Obesity and chronic kidney disease: a cardio-kidney-metabolic framework for renal vulnerability and risk stratification.
TL;DR
A conceptual framework comprising four overlapping CKM-related kidney vulnerability domains is proposed, which may help identify individuals at increased CKD risk, support earlier screening and longitudinal monitoring, and inform preventive strategies.
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.