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BioMed Research International 2021Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide. Chronic hyperglycemia and high blood pressure are the main risk factors for the... (Review)
Review
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide. Chronic hyperglycemia and high blood pressure are the main risk factors for the development of DN. In general, screening for microalbuminuria should be performed annually, starting 5 years after diagnosis in type 1 diabetes and at diagnosis and annually thereafter in type 2 diabetes. Standard therapy is blood glucose and blood pressure control using the renin-angiotensin system blockade, targeting A1c < 7%, and <130/80 mmHg. Regression of albuminuria remains an important therapeutic goal. However, there are problems in diagnosis and treatment of nonproteinuric DN (NP-DN), which does not follow the classic pattern of DN. In fact, the prevalence of DN continues to increase, and additional therapy is needed to prevent or ameliorate the condition. In addition to conventional therapies, vitamin D receptor activators, incretin-related drugs, and therapies that target inflammation may also be promising for the prevention of DN progression. This review focuses on the role of inflammation and oxidative stress in the pathogenesis of DN, approaches to diagnosis in classic and NP-DN, and current and emerging therapeutic interventions.
Topics: Blood Glucose; Diabetic Nephropathies; Humans; Inflammation; Kidney; Oxidative Stress; Risk Factors
PubMed: 34307650
DOI: 10.1155/2021/1497449 -
Clinical Journal of the American... Dec 2017Diabetic kidney disease develops in approximately 40% of patients who are diabetic and is the leading cause of CKD worldwide. Although ESRD may be the most recognizable...
Diabetic kidney disease develops in approximately 40% of patients who are diabetic and is the leading cause of CKD worldwide. Although ESRD may be the most recognizable consequence of diabetic kidney disease, the majority of patients actually die from cardiovascular diseases and infections before needing kidney replacement therapy. The natural history of diabetic kidney disease includes glomerular hyperfiltration, progressive albuminuria, declining GFR, and ultimately, ESRD. Metabolic changes associated with diabetes lead to glomerular hypertrophy, glomerulosclerosis, and tubulointerstitial inflammation and fibrosis. Despite current therapies, there is large residual risk of diabetic kidney disease onset and progression. Therefore, widespread innovation is urgently needed to improve health outcomes for patients with diabetic kidney disease. Achieving this goal will require characterization of new biomarkers, designing clinical trials that evaluate clinically pertinent end points, and development of therapeutic agents targeting kidney-specific disease mechanisms (, glomerular hyperfiltration, inflammation, and fibrosis). Additionally, greater attention to dissemination and implementation of best practices is needed in both clinical and community settings.
Topics: Diabetic Nephropathies; Disease Progression; Glomerular Filtration Rate; Humans; Hyperglycemia; Hypertension; Hypoglycemic Agents; Kidney Failure, Chronic; Risk Factors
PubMed: 28522654
DOI: 10.2215/CJN.11491116 -
Diabetes & Vascular Disease Research 2021Type 2 diabetes mellitus is a pathology of heterogeneous etiology characterized by hyperglycemia resulting from lack of insulin action, insulin secretion, or both, and... (Review)
Review
Type 2 diabetes mellitus is a pathology of heterogeneous etiology characterized by hyperglycemia resulting from lack of insulin action, insulin secretion, or both, and the population with diabetes mellitus is predicted to be about 439 million worldwide by 2030. Prolong diabetes has been related with microvascular complications especially diabetic nephropathy. DN is the most common complication of type 2 diabetes mellitus, and it is the leading cause of end-stage renal disease worldwide. It is crucial to diagnose patients who are more sensible to develop DN for better control of the process of disease. Several factors and mechanisms contribute to the development and outcome of diabetic nephropathy. Microalbuminuria is an early marker of DN and use it as a routine for screening, but the renal damages may be happening even without microalbuminuria. There are several significant kidney damage and disease biomarkers which helps in early detection of DN. An early biomarker may allow earlier diagnosis, treatment reduces DN prevalence and slows DN progression. Therefore, this review focuses on laboratory biomarkers that are earlier, more validation of an early and specific biomarker could potentially make it possible for early diagnosis, treatment, and retardation of progression of diabetic nephropathy.
Topics: Albuminuria; Biomarkers; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Early Diagnosis; Humans
PubMed: 34791910
DOI: 10.1177/14791641211058856 -
Journal of Diabetes Research 2017Diabetic nephropathy (DN) is a major cause of end-stage renal disease throughout the world in both developed and developing countries. This review briefly introduces the... (Review)
Review
Diabetic nephropathy (DN) is a major cause of end-stage renal disease throughout the world in both developed and developing countries. This review briefly introduces the characteristic pathological changes of DN and Tervaert pathological classification, which divides DN into four classifications according to glomerular lesions, along with a separate scoring system for tubular, interstitial, and vascular lesions. Given the heterogeneity of the renal lesions and the complex mechanism underlying diabetic nephropathy, Tervaert classification has both significance and controversies in the guidance of diagnosis and prognosis. Applications and evaluations using Tervaert classification and indications for renal biopsy are summarized in this review according to recent studies. Meanwhile, differential diagnosis with another nodular glomerulopathy and the situation that a typical DN superimposed with a nondiabetic renal disease (NDRD) are discussed and concluded in this review.
Topics: Diabetic Nephropathies; Diagnosis, Differential; Humans; Kidney Diseases
PubMed: 28316995
DOI: 10.1155/2017/8637138 -
Frontiers in Endocrinology 2022Diabetic nephropathy (DN) and diabetic retinopathy (DR) are microvascular complications of diabetes. Microvascular endothelial cells are thought to be the major targets... (Review)
Review
Diabetic nephropathy (DN) and diabetic retinopathy (DR) are microvascular complications of diabetes. Microvascular endothelial cells are thought to be the major targets of hyperglycemic injury. In diabetic microvasculature, the intracellular hyperglycemia causes damages to the vascular endothelium, via multiple pathophysiological process consist of inflammation, endothelial cell crosstalk with podocytes/pericytes and exosomes. In addition, DN and DR diseases development are involved in several critical regulators including the cell adhesion molecules (CAMs), the vascular endothelial growth factor (VEGF) family and the Notch signal. The present review attempts to gain a deeper understanding of the pathogenesis complexities underlying the endothelial dysfunction in diabetes diabetic and retinopathy, contributing to the development of new mechanistic therapeutic strategies against diabetes-induced microvascular endothelial dysfunction.
Topics: Diabetes Mellitus; Diabetic Nephropathies; Diabetic Retinopathy; Endothelial Cells; Humans; Hyperglycemia; Vascular Endothelial Growth Factor A
PubMed: 35692405
DOI: 10.3389/fendo.2022.816400 -
International Journal of Molecular... Apr 2020Diabetic nephropathy (DN) is the leading cause of end-stage renal disease globally. The primary initiating mechanism in DN is hyperglycemia-induced vascular dysfunction,... (Review)
Review
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease globally. The primary initiating mechanism in DN is hyperglycemia-induced vascular dysfunction, but its progression is due to different pathological mechanisms, including oxidative stress, inflammatory cells infiltration, inflammation and fibrosis. Macrophages (Mφ) accumulation in kidneys correlates strongly with serum creatinine, interstitial myofibroblast accumulation and interstitial fibrosis scores. However, whether or not Mφ polarization is involved in the progression of DN has not been adequately defined. The prevalence of the different phenotypes during the course of DN, the existence of hybrid phenotypes and the plasticity of these cells depending of the environment have led to inconclusive results. In the same sense the role of the different macrophage phenotype in fibrosis associated or not to DN warrants additional investigation into Mφ polarization and its role in fibrosis. Due to the association between fibrosis and the progressive decline of renal function in DN, and the role of the different phenotypes of Mφ in fibrosis, in this review we examine the role of macrophage phenotype control in DN and highlight the potential factors contributing to phenotype change and injury or repair in DN.
Topics: Animals; Cell Polarity; Diabetic Nephropathies; Fibrosis; Humans; Kidney; Macrophages; Oxidative Stress; Phenotype
PubMed: 32316547
DOI: 10.3390/ijms21082806 -
Acta Biochimica Et Biophysica Sinica Jan 2022Diabetic nephropathy (DN), which is a common microvascular complication with a high incidence in diabetic patients, greatly increases the mortality of patients. With... (Review)
Review
Diabetic nephropathy (DN), which is a common microvascular complication with a high incidence in diabetic patients, greatly increases the mortality of patients. With further study on DN, it is found that epigenetics plays a crucial role in the pathophysiological process of DN. Epigenetics has an important impact on the development of DN through a variety of mechanisms, and promotes the generation and maintenance of metabolic memory, thus ultimately leading to a poor prognosis. In this review we discuss the methylation of DNA, modification of histone, and regulation of non-coding RNA involved in the progress of cell dysfunction, inflammation and fibrosis in the kidney, which ultimately lead to the deterioration of DN.
Topics: Diabetes Mellitus; Diabetic Nephropathies; Epigenesis, Genetic; Epigenomics; Histones; Humans; Kidney
PubMed: 35130617
DOI: 10.3724/abbs.2021016 -
Annual Review of Pathology 2011Diabetic nephropathy is a well-known complication of diabetes and is a leading cause of chronic renal failure in the Western world. It is characterized by the... (Review)
Review
Diabetic nephropathy is a well-known complication of diabetes and is a leading cause of chronic renal failure in the Western world. It is characterized by the accumulation of extracellular matrix in the glomerular and tubulointerstitial compartments and by the thickening and hyalinization of intrarenal vasculature. The various cellular events and signaling pathways activated during diabetic nephropathy may be similar in different cell types. Such cellular events include excessive channeling of glucose intermediaries into various metabolic pathways with generation of advanced glycation products, activation of protein kinase C, increased expression of transforming growth factor β and GTP-binding proteins, and generation of reactive oxygen species. In addition to these metabolic and biochemical derangements, changes in the intraglomerular hemodynamics, modulated in part by local activation of the renin-angiotensin system, compound the hyperglycemia-induced injury. Events involving various intersecting pathways occur in most cell types of the kidney.
Topics: Diabetic Nephropathies; Humans; Kidney
PubMed: 21261520
DOI: 10.1146/annurev.pathol.4.110807.092150 -
Journal of the Formosan Medical... Aug 2018Diabetic kidney disease (DKD) is a major cause of morbidity and mortality in patients with diabetes mellitus and the leading cause of end-stage renal disease in the... (Review)
Review
Diabetic kidney disease (DKD) is a major cause of morbidity and mortality in patients with diabetes mellitus and the leading cause of end-stage renal disease in the world. The most characteristic marker of DKD is albuminuria, which is associated with renal disease progression and cardiovascular events. Renal hemodynamics changes, oxidative stress, inflammation, hypoxia and overactive renin-angiotensin-aldosterone system (RAAS) are involved in the pathogenesis of DKD, and renal fibrosis plays the key role. Intensified multifactorial interventions, including RAAS blockades, blood pressure and glucose control, and quitting smoking, help to prevent DKD development and progression. In recent years, novel agents are applied for preventing DKD development and progression, including new types of glucose-lowering agents, pentoxifylline, vitamin D analog paricalcitol, pyridoxamine, ruboxistaurin, soludexide, Janus kinase inhibitors and nonsteroidal minerocorticoid receptor antagonists. In this review, recent large studies about DKD are also summarized.
Topics: Albuminuria; Biomarkers; Diabetic Nephropathies; Disease Progression; Humans; Kidney Failure, Chronic; Pentoxifylline; Renin-Angiotensin System
PubMed: 29486908
DOI: 10.1016/j.jfma.2018.02.007 -
Minerva Medica Jun 2018Diabetic nephropathy (DN) also named diabetic kidney disease (DN) is one of the leading causes of mortality in people with diabetes. The aim of this review is to update... (Review)
Review
Diabetic nephropathy (DN) also named diabetic kidney disease (DN) is one of the leading causes of mortality in people with diabetes. The aim of this review is to update the medical literature, the theories behind its early natural history, the pathways of its pathogenesis, its diagnosis and treatment. Poor glycemic control, hyperlipidemia, smoking, oxidative stress, accumulation of advanced glycated end products, environmental, genetic and epigenetic factors play an important role in the pathophysiological development of DN. Microalbuminuria has been traditionally used as the primary early diagnostic marker of microvascular complication unraveling the risk for progress to severe cardiorenal outcomes, but its prognostic role has been recently debated. The disease often leads to end-stage renal disease and it is often associated with major cardiovascular outcomes. Its early diagnosis is crucial for the patients in order to have a chance for proper treatment.
Topics: Diabetes Mellitus, Type 1; Diabetic Nephropathies; Humans; Risk Factors
PubMed: 29205998
DOI: 10.23736/S0026-4806.17.05496-9