|Year : 2016 | Volume
| Issue : 4 | Page : 101-108
Reflections on the Medical History of the Kidney: From Alcmaeon of Croton to Richard Bright - Standing on the Shoulders of Giants
Donald E Greydanus, Musunkumuki Kadochi
Department of Pediatric and Adolescent Medicine, Western Michigan University, Homer Stryker M.D. School of Medicine, Kalamazoo, MI 49008-1284, USA
|Date of Web Publication||7-Nov-2016|
Donald E Greydanus
Department of Pediatric and Adolescent Medicine, Western Michigan University, Homer Stryker M.D. School of Medicine, 1000 Oakland Drive, Kalamazoo, MI 49008-1284
Source of Support: None, Conflict of Interest: None
Although renal disease has been present for over 200 millennia of Homo sapiens' existence, knowledge of the causes and management of these disorders has only emerged during the last 4000 years. Brilliant insights into human disease probably emerged from time to time over the long period of human existence, but observations could only be advanced after writing began in 3200 BC. Humans could then make observations, record these thoughts, and have others in their present and future critique them leading to improvement in this information. This discussion selectively considers some of the medical giants who led the way to clinical nephrology of the 21st century. It reflects on who taught us basic principles of renal disease that led to our current knowledge. Attention is given to the ancient Egyptians, Ancient Greeks, Galen of Pergamon, the Byzantine Greeks of the 5th-9th centuries, the Arab/Persian Physicians of the 9th-12th centuries, Moses Maimonides of the 12th century, selective Renaissance Physicians, and the father of modern nephrology - Richard Bright MD. This reflection celebrates au courant renal sagacity by celebrating the past clinicians who led the way from their eras to ours.
Keywords: Galen, Hippocrates, History, Kidney, Richard Bright
|How to cite this article:|
Greydanus DE, Kadochi M. Reflections on the Medical History of the Kidney: From Alcmaeon of Croton to Richard Bright - Standing on the Shoulders of Giants. J Integr Nephrol Androl 2016;3:101-8
|How to cite this URL:|
Greydanus DE, Kadochi M. Reflections on the Medical History of the Kidney: From Alcmaeon of Croton to Richard Bright - Standing on the Shoulders of Giants. J Integr Nephrol Androl [serial online] 2016 [cited 2018 Dec 19];3:101-8. Available from: http://www.journal-ina.com/text.asp?2016/3/4/101/193496
| Introduction|| |
An analysis of almost any scientific problem leads automatically to a study of its history (LN Magner ).  Renal diseases have been found in Homo sapiens from the earliest writings about medical diseases such as found in the cuneiform clay tablets of Ancient Mesopotamia dating back to 3200 BC with descriptions reflective of urinary obstruction with stones and cysts. ,,,, The Babylonian Physicians offered medical diagnoses based on linking the appearance of urine to their local products or chemicals such as beer, beet juice, paint, or alcohol; as was common with ancient and modern humans, therapy for renal disorders was based on the use of available plants or minerals. , An early model of a kidney has been found in the 13 th century Kition, Cyprus which historians have interpreted either as being an illustration of an offering to the Gods of the local temple by an individual with renal disease or as being a pedagogic aid of local temple priest-physicians. 
| Ancient egyptian nephrology|| |
Modern medicine of the Western civilization often dates its knowledge to the insights of brilliant Egyptian Physicians, whose work was reflected in the classic medical document of antiquity - the Ebers Papyrus (1550 BC). , Understanding of medicine at this time was precipitated by the German Egyptologist Georg Ebers (1837-1989) who discovered the Ebers Papyrus in 1875 that dates to the regime of Amenophis I, the second King of the 18 th Dynasty, in 1536 BCE. ,,,
Studies of the Egyptian mummies illustrate humans with kidney disease that includes renal cysts and stones. There was a recommendation of using ointments made from cooked old papyri books in oil to improve a condition involving fluid retention (dropsy). , They also wrote about red urine since schistosomiasis-induced hematuria was common then as now because of Schistosoma haematobium eggs implanted in the bladder wall.  These ancient Egyptian healers dealt with patients having dysuria, urinary frequency (including nocturnal enuresis), and urinary retention.
Ancient Egyptian Physicians had minimal recognition of the function of the kidneys; however, they concluded that kidneys were important for human beings. For example, kidneys were linked to the heart in the famous Egyptian "Book of the Dead" (1550-50 BC), which was used to assist the dead in their proposed afterlife. , Important people were mummified and all organs were removed, except the heart and the kidneys. The heart was identified as the center of human thought (as well as emotion and memory), and in the afterlife, it was weighed on what was called the "Scale of Maat" and compared to the weight of the "feature of truth" by the jackal-headed Anubis.  The result was recorded by the ibis-headed Thoth, who was the scribe for the Egyptian Gods, and if the result was good (i.e., the heart weighed the same as the feather of truth), the person was allowed to enter the afterlife in a positive manner. If the result was unfavorable, the heart was consumed by the terrible Ammit with the combined bodies of a crocodile, lion, and hippopotamus. In this supreme, sovereign process, the kidneys were assigned the critical role of advising the heart. ,,
"Homage to thee, O my heart! Homage to you, O my kidneys!" (Book of the Dead). 
Rudimentary knowledge of renal physiology and disease was found in ancient civilizations. Concepts were passed from civilization to civilization as seen from the ancient Sumerians in 3500 BC to the Akkadian, Babylonian, Assyrian empires, and eventually the ancient Egyptian civilizations. The kidney was identified as being important, but its exact role was not clear. Ancient Hebrew medicine and culture also concluded that these bean-shaped structures were essential structures. The concept of a renal-heart connection established in ancient Egypt made its way into Hebrew literature and religion that concluded kidneys ("reins") were needed to provide advice to the heart and both were involved in the testing that the Hebrew God did to humans. 
"… Examine me, O Lord, and prove me; try my reins and my heart." (Psalms 26:2 - 1000 BC).
"… I, the Lord, search the heart, I try the reins, even to give every man according to his ways, and according to the fruit of his doings." (Jeremiah [Yirmeyahu] 17:10 - 600 BC).
| Ancient greek nephrology|| |
The natural curiosity and desire to understand the human body continued as different peoples learned from others and sought to advance knowledge. Paramount to the current medicine of the Western civilization was the monumental work of the Ancient Greek Scientists, Philosophers, and Physicians. Ancient Greek scholars established the first known Greek School of Medicine in Cnidus in 700 BC, allowing much thought to arise about the world around them. The acclaimed Ionian Mathematician and Philosopher, Pythagoras (570 BC-490 BC), had many famous students; one of these physicians was the medical scholar, Alcmaeon of Croton (born 510 BC), who was one of the earliest known physicians from the Medical School in Cnidus.  Research at this time was not about the kidney but centered on the brain and the mind encouraging Alcmaeon to focus on the nervous system dealing with the brain, mind, and soul. , Although he did not focus on the kidney, his teachings about the importance of empirical observations to learn information in contrast to religious teaching set the stage for latter discoveries about renal diseases. ,
These early Greek scholars taught that conclusions about life including disease should be based on verifiable data as emphasized by the preeminent Greek political philosopher, general, and historian, Thucydides (455-396 BC) of Athens, who detailed the history of the Peloponnesian War and the great plague of Athens of 430 BC.  He is called the father of scientific history who sought to have correct, verifiable facts of history versus history written based on the fictitious dramas of the Greek Gods.  Historians and clinicians were able to emphasize rudiments of science as they interacted in ancient Greece to advance knowledge. 
Such an erudite period emphasizing empirical observations and scientific data led to a milieu from which the father of clinical nephrology arose - Hippocrates of Kos (460 BC-370 BC). Hippocrates was able to take the wisdom of the ancient Egyptian Physicians and extend it with his own observations that were collected by his students into the Corpus Hippocraticum, which became a collection of over sixty medical treatises and became the standard of Western medicine for nearly two millennia.  He described symptoms of urinary (bladder) stones and this was a part of descriptions of various urinary conditions that involved painful or difficult urination, urinary incontinence, and urinary retention. ,,, He described renal colic, renal tuberculosis, and chronic renal infection. The cause of renal stones was drinking water with high levels of minerals according to Hippocrates, who concluded that urine was formed at the bladder.  Treatment for urinary disorders was varied and included combinations of conclusions of the Cnidus School and the Kos School of Medicine: Warm applications, baths, medicines such as plant-derived diuretics, and diet; incision over the kidney was suggested for urinary stones.
"Bubbles appearing on the surface of the urine indicate disease of the kidneys and a prolonged illness…. Colorless urine is bad… the sudden appearance of blood in the urine indicates that a small renal vessel has burst…" (Corpus Hippocraticum) 
Despite such progress, clinicians remained confused over the actual role of the human kidneys as noted by the preeminent Greek Philosopher and Physician, Aristotle (387-322 BC), who, in his texts, De Partibus Animalium (On the Parts of Animals) and Historia Animalium (History of Animals), wrote that the kidney was not necessary for human life based on his observations of animals that included finding no kidneys in fish and birds.  He described renal anatomy but concluded that kidney separated extra liquid from the blood inside what was called renal meat and referred to urine as the residuum of this conversion.  Kidneys were also felt to provide support for blood vessels. ,
The contributions of the early Greek scholars, as Alcmaeon of Croton, Hippocrates of Kos, and Aristotle, included the reliance on understanding one's world from careful observations and not merely accepting sacerdotal or mythological proclamations. Knowledge regarding the kidney was limited, but the needle was moving forward as more and more physicians sought to unravel its complex mysteries. First-century physicians, often Greeks from Anatolia (Asia Minor, now present day Turkey) joined in this search for knowledge of renal physiology and disease.
Pliny the Elder (23-65 AD) was a Roman historian and encyclopedist who wrote Naturalis Historia, in which 16 of 37 books involved botany that listed 130 plants recommended for renal disorders. , Pedanius Dioscorides (40-90 AD) was a Greek Physician, Botanist, and Pharmacologist in the first century. In 60 AD, he developed an encyclopedic treatise on herbs and medications called De Materia Medica (On Medical Material); it was a five-volume work that was utilized extensively until the Renaissance period and included 200 herbs for the management of renal disease such as recommending enemas with ptisan or mallow for renal failure. ,,,,,
In the second century, Aretaeus of Cappadocia (81-138 AD) taught about anemia that resulted from renal conditions such as renal insufficiency, renal colic, and hydronephrosis. ,, He is from the late Hellenistic period and best known to modern scholars for his early description of diabetes mellitus as a condition with "melting away of flesh into urine." ,,,, He wrote an eight-volume Greek book called "On the Causes, Symptoms, and Cure of Acute and Chronic Diseases." 
| Galen of Pergamon (130-201 AD)|| |
The most famous post-Hippocrates Greek Physician was Galen of Pergamon (130-201 AD), who was the surgeon to emperors and gladiators; he described various conditions including renal disorders and ligated ureters to show that urine flows from kidneys to the bladder. ,,,,,,,,, Galen wrote about the filtering capacity of the kidneys and argued against the prevailing theory of his day that urine was made in the large renal vessels.  He was the first to perceive that a major function of the kidneys was to produce urine - a critical concept that took thousands of years of human history to crystallize. 
As Galen focused on the kidney, he did not understand that study of the urine would lead to diagnostic clues for systematic disease - a concept that would take several 100 years to fathom.  He also concluded that the baffling disorder of increased thirst and urination, he called diarrhea urinosa (diarrhea of the urine), was a disorder of the kidneys and not as his contemporaries, a disorder of the stomach. 
However, his views of the kidney as a filter continued to flourish and this concept was continued by Oribasius of Pergamum (326-403 AD) in Western Turkey with writings noting that urine was absorbed from the blood by the kidneys to form urine; this Byzantine scholar also used the term "ureter" and clinicians were finally able to distinguish ureter from urethra. , Oribasius discussed kidney circulation that included blood flowing through the renal artery branch of the aorta with venous return from the renal vein of the inferior vena cava.  He was among the most important physicians of his time as he was able to preserve many of the works of ancient physicians in work called "Collectiones Medicae." ,,
| Postfall of Rome era: Byzantine physicians/writers: 5th-9th centuries|| |
The fall of the Roman Empire in 476 AD initiated the Dark Ages in the West that continued until 1000 AD with loss of knowledge in many areas including medicine. There were some physicians, however, who helped to maintain and advance medical knowledge including renal disorders. These Byzantine Scholars include Stephanus Alexandriensis (550-622 AD), Alexander Traillianus (Alexander of Tralles; 525-605 AD), Aetius Amidenus (Aëtius of Amida; mid-5 th -6 th century AD), Paul of Aegina (625-690 AD), Theophilus Protospatharius (7 th century AD), Stephanus of Athens (7 th century AD), and Leon of Pella (9 th century AD). A few comments are now provided regarding Alexander of Tralles, Aetius of Amida, Paul of Aegina, and Theophilus Protospatharius. 
Alexander Traillianus (Alexander of Tralles; 525-605 AD) was a Greek physician who authored a number of works on medicine including Therapeutics (Twelve Books on Medicine).  As noted with other Byzantine writers, he concluded that those with polydipsia, polyuria, and weight loss had a kidney condition. He wrote, "I like to use every possible means in treating my patients." ,,,
Aetius of Amida (mid-5 th -6 th century AD) was a Greek-born in Amida that is now Diyarbakir, Turkey. He wrote about a variety of medical topics including diabetes (as a kidney disease) and urologic disorders. ,,,, Paul of Aegina (Paulus Aegineta; 626-690 AD) was a 7 th century Byzantine physician whose most well-known book was called Epitome medicae libri septem (Medical Compendium in Seven Books); it summarized contemporary thinking in Western medicine based on Galen and Oribasius. ,, Management of diabetes, also identified as a kidney disease, included venesection, myrtle, lettuce, knotgrass juice, dates, and dark wine.
Theophilus Protospatharius was a 7 th century physician-writer who is often classified by medical historians as the Byzantine Founder of Urology with his practical handbook called De Urinis. ,,, His work contributed to the growing fame of the Medical School of Salerno, Italy.  His treatments included bloodletting, herbs, and poultices for dermal infections. He taught that the urine appearance should be used with other physical signs to indicate various diseases and his work on uroscopy in De Urinis became standard teaching in Western medicine for many centuries including the 12 th and 13 th centuries' medical curriculum. ,,,
| Arab/persian physicians: 9th-12th centuries|| |
As the West was struggling to survive after the Fall of Rome in 476 AD, various Arab/Persian Physicians continued to preserve and advance medicine as seen with the Byzantine Physicians already discussed. These medical scholars used the Ancient Greek texts of medicine and added their own observations written in Arabic and/or Persian. A partial list of these brilliant Arab/Persian Physicians in this golden age of the Islamic era includes Ali al-Tabari (838-870 AD), Ar-Razi (Rhazes: 865-925 AD), Ali Ibn al-Abbas al-Majusi (Haly: died around 990 AD), ibn al-Qasim al-Zahrawi (Abulcasis: 936-1013 AD), ibn al-Haytam (Alhazen: 965-1040 AD), ibn Sina (Avicenna: 980-1037 AD), ibn Abi al-Alaq Zuhr (Avenzoar: 1091-1131 AD), ibn Rushd (Averroes: 1126-1198 AD), Muhadhdhab Al-Deen Al-Baghdadi (1117-1213), ibn al-Baitar (1197-1248 AD), and ibn al-Nafis (1213-1288 AD). ,, Persian-born physicians include Doctors Tabari, Majusi, and Rhazes. 
Issues dealt with during this golden age include various contributions to renal and urinary disorders, nocturnal enuresis, kidney/bladder calculi, bladder anatomy and physiology, uroscopy, bladder catheterization, and stone removal techniques.  A few of these clinicians are discussed including Ar-Razi (Rhazes: 865-925 AD), ibn Sina (Avicenna: 980-1037 AD), Muhadhdhab Al-Deen Al-Baghdadi (1117-1213), and ibn al-Nafis (1213-1288 AD).
Ar-Razi (Rhazes: 865-925 AD)
Rhazes (Abū Bakr Muhammad ibn Zakariyyā al-Rāzī; 865-925) was the most famous of the Ancient Persian Physicians. He was a musician/philosopher who became a doctor and is considered by some as one of the fathers of pediatrics as well as one of the most distinguished physicians from his era to the 17 th century. ,, He wrote about a wide variety of urinary tract disorders, use of diagnostic urinalysis, sexually transmitted diseases, nocturnal enuresis, renal/bladder stones, and neuropathic bladder due to vertebral fracture. ,,, He provided advice on prevention of hypercalciuria and other causes of calculi. Rhazes also wrote about complications of diabetes mellitus including vision damage, ulcerations, and furuncles.
ibn Sina (Avicenna: 980-1037 AD)
Perhaps, the most revered of the Islamic Physicians of the Islamic golden era was ibn Sina (Avicenna; Abu Ali al-Husayn ibn-Abdullah ibn Sina; 980-1037 AD) who was author of the famous medical encyclopedia called Canon of Medicine (Qanun fil-tibb) and The Book of Healing. ,,,,,,,, Avicenna was prolific in many fields including astronomy, Islamic theology, mathematics, physics, poetry, and medicine. He wrote about the importance of urine examination and he was a forerunner of the science of uroscopy. ,,,,,,,,, Improvement of urination was induced by urethral insertion of a louse in his view. , He wrote about concepts of cardiology and treated diabetes mellitus with lukewarm baths, exercise (horseback riding), agents to induce emesis, and avoidance of agents causing diuresis.  He called diabetes a water wheel (aldulab) and wrote about kidney diarrhea (zalkh el kuliah) as well as differentiating different types of diseases causing excessive urination. 
Muhadhdhab Al-Deen Al-Baghdadi (1117-1213)
Muhadhdhab Al-Deen Al-Baghdadi wrote a four-volume book in Arabic called Al-Mukhtar Fi Al-Tibb (Choice Book on Medicine) that included anatomical drawings and provided details of renal and urologic disorders. He provided descriptions of the anatomy of the ureterovesical junction as well as antireflux and urination mechanisms that were more accurate than found in the writings of Galen.  He recommended 83 medications for treatment of urinary stones and described a number of surgical procedures including urethral catheterization, perineal cystolithotomy, and perineal cystolithotripsy. 
ibn al-Nafis (1213-1288 AD)
ibn al-Nafis (1213-1288 AD) was an Arab physician who has been called the second Avicenna and became well-known for his contributions to medicine including in the fields of cardiology, pulmonary circulation, ophthalmology, and urology. ,,,, His works were translated and later appeared in key texts in the Renaissance period in Europe. 
| Maimonides: Physician and nephrologist of the 12th century|| |
Moses Maimonides (1138-1204) was born in Cordoba, Spain, and he was the son of a Jewish rabbi. He grew to become a scholar in religious and medical studies and became the physician to the Sultan Saladin (An-Nasir Salah ad-Din Yusuf ibn Ayyub; 1137-1193). Maimonides wrote a number of medical treatises including Medical Aphorisms of Moses that dealt with various medical conditions including renal and urologic disorders. ,,,, He wrote about a condition with red urine that was identified in the 19 th century by Richard Bright as glomerulonephritis. Maimonides wrote about black urine (malaria): "… I have never seen anyone who urinated black urine who survived." , He was one of the great physicians of the 12 th century and his writings on nephrology advanced this field and paved the way for discoveries in nephrology later in this millennium. ,,,, He taught his current and future contemporaries: "You must accept the truth from whatever source it comes." 
| Renaissance: Initiation of modern nephrology|| |
Modern nephrology began with the luminous lights of the Renaissance - Scientists and Physicians who took material from the ancient Greeks, Byzantine Greeks, and the Islamic Physicians and moved the needle of knowledge into the modern age. The Belgian Andreas Vesalius (1514-1564) is called by history the father of anatomy with his inaugural treatise, De Humani Corporis Fabrica (1543) that illustrated renal anatomy utilizing works of previous scholars such as Galen and ibn Al-Nafis. ,,,,, Paracelsus (Theophrastus Bombastus von Hohenheim: 1493-1541) was a Swiss physician who wrote about edema (originally called dropsy and taken from 13 th century work), hematuria, proteinuria, and gout; his observations were the harbinger leading to using specific gravity in urinalysis. ,
Marcello Malpighi (1628-1694) is called the father of microscopic anatomy and published in 1666 his acclaimed De viscerum structura exercitatio anatomica, in which he identified the glomerulus (Malpighian corpuscle); he wrote about the pyramids of the renal medulla, collecting ducts, and other renal microscopic details. ,,,,, Injection of dye to outline renal tissue resulted in his classic description of glomeruli as "… hanging like apples from the blood vessels, which, swollen with the black fluid, look like a beautiful tree." 
The field of modern clinical nephrology was now set based on the brilliant work of scholars from Alcmaeon and Hippocrates to ibn al-Nafis, Moses Maimonides, and Malpighi.  Many more followed that included Lorenzo Bellini (1748-1795: Bellini's ducts) in his Exercitatio Anatomica de Structura Usu Renum (1762). ,, After millennia of struggle by clinicians to understand nephrology, it was left to one giant of medicine in the West to put previous and former observations together: The great English Scholar of Nephrology and Neurology - Richard Bright (1789-1858).
| The father of modern clinical nephrology|| |
Richard Bright (1789-1858) was one member of the well-known triumvirate of his Victorian day at the Guy's Hospital in London in the 19 th century; this group included Thomas Hodgkin (1798-1866) and Thomas Addison (1793-1860) along with Dr. Bright who each have diseases illuminated with their names. He was called the "greatest physician of his day and one of the five or six great physicians of all time."  He observed that patients with albuminuria and edema indicated a diagnosis of renal disease. Richard Bright developed the first hospital medical research unit and provided written postmortem observations of persons with advanced kidney diseases that are still preserved at the Gordon Museum at London's Guy's Hospital. ,,,,,,
He provided clinically useful descriptions of various kidney disorders such as the nephrotic syndrome, acute nephritis, uremia, and small as well as enlarged kidneys; he noted a link between renal disease and enlarged ventricles of the heart. ,,,,, His excellent descriptions of chronic nephritis inspired nephrologists long after his death to name this disorder Bright's disease. Reevaluation of some of his descriptions in the 20 th century noted two of his patients had mesangiocapillary (membranoproliferative) glomerulonephritis; one died with severe nephrotic syndrome after 3-4 months of symptoms and another died from chronic renal failure with uremia after a 5-year history of renal symptoms. ,
| Conclusions|| |
Our current and evolving knowledge of modern clinical nephrology began thousands of years ago and human beings began to ask questions about their bodies, make observations, and record them for their current and future peers.  The ancient Egyptians took knowledge from their past and provided inaugural insights for others. The ancient Greeks acquired this knowledge and continued to study the complexities of their world including the human body. The first Greek Medical School was established in Cnidus in 700 BC, and the need for careful observations was emphasized by such intellectual Greek giants as Alcmaeon of Croton (born 510 BC) and the founding father of ancient nephrology - Hippocrates of Kos (460 BC-370 BC).
Brilliant Greeks living in the Roman Empire advanced this field further as exemplified by the great Galen of Pergamon (130-201 AD), who developed concepts of medicine and surgery that were the standard of Western medicine for over 1500 years. Despite the Fall of Rome in 476 AD, medicine was saved by the amazing Byzantine Greek physicians of the 5 th to the 9 th centuries and further advanced by the brilliant Arab/Persian physicians of the 9 th to the 12 th centuries. These geniuses of medicine in the Islamic Golden age of medicine were illustrated by Ar-Razi (Rhazes: 865-925 AD), ibn Sina (Avicenna: 980-1037 AD), Muhadhdhab Al-Deen Al-Baghdadi (1117-1213), and ibn al-Nafis (1213-1288 AD).
One of the greatest physicians of the 12 th century was Moses Maimonides (1138-1204). As the Renaissance brought Europe officially out of the chaos of the Dark Ages, new giants emerged to lead the way in medicine including nephrology as seen with Andreas Vesalius (1514-1564) - the father of anatomy, and Marcello Malpighi (1628-94) - the father of microscopic anatomy. The stage was set from these and other scholars for the English giant, Richard Bright (1789-1858), to arrive on the scene and become the father of modern nephrology. From the Ancient Egyptians to Alcmaeon and Hippocrates to Richard Bright, the story of slow but steady progress in clinical nephrology is inspiring to those of us in the 21 st century. We are heartened to understand our past and inspired to make progress in our present for the future in the model set by our great ancestors of nephrology. 
If I have seen further than others, it is by standing upon the shoulders of giants.
-Sir Isaac Newton (1642-1727)
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