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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 -
The Medical Clinics of North America Jul 2023Diabetes is a major public health challenge and diabetic kidney disease (DKD), a broader diagnostic term than diabetic nephropathy, is the leading cause of chronic... (Review)
Review
Diabetes is a major public health challenge and diabetic kidney disease (DKD), a broader diagnostic term than diabetic nephropathy, is the leading cause of chronic kidney disease and end-stage kidney disease in the United States and worldwide. A better understanding of the underlying pathophysiological mechanisms of DKD, and recent clinical trials testing new therapeutic interventions, have shown promising results to curb this epidemic. Given the global health burden of DKD, it is extremely important to prioritize prevention, early recognition, referral, and aggressive management of DKD in the primary care setting.
Topics: Humans; Diabetic Nephropathies; Kidney Failure, Chronic; Renal Insufficiency, Chronic; Diabetes Mellitus, Type 2
PubMed: 37258007
DOI: 10.1016/j.mcna.2023.03.004 -
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 -
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 -
Primary Care Dec 2020Diabetic kidney disease (DKD) is the most common cause of chronic kidney disease in the United States. Approximately 30% to 40% of individuals with diabetes mellitus... (Review)
Review
Diabetic kidney disease (DKD) is the most common cause of chronic kidney disease in the United States. Approximately 30% to 40% of individuals with diabetes mellitus develop DKD, and the presence of DKD significantly elevates the risk for morbidity and mortality. Understanding of DKD has grown in recent years. This review describes the pathogenesis of DKD and expands on evidence-based strategies for DKD management, integrating traditional approaches for hyperglycemia, hypertension, and albuminuria management with emerging therapeutic options. Given the public health burden of DKD, it is essential to prioritize prevention, recognition, and management of DKD in the primary care setting.
Topics: Albuminuria; Blood Pressure; Comorbidity; Diabetic Nephropathies; Disease Progression; Glucagon-Like Peptide 1; Glycemic Control; Humans; Hypoglycemic Agents; Primary Health Care; Referral and Consultation; Renin-Angiotensin System; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 33121634
DOI: 10.1016/j.pop.2020.08.004 -
International Journal of Molecular... Apr 2020Lipotoxicity is characterized by the ectopic accumulation of lipids in organs different from adipose tissue. Lipotoxicity is mainly associated with dysfunctional... (Review)
Review
Lipotoxicity is characterized by the ectopic accumulation of lipids in organs different from adipose tissue. Lipotoxicity is mainly associated with dysfunctional signaling and insulin resistance response in non-adipose tissue such as myocardium, pancreas, skeletal muscle, liver, and kidney. Serum lipid abnormalities and renal ectopic lipid accumulation have been associated with the development of kidney diseases, in particular diabetic nephropathy. Chronic hyperinsulinemia, often seen in type 2 diabetes, plays a crucial role in blood and liver lipid metabolism abnormalities, thus resulting in increased non-esterified fatty acids (NEFA). Excessive lipid accumulation alters cellular homeostasis and activates lipogenic and glycogenic cell-signaling pathways. Recent evidences indicate that both quantity and quality of lipids are involved in renal damage associated to lipotoxicity by activating inflammation, oxidative stress, mitochondrial dysfunction, and cell-death. The pathological effects of lipotoxicity have been observed in renal cells, thus promoting podocyte injury, tubular damage, mesangial proliferation, endothelial activation, and formation of macrophage-derived foam cells. Therefore, this review examines the recent preclinical and clinical research about the potentially harmful effects of lipids in the kidney, metabolic markers associated with these mechanisms, major signaling pathways affected, the causes of excessive lipid accumulation, and the types of lipids involved, as well as offers a comprehensive update of therapeutic strategies targeting lipotoxicity.
Topics: Adipose Tissue; Animals; Biomarkers; Clinical Decision-Making; Diabetic Nephropathies; Disease Management; Disease Susceptibility; Dyslipidemias; Fatty Acids, Nonesterified; Glycogen; Humans; Kidney; Lipid Metabolism; Mitochondria; Obesity; Prognosis; Signal Transduction
PubMed: 32290082
DOI: 10.3390/ijms21072632 -
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 -
Frontiers in Immunology 2023Diabetic nephropathy (DN) often leads to end-stage renal disease. Oxidative stress demonstrates a crucial act in the onset and progression of DN, which triggers various... (Review)
Review
Diabetic nephropathy (DN) often leads to end-stage renal disease. Oxidative stress demonstrates a crucial act in the onset and progression of DN, which triggers various pathological processes while promoting the activation of inflammation and forming a vicious oxidative stress-inflammation cycle that induces podocyte injury, extracellular matrix accumulation, glomerulosclerosis, epithelial-mesenchymal transition, renal tubular atrophy, and proteinuria. Conventional treatments for DN have limited efficacy. Polyphenols, as antioxidants, are widely used in DN with multiple targets and fewer adverse effects. This review reveals the oxidative stress and oxidative stress-associated inflammation in DN that led to pathological damage to renal cells, including podocytes, endothelial cells, mesangial cells, and renal tubular epithelial cells. It demonstrates the potent antioxidant and anti-inflammatory properties by targeting Nrf2, SIRT1, HMGB1, NF-κB, and NLRP3 of polyphenols, including quercetin, resveratrol, curcumin, and phenolic acid. However, there remains a long way to a comprehensive understanding of molecular mechanisms and applications for the clinical therapy of polyphenols.
Topics: Humans; Diabetic Nephropathies; Polyphenols; Endothelial Cells; Oxidative Stress; Antioxidants; Inflammation; Diabetes Mellitus
PubMed: 37545494
DOI: 10.3389/fimmu.2023.1185317 -
Methods in Molecular Biology (Clifton,... 2020Diabetic nephropathy (DN) is one of the most feared diabetic chronic microvascular complications and the major cause of end-stage renal disease (ESRD). The classical...
Diabetic nephropathy (DN) is one of the most feared diabetic chronic microvascular complications and the major cause of end-stage renal disease (ESRD). The classical presentation of DN is characterized by hyperfiltration and albuminuria in the early phases which is then followed by a progressive renal function decline. The presentation of diabetic kidney disease (DKD) can vary especially in patients with T2DM where concomitant presence of other glomerular/tubular pathologies and severe peripheral vascular disease can become important confounders. All-cause mortality in individuals with DKD is approximately 30 times higher than that in diabetic patients without nephropathy and a great majority of patients with DKD will die from cardiovascular disease before they reach ESRD. The management of metabolic and hemodynamic perturbations for the prevention and for the delay of progression of DKD is very important. DKD is a global challenge and a significant social and economic burden; research should aim at developing new ideas to tackle this devastating condition.
Topics: Cardiovascular Diseases; Confounding Factors, Epidemiologic; Cost of Illness; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Progression; Humans; Kidney Failure, Chronic
PubMed: 31701441
DOI: 10.1007/978-1-4939-9841-8_1 -
The Veterinary Clinics of North... May 2023The pathomechanisms implicated in diabetic kidney disease in people are present in dogs and cats and, in theory, could lead to renal complications in companion animals... (Review)
Review
The pathomechanisms implicated in diabetic kidney disease in people are present in dogs and cats and, in theory, could lead to renal complications in companion animals with long-standing diabetes mellitus. However, these renal complications develop during a long period, and there is little to no clinical evidence that they could lead to chronic kidney disease in companion animals.
Topics: Animals; Cats; Dogs; Cat Diseases; Diabetes Mellitus; Diabetic Nephropathies; Dog Diseases; Kidney
PubMed: 36854633
DOI: 10.1016/j.cvsm.2023.01.006