Functional and structural changes in the kidney in the early stages of obesity

The purpose of this study was to examine the histologic and functional chan ges that occur in the kidney in the early stages of obesity caused by a hig h-fat diet. Lean dogs (n = 8) were fed a standard kennel ration, and obese dogs (n = 8) were fed the standard kennel ration plus a supplement of cooke d beef fat each day for 7 to 9 wk or 24 wk. Body weights were 58 +/- 5% gre ater and kidney weights were 31 +/- 7% greater in obese dogs, compared with the average values for lean dogs. Plasma renin activity and insulin concen trations were both 2.3-fold greater in obese dogs, compared with lean dogs. Obesity was associated with a mean arterial pressure increase of 12 +/- 3 mmHg, a 38 +/- 6% greater GFR, and a 61 +/- 7% higher renal plasma flow, co mpared with lean dogs. The glomerular Bowman's space area was significantly greater (+41 +/- 7%) in dogs fed the high-fat diet, compared with lean ani mals, mainly because of expansion of Bowman's capsule (+22 +/- 7%). There w as also increased mesangial matrix and thickening of the glomerular and tub ular basement membranes and the number of dividing cells (proliferating cel l nuclear antigen-stained) per glomerulus was 36 +/- 8% greater in obese do gs, compared with lean dogs. There was also a trend for glomerular transfor ming growth factor-beta1 expression, as estimated by semiquantitative immun ohistochemical analysis, to be elevated with the high-fat diet. Therefore, a high-fat diet caused increased arterial pressure, hyperinsulinemia, activ ation of the renin-angiotensin system, glomerular hyperfiltration, and stru ctural changes in the kidney that may be the precursors of more severe glom erular injury associated with prolonged obesity.