study groups were compared. Age and LVH independently predicted AsVD. Conclusion Atherosclerotic vascular disease was more prevalent among CAPD patients compared to pre-dialysis CKD and HD patients. Among all lipoprotein ratios assessed, non-HDL-C showed the most consistent significant difference between the groups. Age (> 40 years) and presence of LVH were independent predictors of AsVD.

Clinical imaging of vascular disease in chronic kidney disease

2016 ◽  
Vol 48 (6) ◽  
pp. 827-837 ◽  
Author(s):  
Alan A. Sag ◽  
Adrian Covic ◽  
Gerard London ◽  
Marc Vervloet ◽  
David Goldsmith ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Vascular Disease ◽  
Clinical Imaging

Association of Quantitative and Qualitative Abnormalities of Von Willebrand Factor and Risk of Death In Hemodialysis Patients

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2217-2217
Author(s):  
Rachel Holden ◽  
Angie Tuttle ◽  
Francis MacLeod ◽  
Toni Burbidge ◽  
Carol Hegadorn ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Vascular Disease ◽  
Von Willebrand Factor ◽  
Functional Activity ◽  
Conflicts Of Interest ◽  
Proteolytic Processing ◽  
Risk Of Death ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Abstract 2217 In order to evaluate the possible role of abnormalities of von Willebrand factor in the hemostatic defects seen in indivdiuals with chronic kidney disease (CKD), a cohort study was performed evaluating pre- and post-dialysis levels of von Willebrand factor (VWF), VWF multimer profiles and levels of its cleaving protease, ADAMTS-13. There were 57 subjects (31 males, 26 females) enrolled with CKD with a mean age of 75 years (range 60 – 90). Subjects with known vascular disease were recruited; 49 (86%) had documented ischemic heart disease, 16 (29%) had cerebrovascular disease and 17 (31%) had peripheral vascular disease. A little over half had diabetes mellitus (30 subjects or 54%), 37 (67%) were on antiplatelet therapy and 7 (13%) were chronically anticoagulated with warfarin. Blood samples were drawn immediately pre- and again post-dialysis and all results were compared with a group of age-matched normal controls (Table 1). As has been previously reported, VWF antigen levels (VWF:Ag) and VWF functional activity as measured by the ristocetin cofactor assay (VWF:RCo) were higher in the pre-dialysis samples compared with controls, and both levels were increased even further following dialysis. Additionally, the percentage of high molecular weight VWF multimers (% HMWM) were significantly increased in the pre-dialysis samples compared with controls. This is a novel finding, and the level of % HMWM seen in the subjects is similar to what has been reported in individuals with Thrombotic Thrombocytopenic Purpura (TTP). This difference decreased following dialysis, potentially due to the effect of shear stress on VWF and the resultant proteolytic processing, however still remained significantly higher when compared with controls. ADAMTS-13 functional activity was lower in the subjects compared with controls, providing a possibly explanation for the increase in % HMWM. IL-6 levels are higher in subjects compared with controls. IL-6, which is an inflammatory cytokine known to be increased in patients with CKD, has been previously reported as a marker of inactivation of ADAMTS-13. Two years after enrollment, follow up of the subjects revealed that 22 had died, 17 from documented cardiovascular events. Higher VWF levels at the time of enrollment significantly correlated with risk of death (p=0.041) during the study period. The increase in % HMWM suggests that a “TTP-like phenotype” may also be playing a role. Taken together, these data suggest that both quantitative and qualitative abnormalities of VWF contribute to the risk of thrombotic death in chronic kidney disease. Disclosures: No relevant conflicts of interest to declare.

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