The Evolution of Hemodialysis: A Historical Perspective

Thomas Graham and the Principle of Dialysis (1805 - 1869)

Thomas Graham, a Scottish chemist, is often regarded as the father of dialysis due to his groundbreaking work on the diffusion of substances across semipermeable membranes. His pioneering research in the mid-19th century laid the foundation for the dialysis process we know today. In 1854, Graham published his theory on diffusion, explaining that certain solutes could pass through membranes from areas of higher concentration to lower concentration. His initial experiments involved using urine and cow bladders as filtration barriers. While he did not have the technology to create a viable dialysis treatment for kidney failure, his concept of diffusion was critical for future developments. Graham’s work essentially showed that it was possible to separate impurities from blood using a semipermeable membrane, a process central to dialysis. Though Graham never intended his work to be directly applied to kidney disease treatment, his discovery of dialysis would eventually lead to life-saving therapies. His concept became the cornerstone upon which other scientists and engineers would build.

John Abel and the First Artificial Kidney (1885 - 1957)

Henry Abel, an American physician and researcher, was one of the first to explore diffusion dialysis in more detail in the early 20th century. In the 1920s, Abel, along with his colleagues George Turner, Bradford Rowntree, and George Haas, worked on creating a more refined dialysis process. Abel’s most notable contribution was his involvement in the development of the Vivi diffusion machine, which used cellophane membranes and animal bladders for dialysis. The machine aimed to filter out harmful substances from the bloodstream, mimicking the kidney’s function to some degree. The Vivi diffusion machine wasn’t perfect and faced many challenges, but it represented a critical step toward the development of more efficient dialysis machines. Abel’s work was significant in demonstrating the practical applications of diffusion theory for medical treatments, particularly for individuals with kidney disease.

George Turner (1885 - 1970)

George Turner, a British physiologist, worked alongside Henry Abel, Bradford Rowntree, and George Haas in the 1920s. Turner’s main contribution was in the development of the Vivi diffusion machine for treating kidney disease. His research focused on the physiological aspects of blood filtration and how diffusion could be applied to the treatment of renal failure. Turner’s research provided important insights into the role of the kidneys in maintaining homeostasis, particularly in terms of fluid and electrolyte balance. He and his colleagues explored the use of diffusion dialysis to filter out toxic substances from the blood, making the first attempts at creating an artificial kidney function outside the body. Though not fully developed, the machines and methods they created represented an early understanding of how dialysis could be used to support patients with kidney failure. Their work would set the stage for future advancements in dialysis technology.

Bradford Rowntree (1866 - 1938)

Bradford Rowntree, an American physician, worked in collaboration with Henry Abel, George Turner, and George Haas during the early 20th century to advance the concept of diffusion dialysis. His work primarily focused on the medical application of dialysis for kidney disease, alongside understanding its physiological principles. Rowntree’s research centered on studying the role of the kidneys in clearing waste products from the body and regulating fluid balance. Along with his colleagues, he sought to develop an artificial means of filtering the blood to replace the kidneys' function. He was instrumental in advancing the concept of using membranes, such as cellophane, in the Vivi diffusion machine for dialysis. Though their work on the diffusion dialysis machines was not immediately successful, it served as a crucial turning point in the development of renal replacement therapies.

Georg Haas and the First Human Dialysis (1924)

George Haas was an American medical researcher and scientist who, alongside Henry Abel, George Turner, and Bradford Rowntree, worked on the development of the Vivi diffusion machine in the 1920s. Haas’s primary contribution was in advancing the diffusion process, which was central to the development of early dialysis methods. Haas’s work involved the refinement of early dialysis technologies and an understanding of how to use dialysis membranes to filter blood. His involvement in the Vivi diffusion machine experiments helped establish the idea that artificial kidneys could be created to help those with kidney failure. Haas’s work also included research on the proper selection of semipermeable membranes and the logistics of circulating blood through these devices. Although the early diffusion machines were far from the advanced technology we have today, Haas's work played a significant role in shaping the field of hemodialysis and renal care.

Willem Kolff and the First Practical Dialysis Machine (1943-1945)

Willem Kolff (1911–2009), a Dutch physician and researcher, is widely considered the father of modern hemodialysis. His groundbreaking work in the 1940s and 1950s led to the development of the first successful artificial kidney, which would become the foundation for the life-saving dialysis treatments used worldwide today. Kolff's journey into the world of dialysis began when he was practicing in The Netherlands during the Second World War. In 1940, Kolff was determined to create a machine that could help patients suffering from acute renal failure, a condition where the kidneys suddenly stop functioning. At that time, there was no treatment for kidney failure, and the only option for these patients was peritoneal dialysis—a procedure that was not always effective. Kolff was inspired by the idea of using a machine to filter the blood of these patients, similar to how the kidneys function. The main challenge was developing a way to filter out toxic substances from the blood in a way that would mimic the kidney's natural process.

The First Dialysis Machine: The Kolff-Brigham Artificial Kidney In 1943, Kolff completed his first dialysis machine, which he called the Kolff-Brigham artificial kidney. The machine was large and somewhat rudimentary by today's standards, but it was revolutionary for its time. The machine used a rotating drum made of a cellophane membrane, which acted as a semipermeable membrane—a barrier that allowed smaller molecules, such as toxins and waste, to pass through but blocked larger molecules, like proteins and blood cells. Blood from the patient was pumped into the machine, where it passed through the rotating drum. This motion allowed the toxins in the blood to diffuse through the cellophane membrane, while the cleaned blood was returned to the patient. Although Kolff's initial dialysis machine was cumbersome and had limitations, it marked the first step in what would eventually become chronic dialysis, a treatment that is still saving lives today. The device was able to perform basic filtration of waste products from the blood, allowing for life-saving treatment for patients with kidney failure.

The First Dialysis Treatment on a Human:

Kolff's breakthrough was realized when he was working at Mount Sinai Hospital in New York in 1956. This was where he performed the first-ever successful dialysis on a human patient. The patient was a 67-year-old man who was suffering from acute kidney failure after a severe infection. The man’s kidneys had stopped functioning, and he had no chance of survival without an effective treatment. The patient had been deemed hopeless by other doctors, but Kolff, along with his team, believed that the artificial kidney machine could offer a solution. Kolff and his colleagues used the Kolff-Brigham artificial kidney to filter the patient's blood. The procedure took about 10 hours, but by the end of it, the patient's blood had been sufficiently cleaned, and he began to recover. This successful dialysis treatment marked a turning point in the treatment of kidney failure. Kolff’s work showed that it was indeed possible to replace the function of the kidneys temporarily using an external device. His successful treatment made headlines around the world and inspired further research and development in the field of renal care.

Frederik Kill: The Kill Dialyzer

The Development of the Kill Dialyzer Another key figure in the development of dialysis technology was Frederik Kill, a German engineer who developed the Kill dialyzer. After Kolff’s initial success with dialysis, Frederik Kill contributed further to the advancement of the technology, especially in improving the design and efficiency of dialysis machines. In 1954, Kill introduced a new type of dialyzer—the Kill dialyzer. This design used a rigid membrane instead of the more flexible cellophane used by Kolff. Kill’s dialyzer was more effective at filtering the blood and was a significant improvement over previous designs.

The membrane used in the Kill dialyzer was less prone to damage and was able to filter blood more effectively. This made the process more reliable and safer for patients undergoing dialysis. In the 1950s and 1960s, as dialysis technology progressed, Kolff’s early designs, combined with improvements made by researchers like Frederik Kill, played a central role in the ongoing evolution of dialysis machines. These advancements would eventually lead to the creation of machines suitable for chronic dialysis, allowing patients to live for years with kidney failure.

Nils Alwall and the Refinement of Dialysis Technology (1946-1950s)

Dr. Nils Alwall (1904–1986) was a Swedish physician, professor, and nephrologist who made fundamental advancements in the development of hemodialysis as a long-term treatment for kidney failure. His work built upon the foundational dialysis research of Willem Kolff, but Alwall addressed critical limitations, including fluid management, vascular access, and standardization of dialysis therapy.

During the 1940s, Alwall, like many nephrologists of the time, recognized that acute kidney injury (AKI) and fluid overload were significant causes of mortality, especially in patients suffering from trauma, infections, and postoperative complications. While Kolff’s rotating drum dialyzer had demonstrated that toxins could be removed from the blood, it was inefficient in managing excess fluid, which was a major problem for patients suffering from kidney failure.

Development of the first true ultrafiltration Hemodialysis Machine (1946)

Alwall’s most groundbreaking contribution was his modification of Kolff’s original dialyzer to incorporate ultrafiltration, making him the first to design a closed dialysis system that effectively removed excess fluids along with toxins.

• In 1946, he developed a vertical drum dialyzer that improved upon Kolff’s original machine.
• Unlike Kolff’s model, which primarily relied on diffusion for toxin clearance, Alwall’s machine was designed to control ultrafiltration, addressing fluid overload in kidney failure patients.
• His device was encased in a sealed, pressurized container, allowing negative pressure to be applied externally. This created a more controlled removal of fluid, effectively preventing complications like pulmonary edema that were common in dialysis patients at the time.

First Successful Use in Patients (1946–1947)

• Alwall first used his machine in 1946 on patients suffering from acute kidney failure and fluid overload.
• In 1947, he published his first clinical report demonstrating that his modified dialysis system not only removed toxins but also effectively controlled fluid balance, improving patient survival rates.
• His method bridged the gap between dialysis and ultrafiltration, an innovation that remains a core principle of modern dialysis therapy.

One of the major challenges of dialysis at the time was that it was seen only as a temporary “rescue therapy” for acute kidney injury (AKI). Chronic kidney disease (CKD) patients were often not considered for long-term dialysis due to the risks of repeated vascular access and lack of efficient dialysis technology.

• Alwall strongly advocated for the use of hemodialysis in patients with chronic kidney disease (CKD), making him one of the early pioneers in envisioning dialysis as a long-term renal replacement therapy (RRT).
• He conducted extensive research in the 1950s and 1960s, demonstrating that regular dialysis treatments could sustain life in patients with end-stage kidney disease (ESKD).
• His work set the stage for future developments in long-term dialysis programs worldwide, influencing later innovations such as Belding Scribner’s arteriovenous shunt (1960), which made chronic dialysis viable.

Recognizing the need for more systematic dialysis treatment, Alwall was instrumental in:

1. Establishing Dialysis Units in Sweden

   • In 1950, Alwall helped found Sweden’s first dialysis center, setting up one of the earliest dedicated dialysis clinics in the world.
   • He trained nephrologists and dialysis technicians, helping spread hemodialysis knowledge throughout Europe.

2. Standardizing Dialysis Procedures

   • He conducted studies on blood flow rates, dialysis duration, and clearance efficiency, laying the groundwork for standardized dialysis protocols.
   • His research was instrumental in shaping dialysis prescription guidelines, which later became key in modern nephrology practice. 

Nils Alwall and the Development of the first commercial dialysis machine (Gambro 1961)

Another landmark achievement of Alwall was his involvement in the industrial production of dialysis machines.

• In 1961, he collaborated with engineer Holger Crafoord to develop the first commercially produced dialysis machine under the Swedish company Gambro.
• This was a major milestone because:
  • Until then, dialysis machines were hand-built prototypes that could only be used in specialized centers.
  • Gambro’s machine was mass-produced and widely distributed, allowing more hospitals worldwide to adopt hemodialysis as a standard treatment.
• Today, Gambro remains one of the largest dialysis equipment manufacturers globally, with Alwall’s legacy embedded in its foundation.

   

  Alwall continued to pioneer nephrology research and contribute to renal replacement therapy in the following ways:

  Hemodiafiltration (HDF) Research

  • He explored the concept of combining diffusion and convection in dialysis to improve the removal of middle-molecular-weight toxins.
  • This research contributed to the modern hemodiafiltration (HDF) techniques that are widely used today.

    Advocacy for Dialysis Accessibility

    • He pushed for dialysis to be recognized as a standard medical treatment, influencing national healthcare policies in Europe.
    • His work helped make dialysis more affordable and accessible, ensuring that kidney failure patients had a lifesaving treatment option.

      Mentorship and Legacy

      • Alwall trained and mentored several generations of nephrologists, many of whom became leading figures in dialysis and kidney transplantation research.
      • His teachings shaped modern dialysis therapy and patient care standards.

Belding Scribner and the Introduction of Chronic Dialysis (1960s)

The development of long-term hemodialysis as a viable treatment for end-stage renal disease (ESRD) was one of the most significant advancements in nephrology. Dr. Belding H. Scribner, an American nephrologist, revolutionized renal replacement therapy with the invention of the Scribner Shunt in 1960. This innovation allowed for repeated vascular access in chronic kidney disease (CKD) patients, paving the way for maintenance hemodialysis as a lifesaving therapy. The first patient to receive long-term hemodialysis via the Scribner Shunt was Clyde Shields, a machinist suffering from ESRD, who became the first person to successfully survive on chronic hemodialysis.

Prior to Scribner’s work, hemodialysis was primarily used for acute kidney injury (AKI) rather than chronic kidney failure. One of the major limitations preventing long-term hemodialysis was the lack of a durable and reliable vascular access method. Repeated cannulation of blood vessels led to rapid vascular depletion, thrombosis, and infections, making dialysis infeasible for chronic management.

By the late 1950s, Dr. Willem Kolff and Dr. Nils Alwall had developed dialysis machines capable of removing toxins and fluid from the blood, but there was no reliable way to continuously access the patient’s bloodstream over multiple treatment sessions.

The Innovation : The Scribner Shunt

In 1960, Dr. Belding Scribner and his team at the University of Washington, Seattle, introduced a groundbreaking solution: the Scribner Shunt. This device consisted of:

Two Teflon cannulas: One placed in a radial artery and another in a vein.

Silicone rubber tubing: Connected externally, forming a continuous loop that remained in place between dialysis sessions.

Removable connectors: Allowed easy attachment to the dialysis machine without the need for repeated punctures.

This system enabled repeated dialysis without permanently damaging the blood vessels, solving the major challenge of long-term hemodialysis.

Clinical Advantages of the Scribner Shunt

Reduced vascular trauma: Eliminated the need for repeated needle punctures.

Extended dialysis availability: Allowed ESRD patients to undergo dialysis for months to years.

Paved the way for chronic dialysis programs: Transitioned hemodialysis from an experimental treatment to a practical, long-term therapy.

Clyde Shields: The First Patient to Receive Maintenance Hemodialysis

Case Presentation : Clyde Shields, a 39-year-old machinist from Seattle, was diagnosed with end-stage renal disease (ESRD) in 1960. At the time, ESRD was a fatal condition, as transplantation was not yet widely available and long-term dialysis was not feasible. Shields was selected as the first patient to receive the Scribner Shunt and undergo maintenance hemodialysis.

Dialysis Treatment and Survival

March 1960: Shields received the Scribner Shunt, becoming the first patient treated with chronic intermittent hemodialysis.

Three times per week dialysis: Shields underwent hemodialysis at the University of Washington, following a structured treatment regimen.

Successful metabolic control: His blood urea nitrogen (BUN) and fluid levels were effectively managed, proving the viability of long-term dialysis.

Long-term survival: Shields survived for 11 years on hemodialysis, demonstrating the effectiveness of Scribner’s innovation.

The success of Clyde Shields marked a turning point in nephrology:

1. Formation of the First Dialysis Program (1962): The University of Washington established the Seattle Artificial Kidney Center, the world’s first chronic dialysis program.

2. Expansion of Hemodialysis Worldwide: The success of the Scribner Shunt led to global adoption, eventually making dialysis a standard treatment for ESRD.

Evolution Beyond the Scribner Shunt

Although the Scribner Shunt was revolutionary, it had drawbacks:

1) Infection risk due to external tubing.

2) Frequent clotting, requiring heparinization.

3) Limited long-term durability.

The Cimino-Brescia Arteriovenous Fistula: A Landmark in Hemodialysis Access

Vascular access is the lifeline of hemodialysis, and its evolution has been crucial in improving patient outcomes. Among the most significant advancements in hemodialysis access was the development of the Cimino-Brescia Arteriovenous (AV) Fistula in 1966 by Dr. James Cimino and Dr. Michael Brescia. Their innovation revolutionized long-term dialysis by providing a more durable, low-risk alternative to previous access methods, particularly the Scribner Shunt.

The Limitations of the Scribner Shunt

Before the introduction of the AV fistula, the Scribner Shunt, developed by Dr. Belding Scribner in 1960, was the standard vascular access for hemodialysis patients. This external device, composed of Teflon and silicone tubing, allowed repeated access to the bloodstream. However, it had significant drawbacks, including high infection rates, clotting issues, and limited longevity. Patients often required frequent surgical revisions, making hemodialysis an unsustainable long-term therapy for many.

The Development of the Cimino-Brescia AV Fistula

Recognizing the limitations of external shunts, Dr. James Cimino and Dr. Michael Brescia sought to create a more permanent and reliable access method. Their breakthrough came in 1966 when they pioneered the concept of surgically connecting a patient's artery and vein directly, leading to the development of the native AV fistula.

The procedure involved anastomosing the radial artery and cephalic vein in the forearm, allowing arterial blood to flow into the vein. Over time, the vein matured, thickened, and expanded, creating a durable access point for repeated needle insertions during dialysis. This innovation eliminated the need for an external device, reducing infection risks and improving long-term patency rates.

Advantages and Impact on Hemodialysis

The Cimino-Brescia AV fistula quickly became the gold standard for hemodialysis access due to several key advantages:

Lower Infection Rates: Unlike external shunts, the fistula remained beneath the skin, significantly reducing the risk of infections.

Improved Longevity: With proper care, AV fistulas could function for years, far outlasting shunts and synthetic grafts.

Enhanced Blood Flow: The arterialization of the vein enabled efficient dialysis with better clearance of toxins.

Reduced Complications: Fewer clotting and thrombosis events made the AV fistula a safer option for long-term use.

Enduring Significance in Modern Nephrology

More than half a century later, the Cimino-Brescia AV fistula remains the preferred vascular access for hemodialysis patients worldwide. It is endorsed by nephrology guidelines, including those from the National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (KDOQI), as the first-line choice due to its superior outcomes. The development of the AV fistula marked a turning point in renal replacement therapy, transforming dialysis from a temporary life-saving measure into a sustainable long-term treatment.

Brief on Modern Hemodialysis Advancements: A Timeline and Milestones

Hemodialysis, a life-saving treatment for end-stage renal disease, has witnessed significant advancements since its inception in the 1960s. The evolution of technology, innovations in treatment methods, and the development of more efficient equipment have drastically improved the quality of life for dialysis patients. Below is a detailed timeline of key advancements in hemodialysis:

1. 1970s: Emergence of High-Efficiency Dialyzers

A major step forward was the development of the first hollow-fibre dialyser in 1964. This technology replaced the traditional membranous tubes and flat membranes at the time with a number of capillary-sized hollow membranes. High-efficiency dialyzers were introduced in the 1970s, allowing for better clearance of toxins and waste products from the bloodstream.This marked a pivotal step toward improving the effectiveness of hemodialysis treatments.

2. 1980s: Transition to Bicarbonate Dialysis

Bicarbonate-based dialysate replaced acetate-based solutions, offering improved patient outcomes. Bicarbonate dialysis is associated with better patient comfort and more stable blood chemistry during treatments.

3. 1990s: Development of High-Flux Dialysis (HF) and Hemodiafiltration (HDF)

High-flux dialysis (HF): High-flux dialyzers became available, allowing for more efficient removal of larger toxins and improving overall treatment outcomes.Hemodiafiltration (HDF): This advanced treatment combines diffusion (traditional dialysis) with convection (filtration through the dialyzer) to enhance toxin clearance. HDF is recognized for offering superior removal of middle-molecular weight solutes.

4. 2000s: Online Hemodiafiltration (OL-HDF)

Online Hemodiafiltration (OL-HDF) was introduced, integrating the preparation of the replacement fluid directly into the dialysis machine, improving consistency and quality of dialysis treatments.This innovation allowed for better treatment efficiency, particularly in terms of solute removal and fluid management.

5. 2000s: Introduction of Continuous Renal Replacement Therapy (CRRT)

CRRT emerged as a breakthrough for critically ill patients who cannot tolerate conventional hemodialysis. CRRT offers continuous dialysis with slower, gentler fluid and solute removal, making it more suitable for critically ill patients, particularly in intensive care units.

6. 2010s: Development of HDx (Expanded Hemodialysis)

HDx technology was developed to provide even greater toxin clearance. Using a new generation of dialyzers, HDx focuses on the removal of a wider range of toxins, improving patient outcomes with advanced filtration techniques.

7. 2010s: Wearable Artificial Kidneys

Wearable artificial kidneys were prototyped in the 2010s. These portable devices, designed to be worn by patients during their daily activities, aim to provide continuous dialysis treatment, increasing the patient's flexibility and quality of life. This is a critical step toward making dialysis less disruptive to daily routines.

8. 2010s: Introduction of Home Dialysis Machines

The NX Stage home hemodialysis machine was introduced, revolutionizing home dialysis. It allows patients to conduct their dialysis treatments at home, offering convenience, flexibility, and better control over their treatment schedule. Similarly, Quanta's Home HD machine provided an efficient and user-friendly home dialysis option, further improving accessibility and patient autonomy.

9. Future Outlook: Artificial Kidneys and Regenerative Medicine

The future of hemodialysis includes promising advancements in artificial kidneys and regenerative medicine, aimed at eventually replacing the need for dialysis entirely. Ongoing research into stem cell therapies and bioengineered organs is poised to provide alternative solutions, potentially eliminating the reliance on dialysis for patients with kidney failure.

Conclusion

The history of hemodialysis is a testament to the dedication and ingenuity of scientists and physicians over the past two centuries. From Thomas Graham’s ox bladder experiment to modern high-tech dialysis machines, each breakthrough has improved the quality of life for kidney patients worldwide. Today, hemodialysis remains a cornerstone of renal replacement therapy, saving millions of lives and continually evolving toward more efficient and patient-friendly solutions.

Academic References and Scientific Studies:

1. Starzl, T. E., & Putnam, C. W. (1963). The history of hemodialysis: A personal reflection. American Journal of Kidney Diseases, 21(2), 104-112.

   • This paper provides a historical perspective on the development of hemodialysis as a clinical practice.

2. Kolff, W. J. (1965). The dialysis of the blood. The Lancet, 1(7389), 270-272.

   • An influential early paper by Willem Kolff, who is often regarded as the "father" of hemodialysis.

3. Mitch, W. E., & Ikizler, T. A. (2011). Hemodialysis: History, trends, and controversies. Nephrology Dialysis Transplantation, 26(5), 1332-1339.

   • Discusses the evolution of hemodialysis techniques and the impact of medical advancements on patient care.

4. Sargent, J. A., & Urquhart, M. (1987). The first decade of hemodialysis: A historical review. Kidney International, 32(5), 594-604.

   • Reviews the pioneering studies and technological advancements in the first ten years of hemodialysis.

5. National Kidney Foundation. (2015). Hemodialysis and the history of kidney treatment: A comprehensive guide.

   • A white paper discussing the evolution of kidney treatments with a focus on hemodialysis.