The Renal Pathology of Obesity

Abstract

Obesity causes various structural, hemodynamic, and metabolic alterations in the kidney. Most of these are likely to be compensatory responses to the systemic increase in metabolic demand that is seen with obesity. In some cases, however, renal injury becomes clinically apparent as a result of compensatory failure. Obesity-related glomerulopathy is the best known of such disease states. Factors that may sensitize obese individuals to renal compensatory failure and associated injury include the severity and number of obesity-associated conditions or complications, including components of metabolic syndrome, and the mismatch of body size to nephron mass, due to nephron reductions of congenital or acquired origin.

Keywords: chronic kidney disease; hyperfiltration; metabolic syndrome; nephron number; obesity; obesity-related glomerulopathy.

Figure 1

Hemodynamic abnormalities and factors promoting obesity-related renal injury. Renal plasma flow (RPF) and glomerular filtration rate (GFR) increase in obesity. Such renal tubular overload in obesity is characterized by an increase in the filtration fraction (FF: GFR/RPF) and may stimulate sodium and water reabsorption in the proximal tubules, decreasing preglomerular vascular resistance via tubuloglomerular feedback (TGF). A dilation of the glomerular afferent arterioles (AAs) leads to a further increase in GFR, that is, glomerular hyperfiltration. Various factors associated with obesity, including adipose-derived factors, activation of the renin−angiotensin−aldosterone system (RAAS) and renal sympathetic nervous system (RSNS), systemic hypertension, and nephron mass reduction, constitute and promote this vicious circle.

Figure 2

Histopathology of obesity-related glomerulopathy. Representative renal biopsy findings in (a) a nonobese kidney transplantation donor showing normal glomerular density (5.0/mm²), and in (b) a patient with obesity-related glomerulopathy (ORG) showing a low glomerular density (2.0/mm²). Arrows indicate nonsclerotic glomeruli (periodic acid−methenamine silver stain, original magnification ×25). Glomerulus from (c) a nonobese patient showing minimal change nephrotic syndrome, and (d) extremely hypertrophied glomerulus (glomerulomegaly) in an ORG patient (periodic acid−methenamine silver stain, original magnification ×400). In ORG, (e) lesions of segmental glomerular sclerosis are often found in relation to the vascular pole of glomeruli (perihilar variant) (periodic acid−Schiff stain, original magnification ×400). (f) Dilated glomerular afferent arterioles in a patient with ORG (periodic acid−methenamine silver stain, original magnification ×400). Electron micrograph showing (g) mild thickening of glomerular basement membrane, mild podocyte foot process effacement, and widening of the subendothelial space in glomeruli of ORG (original magnification ×5000). Arrows indicate (h) intracytoplasmic lipid vacuoles in glomerular mesangial cells found in ORG (original magnification ×5000).