A History of Uremia Research.

The history of uremia research begins with the discovery of urea and the subsequent association of elevated blood urea levels with the kidney disease described by Richard Bright, a well told story that needs no recounting. What this article highlights is how clinical and laboratory studies of urea launched the analysis of body fluids, first of urine and then of blood, that would beget organic chemistry, paved the way for the study of renal function and the use of urea clearance to determine "renal efficiency," provided for the initial classification of kidney disease, and clarified the concepts of diffusion and osmosis that would lead to the development of dialysis. Importantly and in contrast to how the synthesis of urea in the laboratory heralded the death of "vitalism," the clinical use of dialysis restored the "vitality" of comatose unresponsive dying uremic patients. The quest for uremic toxins that followed has made major contributions to what has been facetiously termed "molecular vitalism." In the course of these major achievements derived from the study of urea, the meaning of "what is life" has been gradually liberated from its past attribution to supernatural forces (vital spirit, archaeus, and vital force) thereby establishing the autonomy of biological life in which the kidney is the master chemist of the living body.

A Historical Perspective on Uremia and Uremic Toxins.

Uremia, also known as uremic syndrome, refers to the clinical symptoms in the final stage of renal failure. The definition of the term has changed over time due to an improved comprehension of the kidney's function and the advancement of dialysis technology. Here, we aim to present an overview of the various concepts that have developed regarding uremia throughout the years. We provide a comprehensive review of the historical progression starting from the early days of Kolff and his predecessors, continuing with the initial research conducted by Niwa et al., and culminating in the remote sensing hypothesis of Nigam. Additionally, we explore the subsequent investigation into the function of these toxins as signaling molecules in various somatic cells.

[The medical history and the death cause of Young-Jo based on the Seungjeongwon Ilgi : royal secretariat logs)].

Young-Jo, 83 years old, was the longest lived king of the Chosun Dynasty. Seungjeongwon Ilgi gives more detail about the diseases and prescriptions of Young-Jo. We could close look at what the Annals of the Chosun Dynasty just described that king received medical attention. In inspecting Jung-Jo`s constitution, to examine his medical history is very important. Yong-jo had a weak constitution, but he was always concerned about health care. Youn-jo complained of colic syndrom and heart fire when young; ascris and shoulder pain since middle age; severe fatigue and gait disturbance caused by edema in his latter years. During his last 20 years, he had taken and resorted to Ken-GongTang, the reason was not psychological disposion, but physical disease. Also, Yong-Jo's condition just before death could be assumed in Seungjeongwon Ilgi and Jonhyeongak Ilgi. According to continuous complaints such as edema of the lower limbs, faint(lethargy) and eating disorder caused by abnormal rising of GI (anorexia), we could presume that the cause of death was uremia. In addition, it has significance to correct feasible misconceaption about the cause of death grounded on The Annals of the Chosun Dynasty.

[Wolfgang Amadeus Mozart. A urological pathography]. / Wolfgang Amadeus Mozart. Eine urologische Pathographie.

The death of Wolfgang Amadeus Mozart was mysterious from the very first day, and cause of wildest speculation and adventurous assertions. Over the last 100 years, medical science has investigated the physical sufferings and the mysterious death of Mozart with increasing intensity. By means of letters from his father Leopold, his sister "Nannerl", himself and reports from his physicians and contemporaries, we would like to create a medical pathography. The rumour that Mozart was poisoned appeared soon after his early death at the age of 35 on December 5th 1791, and was kept up persistently. Accused were the physician van Swieten, Mozart's freemason's loge and the royal band master Salieri. Mozart, however, died due to chronic kidney disease and ultimately due to uraemia. Once the renal damage has reached a certain point, a minimum of additional stress leads to decompensation. This catastrophe occurs typically within the fourth decade of life. When listening to Mozart's music, we should remember that this apparently happy person was actually a premature adult robbed of his childhood, whose short life was an endless chain of indisposition, over fatigue, misery, concern and illness.

On the discovery of UREA. Identification, synthesis and observations that let to establishing the first uraemic retention solute.

Jean Batiste von Helmont (1577-1644) described a salt that "never occurs outside man's body". The substance was further characterized by Hermann Boerhaave from Leiden (1688-1738) in Elementa Chemiae where he described the whole procedure for isolating it from urine of healthy persons. The French scientists Fourcroy and Vauquelin, in 1808, named it "ure" whereas Jean-Etienne Brard from Montpellier established its chemical composition in 1817. The synthesis of urea was accomplished by Friedrich Whler (the first organic substance to be synthesized). Finally in 1851 Friedrich Th. von Frerichs introduced the term "Uraemia".

Georg Ganter--a pioneer of peritoneal dialysis and his tragic academic demise at the hand of the Nazi regime.

First reports in German literature on the effective removal of uremic toxins by means of extracorporeal hemodialysis in bi-nephrectomized, acute uremic dogs were given by Heinrich Necheles and Georg Haas. These methods were viewed with great scepticism by Georg Ganter who criticized in particular the extensive operative procedure by use of the femoral artery and vein, the size and fragility of the dialysers, as well as the potential toxic effects of the anticoagulant hirudin. As an alternative approach, he suggested the use of the peritoneum as an especially large endogenous dialysis membrane. In 1923, in experiments on ureter-ligated guinea pigs and rabbits, he demonstrated that the single or repeated instillation (after effective draining) of physiological NaCl solution improves both the symptoms of uremia and the blood urea nitrogen level. In patients this new procedure was implemented only sporadically and in the form of a single fluid instillation after a first observation in a uremic patient where a pleura exudate was substituted: in a female patient with acute uremia as a consequence of a ureter occlusion, due to uterus carcinoma, and in a patient with a diabetic coma. In spite of these limited experiences, Ganter was convinced of the superiority of his method over the troublesome hemodialysis therapy and recommended its broader clinical application.

[Richard Strauß: a contribution on the occasion of his 150th birthday from an urological point of view]. / Richard Strauß: Ein Beitrag zu seinem 150. Geburtstag aus urologischer Sicht.

Richard Strauß is one of the most important composers of the first half of the 20th century. In this article, his life is represented with special emphasis on the points of contact with urology and on the field of conflict of the time. We give a detailed description of the composer's urological illness, which finally lead to his death. The last works of the master, composed at the beginning and during his last illness, are appreciated as touching creations of his parting. Finally, we compare the treatment of the prominent patient with the contemporary level of urology.

Wolfgang Amadeus Mozart: the death of a genius.

The early and unexpected death of Wolfgang Amadeus Mozart (Salzburg, 1756 - Vienna, 1791) was a mystery from the very first day and the subject of wildest speculations and adventurous assertions. Over the last 100 years, medical science has investigated the physical sufferings and the mysterious death of Mozart with increasing intensity. The aim of this article was to recreate Mozart's pathography relying on the his correspondence with father Leopold and sister Nannerl and on reports from his physicians and contemporaries. The rumour that Mozart was poisoned followed shortly after his death on 5 December 1791, at the age of 35, and has survived to this day. The alleged culprits were his physician van Swieten, Mozart's freemasons lodge, and the Imperial Chapel Master Salieri. Mozart however died of chronic kidney disease and ultimately of uraemia. If kidney damage reaches a critical point, even a minimum additional stress can lead to its failure. This usually occurs in the fourth decade of life. Next time we listen to Mozart, we should remember that this apparently happy person was actually a precocious boy, ripped of his childhood, whose short life was an endless chain of complaints, fatigue, misery, concern, and malady.

Isaac Albeniz (1860-1909): Spanish musician who died of chronic renal disease.

Isaac Albéniz was a Spanish musician and pianist who was best known in France and England. One of his last works for piano, the suite Iberia, is well-known and identifies his country of origin. He died with terminal uraemia following longstanding chronic intestinal and kidney symptoms. Suggestions as to pathology include amyloidosis complicated by kidney stones and hypertension that sometimes manifested itself in the form of hypertensive crisis, accompanied by obesity.