The Molecular Basis of Proteinuria

HIPPOCRATES observed more than 2,000 years ago that "bubbles on the surface of the urine are a sign of diseases of the kidney." One might speak today of protein molecules altering surface tension and thereby producing foam, but the bedside sign described so long ago remains valid. The stately pace of medicine saw two millenia go by uneventfully until Dekkers demonstrated proteinuria in 1695 by boiling acidified urine and producing a precipitate. A century later, in 1798 Cruickshank showed that "the coagulable part of the serum is detected in morbid states of the urine."¹ Bright,² busy laying the foundation of modern nephrology from 1827 to 1840, noted that patients with massive proteinuria could experience hypoproteinemia.

Nineteenth-century workers further developed the concept that the kidney acted as a semipermeable membrane that, in health, prevented the loss of plasma protein in the urine. It was assumed that an injured kidney