Tubule effects of glomerular hyperfiltration: an integrated view

Abstract

An increase in glomerular filtration rate (GFR) induces adaptive changes in tubular function to prevent the urinary loss of water and electrolytes. This is also true for acid-base balance: the increase in filtered bicarbonate load will stimulate H+ secretion at the level of several segments including the proximal tubule, the loop of Henle, and the distal tubule. There is an activation of both the luminal Na+/H+ exchanger and H(+)-ATPase, and basal-lateral Na(+)-HCO3- cotransport which allows an increase in luminal H+ secretion and basal lateral HCO3- exit. The stimulation of electrolyte reabsorption is very important at the level of the thick ascending limb of Henle, a segment that shows consistent hypertrophy in many models of hyperfiltration. Along this segment, increased Na+ and Cl- reabsorption has been found in rats receiving a high-protein diet. The ensuing reduced Na+ and Cl- concentrations, at the level of the macula densa, could weaken the signal responsible for initiating the tubuloglomerular feedback (TGF), thus allowing GFR to increase.