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The concept of replacing failing organs or tissues with healthy ones is as old as civilization itself, but it was not until 1954 that the first successful human kidney transplant was performed. Since then, improved surgical techniques and organ preservation, greater understanding of immunologic barriers, and the development of newer and more potent immunosuppressives have combined to make human organ transplantation relatively routine. Key to the success of transplantation is tacrolimus, originally known as FR000506. The compound, which suppresses interleukin-2 production associated with T-cell activation, inhibits differentiation and proliferation of cytotoxic T cells. Today, it is recognized worldwide as the cornerstone of immunosuppressant therapy.

Twelve consecutive first cadaveric kidney transplant recipients received cyclosporine G (CsG)(initial dose 12 mg/kg per day) as basic immunosuppressive treatment along with prednisone (initial dose 0.5 mg/kg per day) for the first three months after transplantation. Thereafter CsG was replaced by Sandimmun (cyclosporine, CsA). Evaluation of the immunosuppressive efficacy and assessment of possible side effects of CsG was made and compared with the results in 38 historical control patients starting with the same dose of CsA as part of the same immunosuppressive dosage schedule. Statistically, there was no difference in patient survival at three (91% in CsG group versus 95% in CsA group) and twelve months (91% in CsG group versus 92% in CsA group), or in graft survival at three (75% in CsG group versus 89% in CsA group) and twelve months (75% in CsG group versus 84% in the CsA group). At equivalent oral doses of CsG and CsA significantly higher blood levels of CsG were observed (2P less than 0.05). Nephrotoxicity assessed by graft biopsy could be demonstrated to a similar extent in both groups, whereas hepatotoxicity was more pronounced during CsG treatment. Sequential measurements of bilirubin revealed a significant increase in all patients but median values were significantly higher in the CsG patients. A pronounced and concordant elevation of liver enzymes occurred during CsG treatment in three out of 12 patients. Liver biopsies performed in these patients revealed histological alterations consistent with toxic liver injury. Thus, in human kidney transplant recipients CsG and CsA appeared to be equally immunosuppressive and nephrotoxic but more hepatotoxic. On the basis of this limited experience we conclude that in human kidney transplant recipients CsG has no advantage over CsA.

The immunological responsiveness of a panel of 26 consecutive cadaver kidney allograft patients with good graft tolerance was studied against cells from the specific donor. Among these 26 patients, 11 underwent acute cellular rejection and were studied during the rejection episode. An additional eight transplant patients, who lost their graft as a result of cellular rejection, were nephrectomized and studied 6 months after their return to hemodialysis as the control group of patients "at equivalent risk." A low responsiveness against the specific donor was observed in cases of good graft tolerance, but was absent during rejection and in the control group. By using mixing experiments, cells from tolerant patients were able to actively and selectively suppress the response of their autologous pretransplant cells stimulated by the specific donor cells. These suppressor cells were effective only when added during the first 48 hr of the culture and could respond at a suppressor to responder cell ratio from 1:1 to 1:4. Finally, our observations indicate that allogeneic unresponsiveness between donor-recipient pairs may be associated with the presence of suppressor cells affecting the generation of helper T cells only in the specific situation, i.e., donor-recipient, and only in cases of good graft tolerance.

Monoclonal antibodies to human monomorphic class I and class II major histocompatibility complex (MHC) determinants have been used with immunofluorescence and immunoperoxidase techniques, to localize these antigens in normal human kidneys. HLA-DR antigen was located in the glomeruli (probably on endothelium as well as the mesangium) and within the cells of cortical and medullary tubules. Dendritic cells in the renal interstitium stained brightly for the DR antigen and could be distinguished from the staining of capillary endothelium. The vascular endothelium of large vessels stained less densely for the HLA-DR antigen than for HLA-ABC antigens. The glomeruli stained intensely for the HLA-ABC antigens and diffuse staining of HLA-ABC antigens was also noted within renal tubular cells.

Human kidney transplant survival rates at 1 year were compared among centers according to the transplantation activity as measured by the number of renal transplants performed. Statistical methods are described by which a fair assessment can be made of the outcome when small numbers of grafts are involved. The method should also be useful in evaluating subsets of patients in any given center under different treatment protocols. No evidence was found that survival rates of cadaver donor transplants were lower at the smaller centers. Other factors besides size of centers are probably of greater importance in influencing transplant survival rates.

Using antisera to human beta2-microglobulin and an immunofluorescent technique, beta2-microglobulin was found to be localized along tubular and glomerular basement membranes of renal bipsies studied. Since beta2-microglobulin is a subunit of HLA preparations, it may also serve as an indirect marker for the presence of HLA antigens in these structures.

Human kidney tissue obtained at pretransplant nephrectomy from 13 adults and 1 child with end stage renal disease was cultured to provide a source for attempted detection of viruses. Cultures were observed throughout their life span for cytopathogenic viruses. Supernatants from 13 cultures were tested for hemagglutinating viruses (including measles, rubella, influenza, parainfluenza, and mumps) using various species of red blood cells. Kidney cells were cocultivated with Vero and human foreskin cells and indirect immunofluorescence was attempted in one instance. No viruses were detected. Nevertheless 9 of the 14 patients developed infections with herpes group viruses post-transplant. Either replicating viruses were not present in the kidneys of the patients prior to transplant or the techniques used were not adequate to detect them However, the establishment of organ cultures from patients with chronic renal disease is practical and may be a useful method for further virological investigation.

From July 1972 to September 1976, 708 kidneys received through the Interhospital Organ Bank, New England were divided into two groups. Both groups were preserved by continuous pulsatile perfusion. Group 1 (308 kidneys) was maintained at a systolic pressure of 60 mm Hg throughout the preservation period. Group 2 (399 kidneys) was perfused at an initial pressure of 60 mm Hg. The pressure was adjusted to 55 mm Hg at 1 hr, then no further adjustments were made. Comparison reveals that group 2 donors were younger and that the kidneys in group 2 were preserved for longer periods that those in group 1. Both groups had an equivalent number of kidneys that were discarded and kidneys that did not function. The incidence of immediate function was higher in group 2 but this difference is not statistically significant. Compared with conventional preservation, kidneys can be preserved at lower systolic and mean pressures without loss of quality, and in fact, may suffer less damage from perfusion.

THE tabulations compiled by the Registry in Human Kidney Transplantation sponsored by the National Academy of Sciences and National Research Council and under the careful direction of Murray and his associates1 2 3 permit survival data of patients with renal grafts to be calculated by means of conventional technics.4 The published tables are based on worldwide experience with over 500 renal grafts at centers specializing in this technic, and the survival data derived have important implications for the future of isografts and allografts in renal disease, in other disease that may benefit from organ replacement and for the evaluation of artificial organs . . .

The relationship of blood group compatibility and splenectomy to duration of kidney transplant function has been studied in 565 transplants performed during the 3-year period prior to 1(5 March 19(55. The data were analyzed, using conventional life table methods. The following trends are suggested from analysis of data on the ABO, I) or Rh, and P blood group systems: (1) ABO incompatibility tends to increase the incidence of transplants which never function. The difference between the proportions of transplants functioning at various post-transplant intervals appears to be due to other genetic factors acting independently of the ABO blood group system. (2) Compatibility or incompatibility for the D or J\h blood group system does not appear to be related to initiation or duration of transplant function. (3) Incompatibility for the P blood group system seems to have no influence on initial transplant function, but limited data suggest the possibility of ft subsequent, decrease in duration of function. Splenectomy prior to or at time of transplantation had no influence on initiation of transplant function. There is some indication in recipients receiving a related kidney that splenectomy results in a higher proportion of transplants functioning up to 3 months post-transplant. After the initial 3-month period transplants appear to function in about the same proportions in both spleneetomizod and nonsplenectomized recipients.