Obesity, Cardiometabolic Risk, and Chronic Kidney Disease

Abstract

Overweight and obesity have been defined by body mass index. Cardiometabolic health is perhaps a more physiologic way of understanding obesity and its complications, which may enable a more comprehensive definition of obesity. The focus of this chapter will be the relationship between metabolically abnormal obese (MAO) patients and the development of chronic kidney disease (CKD) through metaflammation, which is thought to be the consequence of the proposed mechanisms a–f described in Fig. 14.1. These mechanisms include: (a) nutritional free fatty acids (FFA) in chronic excess of nutritional needs, (b) toll-like receptor-4 (TLR-4) activation through Fetuin-A ligand, (c) fatty liver accumulation through a two-hit hypothesis, (d) maladaptation of the gastrointestinal (GI) microbiome, (e) perirenal sinus fat accumulation, and (f) overstimulation of the renin-angiotensin aldosterone system (RAAS) through various mechanisms (Fig. 14.1). Obesity itself, metaflammation, and insulin resistance all have been implicated in the development of proteinuria and eventual CKD. Weight loss is by far the most effective treatment, however, other areas of possible treatments are being investigated including those affecting PPAR-γ receptors, Fetuin-A receptors, and altering the composition of the gastrointestinal microbiome, among others.