Mechanisms for Obesity Related Kidney Disease

Obesity is a major cause for the initiation and progression of kidney injury resulting in chronic kidney disease (CKD) and end stage renal disease. High body mass index is a major risk factor for new-onset CKD as well. The well recognized kidney disease secondary to obesity is glomerulopathy. Typical histological features of obesity related glomerulopathy include glomerulomegaly and focal segmental glomerulosclerosis. In obese individuals, excess excretory load induces hyperperfusion and hyperfiltration by the kidneys leading to glomerulomegaly. Lipid accumulation in the kidney which accompanies excessive fat deposition in the body is implicated in the development of CKD. Obesity is associated with metabolic abnormalities in the adipose tissue such as increased free fatty acids, hyperinsulinemia, insulin resistance, pro inflammatory conditions, reduced adiponectin, leptin resistance and activation of the renin-angiotensin-aldosterone system, all of which mediate injury to the cells of glomeruli and tubules leading to CKD. Despite much progress in our understanding of the mechanisms of obesity related kidney disease, several questions about the pathogenesis of nephropathy associated with obesity remain to be answered. Delineating obesity linked factors, which lead to adaptive and maladaptive changes in the kidney and predispose patients to renal disease could lead to identification of molecular targets and reno-protective and therapeutic strategies to improve outcomes for obese patients with CKD.