Effect of modest hyperglycemia on tubuloglomerular feedback activity

Tubuloglomerular feedback activity was evaluated in hydropenic rats, using "borrowed," glucose-free hydropenic late proximal tubular fluid as microperfusion solution, and in rats with modest hyperglycemia using both hyperglycemic (glucose-containing) and hydropenic (glucose-free) late proximal fluid as test solutions. Changes in nephron filtration rate (SNGFR) in the same nephron were evaluated in all states at zero and 24.6 nl/min late proximal tubule microperfusion rates (the observed hyperglycemic late proximal flow rate) using a Hampel microperfusion pump. In hydropenia, increased microperfusion rate decreased SNGFR, but in hyperglycemic rats, increased perfusion rate with glucose-containing fluid failed to change SNGFR. But when glucose-free, hydropenic fluid was used, SNGFR decreased numerically less than it did in hydropenia. Renal interstitial hydrostatic pressure increased in hydropenia during hyperglycemia, which may account for part of the inhibition of feedback response. Abolition of tubuloglomerular feedback activity during modest hyperglycemia is due to (1) the effects of glucose in the tubular fluid beyond the late proximal tubule and (2) the extraluminal effects of hyperglycemia on the renal interstitial pressure. These findings may explain the elevated GFR in early diabetes mellitus and excessive urinary volume losses during modest hyperglycemia.