Metabolic Disorder Perturb Renal Homeostasis

Abstract

Obesity related nephropathy disorders have increased ten-folds in recent years. One of the consequences of obesity is an increased Glomerular Filtration Rate (GFR) that leads to an enlargement of the renal glomerulus, i.e., glomerulomegaly. This heightened hyper-filtration in the setting of type 2 diabetes irreparably damages the kidney and leads to the progression of an End Stage Renal Disease (ESRD). Patients suffering from type 2 diabetes have progressive proteinuria, and eventually one third of them develop Chronic Kidney Disease (CKD) and ESRD. For ameliorating the progression of CKD inhibitors of Renin Angiotensin Aldosterone System (RAAS) seemed to be effective, but for short-term basis only. Long term and stable treatment strategies like weight loss via restricted or hypo-caloric diet or bariatric surgery have yielded more promising results in terms of proteinuria and maintenance of GFR. Body Mass Index (BMI) is considered as a traditional marker for obesity onset, but apparently, it is not a reliable indicator, and thus there is a need for more precise evaluation of regional fat distribution and amount of muscle mass. With respect to the pathogenesis, recent investigations have suggested perturbation in fatty acid and cholesterol metabolism as the critical mediators in ectopic renal lipid accumulation, inflammation, increased generation of ROS, RAAS activation and consequential tubulo-interstitial fibrosis. This review summarizes the renewed approaches for obesity assessment and evaluation of the pathogenesis of CKD, altered renal hemodynamics and potential therapeutic targets.