Wnt signaling and podocyte dysfunction in diabetic nephropathy

2017 ◽  
Vol 65 (8) ◽  
pp. 1093-1101 ◽  
Author(s):  
Madhura Bose ◽  
Sadia Almas ◽  
Sharma Prabhakar

Nephropathy is a major microvascular complication of diabetes mellitus and often leads to terminal renal failure in addition to contributing significantly to cardiovascular morbidity and mortality. Despites continuous advances, the pathogenesis of diabetic nephropathy remains poorly understood. Recent studies have underscored the significance of structural and functional changes in podocytes in the development and progression of diabetic nephropathy. The role of podocytes in health and diabetic nephropathy and abnormalities including podocyte hypertrophy, effacement, and apoptosis, and a detailed discussion on the role played by the Wnt-β-catenin signaling pathway in podocyte injury and dysfunction are the focus of this review. In addition, the role played by Wnt signaling in mediating the effects of known therapeutic strategies for diabetic nephropathy is also discussed.

2014 ◽  
Vol 155 (7) ◽  
pp. 263-269 ◽  
Author(s):  
Csaba András Dézsi

In the past two decades the number of diabetic patients has increased dramatically. According to the data of the International Diabetes Federation published in 2012, more than 371 million people suffer from diabetes mellitus, which is responsible for the death of 4.8 million people yearly. Diabetic nephropathy is the most frequent cause of terminal renal failure. The first stage of its development is microalbuminuria. Without an efficient treatment 20–40% of the patients with microalbuminuria suffering from type 2 diabetes mellitus develop chronic renal failure, but only 20% of them become uremic because most of them die beforehand mainly due to cardiovascular disease. The renin-angiotensin-system, which is one of the most important elements of the regulation of blood pressure and water-salt metabolism, plays an important role in the development of diabetic nephropathy. Drugs affecting the function of this system are of great significance in the treatment of hypertension. The author rewiews the results of several important studies and animal experiments to demonstrate the role of ramipril in the therapy of diabetic nephropathy. The author concludes that ramipril is one of the angiotensin-converting enzyme inhibitors with the highest number of evidence based beneficial results. Apart from its blood pressure decreasing effect, ramipril protects target organs and it proved to be effective in the treatment of diabetic nephropathy according to most international multicenter clinical trials. Orv. Hetil., 2014, 155(7), 263–269.


2019 ◽  
Vol 26 ◽  
Author(s):  
Qin zhang ◽  
Ming Yang ◽  
Ying Xiao ◽  
Yachun Han ◽  
Shikun Yang ◽  
...  

: Diabetic nephropathy (DN) is one of the most common and important microvascular complications of diabetes mellitus (DM). The main clinical features of DN are proteinuria and a progressive decline in renal function , which are associated with structural and functional changes in the kidney. The pathogenesis of DN is multifactorial, including genetic, metabolic and haemodynamic factors, which can trigger a sequence of events. Controlling metabolic risks such as hyperglycaemia, hypertension and dyslipidaemia is not enough to slow the progression of DN. Recent studies have emphasized immunoinflammation as a critical pathogenic factor in the progression of DN. Therefore, targeting inflammation is considered a potential and novel treatment strategy for DN. In this review, we will briefly introduce the inflammatory process of DN and discuss the anti-inflammatory effects of antidiabetic drugs when treating DN.


2018 ◽  
Vol 12 (1) ◽  
pp. 23-26 ◽  
Author(s):  
Gandhipuram Periyasamy Senthilkumar ◽  
Melepallappil Sabeenakumari Anithalekshmi ◽  
Md. Yasir ◽  
Sreejith Parameswaran ◽  
Rajaa muthu Packirisamy ◽  
...  

2019 ◽  
Vol 23 (2) ◽  
pp. 218-221
Author(s):  
L. V. Yanitskaya ◽  
L. F. Osinskaya ◽  
A. V. Redko

Hyperglycemia of diabetes mellitus leads to the activation of the polyol way of oxidation of glucose with the activation of the enzymes of aldose reductase and sorbitol dehydrogenase and of their coenzymes NADPH and NAD, which triggers the mechanism of formation of sorbitol. The consequences of these changes lead to microangiopathy of the tissues of the kidneys, which may be one of the pathogenetic mechanisms of diabetic nephropathy. In an accessible literature, the role of coenzymes of sorbitol pathway in the development of diabetic nephropathy is not sufficiently defined. The purpose of the study was to study the content of NAD and NADPH coenzymes, their correlation, and their role in the mechanism of kidney damage in diabetes mellitus and to predict the possible correction of these changes with the NAD-nicotinamide derivative. The study was conducted on a model of streptotrozectinic diabetes mellitus (single administration of streptozotocin in a dose of 60 mg per 1 kg of body weight). Four weeks after induction of diabetes, nicotinamide (100 mg per 1 kg body weight) was injected. The level of glucose was determined by the Accu-chek (Roshe Diagnostics, Switzerland) glucose meter. The content of NAD and NADH was determined in the non-protein extracts. The statistical analysis was carried out using the Microsoft Excel statistical analysis program. The difference between the indicators was considered statistically significant (p<0.05). The NAD level was reduced by 31%, the NAD/NADN ratio was 32%. The dependence of the ratio of NADP/NADPN in conditions of hyperglycemia of diabetes mellitus with clinical manifestations of diabetic nephropathy is determined. A decrease in the ratio of NADP/NADPN to 38% in the rat kidney in the cortical layer was detected. The introduction of nicotinamide normalized the reduced content of NAD diabetic rats. These results provide perspectives for further research in which nicotinamide can be used as a renal protector.


2010 ◽  
Vol 49 (178) ◽  
Author(s):  
P Jha ◽  
BKL Das ◽  
S Shrestha ◽  
S Majhi ◽  
L Chandra ◽  
...  

INTRODUCTION: Diabetic nephropathy is one of the major complications of Diabetes Mellitus characterized by persistent albuminuria, elevated arterial blood pressure, a relentless decline in glomerular filtration rate (GFR) and a high risk of cardiovascular morbidity and mortality. METHODS: In this study, urinary micro-albumin estimation was done in 177 diabetic patients. This study aims to ascertain association of glycemicstatus, lipid profile and proteinuria in Type 2 Diabetes Mellitus with nephropathy. RESULTS: Among 177 patients, 26 had frank proteinuria, 79 had micro-albuminuria and 72 were without proteinuria. Increased frequency ofproteinuria was seen in male than female. Micro-albuminuria and frank proteinuria was seen more in older age group. The multiple comparisons showed the significantly increased levels of urea, creatinine, fasting blood glucose in micro-albuminuria and overt proteinuria patients in comparison to without proteinuria. Glycated hemoglobin level was increased with the increasing age group particularly in overt proteinuric patients. CONCLUSIONS: The glycemic control, monitoring of lipid profile and early urinary protein estimation with better management may delay diabetic nephropathy or its further complications in diabetes mellitus.  KEYWORDS: diabetes mellitus, diabetic nephropathy, frank proteinuria, glycated hemoglobin, micro-albuminuria.


2020 ◽  
Vol 21 (5) ◽  
pp. 1559 ◽  
Author(s):  
Guangbi Li ◽  
Jason Kidd ◽  
Pin-Lan Li

Podocytes are visceral epithelial cells covering the outer surface of glomerular capillaries in the kidney. Blood is filtered through the slit diaphragm of podocytes to form urine. The functional and structural integrity of podocytes is essential for the normal function of the kidney. As a membrane-bound organelle, lysosomes are responsible for the degradation of molecules via hydrolytic enzymes. In addition to its degradative properties, recent studies have revealed that lysosomes may serve as a platform mediating cellular signaling in different types of cells. In the last decade, increasing evidence has revealed that the normal function of the lysosome is important for the maintenance of podocyte homeostasis. Podocytes have no ability to proliferate under most pathological conditions; therefore, lysosome-dependent autophagic flux is critical for podocyte survival. In addition, new insights into the pathogenic role of lysosome and associated signaling in podocyte injury and chronic kidney disease have recently emerged. Targeting lysosomal functions or signaling pathways are considered potential therapeutic strategies for some chronic glomerular diseases. This review briefly summarizes current evidence demonstrating the regulation of lysosomal function and signaling mechanisms as well as the canonical and noncanonical roles of podocyte lysosome dysfunction in the development of chronic glomerular diseases and associated therapeutic strategies.


Author(s):  
O. B. Susla ◽  
Z. I. Litovkina ◽  
O. V. Bushtynska

Systematic analysis of cardiac remodeling peculiarities in patients with V D stage of chronic kidney disease (CKD VD)  caused by diabetes mellitus is important both in the stratification of cardiovascular risk and in the choice of adequate treatment strategies. The purpose of the study was to determine the character of structural and functional reconstruction of myocardium in patients with diabetic nephropathy (DN) on maintenance hemodialysis (HD) by identifying left ventricular hypertrophy (LVH), its geometric types, assessment of the severity of heart dysfunction, pulmonary hypertension (PH), as well as determination of frequency of cardiac valve calcification (CVC), development of defects of mitral (MV) and aortic (AV) valves. Materials and methods. The study included 136 patients on chronic HD (men, 78, age, (53,9±1,0) years, duration of HD, (47,6±4,2) months). Depending on the presence/absence of type 2 diabetes mellitus (DM) with kidney damage, they were divided into two groups: the first one – without DN (n=88); the second one – with DN (n=48). All patients were followed up by standard echocardiography (EchoCG) examination by standard procedure. Results. LVH was diagnosed in 84.6% of patients with CKD VD stage, significantly more often (93.8 vs. 78.4%, p=0.020) in patients with DN, with the incidence of eccentric LVH in the second group being higher (47.9 vs. 28.4%, p=0.023) than in the first one. Prevalence of pseudonormal and restrictive types of LV diastolic dysfunction (62.5 vs. 28.4%, p<0.001), LV systolic dysfunction (27.1 vs. 9.1%, p=0.006) and PH (64.6 vs 35.2%, p=0.001) were significant in HD patients with DN. CVC was detected in 66.6% of patients with type 2 DM with renal injury with a predominance of calcification of both valves (35.4%) over isolated calcification of MV (MVC) (20.8%) and AV (AVC) (10.4 %). Combined valve calcification in the HD patients of the second group was observed 2.6 times more often (p=0.003) than in the first one. Patients with DN, unlike those without diabetes, were associated with a higher prevalence of stenoses of MV (16.7 vs. 3.4%, p=0.007) and AV (39.6 vs. 15.9%, p=0.004), and insufficiency of MV (66.7 vs. 44.3%, p=0.013) and AV (35.4 vs. 14.8%, p=0.006). The most significant EchoCG parameters that distinguished groups of HD patients with the presence of DN were: left atrial diameter (p<0.001), end-diastolic LV dimension (p<0.001), thickness of interventricular septum (p=0.001), LV myocardial mass index (p=0.001), ratio of transmitral flows in early and late diastole (p=0.009), time of deceleration of early diastolic transmitral blood flow (p<0.001), LV ejection fraction (p=0.009), diameter of the right ventricle (RV) (p=0.003), diameter (p=0.007) and mean pulmonary artery pressure (p<0.001). Conclusions. In patients with CKD VD stage with DN the maladaptive cardiac remodeling with predominance of unfavorable types (eccentric (to a greater extent) and concentric) LV hypertrophy, RV dilatation, PH, expressive of LV diastolic and systolic dysfunction, large-scale combined MVC and AVC occurs, which, in turn, leads to the formation of valve defects, can contribute to the progression of diastolic myocardial stiffness and heart failure.


Endocrinology ◽  
2021 ◽  
Author(s):  
Irena Audzeyenka ◽  
Agnieszka Bierżyńska ◽  
Abigail C Lay

Abstract Diabetic Nephropathy (DN) is the leading cause of kidney failure, with an increasing incidence worldwide. Mitochondrial dysfunction is known to occur in DN and has been implicated in the underlying pathogenesis of disease. These complex organelles have an array of important cellular functions and involvement in signalling pathways; and understanding the intricacies of these responses in health, as well as how they are damaged in disease, is likely to highlight novel therapeutic avenues. A key cell type damaged early in DN is the podocyte and increasing studies have focused on investigating the role of mitochondria in podocyte injury. This review will summarise what is known about podocyte mitochondrial dynamics in DN, with a particular focus on bioenergetic pathways, highlighting key studies in this field and potential opportunities to target, enhance or protect podocyte mitochondrial function in the treatment of DN.


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