Edwin J. Smith

Therapy of acute cadaveric renal allograft rejection with adjunctive antithymocyte globulin.

A randomized and controlled study was conducted to evaluate the efficacy of adjunctive antithymocyte globulin (ATG) therapy for the treatment of the initial rejection episode in first cadaveric transplants. When compared to the control group (29), which received only standard antirejection treatment (SAT) of steroid pulsing and local irradiation, the adjunctive ATG treatment group (23) demonstrated significantly faster recovery rates (8.9 ± 4.1 versus 6.9 ± 3.7 days, P = 0.05, respectively) and better graft survival rates (62 ± 9% versus 91 ± 7%, respectively) after the first rejection. ATG treatment did not result in fewer subsequent rejection episodes than SAT but long-term allograft survival rates remained superior to controls for the entire 3-year study period. By avoiding ATG treatment in those patients who never experienced clinical rejection on maintenance immunosuppressive therapy, i.e., nonresponders (23 of 90), complications associated with excessive immunosuppression were minimized. The combined results of the non-responder group of patients and ATG-treated patients resulted in a 1-year patient survival of 97% and graft survival of 86%. These results suggest that the most efficacious use of ATG is therapeutic and not prophylactic in renal transplant patients.

In Vitro Effects Of Cyclosporin A On Lymphocyte Subpopulations: 1. Suppressor Cell Sparing By Cyclosporin A

The fungal metabolite, cyclosporin A, is a potent immunosuppressive compound. Experiments were performed in vitro with both human and nonhuman primate peripheral blood lymphocytes to study the effect of this agent on suppressor cell activity. Cyclosporin A did not affect the generation or function of concanavalin A-induced suppressor lymphocytes as measured by their ability to suppress thymidine uptake of lymphocytes in secondary cultures. No evidence of suppressor cell induction was noted by incubation of lymphocytes with only cyclosporin A. We conclude that, although cyclosporin A does not generate or induce suppressor cell lymphocytes, it does spare them, while inhibiting other subpopulations. This effect may create an imbalance in the immune system which results in profound suppression.

The transmission of Candida albicans by cadaveric allografts.

Two transplant patients suffered Candida infections after receiving homografts from a cadaveric donor whose urine culture yielded Candida albicans greater than 100,000 colonies per ml. In both patients the infections became apparent after large doses of methylprednisolone were administered for acute rejection. Flucytosine proved to be inadequate therapy but modified doses of amphotericin B served to eradicate the infection in each case. Donor urine cultures yielding Candida albicans should be interpreted as representing a transmissible infection.

Pregnancy Following Renal Transplantation in a Patient with Insulin-dependent Diabetes Mellitus

Renal transplantation and peritoneal or hemodialysis are therapeutic options increasingly available to diabetic patients with uremia. We report a patient with insulin-dependent diabetes mellitus (IDDM) and advanced retinopathy and nephropathy who had three pregnancies. Her first pregnancy resulted in a living female with Pierre-Robin syndrome and arthrogryposis. The second pregnancy, 8 mo post-kidney transplantation, necessitated a therapeutic abortion for an anencephalic fetus. Her third pregnancy, 22 mo after kidney transplantation, was associated with intensive diabetes management and resulted in delivery by cesarean section of a healthy boy. Renal and retinal function remained stable during both her second and third pregnancies. As more patients with IDDM achieve fertility post-renal transplantation, aggressive principles of diabetes regulation need to be expanded to include consideration of the interaction of the post-kidney-transplant state and diabetes mellitus during pregnancy.

TIME COURSE OF GLOMERULAR ENDOTHELIAL INJURY RELATED TO PULSATILE PERFUSION PRESERVATION

To elucidate the time course of glomerular and arterial endothelial injury resulting from pulsatile perfusion preservation of human kidneys, we examined two kidneys, one at 16 and the other at 42 hr, for which no suitable recipient could be found. The scanning electron microscope revealed subtle changes at 16 hr in the filtration barrier. These included mild endothelial swelling with an increase in the appearance of bulbous processes, and elongated fenestrae. The visceral epithelial surface was normal as was the arterial endothelial surface. By 42 hr the glomerular endothelial surface displayed very prominent cytoplasmic ridges and clearly distorted fenestrae. The arterial endothelium exhibited a tendency to separate from the vessel wall. The proximal tubular epithelium revealed scattered loss of microvilli. These changes are similar in kind to, albeit less severe than, those described after 60 hr of perfusion. They may represent cell swelling following ischemia, or be the result of altered cell permeability engendered by low temperature. The possibility remains that such changes could be minimized by modifying the perfusate. Scanning electron microscopy provides a versatile tool in the study of vascular and other surfaces of tissues stored with perfusion preservation.

Glomerular Endothelial Injury Related To Renal Perfusion: A Scanning Electron Microscopic Study

To elucidate abnormalities in renal morphology related to perfusion preservation, we examined kidneys perfused for 60 hr with a scanning electron microscope. In addition to tubular necrosis and fused glomerular visceral epithelial foot processes, we identified changes in the glomerular endothelial and arterial endothelial surfaces. The glomerular endothelium revealed fenestrae that were smaller and more irregular than normal, as well as abnormal bulbous projections. The arterial endothelium displayed striking degenerative changes. These abnormalities may account for the altered glomerular function and intravascular coagulation that occur in some kidneys preserved by lengthy perfusion.