Inflammation and the pathogenesis of diabetic nephropathy

2012 ◽  
Vol 124 (3) ◽  
pp. 139-152 ◽  
Author(s):  
Jun Wada ◽  
Hirofumi Makino
Keyword(s):  
Diabetic Nephropathy ◽  
Progressive Increase ◽  
Therapeutic Strategies ◽  
Matrix Expansion ◽  
Problematic Issue ◽  
Pkc Protein Kinase C ◽  
Stage Renal Disease ◽  
End Stage ◽  
Inflammatory Molecules ◽  
The Impact

The most problematic issue in clinical nephrology is the relentless and progressive increase in patients with ESRD (end-stage renal disease) worldwide. The impact of diabetic nephropathy on the increasing population with CKD (chronic kidney disease) and ESRD is enormous. Three major pathways showing abnormality of intracellular metabolism have been identified in the development of diabetic nephropathy: (i) the activation of polyol and PKC (protein kinase C) pathways; (ii) the formation of advanced glycation end-products; and (iii) intraglomerular hypertension induced by glomerular hyperfiltration. Upstream of these three major pathways, hyperglycaemia is the major driving force of the progression to ESRD from diabetic nephropathy. Downstream of the three pathways, microinflammation and subsequent extracellular matrix expansion are common pathways for the progression of diabetic nephropathy. In recent years, many researchers have been convinced that the inflammation pathways play central roles in the progression of diabetic nephropathy, and the identification of new inflammatory molecules may link to the development of new therapeutic strategies. Various molecules related to the inflammation pathways in diabetic nephropathy include transcription factors, pro-inflammatory cytokines, chemokines, adhesion molecules, Toll-like receptors, adipokines and nuclear receptors, which are candidates for the new molecular targets for the treatment of diabetic nephropathy. Understanding of these molecular pathways of inflammation would translate into the development of anti-inflammation therapeutic strategies.

Diabetic kidney disease in thedb/dbmouse

2003 ◽  
Vol 284 (6) ◽  
pp. F1138-F1144 ◽  
Author(s):  
Kumar Sharma ◽  
Peter McCue ◽  
Stephen R. Dunn
Keyword(s):  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Mouse Model ◽  
Renal Disease ◽  
Mouse Models ◽  
Diabetic Kidney Disease ◽  
Diabetic Kidney ◽  
Matrix Expansion ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy is increasing in incidence and is now the number one cause of end-stage renal disease in the industrialized world. To gain insight into the genetic susceptibility and pathophysiology of diabetic nephropathy, an appropriate mouse model of diabetic nephropathy would be critical. A large number of mouse models of diabetes have been identified and their kidney disease characterized to various degrees. Perhaps the best characterized and most intensively investigated model is the db/ db mouse. Because this model appears to exhibit the most consistent and robust increase in albuminuria and mesangial matrix expansion, it has been used as a model of progressive diabetic renal disease. In this review, we present the findings from various studies on the renal pathology of the db/ db mouse model of diabetes in the context of human diabetic nephropathy. Furthermore, we discuss shortfalls of assessing functional renal disease in mouse models of diabetic kidney disease.

scholarly journals Revisiting Experimental Models of Diabetic Nephropathy

2020 ◽  
Vol 21 (10) ◽  
pp. 3587
Author(s):  
Anna Giralt-López ◽  
Mireia Molina-Van den Bosch ◽  
Ander Vergara ◽  
Clara García-Carro ◽  
Daniel Seron ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Experimental Models ◽  
Diabetic Patients ◽  
Rodent Models ◽  
Basement Membrane Thickening ◽  
Matrix Expansion ◽  
Risk Biomarkers ◽  
Stage Renal Disease ◽  
End Stage

Diabetes prevalence is constantly increasing and, nowadays, it affects more than 350 million people worldwide. Therefore, the prevalence of diabetic nephropathy (DN) has also increased, becoming the main cause of end-stage renal disease (ESRD) in the developed world. DN is characterized by albuminuria, a decline in glomerular filtration rate (GFR), hypertension, mesangial matrix expansion, glomerular basement membrane thickening, and tubulointerstitial fibrosis. The therapeutic advances in the last years have been able to modify and delay the natural course of diabetic kidney disease (DKD). Nevertheless, there is still an urgent need to characterize the pathways that are involved in DN, identify risk biomarkers and prevent kidney failure in diabetic patients. Rodent models provide valuable information regarding how DN is set and its progression through time. Despite the utility of these models, kidney disease progression depends on the diabetes induction method and susceptibility to diabetes of each experimental strain. The classical DN murine models (Streptozotocin-induced, Akita, or obese type 2 models) do not develop all of the typical DN features. For this reason, many models have been crossed to a susceptible genetic background. Knockout and transgenic strains have also been created to generate more robust models. In this review, we will focus on the description of the new DN rodent models and, additionally, we will provide an overview of the available methods for renal phenotyping.

Effects of curcumin in experimental diabetic nephropathy

2016 ◽  
Vol 65 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Sharma S Prabhakar
Keyword(s):  
Diabetic Nephropathy ◽  
End Stage Renal Disease ◽  
Complementary Therapies ◽  
Clinical Evidence ◽  
Therapeutic Strategies ◽  
Disease States ◽  
The World ◽  
Health And Disease ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy (DN) is currently well established as the most common cause of end-stage renal disease in most parts of the world. Notwithstanding the expanding basic and clinical research in this field, the pathogenesis remains far from clear and hence the treatment of DN remains suboptimal. There is a critical need for the development of newer therapeutic strategies including alternative and complementary therapies. One of the natural products that was extensively studied in cancer and other chronic disease states such as diabetes is curcumin, an active ingredient in turmeric, a spice extensively used in India. In this manuscript, we present a critical review of the experimental and clinical evidence that supports the use of curcumin and its analogs in DN as well as the various proposed mechanisms for its biological actions in health and disease states.

scholarly journals Development of Biomarkers and Molecular Therapy Based on Inflammatory Genes in Diabetic Nephropathy

2021 ◽  
Vol 22 (18) ◽  
pp. 9985
Author(s):  
Amit K. Maiti
Keyword(s):  
Diabetic Nephropathy ◽  
Molecular Therapy ◽  
Renal Physiology ◽  
Complex Nature ◽  
Diabetic Patients ◽  
Renal Tubules ◽  
Stage Renal Disease ◽  
End Stage ◽  
Inflammatory Molecules

Diabetic Nephropathy (DN) is a debilitating consequence of both Type 1 and Type 2 diabetes affecting the kidney and renal tubules leading to End Stage Renal Disease (ESRD). As diabetes is a world epidemic and almost half of diabetic patients develop DN in their lifetime, a large group of people is affected. Due to the complex nature of the disease, current diagnosis and treatment are not adequate to halt disease progression or provide an effective cure. DN is now considered a manifestation of inflammation where inflammatory molecules regulate most of the renal physiology. Recent advances in genetics and genomic technology have identified numerous susceptibility genes that are associated with DN, many of which have inflammatory functions. Based on their role in DN, we will discuss the current aspects of developing biomarkers and molecular therapy for advancing precision medicine.

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.

scholarly journals Antioxidants in Kidney Diseases: The Impact of Bardoxolone Methyl

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Jorge Rojas-Rivera ◽  
Alberto Ortiz ◽  
Jesus Egido
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
End Stage Renal Disease ◽  
Renal Damage ◽  
Kidney Diseases ◽  
New Drugs ◽  
Stage Renal Disease ◽  
End Stage ◽  
The Impact

Drugs targeting the renin-angiotensin-aldosterone system (RAAS) are the mainstay of therapy to retard the progression of proteinuric chronic kidney disease (CKD) such as diabetic nephropathy. However, diabetic nephropathy is still the first cause of end-stage renal disease. New drugs targeted to the pathogenesis and mechanisms of progression of these diseases beyond RAAS inhibition are needed. There is solid experimental evidence of a key role of oxidative stress and its interrelation with inflammation on renal damage. However, randomized and well-powered trials on these agents in CKD are scarce. We now review the biological bases of oxidative stress and its role in kidney diseases, with focus on diabetic nephropathy, as well as the role of the Keap1-Nrf2 pathway and recent clinical trials targeting this pathway with bardoxolone methyl.

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 Depression among end-stage renal disease patients undergoing hemodialysis: a cross-sectional study from Palestine

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Samah W. Al-Jabi ◽  
Ansam Sous ◽  
Fatimah Jorf ◽  
Mahmoud Taqatqa ◽  
Mahdi Allan ◽  
...  
Keyword(s):  
Renal Disease ◽  
Low Income ◽  
End Stage Renal Disease ◽  
West Bank ◽  
Psychological Status ◽  
The West ◽  
Depression Prevalence ◽  
Stage Renal Disease ◽  
End Stage ◽  
The Impact

Abstract Background The impact of end-stage renal disease on the patient’s psychological status necessitates the value of increasing depression awareness. The current study aimed to assess the depression prevalence among Palestinian hemodialyzed patients and its association with patients’ characteristics. Methods A convenience clustered sampling technique was followed. Sample was collected from ten hemodialysis centers in the West Bank, Palestine, during 3 months in 2015. We used the Beck Depression Inventory-II scale (BDI-II) to evaluate depression among participants. All data were analyzed using Statistical Package for the Social Sciences version 16.0. Results Two hundred and eighty-six hemodialyzed patients were interviewed. The mean age (± standard deviation) of the patients was 52.0 ± 14.3 years, and most participants were males 172 (60.1%). Regarding the dialysis characteristics, the median of years of dialysis was 2 years (1–4). The prevalence of depression was 73.1%. Elderly patients (p = 0.001), female (p = 0.036), living in rural areas or camp (p = 0.032), low income (p = 0.041), unemployment (p = 0.001), not doing regular exercise (p = 0.001), and having multi comorbidities (p = 0.001) were significantly associated with more depression scores. The results of binary logistic regression showed that only patients who were living in camps, patients who were previously employed, and patients who were not practicing exercise remained significantly associated with a higher depression score. Conclusions This study is the first one confirmed about depression and its prevalence among hemodialyzed patients in the West Bank, Palestine. Compared to other communities, the study found a higher depression prevalence rate. There is a need to offer psychological interviews and non-pharmacological and pharmacological interventions.

scholarly journals Therapeutic Strategies for Diabetic Kidney Disease

Diabetology ◽  
2021 ◽  
Vol 2 (1) ◽  
pp. 31-35
Author(s):  
Keiichiro Matoba
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Intensive Therapy ◽  
Therapeutic Strategies ◽  
Therapeutic Interventions ◽  
Hemodynamic Changes ◽  
Diabetic Kidney ◽  
Global Epidemic ◽  
Stage Renal Disease ◽  
End Stage

Diabetic kidney disease (DKD) is a global epidemic leading to end-stage renal disease (ESRD) and susceptibility to cardiovascular disease, with few therapeutic interventions. A hallmark of DKD is the activation of the renin-angiotensin-aldosterone system and hemodynamic changes in glomerulus. Although intensive therapy with agents that targets those abnormalities lowers the risk of DKD progression, it does not completely abolish the risk of ESRD and cardiovascular events. Recent studies have illustrated the importance of renal inflammation, oxidative stress, and activated Rho-associated protein kinase (ROCK) signaling as essential pathogenesis for the development of DKD. In this commentary, these topics will be discussed.

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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