Nephrology beginnings

1. Why the history of nephrology?

“To understand a science it is necessary to know its history,” said August Comte (1798–1857), founder of modern sociology. Rooted in sociology, this saying evolved into what is now known as the theory of path dependence, which explains how decisions made in any given new circumstance are determined and limited by decisions made in the past, even though past circumstances may no longer be directly relevant to present ones. This almost intuitively self-evident truth of social behavior applies to the science of decision making in general and has led to three Nobel Prizes. This is why the history of any science, and that of nephrology in particular, does matter.

Broadly defined, one can argue that the history of diseases of the kidney can be traced to antiquity. On the other hand, strictly defined, the specialty dedicated to the study of the kidney and its diseases, nephrology, is a relatively new discipline that emerged in the latter half of the 20th century. Although the term nephrology appears in medical dictionaries of the 1840s, and most nephrologists trace their origins to Richard Bright’s description of the association of proteinuria with kidney disease in 1827, the term did not enter medical parlance until the 1960s (see the following section of this chapter). As such, nephrology has a rather short albeit rapidly expanding history.

Why then the history of nephrology? From the outset, it is important to admit that historical knowledge is not necessary to the practice of good medicine by any well-rounded nephrologist, or to doing solid nephrology research by any well-trained investigator. The once lofty answer that, as a learned profession, medicine has interests that transcend its utilitarian purpose is no longer tenable. However, the fact remains that most notable leaders and contributors to the medical sciences are well versed in the humanities and knowledgeable of the history of their discipline as any reading of the acceptance lectures of past Nobel laureates in chemistry or physiology or medicine will clearly reveal (see: ). And as stated by a founder of scientific medicine, William Osler (1849–1919), “History and the knowledge of men are as much part of medicine as the latest technical devices and the knowledge of science.”

That may sound as a tenuous argument, particularly by those enamored with the rapid pace of nephrologic advances, who in their quest for new truths reject the past as obsolescent. In this regard, it is worth noting that current research can be appreciated best when considered in its historical context. This should be evident to all medical investigators, no matter how narrow their field of research and whether or not they realize it, and not only because they are part of a grand historical tradition. More importantly, however limited their care for the history of nephrology, their ultimate research motivation is to discover some new truth to change the course of their very research topic. Stated otherwise, they are actually doing research in a quest for a place in history. As such, the realization of their own rich professional heritage and the very raison d’être of research can only enrich their intellectual satisfaction and will provide them with reassurance when facing the trials and tribulations of research. In essence, belittling the past is detrimental only to their own full appreciation of the very work they are engaged in.

By the same token, one may ask whether the practice of nephrology deprived of its history makes one an inferior clinician. Surely not. However, as a first consideration, it is worth noting that history is engrained in the very practice of medicine. Any good clinician—even those with no interest in history—must be a good historian who can dig up and record the facts of the “past medical history” of every patient encountered. That is the aim of every aspiring clinician so well promulgated by one considered the ultimate clinical scholar, William Osler, whose statement on the importance of the history of medicine has been quoted earlier. Osler’s statement can be taken with a grain of salt in current rapidly evolving science of medicine, but familiarity with the work of one’s predecessors does add to the appreciation and enjoyment of one’s daily practice of medicine.

To sum up, why history in general, and that of nephrology in particular, is important may have been answered best by the English historian, Thomas Fuller (1608–1661):

History maketh a young man to be old, without either wrinkles or grey hairs; privileging him with the experiences of age, without either the infirmities or inconveniences thereof. Yea, it not only maketh things past, present; but enableth one to make a rational conjecture of things to come.

August Comte may have been right after all. Knowing the history of nephrology will not only make it easier to understand the science of nephrology but will also enrich its daily practice by those pursuing it as an avocation.

2. When did nephrology emerge as a medical specialty?

Words involving the Greek root nephros for the kidney have been used for centuries. The word “nephrology” as a discipline for the study of the kidney in health and disease came into use in the opening decades of the 19th century but did not actually enter the parlance of medicine until the middle of the 20th century, at which time several events contributed to the emergence of nephrology as a medical specialty. First was the continued and increasing number of published articles on kidney function that had been prompted by the World War II medical effort to study shock, climatic adaptation, renal clearance of drugs, and hemodynamics. Second was technological advances that were of direct clinical relevance to kidney disease, specifically dialysis, kidney transplantation, and kidney biopsy.

The first physician to call himself a “nephrologist,” as one who specializes in diseases of the kidney, was Arthur Arnold Osman (1893–1972) in 1945, who went on to help found the U.K. Renal Association in 1950 and served as its first president for the next 6 years. The Italian Società Italiana di Nefrologia was founded thereafter in 1957, and the French Société de Nephrologie in 1959. The first medical publication devoted to the discipline, Minerva Nefrologica, appeared in Italy in 1957. As the number of physiologists, pathologists, and clinicians interested in the kidney increased, the membership of these societies increased and new national organizations were established. In 1960 the first international meeting of nephrologists was held in Evian, leading to the establishment of the International Society of Nephrology in 1961 and the launching of its first official journal, Nephron, in 1964. The American Society of Nephrology was founded in 1966, and its official journal, the Journal of the American Society of Nephrology, was published in 1990.

As a result, all the “nephrophiles” of the past and the budding “nephrologists” thereafter now had a discipline to rally around.

3. When was the first artificial kidney used in humans?

Thomas Graham (1805–1869), a physical chemist whose seminal work on osmotic forces of fluids paved the way to hemodialysis, has been dubbed the father of modern dialysis. His studies on the behavior of biological fluids across a semipermeable membrane presaged the development of an artificial kidney and formulated the scientific basis of clinical dialysis, specifically that blood flowing in a semipermeable membrane that is in contact with an electrolyte solution (dialysate) allowed for the diffusion of small molecules from blood into the dialysate.

The first use of dialysis in vivo, so called vividiffusion, was in rabbits and dogs by John Jacob Abel (1857–1928) and his associates at Johns Hopkins in 1912 and 1913. His primitive attempts at dialyzing a few patients were utter failures, but it was his machine that was first dubbed an “artificial kidney” by a correspondent of the London Times . Tentative attempts at dialysis of humans were undertaken by Georg Haas (1886–1971) in Giessen in the 1920s, using collodion membranes and hirudin as anticoagulant that had also been used by Abel. Collodion and hirudin had to be prepared fresh, were not standardized, were difficult to sterilize, and soon led to the abandonment of clinical dialysis.

Practical dialysis became possible in the early 1940s as a result of two new substances: a cellulose acetate (cellophane) membrane and a new anticoagulant heparin. Three early pioneers to use the new membrane and anticoagulant in clinical dialysis were Gordon Murray (1884–1972) in Canada, Niels Alwall (1906–1986) in Sweden, and Willem Kolff (1911–2009) in the Netherlands; but it was Kolff working in Kampen under the tensions and difficult conditions of war-torn Holland who achieved the first clinically successful hemodialysis in humans. Kolff’s “rotating drum hemodialyzer” was a wooden, pumpless drum, wrapped 30 times with 130 feet of cellophane tubing (connected to the circulation) immersed in a ceramic bathtub containing a saline solution. Beginning in 1942, Kolff experimented with his artificial kidney. His first 16 patients never recovered and went on to succumb to kidney failure. Only 2.5 years later did his first patient, Sofia Maria Schafstadt, survive. Ironically, she had been a Nazi collaborator who was actually imprisoned. She had cholecystitis, developed septicemia, and was treated with one of the recently available sulfonamides. Her acute kidney injury was a result of sulfonamide crystal precipitation in the tubules, a common side effect of these early wonder antibacterial drugs then in use.

4. Who was the first patient to benefit from chronic maintenance hemodialysis?

The artificial kidney introduced after World War II remained experimental and was used mainly in exploratory attempts to sustain the lives of selected patients with acute kidney injury through the 1950s. The need for repeated access to the circulation limited the use of hemodialysis to the short term only in patients with acute kidney injury. Even in patients with acute kidney injury with delayed recovery, prolonged dialysis presented insurmountable problems that led to its abandonment before kidney function had recovered. The breakthrough came in March 1960, when Belding Scribner (1921–2003), a nephrologist, and Wayne Quinton (1921–2015), an engineer, working in Seattle, developed the so-called Quinton-Scribner shunt using Teflon, which had become available recently and was being used to coat implantable cardiac pacemakers. Shortly thereafter, the shunt was modified to be made from more flexible silicone tubing with Teflon tips inserted into the radial vasculature. The first patient to benefit from this new device was Clyde Shields (1921–1971), a 39-year-old Boeing machinist. In April 1960 Scribner took Clyde to the annual meeting of the American Society for Artificial Internal Organs in Atlantic City, New Jersey for a private demonstration of the shunt. The news traveled with lightning speed, and suddenly long-term maintenance hemodialysis became possible. For the first time in medicine, technology and creativity allowed the replacement of the functions of a vital body organ. Literally overnight, repeated hemodialysis allowed survival from the otherwise fatal disease described by Richard Bright (1789–1858) some 150 years earlier.

That was when dialysis moved from its rudimentary beginnings in the 1950s to a chronic life-sustaining modality of treatment, for which Kolff and Scribner were to share the Lasker Award in 2002. Unfortunately, the extremely limited resources then available in Seattle necessitated the creation of a committee to select who received maintenance dialysis (later dubbed “Life and Death Committee”). Even when restricted funds were made available, dialysis remained limited and choices of who was dialyzed continued to be made, albeit based on “medical criteria” and “first come, first served” basis imposed by the limited means and available dialysis machines. It was not until 1973, when Public Law 92-603 amendment to the 1972 Social Security Act went into effect, that dialysis care became accessible to almost everyone.

In response to mounting needs for maintenance dialysis, hospital-based dialysis centers moved into for-profit outpatient facilities and proliferated. The rush to save the life of otherwise dying patients outpaced the science of dialysis, resulting in the delivery of a treatment that was primarily empiric. Over the decades that followed, the complications of dialysis and the significant morbidity and mortality associated with it emerged as serious concerns of all stakeholders. Some of the early complications of dialysis (aluminum toxicity, water purity, hepatitis, anemia) were soon resolved; others (mineral bone disease, cardiovascular disease) linger on, while that of adequacy of dialysis still awaits resolution.

All those problems and concerns notwithstanding, Clyde Shields survived 11 years on dialysis, succumbing to a myocardial infarction in 1971.

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Jul 23, 2019 | Posted by in NEPHROLOGY | Comments Off on Nephrology beginnings

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