Abstract
BackgroundObesity is associated with glomerular hyperfiltration, increased proximal tubular sodium reabsorption, glomerular enlargement and renal hypertrophy. A single experimental study reported an increased glomerular urinary space in obese dogs. Whether proximal tubular volume is increased in obese subjects and whether their glomerular and tubular urinary spaces are enlarged is unknown.ObjectiveTo determine whether proximal tubules and glomerular and tubular urinary space are enlarged in obese subjects with proteinuria and glomerular hyperfiltration.MethodsKidney biopsies from 11 non-diabetic obese with proteinuria and 14 non-diabetic lean patients with a creatinine clearance above 50 ml/min and with mild or no interstitial fibrosis were retrospectively analyzed using morphometric methods. The cross-sectional area of the proximal tubular epithelium and lumen, the volume of the glomerular tuft and of Bowman’s space and the nuclei number per tubular profile were estimated.ResultsCreatinine clearance was higher in the obese than in the lean group (P=0.03). Proteinuria was similarly increased in both groups. Compared to the lean group, the obese group displayed a 104% higher glomerular tuft volume (P=0.001), a 94% higher Bowman’s space volume (P=0.003), a 33% higher cross-sectional area of the proximal tubular epithelium (P=0.02) and a 54% higher cross-sectional area of the proximal tubular lumen (P=0.01). The nuclei number per proximal tubular profile was similar in both groups, suggesting that the increase in tubular volume is due to hypertrophy and not to hyperplasia.ConclusionsObesity-related glomerular hyperfiltration is associated with proximal tubular epithelial hypertrophy and increased glomerular and tubular urinary space volume in subjects with proteinuria. The expanded glomerular and urinary space is probably a direct consequence of glomerular hyperfiltration. These effects may be involved in the pathogenesis of obesity-related renal disease.
Highlights
Obesity is an independent risk factor for chronic kidney disease and for the need for renal replacement therapy
Compared to the lean group, the obese group displayed a 104% higher glomerular tuft volume (P=0.001), a 94% higher Bowman’s space volume (P=0.003), a 33% higher cross-sectional area of the proximal tubular epithelium (P=0.02) and a 54% higher cross-sectional area of the proximal tubular lumen (P=0.01)
The nuclei number per proximal tubular profile was similar in both groups, suggesting that the increase in tubular volume is due to hypertrophy and not to hyperplasia
Summary
Obesity is an independent risk factor for chronic kidney disease and for the need for renal replacement therapy. Obesity and overweight are associated with increased glomerular filtration rate, renal plasma flow and/or filtration fraction [6,7,8,9,10,11,12,13,14]. The improvement of these renal hemodynamic abnormalities following weight loss [15] supports a cause-and-effect relationship between adiposity and glomerular hyperfiltration. Obesity is associated with glomerular hyperfiltration, increased proximal tubular sodium reabsorption, glomerular enlargement and renal hypertrophy. Whether proximal tubular volume is increased in obese subjects and whether their glomerular and tubular urinary spaces are enlarged is unknown
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