Glomerular hyperfiltration in experimental diabetes mellitus: Potential role of tubular reabsorption

An increase in Na+/glucose cotransport upstream to the macula densa might c ontribute to the increase in single nephron GFR (SNGFR) in early diabetes m ellitus by lowering the signal of the tubuloglomerular feedback, i.e., the luminal Na+, Cl-, and K+ concentration sensed by the macula densa. To exami ne this issue, micropuncture experiments were performed in nephrons with su perficial glomeruli of streptozotocin-induced diabetes mellitus in rats. Fi rst, in nondiabetic control rats, ambient early distal tubular concentratio ns of Na+, Cl-, and K+ were about 21, 20, and 1.2 mM, respectively, suggest ing collection sites relatively close to the macula densa. Second, glomerul ar hyperfiltration in diabetic rats was associated with a reduction in ambi ent early distal tubular concentrations of Na+, Cl-, and K+ by 20 to 28%, r eflecting an increase in fractional reabsorption of these ions up to the ea rly distal tubule. Third, in diabetic rats, early proximal tubular applicat ion of phlorizin, an inhibitor of Na+/glucose cotransport, elicited (1) a g reater reduction in absolute and fractional reabsorption of Na+, Cl-, and K + up to the early distal tubule, and (2) a greater increase in early distal tubular concentration of these ions, which was associated with a more pron ounced reduction in SNGFR. These findings support the concept that stimulat ion of tubular Na+/glucose cotransport by reducing the tubuloglomerular fee dback signal at the macula densa may contribute to glomerular hyperfiltrati on in diabetic rats. Glomerular hyperfiltration in diabetic rats serves to compensate for the rise in fractional tubular reabsorption to partly restor e the electrolyte load to the distal nephron.