It is vital that the magnitude and duration of such responses are tightly regulated. Several highly conserved pathways orchestrate its onset and progression to ensure an effective and adequately controlled pro-inflammatory response to safely remove pathogens and damaged tissue components and facilitate tissue repair. ![]() Inflammation is a critical component of appropriate host defence. The key role of inflammation in the macrovascular and microvascular complications of metabolic disease has led to considerable interest in exploring this pathogenic factor as a therapeutic target. Both obesity and diabetes-associated CKD share common initiating events that involve interactions between metabolic and haemodynamic factors, which lead to the activation of common intracellular signalling pathways and the production of pro-inflammatory cytokines, growth factors and lipids. Although studies clearly indicate that obesity-associated CKD can be driven by diabetes and hypertension, we now appreciate that obesity is also an independent risk factor for CKD. Obesity, diabetes hypertension and cardiovascular disease are major risk factors for the development and progression of chronic kidney disease (CKD) 3. Given the prevalence of diabetes and obesity, population growth and increased lifespan, the impact of diabetes and its complications on resource allocations and quality of life cannot be overemphasized. The finding that reported improvements in the epidemiology of chronic complications of diabetes from 1990 to 2010 were superseded by a resurgence of complications between 20 is cause for concern 2. The escalating prevalence of diabetes is paralleled by rising levels of obesity (with ~650 million adults classified as obese in 2016), and increasing morbidity and mortality associated with chronic microvascular complications, cardiovascular disease and other conditions frequently associated with diabetes, including infections, dementia and cancer. In 2019, an estimated 463 million people were living with diabetes mellitus, and this figure is predicted to rise to 700 million by 2045 (ref. ‘Resolution pharmacology’ is a novel therapeutic paradigm that seeks to make targeted use of endogenous pro-resolving mediators to treat chronic inflammation, such as occurs in diabetic kidney disease. The discovery of endogenously generated lipid mediators that promote the resolution of inflammation and attenuate microvascular and macrovascular complications of diabetes and obesity highlights potential opportunities for therapeutic intervention. The initiation and resolution of inflammation occurs via a coordinated host response, involving pro-inflammatory and anti-inflammatory or pro-resolving mediators, which are produced at the site of organ injury in a temporally controlled manner. ![]() The role of inflammation in the pathogenesis of diabetes and obesity-associated kidney disease is increasingly appreciated cytokines and pro-inflammatory lipids have important roles as drivers of inflammation and in the pathogenesis of impaired glucose tolerance, insulin resistance and diabetes. The discovery of endogenously generated lipid mediators - specialized pro-resolving lipid mediators and branched fatty acid esters of hydroxy fatty acids - which promote the resolution of inflammation and attenuate the microvascular and macrovascular complications of obesity and diabetes mellitus highlights novel opportunities for potential therapeutic intervention through the targeting of pro-resolution, rather than anti-inflammatory pathways. ![]() In self-limiting inflammation, the evolving inflammatory response is coupled to distinct processes that promote the resolution of inflammation and restore homeostasis. The initial phase of the inflammatory response to injury or metabolic dysfunction reflects the release of pro-inflammatory mediators including peptides, lipids and cytokines, and the recruitment of leukocytes. Thus, considerable interest exists in approaches that target inflammation as a strategy to manage CKD. Chronic, low-grade inflammation is recognized as a major pathogenic mechanism that underlies the association between CKD and obesity, impaired glucose tolerance, insulin resistance and diabetes, through interaction between resident and/or circulating immune cells with parenchymal cells. Obesity, diabetes mellitus, hypertension and cardiovascular disease are risk factors for chronic kidney disease (CKD) and kidney failure.
0 Comments
Leave a Reply. |
Details
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |