Tuesday, October 21, 2014
Historical Contribution: 1954, DeKlerk, Scott & Scott, Renal Transplantation
de Klerk JN, Scott HW, Scott WW. Renal Homotransplantation: I. The Effect of Crotisone on Transplant; II. The Effect of the Transplant on the Host. Annals of Surgery. 1954;140:5:711-19.
The first kidney transplant was performed in 1950, although the kidney was rapidly rejected as no immunosuppressive therapy was available. The first successful kidney transplant was performed in 1954 at the Brigham Hospital in Boston, by a team led by Dr. Joseph Murray (who later was awarded the Nobel Prize). This transplant was performed between a set of identical twins, eliminating rejection and the need for immunosuppression. It would take another decade before the discovery and perfection of tissue typing and the immunosuppressive regimen needed for a successful transplant between two unrelated individuals.
In the early 1950's, surgeons were still working to overcome the technical challenges of the disease – reinstituting blood supply to the kidney in a timely and functional manner. Working in models of autotransplantation (moving a kidney from its natural resting place to another abdominal location in the same subject), a number of investigators were unable to perform an operation that resulted in a well-functioning kidney that concentrated urine, excreted waste (urea) and resorbed electrolytes efficiently. Based on animal literature suggesting that adrenal insufficiency due to physiologic stress at the time of transplant led to the rapid decline of the animal after transplant; deKlerk, Scott and Scott sought to investigate the use of steroids (cortisone) at the time of transplant to supplant the adrenal insufficiency.
In a simultaneous dog experiment, where kidneys from a pair of dogs were exchanged, the researchers examined the use of daily cortisone (10mg/kg) on kidney function and a variety of blood and urine tests. The renal allografts were noted to make urine with a low specific gravity, increasing proteinuria and pyuria – consistent with prior studies where the transplant failed to work. In addition, the ureters were noted to become gray, slough and obstruct. In all animals, the transplants failed and the animals died of renal failure – with the longest living 21 days. The concepts of rejection were not well elucidated during this time period, however the transplanted kidneys were noted to have "progressive small round cell infiltration," cytoplasmic vacuolization, desquamation and loss of tubular architecture. Interestingly, the longest living animal, which was given cortisone, did not have the microscopic appearance seen in the other animals – indicating that the cortisone may have had a beneficial influence on graft function in this animal.
In the second part of the experiment, the authors looked at a variety of blood and urine tests. They demonstrated a rapid drop in eosinophil counts (eosinopenia), serum sodium levels, and rising potassium levels (see Figure). The eosinopenia was indicative of the mounting immune response – a phenomenon the authors were not aware of. The electrolyte imabalances were secondary to failing transplants.
The authors blamed the graft failures on the "severe stress which the act of renal homotransplantation produces in the animals." And felt that the addition of cortisone could "dampen" the effect on the adrenal before surgery.
This manuscript offers a fascinating view of the state of renal transplantation in the early 1950's.
To read the entire manuscript: follow the link above, visit the Centennial Website or click here.
HISTORICAL CONTRIBUTIONS highlight the greatest academic manuscripts from the Brady Urological Institute over the past 100 years. As the Brady Urological Institute approaches its centennial, we will present a HISTORICAL CONTRIBUTION from each of the past 100 years. In the most recent experience, the most highly cited article from each year is selected; older manuscripts were selected based on their perceived impact on the field. We hope you enjoy!