Obesity-initiated metabolic syndrome and the kidney: a recipe for chronic kidney disease?

Metabolic syndrome, originally described in 1988 as “syndrome X” by Reaven et al. (1), has evolved in our collective thinking from a vague association of common chronic disease states to a formally defined cluster of clinical traits with adverse impact on cardiovascular risk (2). The cause is incompletely understood but represents a complex interaction among genetic, environmental, and metabolic factors, clearly including diet (3,4) and level of physical activity (4,5). These abnormalities are mediated by—and interconnected by—complex pathways that affect energy homeostasis at cellular, organ, and whole-body levels. This review focuses on obesity-initiated metabolic syndrome, first to provide a pathogenetic overview of extrarenal metabolic derangements; second to consider predisposing conditions shaped by genetic or environmental factors, including growth constraints in utero; and finally to consider the impact of metabolic syndrome on the kidney in its prediabetic phase. The pathogenesis of hypertension in the context of metabolic syndrome is considered separately in this series. Similarly, central nervous system pathways that contribute to disordered energy homeostasis is addressed in detail by others. The mechanisms of irreversible renal injury from hypertension and overt diabetes are well documented and are beyond the scope of this review; nonetheless, they loom large in the long-term renal future of the patient with metabolic syndrome. The current worldwide epidemic of obesity-initiated metabolic syndrome, with its potential for renal damage, mandates our commitment to early renal protection in the obese and to vigorous prevention of obesity in both pediatric and adult populations.