Within a few years of its occurrence, American clinicians became aware of the discovery by Bright in 1827 that albuminuria in edematous patients was associated with granular degeneration of the kidney. Yet, there was a paucity of important original observations in nephrology from American in the first half of the 19th century. By the mid-19th century, however, the primitive concepts of clinical nephrology, renal physiology, and renal pathology were becoming established in the United States, after enlightenment from Europe. Because of the dreadful course of anasarca and uremia and stimulated by the advantages of innovations in microscopy, renal disease began at that time to attract the attention of eminent American clinician-pathologists. Their early observations would add to the knowledge base on which later developments such as bacteriology, radiology, clinical chemistry, and other scientific advances would build.