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American Journal of Kidney Diseases :... Jun 2018Diabetic kidney disease and diabetic nephropathy are the leading cause of end-stage kidney disease in the United States and most developed countries. Diabetes accounts... (Review)
Review
Diabetic kidney disease and diabetic nephropathy are the leading cause of end-stage kidney disease in the United States and most developed countries. Diabetes accounts for 30% to 50% of the incident cases of end-stage kidney disease in the United States. Although this represents a significant public health concern, it is important to note that only 30% to 40% of patients with diabetes develop diabetic nephropathy. Specific treatment of patients with diabetic nephropathy can be divided into 4 major arenas: cardiovascular risk reduction, glycemic control, blood pressure control, and inhibition of the renin-angiotensin system (RAS). Recommendations for therapy include targeting a hemoglobin A concentration < 7% and blood pressure < 140/90mmHg with therapy anchored around the use of a RAS-blocking agent. The single best evidence-based therapy for diabetic nephropathy is therapy with a RAS-blocking medication. This Core Curriculum outlines and discusses in detail the epidemiology, pathophysiology, diagnosis, and management of diabetic nephropathy.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Curriculum; Diabetic Nephropathies; Disease Progression; Female; Humans; Kidney Failure, Chronic; Prognosis; Renal Dialysis; Renin-Angiotensin System; Risk Assessment; Severity of Illness Index; Survival Analysis
PubMed: 29398179
DOI: 10.1053/j.ajkd.2017.10.026 -
The Review of Diabetic Studies : RDS 2015Diabetic nephropathy is the leading cause of end-stage renal disease. Patients with diabetic nephropathy have a high cardiovascular risk, comparable to patients with... (Review)
Review
Diabetic nephropathy is the leading cause of end-stage renal disease. Patients with diabetic nephropathy have a high cardiovascular risk, comparable to patients with coronary heart disease. Accordingly, identification and management of risk factors for diabetic nephropathy as well as timely diagnosis and prompt management of the condition are of paramount importance for effective treatment. A variety of risk factors promotes the development and progression of diabetic nephropathy, including elevated glucose levels, long duration of diabetes, high blood pressure, obesity, and dyslipidemia. Most of these risk factors are modifiable by antidiabetic, antihypertensive, or lipid-lowering treatment and lifestyle changes. Others such as genetic factors or advanced age cannot be modified. Therefore, the rigorous management of the modifiable risk factors is essential for preventing and delaying the decline in renal function. Early diagnosis of diabetic nephropathy is another essential component in the management of diabetes and its complications such as nephropathy. New markers may allow earlier diagnosis of this common and serious complication, but further studies are needed to clarify their additive predictive value, and to define their cost-benefit ratio. This article reviews the most important risk factors in the development and progression of diabetic nephropathy and summarizes recent developments in the diagnosis of this disease.
Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Progression; Humans; Kidney Failure, Chronic; Risk Factors
PubMed: 26676664
DOI: 10.1900/RDS.2015.12.110 -
The American Journal of Chinese Medicine 2022Diabetic nephropathy (DN) is a common microvascular complication of diabetes mellitus (DM), which can lead to renal failure in diabetic patients. At present, the... (Review)
Review
Diabetic nephropathy (DN) is a common microvascular complication of diabetes mellitus (DM), which can lead to renal failure in diabetic patients. At present, the first-line drugs for DN are mainly the renin-angiotensin system (RAS) inhibitors or angiotensin receptor blockers, and the latest approved aldosterone receptor antagonist finerenone, which delay the progression of DN to end-stage renal disease (ESRD), but the therapeutic effect is still not ideal. With a history of thousands of years, traditional Chinese medicine (TCM) has rich experience in the treatment of DN. Based on the theory of TCM, the clinical treatment of DN mainly focuses on generating fluid and nourishing blood, nourishing and , detoxifying and detumescent. In recently years, the therapeutic effects and mechanisms of TCM prescription, Chinese herbal medicine, and its active components on DN have received extensive attention in new drug development. This paper reviews the research progress of the mechanism of TCM on DN.
Topics: Humans; Medicine, Chinese Traditional; Diabetic Nephropathies; Drugs, Chinese Herbal; Antihypertensive Agents; Diabetes Mellitus
PubMed: 36222120
DOI: 10.1142/S0192415X22500744 -
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 -
Frontiers in Immunology 2020Diabetic nephropathy (DN) is a major microvascular complication of diabetes mellitus. It is the most frequent cause of end-stage renal disease with no definitive therapy... (Review)
Review
Diabetic nephropathy (DN) is a major microvascular complication of diabetes mellitus. It is the most frequent cause of end-stage renal disease with no definitive therapy available so far. Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, are nano- and micron-sized heterogeneous vesicles that can be secreted by almost all cell types. Importantly, EVs contain many biologically active materials, such as RNAs, DNAs, proteins, and lipids, from their parental cells, which can be transported to their recipient cells to mediate intercellular communication and signaling. Accumulating studies demonstrated that EVs, mainly exosomes and microvesicles, participated in the pathophysiological process of DN. Recently emerging studies also found that the contents of EVs in the urine (miRNAs, mRNAs, and proteins) could be used as potential biomarkers for DN. Therefore, in this mini-review, the generation, isolation methods, and biological function of EVs were introduced, and then the current information about the mechanism and the diagnostic value in the development of DN was summarized. Moreover, the review also discussed the future challenges of exploring the role of EVs in kidney disease.
Topics: Animals; Biomarkers; Cell Communication; Diabetic Nephropathies; Extracellular Vesicles; Humans; Kidney; Signal Transduction
PubMed: 32582146
DOI: 10.3389/fimmu.2020.00943 -
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 -
International Journal of Molecular... May 2020Diabetic 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... (Review)
Review
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.
Topics: Animals; Anti-Inflammatory Agents; Diabetic Nephropathies; Humans; Hypoglycemic Agents; Immunosuppressive Agents
PubMed: 32471207
DOI: 10.3390/ijms21113798 -
Drug Design, Development and Therapy 2021Oxidative stress and inflammation play essential roles in the development and progression of diabetic nephropathy (DN). Baicalin (BAI), a natural flavonoid, has been...
BACKGROUND
Oxidative stress and inflammation play essential roles in the development and progression of diabetic nephropathy (DN). Baicalin (BAI), a natural flavonoid, has been showed to have a renoprotective effect in various renal diseases. However, its underlying mechanisms in DN remain unclear. In this study, we explored the potential effects and underlying mechanisms of BAI on DN using a spontaneous DN model.
METHODS
The protective effects of BAI on DN have been evaluated by detecting DN-related biochemical indicators, kidney histopathology and cell apoptosis. After that, we examined the level of renal oxidative stress and inflammation to explain BAI's renoprotective effects. Then, Nrf2 pathway was tested to clarify its antioxidant activity, and kidney transcriptomics was conducted to elucidate its anti-inflammatory activity. Finally, Western blot was applied for final mechanism verification.
RESULTS
Our results found that BAI effectively ameliorated diabetic conditions, proteinuria, renal histopathological changes and cell apoptosis in DN. BAI significantly improved the kidney levels of glutathione peroxidase (GSH-PX), superoxide dismutase (SOD) and catalase (CAT), and reduced malondialdehyde (MDA) level. Meanwhile, the infiltration of inflammatory cells including T-lymphocytes, T-helper cells, neutrophils and macrophages, and the mRNA levels of pro-inflammatory cytokines (IL-1β, IL-6, MCP-1 and TNFα) were also obviously inhibited by BAI. Afterward, Western blot found that BAI significantly activated Nrf2 signaling and increased the expression of downstream antioxidant enzymes (HO-1, NQO-1). Kidney transcriptomics revealed that the inhibition of MAPK signaling pathway may contribute to BAI's anti-inflammatory activity, which has also been verified in later experiment. BAI treatment did obviously inhibit the activation of canonical pro-inflammatory signaling pathway MAPK family, such as Erk1/2, JNK and P38.
CONCLUSION
In summary, our data demonstrated that BAI can treat DN by alleviating oxidative stress and inflammation, and its underlying mechanisms were associated with the activation of Nrf2-mediated antioxidant signaling pathway and the inhibition of MAPK-mediated inflammatory signaling pathway.
Topics: Animals; Apoptosis; Diabetic Nephropathies; Flavonoids; Inflammation; MAP Kinase Signaling System; Male; Mice; NF-E2-Related Factor 2; Oxidative Stress
PubMed: 34321869
DOI: 10.2147/DDDT.S319260 -
Nature Communications Jan 2023Statins play an important role in the treatment of diabetic nephropathy. Increasing attention has been given to the relationship between statins and insulin resistance,...
Statins play an important role in the treatment of diabetic nephropathy. Increasing attention has been given to the relationship between statins and insulin resistance, but many randomized controlled trials confirm that the therapeutic effects of statins on diabetic nephropathy are more beneficial than harmful. However, further confirmation of whether the beneficial effects of chronic statin administration on diabetic nephropathy outweigh the detrimental effects is urgently needed. Here, we find that long-term statin administration may increase insulin resistance, interfere with lipid metabolism, leads to inflammation and fibrosis, and ultimately fuel diabetic nephropathy progression in diabetic mice. Mechanistically, activation of insulin-regulated phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway leads to increased fatty acid synthesis. Furthermore, statins administration increases lipid uptake and inhibits fatty acid oxidation, leading to lipid deposition. Here we show that long-term statins administration exacerbates diabetic nephropathy via ectopic fat deposition in diabetic mice.
Topics: Animals; Mice; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Fatty Acids; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Insulin Resistance; Lipids; Mammals
PubMed: 36693830
DOI: 10.1038/s41467-023-35944-z -
Indian Journal of Ophthalmology Nov 2021To evaluate the presence of nephropathy and neuropathy in patients with diabetic retinopathy (DR) and to correlate the severity of DR to that of diabetic nephropathy and...
PURPOSE
To evaluate the presence of nephropathy and neuropathy in patients with diabetic retinopathy (DR) and to correlate the severity of DR to that of diabetic nephropathy and diabetic neuropathy.
METHODS
This prospective noninterventional hospital-based study included 57 consecutive cases of DR of either sex, presenting to the eye OPD between January 2019 and November 2020 with minimum 5-year duration of Type 1 and 2 DM. Complete ophthalmic examination was done and DR was classified according to early treatment diabetic retinopathy study classification. Severity of diabetic nephropathy was based on urine albumin creatinine ratio and estimated glomerular filtration rate. Severity of diabetic neuropathy was based on nerve conduction velocity.
RESULTS
The study was conducted on 57 patients of whom patients 45 were males and 12 were females. Mild nonproliferative diabetic retinopathy was present in 22 patients, moderate in 14 patients, severe in 18 patients, and proliferative diabetic retinopathy in 3 patients. In our study, group 30 patients of DR presented without clinically significant macular edema (CSME) and 27 patients presented with CSME. The distribution of severity of DR according to CSME was observed to be statistically significant (P<<0.05). The association of severity of DR with severity of diabetic nephropathy was observed to be statistically significant (P<<0.05). The association of severity of DR with that of diabetic neuropathy was inconclusive.
CONCLUSION
The association of severity of DR with severity of diabetic nephropathy and diabetic neuropathy can be used as a marker for future chronic kidney diseases progression and also to prognosticate neurological outcomes in diabetic patients.
Topics: Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Female; Humans; Macular Edema; Male; Prospective Studies; Risk Factors
PubMed: 34708806
DOI: 10.4103/ijo.IJO_1237_21