History of Kidney Transplantation

History of Kidney Transplantation

The history of kidney transplantation is a saga of surgical brilliance, biological mystery, and the relentless pursuit of life-saving innovation. What began as rudimentary skin grafts in ancient India has evolved into a sophisticated field of medicine that saves hundreds of thousands of lives annually.

1. Ancient Foundations and Early Vascular Surgery

The concept of moving tissue is millennia old. In the 4th–5th Century BC, the Indian physician Sushruta documented plastic surgical transplants for reconstructing noses and earlobes—amputated as punishment—in the Sushruta Samhita (ca. 500 BC).

Modern transplantation required the ability to reconnect blood vessels. Erwin Payr (1871–1946) developed the first workable vascular suturing, leading to a surge of interest in Vienna, Berlin, and Lyon. This was perfected by Alexis Carrel, who developed the end-to-end vascular suture techniques still used today ([suspicious link removed]).

Carrel’s astounding research with Charles Guthrie at the University of Chicago (1904–1906) described the ability to reattach limbs and transplant organs (Carrel, 1905), earning him the Nobel Prize in 1912.

2. The Era of Xenotransplantation (1902–1936)

Before human-to-human trials, surgeons looked to the animal kingdom:

• 1902: Emerich Ullmann performed the first kidney transplant, moving a dog’s kidney to its neck (Ullmann, 1902). It lasted five days.

• 1905: In Bordeaux, M. Princeteau inserted rabbit kidney slices into a child with renal insufficiency; the child died 16 days later (Princeteau, 1905).

• 1906: Mathieu Jaboulay transplanted a pig kidney into a woman’s elbow and later a goat kidney into another patient (Jaboulay, 1906). Both failed due to early thrombosis.

• 1910: Ernst Unger in Berlin transplanted monkey kidneys into a girl, concluding the “biochemical barrier” was insoluble (Unger, 1910).

• 1923: Harold Neuhof transplanted a lamb kidney into a patient with mercury poisoning. Though the patient died 9 days later, Neuhof remained optimistic (Neuhof, 1923).

• 1926: Carl S. Williamson at the Mayo Foundation grafted goat kidneys into dogs, leading to immediate death and a decade-long lull in research.

3. The First Human Allografts (1933–1949)

Interest resumed in the 1930s with Yuri Voronoy. On April 3rd, 1933, he performed the first human-to-human kidney transplant (Voronoy, 1936).

• The Procedure: A kidney from a 60-year-old deceased man was transplanted into the thigh of a 26-year-old woman in a uremic coma.

• The Result: The kidney was ABO-incompatible (B to O). The recipient died 48 hours later without producing urine.

4. Immunological Breakthroughs (1943–1953)

During WWII, the British Medical Research Council tasked Peter Medawar and Thomas Gibson with studying skin grafts for burn victims.

• 1943: Gibson and Medawar showed rejection was an immunological process (Gibson & Medawar, 1943).

• 1944: Medawar characterized the “second-set response,” proving the body forms antibodies against foreign tissue (Medawar, 1944).

• 1951: Medawar and Rupert Billingham published their landmark paper on immune tolerance (Billingham & Medawar, 1951). This work earned Medawar the 1960 Nobel Prize.

5. The First Clinical Successes (1945–1953)

• 1945 (Boston): Hufnagel, Landsteiner, and Hume attached a deceased donor kidney to a woman’s arm vessels. It functioned for four days, allowing her own kidneys to recover from acute failure (Hume et al., 1955).

• 1950 (Chicago): Richard Lawler performed the first intra-abdominal cadaveric transplant into Ruth Tucker. The kidney worked for 53 days (Lawler, 1950).

• 1951 (The “Küss Procedure”): In France, René Küss, Charles Dubost, and Marceau Servelle performed the first extraperitoneal transplants, a surgical approach still used today (Küss, 1951).

• 1952 (Toronto): Gordon Murray achieved a long-term success where the patient remained well for 21 years (Murray, 1954).

• 1952 (Paris): Jean Hamburger and Louis Michon performed the first living volunteer transplant (mother-to-son). It worked for 3 weeks (Michon, 1953).

6. The Boston Era and Identical Twins (1954–1960)

On December 23, 1954, Joseph Murray, John Merrill, and J. Hartwell Harrison performed the first successful transplant between identical twins, Ronald and Richard Herrick (Murray, 1955).

• Result: Because they were genetically identical, no immunosuppression was needed. Richard lived for 8 years.

• 1959: Joseph Murray used total body irradiation (TBI) for the first successful non-identical twin transplant (Merrill, 1960).

7. The Age of Immunosuppression (1960–1978)

The 1960s transformed the field from surgery to “dual therapy”:

• 1960: Willard Goodwin used corticosteroids to reverse rejection (Goodwin, 1963).

• 1960: Roy Calne discovered 6-mercaptopurine (6-MP) prevented rejection in dogs (Calne, 1960).

• 1962: Calne and Murray first used Azathioprine (Calne, 1962).

• 1963: Thomas Starzl combined Azathioprine and Prednisolone, establishing the first effective “dual therapy” (Starzl, 1963).

• 1963: Keith Reemtsma transplanted chimpanzee kidneys into humans; one patient lived for 9 months (Reemtsma, 1964).

• 1966: Terasaki refined HLA tissue matching, significantly improving graft longevity (Terasaki, 1966).

• 1978: Roy Calne introduced Ciclosporin, which revolutionized survival rates (Calne, 1978).

• 1983: The FDA approved Ciclosporin, making transplantation a standard therapy (Borel, 1983).

• 1990s: The introduction of Tacrolimus (Starzl, 1989) and Mycophenolate Mofetil (Sollinger, 1995) further reduced rejection episodes.

8. The 21st Century: Xenotransplantation Resurgence

While 1-year graft survival is now ~95%, the organ shortage remains. Recent breakthroughs have revived the dreams of Ullmann and Jaboulay:

• 2021: NYU Langone successfully attached a genetically modified pig kidney to a human deceased recipient (Montgomery, 2021).

• 2024: The first successful transplant of a genetically modified pig kidney into a living human was performed at Massachusetts General Hospital (He et al., 2024).