Hippocrates' Intuition on the Renal Tubule's Role in Ion Exchange.

OBJECTIVES: The goal of this article was to trace any similarity between the current knowledge on the physiology of the afferent, efferent convoluted tubules, the Loop of Henle, and a passage of Hippocrates' work "Regimen." MATERIALS AND METHODS: We compared the function of the renal tubule with the Regimen (1.6) passage on the similarity between the sawing of a tree and the body's function. RESULTS: The renal tubule, from its beginning to its end, pushes electrolytes, micronutrients, and water out of its interior into the interstitial space and, following the opposite procedure, reabsorbs some of them, eventually achieving internal equilibrium. The Regimen passage elaborated as follows: "All other things are set in due order […] Those that take give increase, those that give make diminution. Men saw a log; the one pulls and the other pushes, but herein they do the same thing, and while making less they make more. Such is the nature of man. One part pushes, the other pulls; one part gives, the other takes." CONCLUSIONS: Hippocrates did not, and could not, know the details of renal function. Although his hypothesis is crude, we are justified to consider it as the medical ancestor of our current physiological knowledge about the role of the renal tubules.

Publications With Nephrological Themes Appearing Diachronically in the PubMed Bibliographical Database.

OBJECTIVES: Nephrology in the last 50 years has undergone important scientific developments, which have formally revolutionized clinical practice, including renal biopsy, renal replacement therapy, and transplantation. The understanding of the pathogenesis and the clinical course of renal disease has also steadily improved, resulting in renewal of definitions, classifications, and therapeutics in nephrology. In this context, publications with nephrological content are also expanding. The aim of this bibliographic study was to analyze publications related to nephrology-specific key words in the PubMed database. MATERIALS AND METHODS: We included the key words "nephrology," "acute renal failure," "renal biopsy," "hemodialysis," "peritoneal dialysis," and "renal transplantation" as search terms in PubMed in May 2022. We also used the term "kidney" as an alternative to "renal." RESULTS: "Nephrology" appeared 185 545 times in searches, with its appearance expanding in the past 3 decades since 1948. The term "acute renal failure" was found in 1932 in 1 publication and in a total number of 92 278 publications. Renal biopsy appeared since 1943 in 18 048 publications. "Hemodialysis" appeared in 182 730 citations, with the first in 1915. "Peritoneal dialysis" appeared in 32 266 citations for the first time in 1901 and in 1946 in human application. One publication on "renal transplantation" appeared in 1946, with 106 075 total publications related to renal transplantation. CONCLUSIONS: We viewed a clear expansion of nephro-logical publications in the past decades. Hemodialysis remains the most frequently used term in nephrology-related publications. Historical analysis of the PubMed database is useful as a tool to understand the research and publication trends in nephrology, as we approach the new era of precision medicine.

Emperor's syndrome in the COVID-19 era: Time for patient-centered nephrology?

The coronavirus disease-19 (COVID-19) pandemic has been a wake-up call in which has forced us to react worldwide. Health policies and practices have attracted particular attention in terms of human and financial cost. Before COVID-19, chronic kidney disease was already considered a risk multiplier in patients with diabetes and hypertension, the two now being the major risk factors for COVID-19 infection and adverse outcome. In contrast to the urgent need for action, the nephrology field is considered to be in a state of stagnation regarding the management of chronic kidney disease patients who still experience unacceptably high morbidity and mortality. Ironically and paradoxically in a field lacking robust clinical trials, clinical practice is driven by guidelines-based medicine on weak evidence. The Emperor's syndrome, referring to Hans Christian Andersen's fairy tale, has been described in medicine as voluntary blindness to an obvious truth, being a weak evidence-based therapeutic intervention or weak health care. A promising positive example of improving heart and kidney outcomes is the emerging treatment with sodium-glucose cotransporter 2 inhibitors. COVID-19 could boost actions for patient-centered care as a positive shift in nephrology care.

The Transnationalism of Nephrological Treatises during the Middle Ages.

The paper presents the history of the dissemination of knowledge about renal issues during the Middle Ages based on the transfer of manuscripts from the centres of knowledge of the then known world to the periphery. Starting from the Greco-Roman world it follows the transfer of manuscripts and ideas via three main roads. Firstly, the North Road extends till the remote Ireland on the West and Russia to the East, secondly, the South Road reaching Arabia and Central Africa and thirdly, the East Road otherwise named the Silk Road. Emphasis is given to the role of monks (Greek Orthodox, Catholics, and Taoists) and the Arab intellectuals. The ways by which this transport materialized and the people involved (merchants, pilgrims, soldiers) is also discussed. Allowances are made for the merging of historical and mythological data, all of which represent the way society then was viewing the kidney, its role and its ailments.

Medea's Nuptial Gifts: Myth and Biomedical Reality.

In all art forms, Medea is mainly represented as the tragic witch from Colchis (contemporary Georgia), who slaughtered her sons and killed her erotic rival Glauke and her father, King Creon of Corinth, by offering an elaborate poisonous nuptial garment. Euripides described the victims' symptoms as a sudden extreme inflammation, leading anyone coming into contact with the garment to death. In other version, the inflammation is described as pure fire. The symptoms resemble what current medical knowledge describes as an immune contact sensitivity reaction. The passages with medical interest from the opera based on this tragedy are presented in the original musical form as well as some similar film and theater scenes. Magnified images of harmful insect's Medea's nuptial gifts are shown and their action is discussed.

Tracing the roots of the idea of dialysis: a leap of 20 centuries--from "catharsis" to dialysis.

In this article, we comment on a primitive foresight of Galen's regarding the value of blood purification. His main arguments are based on: (i) The disease-blood concept, i.e., the idea that blood can be unclean (with an either excess or bad-quality humor) and thus cause a disease; (ii) Cure can be achieved if elimination (catharsis in Greek) of the humor (toxin) is possible; (iii) If the toxins are limited in the intravascular space, their elimination will be sufficient for cure by just a single attempt of replacing the unclean blood with pure; (iv) If the toxins have also affected the extravascular space, then repeated attempts will be needed; (v) The whole procedure can be compared with the insufficiency of washing once a dirty clay pot and immediately filling it with a pure liquid. The dirt that has adhered to the pot's walls will contaminate the pure liquid. Thus, repeated washing is needed to achieve cleanliness. Galen's metaphor of washing a dirty pot for a long period and eventually achieving a pure content is strikingly similar to the theory of hemodialysis. According to this, uremic toxins are spread both intravascularly and extravascularly. To eliminate them, long and repeated "washing" of the blood is needed. One of the reasons the first attempts to dialyze failed was that this "washing" procedure was inadequate (the other reasons were clotting of the blood, infections and access problems).

On some exotic urine colors in ancient and Byzantine Greek literature.

This work does not analyze the entire subject of uroscopy but focuses on a very small part thereof: i.e., some rare urine colors, in particular green and blue. These are so rare that most modern nephrologists have never encountered them. We conducted a small survey comparing contemporary knowledge with that of the past, with the participation of 40 Greek nephrologists (25 juniors and 15 seniors). Of these, 63% rejected the notion that green or blue urine even exists, while of those who were aware of them, only 20% had personally encountered them. According to our search of the modern literature, such colors result from either consumption of green or blue pigments, liver dysfunction or urine infection by certain bacteria. We searched and traced several passages on these rare urine colors, referred to in ancient Greek fewer than 7 different names, in the Greek medical literature of the Classical, Roman and Byzantine eras. In these passages, the authors not only gave detailed descriptions of the medical conditions of the corresponding patients but also explained this appearance of the urine. Surprisingly, in the studied texts we also found identical explanations with those in modern texts: consumption of certain foods, liver disease and inflammation. We present and comment on these passages, concluding that many uroscopical findings of antiquity were not quackery, but rather reliable medical statements based on thorough observation and rational reasoning.

Juxtaposition of Actuarius' versus Galen's ideas on renal physiology: the impact of 12 centuries.

Although some elements of renal physiology can be traced to scattered references in Greek medical writings, mainly in Hippocrates' and Erasistratus' works, it was Galen who made the first breakthrough observations regarding the function of the kidneys. He often wrote his observations not as a diatribe, but as a confrontation with other physicians, mainly of the Erasistratian School. He outlined the great importance of the disproportionally large blood supply of the kidneys, an over-proportion not observed in any other organ, rightly arguing that this is a teleological procedure to achieve satisfactory body clearance. He challenged the dominant idea that blood purification and hence the formation of urine took place in the large branches of the renal vessels. He strongly argued that the special structure of the kidney tissue was responsible for their cathartic ability. Although he had no idea of the histology of the kidney, he made some beautiful similitudes to explain the filtering capacity of the renal tissue. From Galen onwards, very few changes and additions can be traced in Greek and thereafter Byzantine medical texts, regarding renal physiology. It is Johannes Actuarius who, 12 centuries later, writes an extensive treatise on urine and presents his point of view on renal physiology, mainly as conclusions from the pathological findings of uroscopy. In the present paper, we compare the 2 physicians' approaches on the function of the kidneys, which can be attributed to the accumulation of medical knowledge over the 12 centuries that separate them.

Thirty-six Hippocratic aphorisms of nephrologic interest.

In this article, we discuss the nephrologic content within Hippocrates' Aphorisms. Although similar attempts have taken place ever since antiquity, we believe that in each era new insights may be gained by examining the aphorisms through the prism of current medical knowledge. Of the 400 aphorisms in the Hippocratic text, we discuss the 36 that we consider to be most relevant to nephrology. We conclude that these aphorisms support the concept of Hippocrates as the "Father of Clinical Nephrology."

The use of the kidneys in secular and ritual practices according to ancient Greek and Byzantine texts.

The use of kidneys in secular and spiritual practices was very common for centuries. In this article we present some references on their employment as sacrificial offers, as plain food or as a source for medicaments. Our material derives from Greek texts of the Classical, Hellenistic, Roman, and Byzantine eras. Relevant extracts from the Old Testament are also included, as they have become part of a common cultural heritage in that period of syncretism, when Jews were Hellenized and Greeks orientized. From the fragments cited in this article, it is obvious that the practical use of kidneys by priests, doctors, and lay persons in the periods under discussion was widespread. The sacrificial offering was based on the religious significance of the organ. The dietary consumption of the kidneys was limited by their function as urine producers. Their medicinal use was dictated first, by the abundance of the adipose tissue surrounding them, which was an ideal warming and binding substance. Second, it may be explained by the deeply rooted conviction that eating a particular organ led to the incorporation of its strength, thus protecting the corresponding eater's organs. Those practices should not surprise us in view of their corresponding modern use. Currently, kidney donors offer their organs in a sacrificial gesture, kidneys are consumed as a delicacy worldwide, and renal tissue is therapeutically used in transplantations and, until very recently, as a source for hormonal substances.