scholarly journals Mesenchymal Stem Cells: An Overview of Their Potential in Cell-Based Therapy for Diabetic Nephropathy

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yan Wu ◽  
Chunlei Zhang ◽  
Ran Guo ◽  
Dan Wu ◽  
Jiayi Shi ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Drug Targets ◽  
Renal Diseases ◽  
Beneficial Effects ◽  
Tissue Repair And Regeneration ◽  
Cell Based Therapy ◽  
Promising Strategy ◽  
Potential Benefits ◽  
Recent Phase ◽  
End Stage

Diabetic nephropathy (DN) is a devastating complication associated with diabetes mellitus, and it is the leading cause of end-stage renal diseases (ESRD). Over the last few decades, numerous studies have reported the beneficial effects of stem cell administration, specifically mesenchymal stem or stromal cells (MSCs), on tissue repair and regeneration. MSC therapy has been considered a promising strategy for ameliorating the progression of DN largely based on results obtained from several preclinical studies and recent Phase I/II clinical trials. This paper will review the recent literature on MSC treatment in DN. In addition, the roles and potential mechanisms involved in MSC treatment of DN will be summarized, which may present much needed new drug targets for this disease. Moreover, the potential benefits and related risks associated with the therapeutic action of MSCs are elucidated and may help in achieving a better understanding of MSCs.

P0123THE IMPORTANCE OF PPAR-ALPHA IN AKI TO CKD TRANSITION IN NEPHROPATHY INDUCED BY FOLIC ACID

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Gabriel Estrela ◽  
Adriano Arruda ◽  
Leandro Freitas-Lima ◽  
Jonatan Barrera-Chimal ◽  
Ronaldo Araujo
Keyword(s):  
Folic Acid ◽  
Chronic Phase ◽  
Kidney Injury ◽  
Tnf Alpha ◽  
Renal Diseases ◽  
Tubular Injury ◽  
Ppar Alpha ◽  
Beneficial Effects ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background and Aims PPAR-alpha is a nuclear receptor which plays major role in the regulation of lipid metabolism, activation of PPAR-alpha has been shown to have beneficial effects in renal diseases. Acute kidney injury (AKI), even if followed by renal recovery, is a risk factor for the future development of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Our main objective was to determine the importance of PPAR-alpha in AKI to CKD transition in folic acid induced nephropathy. Method Male C57/Bl6 and PPARKO (C57Bl6 background) mice were divided in 4 groups, Control, Folic Acid, Gemfibrozil + Folic Acid and PPARKO + Folic Acid. Animals has been treated with single dose of Folic Acid (250mg/kg i.p) and Gemfibrozil (150mg/kg gavage) euthanized after 48 hours for AKI assessment and 28 days for CKD. Renal parameters, histology, real time PCR were performed to investigate renal injury, inflammation and fibrosis. Results After 48 hours of folic acid inducing AKI, PPARKO mice showed decreased urea levels (Folic Acid: 178,9±25,2 PPARKO: 92,4±15,5), less tubular injury (Folic Acid: 0,61±0,05 PPARKO: 0,21±0,03), lower mRNA expression of NGAL (Folic Acid; 32,2±7,67 PPARKO 3,74±1,71), KIM-1 (Folic Acid: 671,8±170,2 PPARKO: 43,4±29,7) and TNF-alpha (Folic Acid: 2,81±0,58 PPARKO: 0,67±0,14), while PPAR-alpha activation with gemfibrozil showed to have no effects in AKI. After 28 days of folic acid inducing CKD. PPARKO showed same levels of injury than folic acid alone treated mice, however PPAR-alpha activation with gemfibrozil decreased urea levels (Folic Acid: 79,2±3,2 Gemfibrozil: 46,1±3,8), showed less tubulointerstitial fibrosis (Folic Acid: 0,60±0,05 Gemfibrozil: 0,18±0,02) and lower urine protein/creatinine ratio (Folic Acid: 5,48±0,58 Gemfibrozil: 2,53±0,12), Conclusion PPAR-alpha deletion protects against AKI induced by folic acid but did not showed protection in chronic phase, in the other hand ppar-alpha activation with gemfibrozil did not protect in AKI but show to be effective in CKD.

scholarly journals A massive natural disaster, the Great East Japan Earthquake, and the incidence of dialysis due to end-stage kidney disease

2021 ◽  
Author(s):  
Michiaki Abe ◽  
Tetsuya Akaishi ◽  
Koto Ishizawa ◽  
Hirohisa Shinano ◽  
Hiroshi Ohtomo ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Renal Disease ◽  
Great East Japan Earthquake ◽  
Dialysis Initiation ◽  
Renal Diseases ◽  
City Hospital ◽  
End Stage Kidney Disease ◽  
Significant Difference ◽  
End Stage

Abstract Background Disaster-related stress can increase blood pressure and the incidence of cardiovascular diseases. However, the role of massive disasters in the development of end-stage kidney disease (ESKD) remains unknown. We investigated the incidence and different causes of dialysis initiation in patients with chronic kidney disease in a city affected by the Great East Japan Earthquake. Methods This was a single-center, retrospective observational study. All patients who initiated or were treated with dialysis at Kesennuma City Hospital between 2007 and 2020 were enrolled. The year of dialysis initiation was retrospectively determined based on the initiation date. The causative renal diseases that led to the need for dialysis initiation were divided into four groups: diabetic nephropathy, hypertensive renal disease, glomerulonephritis, and others. Results Age at dialysis initiation differed significantly among the four groups (p = 0.0262). There was a significant difference in the numbers of the four groups before and after the Great East Japan Earthquake (p = 0.0193). The age of hypertensive renal disease patients was significantly higher than those of patients with diabetic nephropathy (p = 0.0070) and glomerulonephritis (p = 0.0386) after the disaster. The increasing number of dialysis initiations after the Great East Japan Earthquake appeared to be associated with changes in hypertensive renal diseases; the number peaked after 10 years. Conclusions There was an increase in the number of dialysis initiations, especially caused by hypertensive renal diseases, for up to 10 years after the Great East Japan Earthquake. Graphic abstract

scholarly journals Endothelin Receptor Antagonists in Diabetic Nephropathy

2010 ◽  
Vol 8 (1) ◽  
pp. 32
Author(s):  
René R Wenzel ◽  
Eberhard Ritz ◽  
Maximilian Q Wenzel ◽  
◽  
◽  
...  
Keyword(s):  
Clinical Trials ◽  
Diabetic Nephropathy ◽  
Collecting Duct ◽  
Water Excretion ◽  
Beneficial Effects ◽  
Subtype B ◽  
Microvascular Architecture ◽  
High Doses ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease and affects an estimated 150 million people worldwide. Despite optimal treatment, including glycaemic control and antihypertensive therapy (e.g., renin–angiotensin–aldosterone system [RAS] blockade), the disease progresses. A ‘late escape’ phenomenon has been described, where proteinuria reappears despite continued RAS blockade. The endothelin (ET) system is strongly involved in the pathophysiology of the disease and contributes to vasoconstriction, inflammation and proliferation. ET antagonists are promising drugs that potently slow down disease progression in animal models and have beneficial effects on cardiac structure, mitochondrial damage and microvascular architecture. However, the available ET antagonists, at least in higher doses, may also inhibit tubular endothelin receptors subtype B, which promote sodium and water excretion. The three clinical trials with avosentan and atrasentan published so far show the unique nephroprotective effects of these drugs, with a reduction of up to 45 % in albuminuria. However, fluid retention, oedema and, in higher stages of chronic kidney disease, heart failure limit their use. The reason may be that we have been using too high doses of these ET antagonists so far and they are inhibiting tubular sodium and water excretion. Thus, we will need to learn more about the role of ET and its antagonists in the tubular and collecting duct system, and on how to use these potent drugs in DN. ET antagonists are among the most promising molecules for the treatment of nephropathies. We should definitely not abandon these drugs because of the initial drawbacks in the first clinical trials.

scholarly journals The Ascent of Mineralocorticoid Receptor Antagonists in Diabetic Nephropathy

2019 ◽  
Vol 14 (2) ◽  
pp. 78-83 ◽  
Author(s):  
Luxitaa Goenka ◽  
Raghavan Padmanaban ◽  
Melvin George
Keyword(s):  
Diabetic Nephropathy ◽  
Mineralocorticoid Receptor ◽  
Enzyme Inhibitor ◽  
Angiotensin Receptor Blockers ◽  
Renal Diseases ◽  
Channel Blockers ◽  
Mineralocorticoid Receptor Antagonists ◽  
Receptor Antagonists ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy is defined as a decline in the renal function and an increase in the amount of albuminuria (>300 mg/day). The interruption of the renin-angiotensin-aldosterone system (RAAS) by well-established therapies such as angiotensin-converting enzyme inhibitor, angiotensin receptor blockers, calcium channel blockers or diuretics has been beneficial in reducing the progression of renal diseases; however, there is an increase in the levels of aldosterone due to the aldosterone escape phenomenon. Newer and novel approaches to counteract this aldosterone breakthrough while accentuating the anti-hypertensive and anti-proteinuric effects of these agents would be ideal and mineralocorticoid receptor antagonists fit in this slot perfectly. This review attempted to evaluate the safety and efficacy of and mineralocorticoid receptor antagonists for diabetic nephropathy. Presently mineralocorticoid receptor antagonists such as spironolactone, eplerenone and finerenone are being investigated as both monotherapies and as additional therapies. Clinical studies have shown that these drugs have been effective in the reduction of blood pressure, urinaryalbumin- excretion and estimated glomerular filtration rate. The commonly observed adverse effects are hyperkalemia, gynaecomastia and vaginal bleeding, that are bothersome with spironolactone seems to be avoidable if these patients are switched to non-steroidal and mineralocorticoid receptor antagonists such as finerenone and eplerenone. Most of the studies have only evaluated the shortterm effects of mineralocorticoid receptor antagonists on diabetic nephropathy. Hard outcomes such as cardiovascular events, creatinine doubling, progression to end-stage renal disease, mortality and the need for temporary or permanent dialysis need to be studied with these molecules.

scholarly journals Efficacy of Treatment in Ayurveda for the Management of Diabetic Nephropathy: A Case Study

2021 ◽  
pp. 1-7
Author(s):  
Rashi Sharma ◽  
Punam Sawarkar ◽  
Meenu Bharti Sharma ◽  
Nitin Sharma ◽  
Gaurav Sawarkar
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Saccharum Officinarum ◽  
Continuous Treatment ◽  
Research Centre ◽  
Renal Diseases ◽  
College Hospital ◽  
Main Culprit ◽  
Saccharum Munja ◽  
End Stage

Diabetic Nephropathy is one of the serious clinical condition that originated as a complication of the Diabetes Mellitus. It is the main culprit for end-stage renal diseases, which ultimately may lead to life-threatening conditions. A 58 years old male patient was having diabetes mellitus and hypertension for 15 years came to Mahatma Gandhi Ayurved College, Hospital and research centre, Wardha, Maharashtra (India) having bilateral pedal edema, vomiting, nausea, general weakness, frequent nocturnal micturition, hiccough from last two months. He was treated with Gokshuradi Guggulu, Chandraprabha Vati, Bhumyamalaki Churna, a freshly prepared decoction of Trunpanchmula [combination of Kush (Desmostachya bipinnata), Kash (Saccharum pontaneum), Darbha(Saccharum munja), Nal (Saccharum officinarum)and kandeshu]  50 ml daily twice a day after food. All other allopathic treatments for hypertension and Diabetes were continued as before, but the patient took only Ayurveda’s treatment for Nephropathy. After continuous treatment for two months, Blood Urea level was remarkably decreased from 51 mg/dl to 45 mg/dl & Serum Creatinine also reduced from 3.0 mg/dl to 1.5 mg/dl with a gross decrease in proteinuria. Both Blood sugar fasting & post- prandial were also reduced from 246mg/dl & 346 mg/dl to 190mg/dl & 225mg/dl respectively. The present Case report is discussed here to show the efficacy of Ayurveda in diabetic Nephropathy.

Murine Models of Diabetic Nephropathy

2012 ◽  
Vol 120 (04) ◽  
pp. 191-193 ◽  
Author(s):  
V. Peters ◽  
C. Schmitt
Keyword(s):  
Diabetic Nephropathy ◽  
Animal Models ◽  
Mouse Models ◽  
Critical Analysis ◽  
Disease Process ◽  
Diabetic Animal ◽  
Renal Diseases ◽  
Murine Models ◽  
Renal Changes ◽  
End Stage

AbstractDiabetic nephropathy is the leading cause of end stage renal diseases worldwide. Even though several diabetic animal models exist, not a single one develops renal changes sufficiently reflecting those seen in humans. This review provides an overview on mouse models presenting with various features of diabetic nephropathy. The critical analysis and comparison of existing mouse models substantially enhances our understanding of the disease process and should provide a guide for choosing the most suitable mouse model for the investigation of diabetic nephropathy.

scholarly journals Therapeutic Implications of Mesenchymal Stem Cells in Liver Injury

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Maria Ausiliatrice Puglisi ◽  
Valentina Tesori ◽  
Wanda Lattanzi ◽  
Anna Chiara Piscaglia ◽  
Giovanni Battista Gasbarrini ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Liver Diseases ◽  
Inflammatory Responses ◽  
Therapeutic Effects ◽  
Therapeutic Implications ◽  
Hepatic Cells ◽  
Cell Based Therapy ◽  
Potential Benefits ◽  
End Stage

Mesenchymal stem cells (MSCs), represent an attractive tool for the establishment of a successful stem-cell-based therapy of liver diseases. A number of different mechanisms contribute to the therapeutic effects exerted by MSCs, since these cells can differentiate into functional hepatic cells and can also produce a series of growth factors and cytokines able to suppress inflammatory responses, reduce hepatocyte apoptosis, regress liver fibrosis, and enhance hepatocyte functionality. To date, the infusion of MSCs or MSC-conditioned medium has shown encouraging results in the treatment of fulminant hepatic failure and in end-stage liver disease in experimental settings. However, some issues under debate hamper the use of MSCs in clinical trials. This paper summarizes the biological relevance of MSCs and the potential benefits and risks that can result from translating the MSC research to the treatment of liver diseases.

scholarly journals The Multi-Therapeutic Role of MSCs in Diabetic Nephropathy

2021 ◽  
Vol 12 ◽  
Author(s):  
Yi Wang ◽  
Su-Kang Shan ◽  
Bei Guo ◽  
Fuxingzi Li ◽  
Ming-Hui Zheng ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Diabetic Kidney Disease ◽  
Microvascular Complications ◽  
Diabetic Patients ◽  
Differentiation Potential ◽  
Therapeutic Role ◽  
Promising Strategy ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy (DN) is one of the most common diabetes mellitus (DM) microvascular complications, which always ends with end-stage renal disease (ESRD). Up to now, as the treatment of DN in clinic is still complicated, ESRD has become the main cause of death in diabetic patients. Mesenchymal stem cells (MSCs), with multi-differentiation potential and paracrine function, have attracted considerable attention in cell therapy recently. Increasing studies concerning the mechanisms and therapeutic effect of MSCs in DN emerged. This review summarizes several mechanisms of MSCs, especially MSCs derived exosomes in DN therapy, including hyperglycemia regulation, anti-inflammatory, anti-fibrosis, pro-angiogenesis, and renal function protection. We also emphasize the limitation of MSCs application in the clinic and the enhanced therapeutic role of pre-treated MSCs in the DN therapy. This review provides balanced and impartial views for MSC therapy as a promising strategy in diabetic kidney disease amelioration.

Analogs of bardoxolone methyl worsen diabetic nephropathy in rats with additional adverse effects

2013 ◽  
Vol 304 (6) ◽  
pp. F808-F819 ◽  
Author(s):  
Carla Zoja ◽  
Daniela Corna ◽  
Valeria Nava ◽  
Monica Locatelli ◽  
Mauro Abbate ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Degradation Products ◽  
Serum Transaminase ◽  
Tubular Damage ◽  
Advanced Chronic Kidney Disease ◽  
Beneficial Effects ◽  
Zucker Diabetic Fatty Rats ◽  
Recent Phase

Bardoxolone methyl is an antioxidant inflammation modulator acting through induction of Keap1-Nrf2 pathway. Results from a recent phase IIb clinical trial reported that bardoxolone methyl was associated with improvement in the estimated glomerular filtration rate in patients with advanced chronic kidney disease and Type 2 diabetes. However, increases in albuminuria, serum transaminase, and frequency of adverse events were noted. We studied the effect of 3-mo treatment with RTA 405, a synthetic triterpenoid analog of bardoxolone methyl in Zucker diabetic fatty rats with overt Type 2 diabetes. Rats were treated from 3 mo of age with vehicle, RTA 405, ramipril, or RTA 405 plus ramipril. RTA 405 caused severe changes in food intake and diuresis with decline in body weight, worsening of dyslipidemia, and increase in blood pressure. Early elevation in serum transaminase was followed by liver injury. RTA 405 worsened proteinuria, glomerulosclerosis, and tubular damage. Ramipril was renoprotective, but when given with RTA 405 it was not able to limit its worsening effects. These data could be due to degradation products in the drug substance used, as disclosed by the company once the study was concluded. To overcome such a drawback, the company offered to test dh404, a variant of RTA 405, in Zucker diabetic fatty rats. The dh404 did not display beneficial effects on proteinuria, glomerulosclerosis, and interstitial inflammation. Rather, kidneys from three rats receiving dh404 showed the presence of a granulomatous and inflammatory process reminiscent of a pseudotumor. Altogether these data raise serious concerns on the use of bardoxolone analogs in Type 2 diabetic nephropathy.

scholarly journals Pathogenic Pathways and Therapeutic Approaches Targeting Inflammation in Diabetic Nephropathy

2020 ◽  
Vol 21 (11) ◽  
pp. 3798 ◽  
Author(s):  
Sandra Rayego-Mateos ◽  
José Luis Morgado-Pascual ◽  
Lucas Opazo-Ríos ◽  
Melania Guerrero-Hue ◽  
Cristina García-Caballero ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Intracellular Signaling ◽  
Experimental Models ◽  
Diabetic Patients ◽  
Beneficial Effects ◽  
Number Of Patients ◽  
Close Relationship ◽  
Stage Renal Disease ◽  
End Stage ◽  
Inflammatory Molecules

Diabetic nephropathy (DN) is associated with an increased morbidity and mortality, resulting in elevated cost for public health systems. DN is the main cause of chronic kidney disease (CKD) and its incidence increases the number of patients that develop the end-stage renal disease (ESRD). There are growing epidemiological and preclinical evidence about the close relationship between inflammatory response and the occurrence and progression of DN. Several anti-inflammatory strategies targeting specific inflammatory mediators (cell adhesion molecules, chemokines and cytokines) and intracellular signaling pathways have shown beneficial effects in experimental models of DN, decreasing proteinuria and renal lesions. A number of inflammatory molecules have been shown useful to identify diabetic patients at high risk of developing renal complications. In this review, we focus on the key role of inflammation in the genesis and progression of DN, with a special interest in effector molecules and activated intracellular pathways leading to renal damage, as well as a comprehensive update of new therapeutic strategies targeting inflammation to prevent and/or retard renal injury.

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