oalib
Search Results: 1 - 10 of 100 matches for " "
All listed articles are free for downloading (OA Articles)
Page 1 /100
Display every page Item
Role of Duration of Diabetes in the Development of Nephropathy in Type 2 Diabetic Patients  [cached]
Jiji Inassi,R Vijayalakshmy
National Journal of Medical Research , 2013,
Abstract: Introduction: Diabetes has now become the most common single cause of end stage renal disease and about 40% of diabetic patients develop nephropathy. The present study was conducted to find out the relation between duration of diabetes & development of renal disease. Methodology: The study was conducted in 120 patients with Type 2 diabetes. Three groups were selected with 40 patients in each group with diabetes of <5year duration, 5-10year duration and >10year duration. 40 normal healthy adults were included in the control group. Parameters like BP, blood urea, serum creatinine, urine microprotein were compared with controls. Results: As duration increases, there is impairment of renal function as evidenced by increase in blood urea, serum creatinine & microproteinuria. Statistically significant increase in BP was also observed with increase in duration. Both metabolic & hemodynamic factors play a decisive role in the development of nephropathy. AGEs, PDGF, TGFβ, VEGF, and Angiotensin II etc. stimulate growth & fibrotic factors leading to renal damage. Conclusion: Screening for microalbuminuria will allow early identification of patients with nephropathy. It has been shown that meticulous glycemic & bloodpressure control can slow the progression of diabetic nephropathy. Developing countries like India with its large burden of diabetes should evolve strategies for prevention of its secondary complications. [Natl J of Med Res 2013; 3(1.000): 5-8]
Role of Mindin in Diabetic Nephropathy  [PDF]
Maki Murakoshi,Tomohito Gohda,Mitsuo Tanimoto,Kazuhiko Funabiki,Satoshi Horikoshi,Yasuhiko Tomino
Journal of Diabetes Research , 2011, DOI: 10.1155/2011/486305
Abstract: A number of studies have shown that proinflammatory cytokines have important roles in determining the development of microvascular diabetic complications, including nephropathy. Inflammatory biomarkers should be useful for diagnosis or monitoring of diabetic nephropathy. Mindin (spondin 2) is a member of the mindin-/F-spondin family of secreted extracellular matrix (ECM) proteins. Recent studies showed that mindin is essential for initiation of innate immune response and represents a unique pattern-recognition molecule in the ECM. Previously, we demonstrated that the levels of urinary mindin in patients with type 2 diabetes were higher than those in healthy individuals. We propose that urinary mindin is a potent biomarker for the development of diabetic nephropathy. 1. Introduction Diabetic nephropathy is a major cause of end-stage kidney disease (ESKD) in the United States, Japan, and most of Europe [1]. Although the etiology of this insidious disorder is not well understood, hyperglycemia and hypertension may play pivotal roles in the pathogenesis of diabetic nephropathy. Actually, almost 30% of diabetic patients develop diabetic nephropathy despite strict blood glucose and/or blood pressure control [2]. Chronic low-grade inflammation (so-called microinflammation) has been found to play roles in the pathogenesis of diabetes [3, 4] and has been identified as a risk factor for the development of diabetes [5, 6]. Moreover, diabetes has been proposed as a disease of the innate immune system [7]. In addition, the studies in recent years have shown that inflammation and inflammatory cytokines are determinants in the development of microvascular diabetic complications such as neuropathy, retinopathy, and nephropathy [8–11]. In 1991, Hasegawa et al. reported that glomerular basement membranes from diabetic rats induced significantly greater amounts of tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) in cultured peritoneal macrophages than when these cells were incubated with basement membranes from nondiabetic rats [12]. Based on these findings, the authors suggested for the first time that inflammatory cytokines may participate in the pathogenesis of diabetic nephropathy [12]. At present, a number of clinical studies have suggested relationships between inflammatory cytokines and diabetic nephropathy [13, 14]. Inflammatory cytokines, that is, IL-1, interleukin-6 (IL-6), and interleukin-18 (IL-18) [15, 16], vascular endothelial growth factor (VEGF) [17, 18], monocyte chemoattractant protein-1 (MCP-1) [19, 20], and transforming growth factor-β (TGF-β)
Inflammation and Oxidative Stress via Persistent Hyperglycemia in Progression of Diabetic Nephropathy in Type 2 Diabetes Mellitus  [PDF]
D Kafle,N Islam,B Aryal,P Adhikary,Neelina Singh
Journal of Chitwan Medical College , 2013, DOI: 10.3126/jcmc.v3i1.8456
Abstract: Diabetic nephropathy is a major microvascular complication of diabetes, representing the leading cause of end stage renal disease in the world, and a major cause of morbidity and mortality in type 2 diabetic subjects. In the kidney, a number of pathways that generate reactive oxygen species (ROS) such as glycolysis, specific defects in the polyol pathway, uncoupling of nitric oxide synthase, xanthine oxidase, NAD (P) H oxidase, and advanced glycation have been identified as potentially major contributors to the pathogenesis of diabetic kidney disease. Changes in oxidative stress biomarkers, including super-oxide dismutase, catalase, glutathione reductase, glutathione peroxidase, glutathione levels, vitamins, lipid peroxidation, nitrite concentration, nonenzymatic glycosylated proteins have been associated with diabetic nephropathy due to oxidative stress induced hyperglycemia. Oxidative stress in diabetes is responsible for endothelial dysfunction releasing inflammatory markers cytokines from the damaged renal tissue. Hyperglycemia induces intracellular reactive oxygen species in mesan-gial and tubular epithelial cells which induces cytokines, IL-6 and TNF-α production in glomerular mesangial and tubular epithelial cells in diabetic kidney. Antioxidants inhibit high glucose induced transforming growth factors and extra cellular matrix expression in glomerular mesangial and tubular epithelial cells, which ameliorate features of diabetic nephropathy, suggesting that oxidative stress plays an important role in diabetic renal injury causing diabetic nephropathy. Journal of Chitwan Medical College 2013; 3(1): 1-4 DOI: http://dx.doi.org/10.3126/jcmc.v3i1.8456
The Role of Autophagy in the Pathogenesis of Diabetic Nephropathy  [PDF]
Kosuke Yamahara,Mako Yasuda,Shinji Kume,Daisuke Koya,Hiroshi Maegawa,Takashi Uzu
Journal of Diabetes Research , 2013, DOI: 10.1155/2013/193757
Abstract: Diabetic nephropathy is a leading cause of end-stage renal disease worldwide. The multipronged drug approach targeting blood pressure and serum levels of glucose, insulin, and lipids fails to fully prevent the onset and progression of diabetic nephropathy. Therefore, a new therapeutic target to combat diabetic nephropathy is required. Autophagy is a catabolic process that degrades damaged proteins and organelles in mammalian cells and plays a critical role in maintaining cellular homeostasis. The accumulation of proteins and organelles damaged by hyperglycemia and other diabetes-related metabolic changes is highly associated with the development of diabetic nephropathy. Recent studies have suggested that autophagy activity is altered in both podocytes and proximal tubular cells under diabetic conditions. Autophagy activity is regulated by both nutrient state and intracellular stresses. Under diabetic conditions, an altered nutritional state due to nutrient excess may interfere with the autophagic response stimulated by intracellular stresses, leading to exacerbation of organelle dysfunction and diabetic nephropathy. In this review, we discuss new findings showing the relationships between autophagy and diabetic nephropathy and suggest the therapeutic potential of autophagy in diabetic nephropathy. 1. Introduction The increasing prevalence of diabetes mellitus and its vascular complications has become a major health problem worldwide. Diabetic nephropathy is a serious complication of diabetes and is a common cause of end-stage renal disease. Diabetes induces glomerular damage, along with proteinuria, and subsequent tubulointerstitial lesions, leading to end-stage renal disease [1–3]. Initially, the patient shows hyperfiltration, represented by high glomerular filtration rates (GFRs) and occasional occurrence of microalbuminuria. Later, the patient shows a gradual decline in the GFR and persistence of microalbuminuria that comes before mild and subsequently moderate proteinuria. Urinary protein seems to be almost entirely reabsorbed in early and late proximal tubules and may induce tubulointerstitial damage [3]. Reducing proteinuria by keeping blood pressure and blood glucose levels under control is therefore a primary therapeutic goal with diabetic nephropathy [4, 5]. Unfortunately, however, some patients develop treatment-resistant proteinuria, resulting in end-stage renal disease. There is now an urgent need to identify new therapeutic target molecules or cellular processes that underlie the pathogenesis of diabetic nephropathy to establish additional
TLR4 Activation Promotes Podocyte Injury and Interstitial Fibrosis in Diabetic Nephropathy  [PDF]
Jin Ma, Steven J. Chadban, Cathy Y. Zhao, Xiaochen Chen, Tony Kwan, Usha Panchapakesan, Carol A. Pollock, Huiling Wu
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0097985
Abstract: Toll like receptor (TLR) 4 has been reported to promote inflammation in diabetic nephropathy. However the role of TLR4 in the complicated pathophysiology of diabetic nephropathy is not understood. In this study, we report elevated expression of TLR4, its endogenous ligands and downstream cytokines, chemokines and fibrogenic genes in diabetic nephropathy in WT mice with streptozotocin (STZ) diabetes. Subsequently, we demonstrated that TLR4?/? mice were protected against the development of diabetic nephropathy, exhibiting less albuminuria, inflammation, glomerular hypertrophy and hypercellularity, podocyte and tubular injury as compared to diabetic wild-type controls. Marked reductions in interstitial collagen deposition, myofibroblast activation (α-SMA) and expression of fibrogenic genes (TGF-β and fibronectin) were also evident in TLR4 deficient mice. Consistent with our in vivo results, high glucose directly promoted TLR4 activation in podocytes and tubular epithelial cells in vitro, resulting in NF-κB activation and consequent inflammatory and fibrogenic responses. Our data indicate that TLR4 activation may promote inflammation, podocyte and tubular epithelial cell injury and interstitial fibrosis, suggesting TLR4 is a potential therapeutic target for diabetic nephropathy.
Role of Mindin in Diabetic Nephropathy  [PDF]
Maki Murakoshi,Tomohito Gohda,Mitsuo Tanimoto,Kazuhiko Funabiki,Satoshi Horikoshi,Yasuhiko Tomino
Experimental Diabetes Research , 2011, DOI: 10.1155/2011/486305
Abstract: A number of studies have shown that proinflammatory cytokines have important roles in determining the development of microvascular diabetic complications, including nephropathy. Inflammatory biomarkers should be useful for diagnosis or monitoring of diabetic nephropathy. Mindin (spondin 2) is a member of the mindin-/F-spondin family of secreted extracellular matrix (ECM) proteins. Recent studies showed that mindin is essential for initiation of innate immune response and represents a unique pattern-recognition molecule in the ECM. Previously, we demonstrated that the levels of urinary mindin in patients with type 2 diabetes were higher than those in healthy individuals. We propose that urinary mindin is a potent biomarker for the development of diabetic nephropathy.
Role of the renin angiotensin system in diabetic nephropathy  [cached]
Tanuj Chawla,Deepika Sharma,Archana Singh
World Journal of Diabetes , 2010,
Abstract: Diabetic nephropathy has been the cause of lot of morbidity and mortality in the diabetic population. The renin angiotensin system (RAS) is considered to be involved in most of the pathological processes that result in diabetic nephropathy. This system has various subsystems which contribute to the disease pathology. One of these involves angiotensin II (Ang II) which shows increased activity during diabetic nephropathy. This causes hypertrophy of various renal cells and has a pressor effect on arteriolar smooth muscle resulting in increased vascular pressure. Ang II also induces inflammation, apoptosis, cell growth, migration and differentiation. Monocyte chemoattractant protein-1 production responsible for renal fibrosis is also regulated by RAS. Polymorphism of angiotensin converting enzyme (ACE) and Angiotensinogen has been shown to have effects on RAS. Available treatment modalities have proven effective in controlling the progression of nephropathy. Various drugs (based on antagonism of RAS) are currently in the market and others are still under trial. Amongst the approved drugs, ACE inhibitors and angiotensin receptor blockers (ARBs) are widely used in clinical practice. ARBs are shown to be superior to ACE inhibitors in terms of reducing proteinuria but the combined role of ARBs with ACE inhibitors in diabetic nephropathy is under debate.
Role of toll receptors in diabetic nephropathy  [PDF]
Mona Mansour, Randa Fayez Salam, Lila Rashed, Heba Salam
Journal of Diabetes Mellitus (JDM) , 2014, DOI: 10.4236/jdm.2014.41005
Abstract:

Objectives: Diabetic nephropathy is the leading cause of chronic kidney disease. The pathogenesis of DN remains incompletely understood. It has been recently demonstrated that inflammatory processes play a significant role in the development and progression of DN. Toll-like receptors play a fundamental role in the innate immune system by triggering proinflammatory signaling pathways. Our aim is to evaluate the expression of TLRs on monocytes and relate their expression with inflammation in HD patients with & without diabetic nephropathy. Method: In a case control study (60) patients from Alkasr El Aini Hospital on hemodialysis were divided into two groups: Group 1, 30 patients on heamodialysis not due to diabetic nephropathy, Group 2, 30 patients on heamodialysis due to diabetic nephropathy, compared to Group 3, including 30 healthy controls. All participants were subjected to: Full medical history, complete physical examination, Serum creatinine, uric acid, A1C, fundus examination, detection of TLR2, TLR expression by real time PCR in peripheral blood mononuclear cells. Data were statically calculated using SPSS, comparision between groups was done using student T test comparing 2 groups, correlation using spearman’s correlation. Results: Diabetic had significantly increased TLR2, TLR4 mRNA in peripheral blood mononuclear cells compared to controls and non diabetics patient on heamodialysis (p < 0.001), TLR2, TLR4 significantly correlated with dialysis duration in diabetic (p < 0.001), no correlation with A1C in relation to TLR2 (p = 0.078), TLR4 (p = 0.163). Conclusion: TLR2, TLR4 were significantly elevated in diabetic on dialysis initiating event in the pathogenesis of DN, providing a link between hyperglycemia and hypoxia with inflammation and fibrosis within the kidney. Hence, therapeutic interventions aimed at targeting the inflammatory component through interruption of TLR signaling may be a novel strategy to target prevention and treatment of DN.

Nuclear NF-κB p65 in Peripheral Blood Mononuclear Cells Correlates with Urinary MCP-1, RANTES and the Severity of Type 2 Diabetic Nephropathy  [PDF]
Bin Yi, Xiaofang Hu, Hao Zhang, Jing Huang, Jishi Liu, Jing Hu, Wei Li, Lihua Huang
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0099633
Abstract: Aims To investigate if nuclear NF-κB p65 expression in ex vivo isolated peripheral blood mononuclear cells correlates with urinary MCP-1 or RANTES and the severity of type 2 diabetic nephropathy. Methods According to their urinary albumin-to-creatinine ratio (uACR), 107 patients with type 2 diabetes (eGFR >60 ml/min) were divided into normal albuminuria group (DN0 group, 38 cases), microalbuminuria group (DN1 group, 38 cases), and macroalbuminuria group (DN2 group, 31 cases), compared with matched healthy normal control group (NC group, 30 cases). Nuclear NF-κB p65 protein expression levels in peripheral blood mononuclear cells were detected by western blotting. Real-time quantitative polymerase chain reaction was used to detect NF-κB p65 mRNA expression and ELISA assay was used to detect the levels of urinary MCP-1 and RANTES. Results Nuclear NF-κB p65 protein and NF-κB p65 mRNA expression levels in peripheral blood mononuclear cells, urinary MCP-1/Cr and RANTES/Cr were all significantly higher in all diabetes groups as compared with NC group. In particular, the increase of nuclear NF-κB p65 protein and NF-κB p65 mRNA expressions, urinary MCP-1/Cr and RANTES/Cr all correlated with the severity of type 2 diabetic nephropathy as indicated by the increase in uACR. Pearson correlation analysis indicated that both urinary MCP-1/Cr and RANTES/Cr were positively correlated with nuclear NF-κB p65 protein or NF-κB p65 mRNA levels. Stepwise multiple regression analysis showed that nuclear NF-κB p65 protein or NF-κB p65 mRNA was an independent variable for urinary MCP-1/Cr, and MCP-1/Cr and RANTES/Cr were two independent variables for uACR. Conclusion Our research demonstrates that nuclear NF-κB p65 protein and mRNA expressions in ex vivo isolated peripheral blood mononuclear cells well correlate with urinary MCP-1/Cr, RANTES/Cr and the severity of type 2 diabetic nephropathy.
Role of metabolic control on diabetic nephropathy
Macedo, Célia Sperandéo;Capelletti, Sonia Maria;Mercadante, Maria Cecília Salgado;Padovani, Carlos Roberto;Spadella, César Tadeu;
Acta Cirurgica Brasileira , 2002, DOI: 10.1590/S0102-86502002000600003
Abstract: objective: the aim of this investigation was studying the influence of glucose metabolic control on diabetic nephropathy. the authors observed the effect of acarbose, insulin, and both drugs on the metabolic control and development of mesangial enlargement of kidney glomeruli in alloxan-diabetic rats. methods: five groups of wistar rats were used: normal rats (n), non-treated alloxan-diabetic rats (d), alloxan-diabetic rats treated with acarbose (ad), alloxan-diabetic rats treated with insulin (id), and alloxan-diabetic rats treated with insulin plus acarbose (iad). the following parameters were evaluated: body weight; water and food intake; diuresis; blood and urine glucose levels; and the kidney lesions: mesangial enlargement and tubule cell vacuolization. renal lesions were analysed using a semi-quantitative score 1, 3, 6, 9, and 12 months after diabetes induction. results: diabetic rats showed a marked increase of glycemia, urinary glucose levels, diuresis, water and food intake, and weight loss, while the treated diabetic rats showed significant decreased levels of these parameters. the most satisfactory metabolic control was that of diabetic rats treated with acarbose + insulin. there was a significant mesangial enlargement in diabetic rats compared to normal rats from the third up to the 12th month after diabetes induction, with a significant difference between the animals treated with acarbose + insulin and non-treated diabetic rats. a difference between the animals treated with acarbose or insulin alone and non-treated diabetics rats was not seen. conclusions: the authors discuss the results stressing the role of diabetic metabolic control in the prevention of diabetic nephropathy.
Page 1 /100
Display every page Item


Home
Copyright © 2008-2017 Open Access Library. All rights reserved.