Differential solute clearances were used to characterize glomerular functio
n in 12 nondiabetic subjects with severe obesity (body mass index >38). Nin
e healthy subjects served as the control group. In the obese group, glomeru
lar filtration rate (GFR) and renal plasma flow (RPF) exceeded the control
value by 51 and 31%, respectively. Consequently, filtration fraction increa
sed. The augmented RPF suggested a state of renal vasodilatation involving,
mainly or solely, the afferent arteriole. Albumin excretion rate and fract
ional albumin clearance increased by 89 and 78%, respectively. Oral glucose
tolerance tests were suggestive of insulin resistance. Insulin resistance
was positively correlated with GFR (r = 0.88, P < 0.001) and RPF (r = 0.72,
P < 0.001). Mean arterial pressure was higher than in the control group. F
ractional clearances of dextrans of broad size distribution tended to be lo
wered. The determinants of the GFR were estimated qualitatively by using a
theoretical model of dextran transport through a heteroporous membrane. Thi
s analysis suggests that the high GFR in very obese subjects may be the res
ult of an increase in transcapillary hydraulic pressure difference (Delta P
). An abnormal transmission of increased arterial pressure to the glomerula
r capillaries through a dilated afferent arteriole could account for the au
gmentation in Delta P.