Twenty years ago, Brenner et al1 identified glomerular hyperfiltration as a key mediator of progressive kidney damage caused by a variety of initiating injuries, including diabetes mellitus. As the authors explained, micropuncture studies in rats had shown that an elevation in single-nephron glomerular filtration rate (GFR) is dependent on an increase in glomerular pressure and plasma flow. In addition, in all models of progressive kidney disease characterized by glomerular hyperfiltration, albuminuria had been a consistent finding.