Tubule Effects of Glomerular Hyperfiltration: an Integrated View

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.