New Pandemic: Obesity and Associated Nephropathy

Abstract

Incidence of obesity related renal disorders have increased 10-folds in recent years. One of the consequences of obesity is an increased glomerular filtration rate (GFR) that leads to the 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 progression of end stage renal disease (ESRD). The 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 on a short-term basis only. Long term and stable treatment strategies like weight loss via restricted or hypo-caloric diet or bariatric surgery have yielded better promising results in terms of amelioration of proteinuria and maintenance of normal GFR. Body mass index (BMI) is considered as a traditional marker for the onset of obesity, 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 associated with inflammation, increased generation of ROS, RAAS activation and consequential tubulo-interstitial injury. This review summarizes the renewed approaches for the obesity assessment and evaluation of the pathogenesis of CKD, altered renal hemodynamics and potential therapeutic targets.

Keywords: fibrosis; hyperlipidemia; inflammation; kidney; obesity; oxidant stress.

Figure 1

Complex intricate relationship between obesity and chronic kidney disease. Pathophysiology of obesity is very complex which may include genetic (epigenetic) and environmental factors. Obesity driven hypertension, atherosclerosis, and T2 diabetes may lead to chronic kidney disease. In addition, other ancillary factors like gestational diabetes, low nephron number can also contribute to CKD [Adapted from Stenvinkel et al. (2)].

Figure 2

Schematic presentation depicting the effect of ectopic cellular lipid accumulation resulting in the compromise of glomerular and tubular integrity, and causing albuminuria, altered mitochondrial dynamics, and tubulo-interstitial fibrosis. NEFA: Non-esterified fatty acids, ANGPTL4: Angiopoietin-related protein 4 [Adapted from D'Agati et al. (12)].

Figure 3

Lipid accumulation in renal cortical tissue of mice with obesity associated diabetic nephropathy. (A) Photomicrograph showing Oil red O staining in renal cortical tissue of normal control mice. (B) Oil red O stained photomicrograph of renal cortical tissue from an obese mice administered with high fat diet.