Glomerular hyperfiltration and the salt paradox in early [corrected] type 1 diabetes mellitus: a tubulo-centric view

Diabetes mellitus contributes greatly to morbidity, mortality, and overall health care costs. In major part, these outcomes derive from the high incidence of progressive kidney dysfunction in patients with diabetes making diabetic nephropathy a leading cause of end-stage renal disease. A better understanding of the early dysfunctions observed in the diabetic kidney may permit the development of new strategies to prevent diabetic nephropathy. This review proposes a "tubulo-centric" view of glomerular function in early type I diabetes mellitus. The following are particularly discussed (1) the primary role of an increase in reabsorption by the proximal tubule in early glomerular hyperfiltration, (2) the role of sodium-glucose cotransport and tubular growth under these conditions, and (3) the primary role of reabsorption by the proximal tubule for the paradoxical relationship between dietary salt and glomerular filtration rate. Finally, an outline is presented of potential therapeutic implications for the prevention of diabetic kidney disease.