Obesity and chronic kidney disease: a cardio-kidney-metabolic framework for renal vulnerability and risk stratification

Abstract Obesity is an important risk factor for chronic kidney disease (CKD), yet only a subset of individuals with obesity develops albuminuria, declining estimated glomerular filtration rate (eGFR), and progressive kidney disease. This variability indicates that excess body weight alone is insufficient to explain obesity-induced kidney injury. In this review, we propose that cardio-kidney-metabolic (CKM) syndrome provides a useful framework to understand this heterogeneity. We discuss major pathophysiological contributors to kidney vulnerability in obesity, including haemodynamic stress, metabolic toxicity/insulin resistance, visceral and ectopic fat, inflammation, oxidative stress, adipokine imbalance, and reduced nephron reserve. Several of these contributors converge on a common intrarenal pathway characterized by increased single-nephron workload, maladaptive glomerular hyperfiltration and intraglomerular hypertension, followed by podocyte stress, albuminuria, and progressive kidney injury. On this basis, we propose a conceptual framework comprising four overlapping CKM-related kidney vulnerability domains, which may help identify individuals at increased CKD risk, support earlier screening and longitudinal monitoring, and inform preventive strategies.