History Of Nephrotic Syndrome

Dropsy is an ancient word (first recorded about 1290 AD) meaning oedema. The history of the discovery of what we now call 'nephrotic syndrome', a cause of the dropsy, is very interesting

Stewart Cameron has published a history of nephrotic syndrome (1985), and proteinuria (2003), from which some of the information in this section is taken. In this latter paper, Cameron emphasises the important work done before Bright, who was not the first physician to link oedema with proteinuria and kidney disease

In 1694, a chunky, square book based upon a therapeutic approach to medicine was published in Leiden
in The Netherlands, by Frederick Dekkers, a pupil of Sylvius. In this, he wrote (the original is in Latin, as
was the custom of the time): ‘‘I have also found that these [water of consumptives] when placed on the fire, soon become milky, really smelled like milk, and had the taste of sweet milk .. ". This passage has been interpreted by some, since the as the first description of albuminuria.

One of the earliest description's of nephrotic syndrome in the 'modern era' was made by Theodore Zwinger III of Basel (1658-1724) in his Paedoiatreia practica of 1722. This text is known to some historians of paediatrics, but has been completely ignored by nephrologists. His description of the physical signs of the nephrotic syndrome in chapter 119 is quite remarkable, and is worth quoting in full:

"Oedema, generally called hydrops, is a condition involving swelling of the whole body. From head to foot the skin is a pale dirty yellow, the swelling is oedematous and characterised by inflation of the whole periphery with persistent collections of lymph. The swelling is not hard or tense, but such that the print of a finger remains behind. Commonly, thirst is very great, the bowel action not as free as usual, and the urine is scanty because of obstruction and compression of the tubules of the kidney. The breathing is difficult, often accompanied by anxiety because of the compromised function of chest muscles and diaphragm from the swelling of the skin

Besides, there is a continued fever, and soon a strong desire to sleep appears because the brain is overfull with serum; sleep is poor because of disturbance of the "spiritus animalis". Additionally, there may be a dry cough from irritation of the nerves to the lung by the liquid, salty lymph. At the beginning, the swelling may be small, but later it increases steadily if the remedies used do not have their expected effects, so that legs, abdomen and even the face are blown up with a bluish colour, and one must fear attacks of suffocation

We have seen children of either sex in whom the eyelids were so swollen they could not open their eyes, and also the genitalia were so swollen and full of serum, that they looked almost transparent. In boys, the virile member was so swollen that they could make water only with difficulty".

Thus in 1722, more than 100 years before Bright, Zwinger described the nephrotic syndrome and placed the seat of the disease firmly in the kidneys. This is all the more remarkable, because at this time Morgagni had of course not published his great classic De sedibus et causis morborum, which established the idea that diseases might arise from specific organs. Incidentally, in this latter work one can find one of the first descriptions of the pale, mottled kidneys of the nephrotic patient

Zwinger did not, however, perform any tests on the urine that we know of. Proteinuria had been described for the first time in conjunction with oedema by Domenico Cotugno (1736-1820) in Naples, in his De ischiade nervosa commentarius of 1770. William Wells of St Thomas' Hospital also described protein in the urine (“coagulable urine”) in 1812, 15 years before Richard Bright’s celebrated series of descriptions of “albuminous urine” in 1827 (Bright, 1827). After this Richard Bright (1789-1858) and others put together the triad of proteinuria, diseased kidneys and oedema

German pathologist Friedrich von Muller introduced the term ‘Nephrosis’ in 1905, meaning a non-inflammatory kidney disease, to be distinguished from Nephritis, the inflammatory type of Bright’s disease. This distinction is still useful, but Nephrosis soon became used also to describe the clinical picture of dropsy with proteinuria

The term 'nephrotic syndrome' was first introduced by Leiter in 1931 to differentiate the association of massive proteinuria, oedema, hypoproteinaemia and hypercholesterolaemia due to what may be minimal change disease from glomerulonephritis (from 'lipoid nephrosis)'. Nephrotic syndrome was considered to have the same features without hypertension, nitrogen retention or an excess of red blood cells in the urine


The word 'nephrology' first appeared in Morrin's French Dictionary of 1809. It is derived from the Greek νεφρός (nephros-, 'kidney') and λόγος (-logos, meaning 'a ground, a plea, an opinion, an expectation, word, speech, account, reason or speech')