Prolonged Survival of Skin Homografts in Uremic Patients

Abstract

I n the studies by Hume el al.' on the functional survival of renal homotransplants in patients with chronic renal insufficiency, it was observed that the period of homotransplant function in 4 of 9 recipients ranged from 5 to 25weeks. The course of the renal homotransplant in the normal dog contrasts with this wide range and long duration of the period of functional survival of renal homotransplants in the uremic patient. Irrespective of the manner in which the donor and/or recipient have been modified, including procedures known to suppress antibody formation, functional survival of the renal homotransplant in the dog seldom exceeds 1 week. Since there has been no uniformly successful experimental counterpart of chronic renal insufficiency in the dog, no information is presently available on the renal homotransplant function in the dog under these circumstances. In man, when the recipient does not have a chronic renal insufficiency, as exemplified by the case of Michon et aE.,2 the renal homotransplant functions well for about 3 weeks and then ceases to function rather abruptly, with the homotransplant showing the same morphologic pattern of rejection seen in the dog. This pattern has been interpreted as a morphologic representation of an antigen-antibody reaction; the immune response of the recipient to the renal homotransplant is believed to be the basis for the rejection. A delayed rejection or prolonged acceptance, therefore, may well represent an impaired immune response. Homotransplantation studies by Dempster3 and Simonsen4 have established a close antigenic relationship between the kidney and the skin. Should this relationship apply in man, one would expect the uremic recipient, if the prolonged functional survival is a manifestation of an impaired immune response, likewise to show a prolonged survival of skin homografts. I t was on this basis that the study to be described was undertaken.The first group of patients studied had chronic renal insufficiency with uremia that ranged from 4 months to 6 years in duration (TABLE 1). It may be noted that a variety of chronic lesions is represented, with uremia a common denominator.Skin homografts were accompanied by skin autografts in each case. The grafts were approximately square with an area of 3 to 4 sq. cm. The bed of the recipient site was subcutaneous tissue, and the grafts were full thickness. Biopsies from the homograft and the autograft were obtained simultaneously. Tissues were fixed in buffered 10-per cent formalin and processed through a modified Bouin solution. Hematoxylin and eosin, periodic acid-Schiff, Verhoeff-van Gieson, reticulum, and Feulgen stains were used.TABLE 2 summarizes the data on the recipient, donor type of homograft, the time interval to biopsy, and the estimate of the degree of homograft survival. "Pure" refers to grafts obtained from normal donors, "cortisone" to grafts from 967The upper arm was used as the site for the skin grafts.

Immunologic Studies in Human Organ Transplantation. III. The Relationship of Delayed Cutaneous Hypersensitivity to the Onset of Attempted Kidney Allograft Rejection*

“…In a study of delayed cutaneous hypersensitivity to tuberculin in seven uremic subjects, Dammin and co-workers concluded that delayed reactivity was not impaired in patients with chronic renal disease (2). In the present investigation, 14 of the 26 uremic recipients were found to be unreactive to a panel of antigens.…”

“…Four of the nine kidneys functioned for 5 to 25 weeks even though the therapy given to prevent graft rejection was inadequate by current standards. In a study of six uremic patients, Dammin, Couch, and Murray reported histological evidence of skin allograft survival for as long as 115 days (2). In view of these reports, and because a large number of patients were being evaluated for kidney transplantation, we have undertaken a detailed study of the effect of irreversible kidney failure on a number of parameters of immunological capability.…”

Malignant Tumors Arising De Novo in Immunosuppressed Organ Transplant Recipients

“…One reasonable explanation could be that at least some of these tumors or even some of those with a later appearance were already present at the time of transplantation, but were small and undetected, and grew rapidly under the influence of the immunosuppressive therapy. This raises the question whether chronic renal failure per se may predispose the patient to malignant disease (15) by virtue of the well known depression in uremia of immune responses (6,10,13,32).…”

The Rejection of Skin Homografts in the Normal Human Subject. Part Ii. Histological Findings

“…The second part of this paper will give in detail the histological sequence of events in the skin homografts during the various stages of rejection. Thus far these changes have not been described in detail in the healthy, human subject; studies have been carried out in burned patients (2), in uremics (3), and in patients with lymphomas (4), and criteria have been laid down for the acceptance of skin grafts in man (5). However, most recent studies on human skin grafts have been controlled by gross observation with a stereomicroscope rather than by histological methods (6)(7)(8).…”