What is the origin of the term Nephrotic syndrome ?
Nephrotic syndrome as a diagnostic term came into use in the 1920s to describe the triad of heavy proteinuria, hypoalbuminemia, and edema, usually with associated dyslipidemia and lipiduria. The common presenting symptom of edema, once called dropsy, has an ancient history. It was the association of dropsy with proteinuria that established the link of edema with kidney disease and launched the discipline that was to become nephrology. Dropsy, or the accumulation of fluid, was regarded as an entity of its own until the end of the 18th century. Its association with cirrhosis of the liver was well known in antiquity, its association with kidney disease was also described, particularly in patients with oliguria, but its association with diseases of the heart was indirect and generally ascribed to the broader concept of diseases of the chest, when fluid was detected in the lungs or pleural space of some patients with dropsy. Two landmark publications laid the foundations that were to clarify the role of the kidneys and the heart in dropsy, their interrelationships in health and disease, and ultimately the identification of edema as a symptom of underlying diseases rather than a disease itself.
First was the publication in 1785 of An Account of the Foxglove and Some of Its Medical Uses by William Withering (1741–1799), who showed that the administration of an infusion of the leaves of foxglove (digitalis purpurea) produced a diuresis and an amelioration of dropsical symptoms. However, it was obvious from the outset, including a third of the cases reported by Withering, that not all patients with dropsy responded to the infusion and that some of the nonresponders who died while taking the infusion were suffering from cirrhosis of the liver with ascites. No comment was made on the kidney of these nonresponders. The determination of the kidney as a principal cause of dropsy had to await a second landmark publication in 1827 of the Reports of Medical Cases by Richard Bright (1789–1858), which contained his description of end-stage kidneys and led to the distinction of dropsy as a result of kidney disease by the presence of heat-coagulable albuminous material in the urine.
The link of dropsy with hypoalbuminemia was suspected shortly thereafter from the low specific gravity of the serum of patients with Bright disease who had the heaviest albuminuria reported by Robert Christison (1799–1882) of Edinburgh in 1829 but had to await improved chemical methods to define it as due to hypoalbuminemia.
Although it was clear from the outset that kidney disease is not always associated with dropsy or albuminuria, Bright disease soon came to be accepted as a diagnostic term for albuminuric kidney disease. It was studies to differentiate the various kidney lesions of Bright disease and the evaluation of their possible association with proteinuria that determined the course of subsequent events in the emergence of nephrology. Richard Bright had described three principal types of the gross appearance of the kidneys he reported: (1) a hard, small (one-half normal size) kidney with cysts; (2) a soft, mottled, yellowish-grey kidney of normal size; and (3) a swollen, large (twice normal size), soft, pale kidney. It was the latter, which was associated with anasarca and heavier proteinuria, that ultimately came to be associated with nephrotic syndrome. The descriptive morphologic term nephrosis, derived from the German nephrotische, was introduced in 1905 by Friedrich von Müller (1858–1941), a pathologist working in Munich, to differentiate the morphologic features of these large kidneys from those of the small kidneys due to the inflammatory lesions of nephritis . The subsequent grouping of the common clinical manifestations of the various lesions of nephrosis under the term syndrome of nephrosis , nephrosis syndrome , and nephrotic syndrome were introduced between 1924 and 1929 in the writings of Henry A. Christian (1876–1951) of Boston. Of those, nephrotic syndrome received the better acceptance and entered medical parlance thereafter.
