Role of obesity in chronic kidney disease progression

Obesity is a global health epidemic linked to numerous chronic disease conditions and consequences, including type 2 diabetes mellitus (T2DM), cardiovascular disease, chronic kidney disease (CKD) and premature mortality. CKD, which can progress to end stage renal disease (ESRD) and/or dialysis with limited treatment options beyond slowing its advancement, is increasingly being recognized as a result or consequence of obesity. This review examines the pathophysiological mechanisms connecting obesity to the development and progression of CKD, via a condition known as obesity related kidney disease (ORKD). Importantly, ORKD has a distinct set of pathophysiological lesions from diabetic nephropathy, as free fatty acid and triglyceride deposition in ORKD dominates over hyperglycemia-induced renal injury in the context of diabetes. Since T2DM is commonly associated with obesity, it is important to recognize ORKD as a distinct entity which likely needs a distinct approach towards its management. Although CKD is the end result of many pathophysiological processes including obesity, the process by which it develops in each condition is vastly different. By synthesizing current preclinical and clinical evidence, we highlight the role of obesity as a modifiable risk factor for CKD and explore obesity-targeted interventions that reduce hyperfiltration among potential strategies to reduce CKD incidence and delay progression to ESRD.