Visceral Adiposity and Renal Health: From Pathophysiological Mechanisms to Novel Therapeutic Strategies

Obesity-related chronic kidney disease (ob-CKD) is an increasingly prevalent condition whose pathogenesis extends beyond excess body mass to the metabolic dysfunction of visceral adipose tissue (VAT). This narrative review synthesizes the mechanistic, diagnostic, and therapeutic dimensions of the adiporenal axis: the bidirectional crosstalk between dysfunctional visceral fat and the kidney. From a pathophysiological perspective, VAT promotes renal injury through four converging pathways: hemodynamic overload via the renin-angiotensin-aldosterone system and sympathetic activation; adipokine imbalance (leptin excess/adiponectin deficiency); chronic inflammation mediated by tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6); and direct lipotoxicity from ectopic renal fat deposition. Because body mass index (BMI)fails to capture these pathogenic mechanisms, visceral adiposity-centered assessment (using waist circumference, the visceral adiposity index, and cross-sectional imaging) is essential for accurate risk stratification. The recently proposed ob-CKD classification (types 1-5) links disease stage to therapeutic strategy across the full CKD continuum. The therapeutic landscape now includes agents with combined weight-loss and nephroprotective properties: glucagon-like peptide-1 (GLP-1) receptor agonists (FLOW trial), dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 agonists (tirzepatide), sodium-glucose co-transporter 2 inhibitors (SGLT2i), and non-steroidal mineralocorticoid receptor antagonists (finerenone), alongside metabolic surgery for refractory cases. This review provides an integrative framework for shifting clinical practice from BMI-centric to visceral adiposity-driven approaches in the prevention and management of ob-CKD.