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Nephron 2017Hyperfiltering kidney is a typical feature of diabetes. Improvement observed with regard to glucose control and blood pressure control reduces the high glomerular... (Review)
Review
Hyperfiltering kidney is a typical feature of diabetes. Improvement observed with regard to glucose control and blood pressure control reduces the high glomerular filtration rate and may contribute to retard the appearance and the progression of diabetic renal disease. Although the mechanism of hyperfiltration is still unclear, there is mounting evidence that the increased reabsorption of glucose and sodium by sodium glucose transporter-2 (SGLT-2) is involved in this altered renal function. There is a possibility that SGLT-2 inhibition may correct hyperfiltration in diabetes, adding a new therapeutic approach to halt renal disease in patients with diabetes.
Topics: Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Progression; Glomerular Filtration Rate; Humans; Kidney; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 27978521
DOI: 10.1159/000448183 -
Clinical Science (London, England :... Jan 2019The classification of diabetic nephropathy (DN) as a vascular complication of diabetes makes the possible involvement of histamine, an endogenous amine that is well... (Review)
Review
The classification of diabetic nephropathy (DN) as a vascular complication of diabetes makes the possible involvement of histamine, an endogenous amine that is well known for its vasoactive properties, an interesting topic for study. The aim of the present review is to provide an extensive overview of the possible involvement of histamine in the onset and progression of DN. The evidence collected on the role of histamine in kidney function together with its well-known pleiotropic action suggest that this amine may act simultaneously on glomerular hyperfiltration, tubular inflammation, fibrosis development and tubular hypertrophy.
Topics: Animals; Blood Vessels; Diabetic Angiopathies; Diabetic Nephropathies; Fibrosis; Glomerular Filtration Rate; Hemodynamics; Histamine; Humans; Kidney; Renal Reabsorption; Signal Transduction
PubMed: 30606813
DOI: 10.1042/CS20180839 -
Romanian Journal of Internal Medicine =... 2015Diabetic Nephropathy. In 2014 (according to data published by the World Health Organization) 9% of the global population was affected by Diabetes which was considered to... (Review)
Review
Diabetic Nephropathy. In 2014 (according to data published by the World Health Organization) 9% of the global population was affected by Diabetes which was considered to be directly responsible for 1.5 million deaths just two years prior (in 2012). From the entire number of patients suffering from diabetes, approximately a quarter of them develop renal affection. Diabetic nephropathy has similar physiopathology mechanisms and ultrastructural changes in cell injury characteristics in both Type 1 and Type 2 diabetes. Cell Death. Cell Death was less studied in the renal diabetic disease, although it could represent an important pathogenic mechanism in the appearance and progression of nephropathy. At renal level the cellular loss can be explained by several mechanisms; different stimuli with cellular lesion potential can trigger apoptosis signaling with appearance of regulatory proteins having a double role (they participate in the initiation of the apoptosis path and cell death or in the ending of this process). The types of Cell Death and their relative proportion between themselves in the renal tissue have not been completely elucidated. Caspases. Discovered in the middle of the 1990's, Caspases are a part of the cysteine proteases family and play a role in numerous aspects of physiology (having a role in development, aging and apoptosis), but also in aspects of physiopathology of several degenerative affections, autoimmune diseases, oncologic diseases - having an important part in apoptosis, necrosis and also inflammation.
Topics: Apoptosis; Caspases; Cell Cycle; Diabetic Nephropathies; Humans; Hypertrophy; Kidney
PubMed: 26939205
DOI: 10.1515/rjim-2015-0038 -
Current Opinion in Nephrology and... May 2016Diabetic nephropathy is a long-standing complication of diabetes mellitus and is responsible for more than 40% of end-stage renal disease cases in developed countries.... (Review)
Review
PURPOSE OF REVIEW
Diabetic nephropathy is a long-standing complication of diabetes mellitus and is responsible for more than 40% of end-stage renal disease cases in developed countries. Unfortunately, conventional renin-angiotensin-aldosterone system (RAAS) inhibitor medications only partially protect against the development and progression of diabetic nephropathy. Moreover, RAAS inhibitors have failed as primary prevention therapy in type 1 diabetes. Thus, agents targeting alternative pathogenic mechanisms leading to diabetic nephropathy have been intensively investigated, which is the topic of this review.
RECENT FINDINGS
Promising emerging agents have targeted neurohormonal activation (alternative components of the RAAS and neprilysin inhibition), tubuloglomerular feedback mechanisms (sodium glucose cotransporter 2 inhibition and incretin-based therapy) and renal inflammation/fibrosis.
SUMMARY
Evidence demonstrating the potential of these agents to protect and prevent progression of diabetic nephropathy is summarized in this review. There are dedicated clinical trials ongoing with these therapies, which have the potential to change the clinical practice.
Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Diabetic Nephropathies; Humans; Kidney Failure, Chronic; Renin-Angiotensin System; Treatment Outcome
PubMed: 26890303
DOI: 10.1097/MNH.0000000000000214 -
The American Journal of the Medical... Feb 2020
Topics: Diabetic Nephropathies; History, 20th Century; History, 21st Century; Humans; Kidney; Transforming Growth Factor beta1
PubMed: 32039767
DOI: 10.1016/j.amjms.2019.11.010 -
Mediators of Inflammation 2012Diabetic nephropathy is the leading cause of end-stage kidney disease worldwide but current treatments remain suboptimal. This review examines the evidence for... (Review)
Review
Diabetic nephropathy is the leading cause of end-stage kidney disease worldwide but current treatments remain suboptimal. This review examines the evidence for inflammation in the development and progression of diabetic nephropathy in both experimental and human diabetes, and provides an update on recent novel experimental approaches targeting inflammation and the lessons we have learned from these approaches. We highlight the important role of inflammatory cells in the kidney, particularly infiltrating macrophages, T-lymphocytes and the subpopulation of regulatory T cells. The possible link between immune deposition and diabetic nephropathy is explored, along with the recently described immune complexes of anti-oxidized low-density lipoproteins. We also briefly discuss some of the major inflammatory cytokines involved in the pathogenesis of diabetic nephropathy, including the role of adipokines. Lastly, we present the latest data on the pathogenic role of the stress-activated protein kinases in diabetic nephropathy, from studies on the p38 mitogen activated protein kinase and the c-Jun amino terminal kinase cell signalling pathways. The genetic and pharmacological approaches which reduce inflammation in diabetic nephropathy have not only enhanced our understanding of the pathophysiology of the disease but shown promise as potential therapeutic strategies.
Topics: Cytokines; Diabetic Nephropathies; Humans; Inflammation; Macrophages; T-Lymphocytes
PubMed: 22969168
DOI: 10.1155/2012/146154 -
Frontiers in Endocrinology 2023Diabetic nephropathy (DN) is the most common microvascular complication in diabetes and one of the leading causes of end-stage renal disease. The standard treatments for... (Review)
Review
Diabetic nephropathy (DN) is the most common microvascular complication in diabetes and one of the leading causes of end-stage renal disease. The standard treatments for patients with classic DN focus on blood glucose and blood pressure control, but these treatments can only slow the progression of DN instead of stopping or reversing the disease. In recent years, new drugs targeting the pathological mechanisms of DN (e.g., blocking oxidative stress or inflammation) have emerged, and new therapeutic strategies targeting pathological mechanisms are gaining increasing attention. A growing number of epidemiological and clinical studies suggest that sex hormones play an important role in the onset and progression of DN. Testosterone is the main sex hormone in males and is thought to accelerate the occurrence and progression of DN. Estrogen is the main sex hormone in females and is thought to have renoprotective effects. However, the underlying molecular mechanism by which sex hormones regulate DN has not been fully elucidated and summarized. This review aims to summarize the correlation between sex hormones and DN and evaluate the value of hormonotherapy in DN.
Topics: Male; Female; Humans; Diabetic Nephropathies; Testosterone; Kidney Failure, Chronic; Estrogens; Oxidative Stress; Diabetes Mellitus
PubMed: 37143724
DOI: 10.3389/fendo.2023.1135530 -
International Journal of Molecular... May 2020Diabetes prevalence is constantly increasing and, nowadays, it affects more than 350 million people worldwide. Therefore, the prevalence of diabetic nephropathy (DN) has... (Review)
Review
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.
Topics: Animals; Diabetic Nephropathies; Disease Models, Animal; Glomerular Filtration Rate; Humans; Kidney; Podocytes
PubMed: 32438732
DOI: 10.3390/ijms21103587 -
BioMed Research International 2017Diabetic nephropathy is one of the most important microvascular complications of diabetes mellitus and is responsible for 40-50% of all cases of end stage renal disease.... (Review)
Review
Diabetic nephropathy is one of the most important microvascular complications of diabetes mellitus and is responsible for 40-50% of all cases of end stage renal disease. The therapeutic strategies in diabetic nephropathy need to be targeted towards the pathophysiology of the disease. The earlier these therapeutic strategies can bring about positive effects on vascular changes and prevent the vasculature in patients with diabetes from deteriorating, the better the renal function can be preserved. Studies evaluating anti-inflammatory and antioxidative strategies in diabetic nephropathy demonstrate the need and value of these novel treatment avenues. CaD is an established vasoactive and angioprotective drug that has shown a unique, multitarget mode of action in several experimental studies and in different animal models of diabetic microvascular complications. On the molecular level, CaD reduces oxidative stress and inhibits growth factors such as fibroblast growth factor and vascular endothelial growth factors. Recent findings have demonstrated a strong rationale for its use in reducing urine albumin excretion rate and markers of inflammation as well as improving endothelial function. Its beneficial effects make it an attractive therapeutic compound especially in the early stages of the disease. These findings, although promising, need further confirmation in prospective clinical trials with CaD.
Topics: Antioxidants; Calcium Dobesilate; Diabetic Nephropathies; Endothelium; Free Radical Scavengers; Humans; Intercellular Signaling Peptides and Proteins; Oxidative Stress
PubMed: 29082239
DOI: 10.1155/2017/1909258 -
Journal of Diabetes Research 2015Probably, the most paradigmatic example of diabetic complication is diabetic nephropathy, which is the largest single cause of end-stage renal disease and a medical... (Review)
Review
Probably, the most paradigmatic example of diabetic complication is diabetic nephropathy, which is the largest single cause of end-stage renal disease and a medical catastrophe of worldwide dimensions. Metabolic and hemodynamic alterations have been considered as the classical factors involved in the development of renal injury in patients with diabetes mellitus. However, the exact pathogenic mechanisms and the molecular events of diabetic nephropathy remain incompletely understood. Nowadays, there are convincing data that relate the diabetes inflammatory component with the development of renal disease. This review is focused on the inflammatory processes that develop diabetic nephropathy and on the new therapeutic approaches with anti-inflammatory effects for the treatment of chronic kidney disease in the setting of diabetic nephropathy.
Topics: Animals; Cytokines; Diabetes Complications; Diabetic Nephropathies; Disease Models, Animal; Disease Progression; Humans; Inflammation; Oxidative Stress; Rats; Renal Insufficiency, Chronic
PubMed: 25785280
DOI: 10.1155/2015/948417