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

Figure 2. Vicious cycle of renin–angiotensin–aldosterone system (RAAS) activation in obesity-related kidney disease. This figure illustrates how excess visceral adipose tissue activates the intrarenal and systemic RAAS, leading to angiotensin II-mediated efferent arteriolar vasoconstriction, aldosterone excess, sympathetic nervous system overactivation, and sodium retention. These hemodynamic disturbances converge on glomerular hypertension and hyperfiltration, which drive podocyte injury, proteinuria, and progressive glomerulosclerosis, establishing a self-perpetuating cycle of renal damage. Abbreviations: Ang II: angiotensin II; CKD: chronic kidney disease; GFR: glomerular filtration rate; RAS: renin–angiotensin system; SNS: sympathetic nervous system. ↑ indicates an increase; → indicates a causal or sequential step in the cycle. Based on [10,12,14,27,28].

Figure 1. Stepwise cascade from visceral adiposity to chronic kidney disease. Schematic representation of the seven-step pathophysiological cascade linking visceral adipose tissue accumulation to CKD. The sequence encompasses: (1) visceral fat expansion, (2) adipokine dysregulation and inflammatory signaling, (3) hemodynamic stress (RAAS activation, sympathetic overactivity), (4) glomerular hyperfiltration and hypertension, (5) podocyte injury and proteinuria, (6) tubulointerstitial inflammation and fibrosis, and (7) progressive nephron loss leading to established CKD. Abbreviations: CKD: chronic kidney disease; GFR: glomerular filtration rate; RAAS: renin–angiotensin–aldosterone system; SNS: sympathetic nervous system. Arrows indicate the direction of change: ↑ increased; ↓ decreased.

Figure 3. Inflammatory and oxidative stress pathways in visceral adiposity-driven kidney injury. Overview of the molecular mechanisms by which inflamed visceral and perirenal adipose tissue promotes renal damage. As demonstrated in human adipose tissue biopsies and animal models, hypertrophic adipocytes and crown-like structures release pro-inflammatory cytokines (TNF-α, IL-6) that activate NF-κB and JAK/STAT signaling, stimulate NADPH oxidase-dependent reactive oxygen species generation, and impair endothelial nitric oxide bioavailability. These processes lead to glomerular endothelial dysfunction, podocyte injury, tubular stress, and progressive interstitial fibrosis. The figure also highlights the paracrine effects of perirenal fat and the downregulation of kidney-protective factors (Klotho, PGC1α, NLRP6). Abbreviations: IL-6: interleukin-6; NLRP6: NLR family pyrin domain containing 6; NO: nitric oxide; PGC1α: peroxisome proliferator-activated receptor gamma coactivator 1-alpha; ROS: reactive oxygen species; TNF-α: tumor necrosis factor alpha. ↑ increased; ↓ decreased.

Figure 4. Imaging modalities for visceral and renal fat quantification. Comparative overview of the imaging techniques available for quantifying visceral adipose tissue and renal sinus fat, including computed tomography (CT), magnetic resonance imaging (MRI), ultrasound (US), dual-energy X-ray absorptiometry (DXA), and bioelectrical impedance analysis (BIA). For each modality, the figure presents the measurement principle, anatomical targets, key advantages and limitations, and clinical applicability for risk stratification in obesity-related kidney disease. Abbreviations: CT: computed tomography; PDFF: proton-density fat fraction; VAT: visceral adipose tissue. HU: Hounsfield units; LoA: limits of agreement. ✓ indicates an advantage or strength of the modality; ✗ indicates a limitation.

Figure 5. Histopathological features of obesity-related glomerulopathy (ORG). Representative renal biopsy findings. (A) Glomerulomegaly: the double-headed arrow indicates a maximal glomerular diameter exceeding 250 µm (periodic acid–Schiff). (B) Secondary focal segmental glomerulosclerosis with a perihilar distribution; the arrow indicates the segmental lesion (Masson trichrome). (C) Secondary focal segmental glomerulosclerosis with a perihilar distribution; the arrow indicates the segmental lesion (periodic acid–Schiff). (D) Foam cells with optically empty, finely vacuolated cytoplasm (thin arrow), consistent with lipid dissolved during routine processing, adjacent to an area of segmental sclerosis (block arrow) (Masson trichrome). Abbreviations: FSGS, focal segmental glomerulosclerosis; ORG, obesity-related glomerulopathy; PAS, periodic acid–Schiff.

Figure 6. Proposed therapeutic algorithm for the management of obesity-related chronic kidney disease (ob-CKD). Stepwise therapeutic algorithm for the integrated management of obesity-related CKD, stratified by disease stage. The algorithm proposes a tiered approach: (1) universal lifestyle interventions (caloric restriction, structured aerobic exercise targeting visceral adipose tissue reduction) for all patients; (2) first-line pharmacotherapy with SGLT2 inhibitors (hemodynamic nephroprotection) and GLP-1 receptor agonists or dual GIP/GLP-1 agonists (weight loss and metabolic benefits); (3) addition of non-steroidal mineralocorticoid receptor antagonists (finerenone) for residual cardiorenal risk; (4) consideration of bariatric/metabolic surgery for patients with severe obesity (BMI ≥ 35 kg/m2) or inadequate response to medical therapy; and (5) stage-specific adaptations for dialysis (ob-CKD type 4) and kidney transplant recipients (ob-CKD type 5). Decision nodes incorporate visceral adiposity assessment (VAI, waist circumference, imaging when available) rather than BMI alone. Note: This algorithm represents a pragmatic expert-opinion framework based on currently available evidence and…