Abstract 33: Combination of Allogeneic Mesenchymal and Kidney-derived Stem Cells Promotes Kidney Repair in a Swine Model of Chronic Kidney Disease

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Angela C Rieger ◽  
Bryon A Tompkins ◽  
Makoto Natsumeda ◽  
Victoria Florea ◽  
Jose Rodriguez ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Stem Cells ◽  
Kidney Disease ◽  
Cell Therapy ◽  
Renal Artery ◽  
Swine Model ◽  
Creatinine Ratio ◽  
Urine Protein ◽  
Increased Risk ◽  
Significant Difference

Background: Chronic kidney disease (CKD) has a high prevalence (~14% of the population) and is associated with a significantly increased risk of cardiovascular disease and a 15-fold higher rate of mortality than the general population. Current therapies slow disease progression but do not repair organ damage, leading to end-stage renal disease. Stem cell therapy has the potential to promote repair via neovascularization and antifibrotic effects. We tested the renal reparative capacity of allogeneic mesenchymal stem cells (MSCs) and kidney ckit+ stem cells (c-kit) in an established swine model of CKD. Methods: Yorkshires pigs (n=27) underwent 5/6 nephrectomy via renal artery embolization and 4-weeks later received either: MSC (10х10 6 ), c-kit (10х10 6 ), combination (MSC+c-kit; 1:1 ratio [5х10 6 each]), or placebo (each n=5). Allogeneic cell therapy was delivered via the patent renal artery of the remnant kidney. Kidney functional parameters and renal MRI were measured at baseline, and at 4- and 12-weeks (euthanasia) post-embolization. Results: The CKD model was validated from baseline to 4 weeks by an increased creatinine: (Δ1.1 ± 0.15 mg/dl; p<0.0001), BUN (Δ13.50 ± 2.99mg/dl; p=0.0003), and urine protein/creatinine ratio (Δ0.311mg/g; p=0.018), and decreased GFR (Δ49.82 ±6.41 ml/min; p=0.0002). Mean arterial pressure (MAP) was not different between groups from baseline to 4 weeks. After 12 weeks, there was a significant difference in MAP between groups (p=0.04), with an increase in the placebo group (19.97± 8.65 mmHg, p=0.08). BUN and creatinine levels improved in all of the groups from 4-12 weeks. GFR also improved in all the groups, but with the greatest effect in the combination group (76± 23.83ml/min; p= 0.03) from 4-12 weeks. Urine protein/creatinine ratio did not change in placebo but decreased in cell treated groups. There was no evidence of immune rejection as evaluated in a complete body necropsy. Conclusion: Allogeneic MSCs and kidney-derived stem cells are safe in a CKD swine model. The combination of stem cells was shown to be more efficacious in improving kidney function. These novel findings have important implications for the advancement of cell therapy for CKD.

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.

Abstract 145: Rates of Transfusion and Progression to End-Stage Renal Disease in Chronic Kidney Disease Patients Undergoing Transradial Versus Transfemoral Cardiac Catheterization - An Analysis from the VA CART Program

2014 ◽  
Vol 7 (suppl_1) ◽  
Author(s):  
Amit N Vora ◽  
Maggie A Stanislawski ◽  
John S Rumsfeld ◽  
Thomas M Maddox ◽  
Mladen Vidovich ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Cardiac Catheterization ◽  
High Risk Population ◽  
Post Procedure ◽  
Increased Risk ◽  
Significant Difference ◽  
Independent Association ◽  
Stage Renal Disease ◽  
End Stage

Background: Patients with chronic kidney disease (CKD) are at increased risk of bleeding and transfusion after cardiac catheterization. Whether rates of these complications or progression to new dialysis are increased in this high-risk population undergoing transradial (TR) access compared to transfemoral (TF) access is unknown. Methods: From the Veterans Affairs Clinical Assessment, Reporting, and Tracking (CART) Program between 10/2007-09/2012 we identified 40,160 CKD patients undergoing cardiac catheterization with baseline glomerular filtration rate (GFR) ≤ 60 ml/min. We used multivariable Cox modeling to determine the independent association between TR access and post-procedure transfusion as well as progression to new dialysis using TF as the reference. Results: Overall, 3,828 (9.5%) of CKD patients underwent TR access and tended to be slightly younger but overall had similar rates of CKD severity compared with TF patients (GFR 45-60 ml/min: 77.0% vs. 77.0%; GFR 30-44 ml/min: 19.7% vs. 19.3%; GFR 15-29 ml/min: 3.3% vs. 3.7%, p=0.35). TR patients had longer fluoroscopy times (8.1 vs 6.9 minutes, p=<0.0001) but decreased contrast use (90.0 vs 100.0 ml, p=<0.0001). Among the 31,692 patients with a full year of follow-up, 42 (1.7%) of TR patients and 545 (1.9%) of TF patients progressed to new dialysis within 1 year (p=0.64). However, only 33 (0.9%) of TR patients compared with 570 TF patients (1.6%) needed post-procedure blood transfusion (p=0.0006). After multivariable adjustment, there was no significant difference in progression to ESRD between TR and TF patients but TR was associated with a significant decrease in transfusion (Figure). Conclusion: Among CKD patients undergoing cardiac catheterization in the VA health system, TR access is associated with a decreased risk for post-procedure transfusion compared with TF access. There was no significant difference between the two approaches with respect to progression to ESRD. These data suggest that TR is a reasonable option for patients with any level of CKD undergoing cardiac catheterization.

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.

Types of erythropoiesis-stimulating agents and risk of end-stage kidney disease and death in patients with non-dialysis chronic kidney disease

2020 ◽  
Author(s):  
Roberto Minutolo ◽  
Carlo Garofalo ◽  
Paolo Chiodini ◽  
Filippo Aucella ◽  
Lucia Del Vecchio ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Primary Endpoint ◽  
End Stage Kidney Disease ◽  
Short Acting ◽  
Erythropoiesis Stimulating Agents ◽  
Increased Risk ◽  
Significant Difference ◽  
Long Acting ◽  
End Stage

Abstract Background Despite the widespread use of erythropoiesis-stimulating agents (ESAs) to treat anaemia, the risk of adverse outcomes associated with the use of different types of ESAs in non-dialysis chronic kidney disease (CKD) is poorly investigated. Methods From a pooled cohort of four observational studies, we selected CKD patients receiving short-acting (epoetin α/β; n = 299) or long-acting ESAs (darbepoetin and methoxy polyethylene glycol-epoetin β; n = 403). The primary composite endpoint was end-stage kidney disease (ESKD; dialysis or transplantation) or all-cause death. Multivariable Cox models were used to estimate the relative risk of the primary endpoint between short- and long-acting ESA users. Results During follow-up [median 3.6 years (interquartile range 2.1–6.3)], the primary endpoint was registered in 401 patients [166 (72%) in the short-acting ESA group and 235 (58%) in the long-acting ESA group]. In the highest tertile of short-acting ESA dose, the adjusted risk of primary endpoint was 2-fold higher {hazard ratio [HR] 2.07 [95% confidence interval (CI) 1.37–3.12]} than in the lowest tertile, whereas it did not change across tertiles of dose for long-acting ESA patients. Furthermore, the comparison of ESA type in each tertile of ESA dose disclosed a significant difference only in the highest tertile, where the risk of the primary endpoint was significantly higher in patients receiving short-acting ESAs [HR 1.56 (95% CI 1.09–2.24); P = 0.016]. Results were confirmed when ESA dose was analysed as continuous variable with a significant difference in the primary endpoint between short- and long-acting ESAs for doses &gt;105 IU/kg/week. Conclusions Among non-dialysis CKD patients, the use of a short-acting ESA may be associated with an increased risk of ESKD or death versus long-acting ESAs when higher ESA doses are prescribed.

scholarly journals Association between Chronic Kidney Disease and the Most Common Corneal Ectasia Disease (Keratoconus): a Nationwide Cohort Study

2020 ◽  
Author(s):  
Ren-Long Jan ◽  
Shih-Feng Weng ◽  
Jhi-Joung Wang ◽  
Yuh-Shin Chang
Keyword(s):  
Chronic Kidney Disease ◽  
Health Insurance ◽  
Kidney Disease ◽  
Incidence Rate ◽  
Case Series ◽  
Control Group ◽  
Study Cohort ◽  
Research Database ◽  
Increased Risk ◽  
Significant Difference

Abstract Background: Both keratoconus (KCN) and chronic kidney disease (CKD) are multifactorial conditions with multiple aetiologies and share several common pathophysiologies. However, the few studies that have described the relationship between KCN and CKD are limited to case reports and small case series. This study aimed to evaluate the association between KCN and CKD.Methods: The study cohort included 4,609 new-onset keratoconus patients ≥ 12 years identified by the International Classification of Diseases, Ninth Revision, Clinical Modification, code 371.6 and recruited between 2004 and 2011 from the Taiwan National Health Insurance Research Database. The age- , sex- , and comorbidity-matched control group included 27,654 non-KCN patients, selected from the Taiwan Longitudinal Health Insurance Database, 2000. Information for each patient was collected and tracked from the index date until December 2013. The incidence and risk of CKD were compared between the two groups. The adjusted hazard ratios (HRs) for CKD were calculated with Cox proportional hazard regression analysis. Kaplan–Meier analysis was used to calculate the cumulative CKD incidence rate. Results: The incidence rate of CKD was 1.36 times higher in KCN patients than in controls without statistically significant difference (95% confidence interval [CI] = 0.99–1.86, p = 0.06). In total, 29 male KCN patients and 90 male controls developed CKD during the follow-up period. The incidence rate of CKD was 1.92 times (95% [CI] = 1.26–2.91; p = 0.002) higher in male KCN patients than in controls. After adjusting for potential confounders, including age, hypertension, hyperlipidaemia, and diabetes mellitus, male KCN patients were 1.75 times (adjusted HR = 1.75, 95% [CI] = 1.14–2.68, p < 0.05) more likely to develop CKD. Conclusions: We found that male KCN patients have an increased risk of CKD. Therefore, it is recommended that male KCN patients should be aware of CKD.

Terapia Celular com células tronco mesenquimais em gatos com doença renal crônica / Cell therapy with mesenchymal stem cells in cats with chronic kidney disease

2021 ◽  
Vol 7 (7) ◽  
pp. 70741-70760
Author(s):  
Pedro Henrique Martins De Melo ◽  
Hilana dos Santos Sena Brunel ◽  
Patrícia Furtado Malard ◽  
Carlos Alberto Da Cruz Júnior
Keyword(s):  
Chronic Kidney Disease ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Kidney Disease ◽  
Cell Therapy

scholarly journals Carbohydrate-Rich Diet Is Associated with Increased Risk of Incident Chronic Kidney Disease in Non-Diabetic Subjects

2019 ◽  
Vol 8 (6) ◽  
pp. 793 ◽  
Author(s):  
Ki Heon Nam ◽  
Seong Yeong An ◽  
Young Su Joo ◽  
Sangmi Lee ◽  
Hae-Ryong Yun ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Significant Risk ◽  
Carbohydrate Intake ◽  
Dietary Carbohydrate ◽  
Increased Risk ◽  
Significant Difference ◽  
Incident Chronic Kidney Disease ◽  
The Impact

Despite the potential relationship with metabolic derangements, the association between dietary carbohydrate intake and renal function remains unknown. The present study investigated the impact of dietary carbohydrate intake on the development of incident chronic kidney disease (CKD) in a large-scale prospective cohort with normal renal function. A total of 6746 and 1058 subjects without and with diabetes mellitus (DM) were analyzed, respectively. Carbohydrate intake was assessed by a 24-h dietary recall food frequency questionnaire. The primary endpoint was CKD development, defined as a composite of estimated glomerular filtration rate (eGFR) of ≤60 mL/min/1.73 m2 and the development of proteinuria. CKD newly developed in 20.1% and 36.0% of subjects during median follow-ups of 140 and 119 months in the non-DM and DM subjects, respectively. Categorization of non-DM subjects into dietary carbohydrate density quartiles revealed a significantly higher risk of CKD development in the third and fourth quartiles than in the first quartile (P = 0.037 for first vs. third; P = 0.001 for first vs. fourth). A significant risk elevation was also found with increased carbohydrate density when carbohydrate density was treated as a continuous variable (P = 0.008). However, there was no significant difference in the incident CKD risk among those with DM according to dietary carbohydrate density quartiles. Carbohydrate-rich diets may increase the risk of CKD development in non-DM subjects.

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