Acute hyperglycemia: differential effects on proximal and distal tubular transport

Previous studies in fasted and fed man have suggested that glucose feeding and insulin are antinatriuretic. Utilizing the glucose clamp technique, the authors have examined the effect of acute sustained hyperglycemia on the renal handling of Na, K, Ca and P by recollection micropuncture(N=10 dogs; n=50 tubules). After a 12 hr overnight fast, baseline studies were obtained. Plasma glucose concentration(105±5 mg%) was then acutely raised and maintained at 181±2 mg% with minimal glucosuria (≤5 mg%). Whole kidney inulin clearance was unchanged by hyperglycemia. Proximal tubular fluid/plasma (TF/P) inulin, however, decreased form 1.58±0.08 to 1.38±0.06 (P<0.005) without change in TF/P Na or K or TF/ultrafiltrable Ca and P. Consequently, proximal tubule (PT) fractional reabsorption of Na, K, Ca and P were all decreased by 10% of filtered load. Despite enhanced delivery from PT, fractional excretion (FE) of Na fell from 0.33%±0.07 to 0.20%±0.05 (P<.001), while FE of K, Ca and P were unchanged. In 5 control animals, there were no significant changes in PT transport or in FE of Na, K or Ca while FE of P demonstrated the normal diurnal increase. These data demonstrate that sustained subthreshold elevation of plasma glucose has dual effects in the nephron. In PT, it causes an isonatric inhibition of Na and fluid reabsorption along with K, Ca and P. This is different from mannitol which osmotically lowers PT Na concentration. In the distal nephron, the increased load of these ions is reabsorbed but in addition, net Na transport is enhanced resulting in a significant antinatriuresis and a dissociation between urinary Ca and Na excretion.