scholarly journals Epigenetic Alterations in Podocytes in Diabetic Nephropathy

2021 ◽  
Vol 12 ◽  
Author(s):  
Erina Sugita ◽  
Kaori Hayashi ◽  
Akihito Hishikawa ◽  
Hiroshi Itoh
Keyword(s):  
Dna Damage ◽  
Diabetic Nephropathy ◽  
Epigenetic Changes ◽  
Epigenetic Alterations ◽  
Human Samples ◽  
Differentiated Cells ◽  
Damage Repair ◽  
Patients With Diabetes ◽  
Stage Renal Disease ◽  
End Stage

Recently, epigenetic alterations have been shown to be involved in the pathogenesis of diabetes and its complications. Kidney podocytes, which are glomerular epithelial cells, are important cells that form a slit membrane—a barrier for proteinuria. Podocytes are terminally differentiated cells without cell division or replenishment abilities. Therefore, podocyte damage is suggested to be one of the key factors determining renal prognosis. Recent studies, including ours, suggest that epigenetic changes in podocytes are associated with chronic kidney disease, including diabetic nephropathy. Furthermore, the association between DNA damage repair and epigenetic changes in diabetic podocytes has been demonstrated. Detection of podocyte DNA damage and epigenetic changes using human samples, such as kidney biopsy and urine-derived cells, may be a promising strategy for estimating kidney damage and renal prognoses in patients with diabetes. Targeting epigenetic podocyte changes and associated DNA damage may become a novel therapeutic strategy for preventing progression to end-stage renal disease (ESRD) and provide a possible prognostic marker in diabetic nephropathy. This review summarizes recent advances regarding epigenetic changes, especially DNA methylation, in podocytes in diabetic nephropathy and addresses detection of these alterations in human samples. Additionally, we focused on DNA damage, which is increased under high-glucose conditions and associated with the generation of epigenetic changes in podocytes. Furthermore, epigenetic memory in diabetes is discussed. Understanding the role of epigenetic changes in podocytes in diabetic nephropathy may be of great importance considering the increasing diabetic nephropathy patient population in an aging society.

MO479BLOOD PRESSURE CONTROL AND OUTCOMES IN DIABETIC RENAL DISEASE : EVIDENCE FROM A TUNISIAN COHORT

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Boukhtioua Mariem ◽  
Mami Ikram ◽  
Tlili Syrine ◽  
Ghabi Hiba ◽  
Hela Jbali ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Diabetic Nephropathy ◽  
Renal Disease ◽  
Urinary Albumin Excretion ◽  
Pressure Control ◽  
Urinary Albumin ◽  
Patients With Diabetes ◽  
Group B ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background and Aims Diabetic nephropathy (DN) is associated with a high incidence of cardiovascular morbidity and mortality. The relationship between hypertension and diabetic nephropathy is complex and blood pressure (BP) control is an important management strategy in the prevention of its onset and progression .The aim of this study was to determine whether blood pressure control delays the progression of DN and prevents macrovascular complications in patients with diabetes mellitus. Method Hypertension guidelines advocate treating systolic blood pressure to less than 130 mm Hg and diastolic blood pressure to less than 80 mmHg for patients with diabetes mellitus and overt nephropathy.The relationship between blood pressure and progression of nephropathy was studied in 120 diabetic and hypertensive patients with established diabetic nephropathy. We divided hypertensive patients with stage 1 to 3 CKD already treated with antihypertensive therapy into 2 groups: those with BP < 130/80 mmHg were designated as Group A (n=66) and those with BP> 130/80 as Group B (n=54). Serum creatinine level as well as urinary albumin excretion were measured at 3 months,6 months, one year,2 years and at last visit during follow-up.The GFR was calculated using the Modification of diet in renal disease formula.The kidney disease outcome was defined as time to end-stage renal disease. The cardiovascular outcome was defined as time to myocardial infarction, stroke,ischemic stroke, hospitalization for heart failure, or revascularization. Results During the mean follow up period of 33,8 ± 11,7 months, the primary end point of end-stage renal disease occured in 9 patients (7 patients in Group B versus 2 patients in groupe A) while 11 hypertensive patient experienced a cardiovascular event.  The decline rate in GFR was significantly more important in groupe B (p<0,05). However, little difference existed between the two groups in urinary albumin excretion. Blood pressure control was not associated with improved cardiovascular outcomes when comparing the two groups. Conclusion The results of our study indicate that an uncontrolled hypertension is associated with a rapid progression of kidney impairment in diabetic patients with overt nephropathy but no relationship with the incidence of cradiovascular events was seen in our population.

scholarly journals Inflammatory Targets in Diabetic Nephropathy

2020 ◽  
Vol 9 (2) ◽  
pp. 458 ◽  
Author(s):  
Javier Donate-Correa ◽  
Desirée Luis-Rodríguez ◽  
Ernesto Martín-Núñez ◽  
Víctor G. Tagua ◽  
Carolina Hernández-Carballo ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Cardiovascular Morbidity And Mortality ◽  
Patients With Diabetes ◽  
Progression Of Kidney Disease ◽  
Diabetic Population ◽  
Traditional Risk Factors ◽  
Stage Renal Disease ◽  
End Stage ◽  
Underlying Processes ◽  
New Strategies

One of the most frequent complications in patients with diabetes mellitus is diabetic nephropathy (DN). At present, it constitutes the first cause of end stage renal disease, and the main cause of cardiovascular morbidity and mortality in these patients. Therefore, it is clear that new strategies are required to delay the development and the progression of this pathology. This new approach should look beyond the control of traditional risk factors such as hyperglycemia and hypertension. Currently, inflammation has been recognized as one of the underlying processes involved in the development and progression of kidney disease in the diabetic population. Understanding the cascade of signals and mechanisms that trigger this maladaptive immune response, which eventually leads to the development of DN, is crucial. This knowledge will allow the identification of new targets and facilitate the design of innovative therapeutic strategies. In this review, we focus on the pathogenesis of proinflammatory molecules and mechanisms related to the development and progression of DN, and discuss the potential utility of new strategies based on agents that target inflammation.

scholarly journals The Signaling of Cellular Senescence in Diabetic Nephropathy

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Yabing Xiong ◽  
Lili Zhou
Keyword(s):  
Diabetic Nephropathy ◽  
Cellular Senescence ◽  
Epigenetic Alterations ◽  
Telomere Attrition ◽  
Persistent Inflammation ◽  
Neurologic Disorders ◽  
Important Player ◽  
Signaling Activation ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy is the leading cause of chronic kidney disease (CKD) in western countries. Notably, it has a rapidly rising prevalence in China. The patients, commonly complicated with cardiovascular diseases and neurologic disorders, are at high risk to progress into end-stage renal disease (ESRD) and death. However, the pathogenic mechanisms of diabetic nephropathy have not been determined. Cellular senescence, which recently has gained broad attention, is thought to be an important player in the onset and development of diabetic nephropathy. In this issue, we generally review the mechanisms of cellular senescence in diabetic nephropathy, which involve telomere attrition, DNA damage, epigenetic alterations, mitochondrial dysfunction, loss of Klotho, Wnt/β-catenin signaling activation, persistent inflammation, and accumulation of uremic toxins. Moreover, we highlight the potential therapeutic targets of cellular senescence in diabetic nephropathy and provide important clues for clinical strategies.

scholarly journals Inflammatory Cytokines in Diabetic Nephropathy

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Javier Donate-Correa ◽  
Ernesto Martín-Núñez ◽  
Mercedes Muros-de-Fuentes ◽  
Carmen Mora-Fernández ◽  
Juan F. Navarro-González
Keyword(s):  
Diabetic Nephropathy ◽  
Renal Disease ◽  
Diabetic Complication ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
Molecular Events ◽  
Patients With Diabetes ◽  
Inflammatory Processes ◽  
Stage Renal Disease ◽  
End Stage

Probably, the most paradigmatic example of diabetic complication is diabetic nephropathy, which is the largest single cause of end-stage renal disease and a medical catastrophe of worldwide dimensions. Metabolic and hemodynamic alterations have been considered as the classical factors involved in the development of renal injury in patients with diabetes mellitus. However, the exact pathogenic mechanisms and the molecular events of diabetic nephropathy remain incompletely understood. Nowadays, there are convincing data that relate the diabetes inflammatory component with the development of renal disease. This review is focused on the inflammatory processes that develop diabetic nephropathy and on the new therapeutic approaches with anti-inflammatory effects for the treatment of chronic kidney disease in the setting of diabetic nephropathy.

Peritoneal Dialysis in Patients with Diabetes: Are the Benefits Greater than the Disadvantages?

2007 ◽  
Vol 27 (2_suppl) ◽  
pp. 190-195 ◽  
Author(s):  
Satoru Kuriyama
Keyword(s):  
Diabetic Nephropathy ◽  
Peritoneal Dialysis ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Diabetic Patients ◽  
Dialysis Modality ◽  
Patients With Diabetes ◽  
Stage Renal Disease ◽  
End Stage ◽  
Selection Of

Diabetic nephropathy has been increasing in prevalence in recent years, and it is now the dominant cause of end-stage renal disease (ESRD) worldwide. Because diabetes is frequently associated with multiple complications, nephrologists must be alert to the selection of dialysis modality so as to reduce the accompanying risks. The present review addresses whether the benefits of peritoneal dialysis are greater than its disadvantages in diabetic patients. The answer is quite positive: for most diabetic patients, peritoneal dialysis offers multiple benefits.

scholarly journals Podocyte Autophagy: A Potential Therapeutic Target to Prevent the Progression of Diabetic Nephropathy

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Na Liu ◽  
Liuqing Xu ◽  
Yingfeng Shi ◽  
Shougang Zhuang
Keyword(s):  
Diabetic Nephropathy ◽  
Glomerular Filtration ◽  
Ultrastructural Changes ◽  
Cell Organelles ◽  
Glomerular Filtration Barrier ◽  
Filtration Barrier ◽  
Patients With Diabetes ◽  
Stage Renal Disease ◽  
End Stage ◽  
Protein Cell

Diabetic nephropathy (DN), a leading cause of end-stage renal disease (ESRD), becomes a worldwide problem. Ultrastructural changes of the glomerular filtration barrier, especially the pathological changes of podocytes, lead to proteinuria in patients with diabetes. Podocytes are major components of glomerular filtration barrier, lining outside of the glomerular basement membrane (GBM) to maintain the permeability of the GBM. Autophagy is a high conserved cellular process in lysosomes including impaired protein, cell organelles, and other contents in the cytoplasm. Recent studies suggest that activation of autophagy in podocytes may be a potential therapy to prevent the progression of DN. Here, we review the mechanisms of autophagy in podocytes and discuss the current studies about alleviating proteinuria via activating podocyte autophagy.

Diabetic renal disease

2018 ◽  
Author(s):  
William G. Herrington ◽  
Aron Chakera ◽  
Christopher A. O’Callaghan
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Renal Disease ◽  
Poor Glycaemic Control ◽  
Glycation End Products ◽  
Patients With Diabetes ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy is kidney damage occurring as a result of diabetes mellitus. Overt diabetic nephropathy is defined as proteinuria greater than 0.5 g/day. Diabetic nephropathy has a complicated pathogenesis including glomerular hypertension with hyperfiltration and advanced glycation end products. Poor glycaemic control is associated with progression to microalbuminuria and overt diabetic nephropathy. The lifetime risk is fairly equivalent for type 1 and type 2 diabetes mellitus. Early disease is usually asymptomatic. Hyperglycaemia causes an osmotic diuresis and, thus, diabetes can present with polyuria. Hypertension develops with microalbuminuria; oedema indicates abnormal sodium and water retention and, occasionally, the development of nephrotic syndrome. Patients with diabetes, perhaps due to accompanying cardiac disease, are particularly susceptible to fluid overload and uraemic symptoms. End-stage renal disease can occur as early as when the estimated glomerular filtration rate is 15 ml/min 1.73 m−2.

scholarly journals Geniposide Improves Diabetic Nephropathy by Enhancing ULK1-Mediated Autophagy and Reducing Oxidative Stress through AMPK Activation

2021 ◽  
Vol 22 (4) ◽  
pp. 1651
Author(s):  
Theodomir Dusabimana ◽  
Eun Jung Park ◽  
Jihyun Je ◽  
Kyuho Jeong ◽  
Seung Pil Yun ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Interstitial Fibrosis ◽  
Pathological Feature ◽  
Protective Effects ◽  
Pharmacological Agents ◽  
Patients With Diabetes ◽  
Underlying Mechanisms ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy (DN) is a common pathological feature in patients with diabetes and the leading cause of end-stage renal disease. Although several pharmacological agents have been developed, the management of DN remains challenging. Geniposide, a natural compound has been reported for anti-inflammatory and anti-diabetic effects; however, its role in DN remains poorly understood. This study investigated the protective effects of geniposide on DN and its underlying mechanisms. We used a C57BL/6 mouse model of DN in combination with a high-fat diet and streptozotocin after unilateral nephrectomy and treated with geniposide by oral gavage for 5 weeks. Geniposide effectively improves DN-induced renal structural and functional abnormalities by reducing albuminuria, podocyte loss, glomerular and tubular injury, renal inflammation and interstitial fibrosis. These changes induced by geniposide were associated with an increase of AMPK activity to enhance ULK1-mediated autophagy response and a decrease of AKT activity to block oxidative stress, inflammation and fibrosis in diabetic kidney. In addition, geniposide increased the activities of PKA and GSK3β, possibly modulating AMPK and AKT pathways, efficiently improving renal dysfunction and ameliorating the progression of DN. Conclusively, geniposide enhances ULK1-mediated autophagy and reduces oxidative stress, inflammation and fibrosis, suggesting geniposide as a promising treatment for DN.

L-carnosine and its Derivatives as New Therapeutic Agents for the Prevention and Treatment of Vascular Complications of Diabetes

2020 ◽  
Vol 27 (11) ◽  
pp. 1744-1763 ◽  
Author(s):  
Stefano Menini ◽  
Carla Iacobini ◽  
Claudia Blasetti Fantauzzi ◽  
Giuseppe Pugliese
Keyword(s):  
Diabetic Nephropathy ◽  
Life Quality ◽  
Vascular Complications ◽  
Carbonyl Stress ◽  
Complications Of Diabetes ◽  
Diabetic Vascular Complications ◽  
Reactive Carbonyl Species ◽  
Stage Renal Disease ◽  
Stress Dependent ◽  
End Stage

Vascular complications are among the most serious manifestations of diabetes. Atherosclerosis is the main cause of reduced life quality and expectancy in diabetics, whereas diabetic nephropathy and retinopathy are the most common causes of end-stage renal disease and blindness. An effective therapeutic approach to prevent vascular complications should counteract the mechanisms of injury. Among them, the toxic effects of Advanced Glycation (AGEs) and Lipoxidation (ALEs) end-products are well-recognized contributors to these sequelae. L-carnosine (β-alanyl-Lhistidine) acts as a quencher of the AGE/ALE precursors Reactive Carbonyl Species (RCS), which are highly reactive aldehydes derived from oxidative and non-oxidative modifications of sugars and lipids. Consistently, L-carnosine was found to be effective in several disease models in which glyco/lipoxidation plays a central pathogenic role. Unfortunately, in humans, L-carnosine is rapidly inactivated by serum carnosinase. Therefore, the search for carnosinase-resistant derivatives of Lcarnosine represents a suitable strategy against carbonyl stress-dependent disorders, particularly diabetic vascular complications. In this review, we present and discuss available data on the efficacy of L-carnosine and its derivatives in preventing vascular complications in rodent models of diabetes and metabolic syndrome. We also discuss genetic findings providing evidence for the involvement of the carnosinase/L-carnosine system in the risk of developing diabetic nephropathy and for preferring the use of carnosinase-resistant compounds in human disease. The availability of therapeutic strategies capable to prevent both long-term glucose toxicity, resulting from insufficient glucoselowering therapy, and lipotoxicity may help reduce the clinical and economic burden of vascular complications of diabetes and related metabolic disorders.

scholarly journals Herba Artemisiae Capillaris Extract Prevents the Development of Streptozotocin-Induced Diabetic Nephropathy of Rat

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Jianan Geng ◽  
Xiaoyan Yu ◽  
Chunyu Liu ◽  
Chengbo Sun ◽  
Menghuan Guo ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Tissue Transglutaminase ◽  
Blood Lipid ◽  
High Dose ◽  
Oxygen Species ◽  
Promising Candidate ◽  
Ecm Degradation ◽  
Stage Renal Disease ◽  
End Stage ◽  
Excessive Accumulation

Diabetic nephropathy (DN) is a major cause of end-stage renal disease throughout the world; until now there is no specific drug available. In this work, we use herba artemisiae capillaris extract (HACE) to alleviate renal fibrosis characterized by the excessive accumulation of extracellular matrix (ECM) in rats, aiming to investigate the protective effect of the HACE on DN. We found that the intragastric treatment of high-dose HACE could reverse the effect of streptozotocin not only to decrease the level of blood glucose and blood lipid in different degree but also further to improve renal functions. It is worth mentioning that the effect of HACE treatment was comparable to the positive drug benazepril. Moreover, we found that HACE treatment could on one hand inhibit oxidative stress in DN rats through regulating enzymatic activity for scavenging reactive oxygen species and on the other hand increase the ECM degradation through regulating the activity of metalloproteinase-2 (MMP-2) and the expression of tissue transglutaminase (tTG), which explained why HACE treatment inhibited ECM accumulation. On the basis of above experimental results, we conclude that HACE prevents DN development in a streptozotocin-induced DN rat model, and HACE is a promising candidate to cure DN in clinic.

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