The Immunologie Capability of Uremie Patients

Infection is a serious problem in patients with both acute and chronic renal failure. In patients with acute renal failure, even when maintained by adequate hemodialysis, infection is a major cause of death. In these individuals failure of wound healing is unquestionably a contributory factor. In patients with chronic renal failure infection appears to be less of a problem except around the site of the silastic arteriovenous fistula which is utilized for intermittent hemodialysis with the artificial kidney. It is of interest, however, that in such indi viduals infection of the urinary tract, even in the face of marked oliguria, is virtually nonexistent, and recent studies have shown that even patients with moderate chronic renal failure, significant bacilluria is rare. Dietary protein restric tion commonly used in the treatment of renal failure has been thought to be a contributory cause of susceptibility to infection. Possibly the anemia evident in all patients with renal failure of any duration may also contribute. However, no clear defini tion of the predisposing factor has yet been made. It is of interest that in patients with acute renal failure in whom in fection is certainly the major problem, no specific reason for this susceptibility has been found other than the presence of trauma and surgical wounds which so frequently accompany the initial cause of acute renal failure. Phagocytosis and anti body production are apparently normal in such individuals ( 1). Our own interest in the immunologie capability of patients with chronic renal failure began with our studies of human renal allografting (5). Previous studies of renal allografts in dogs had shown that functional survival of the transplant seldom exceeded 1 week. However, in 4 of the 9 human recipients reported in our early study survival ranged from 5 to 25 weeks, and the histology of the kidney grafts at autopsy was quite different from that of the rejecting dog kidneys. During our studies, however, a case was reported by Michon et al. (8) in which a kidney was transplanted into a previously healthy young man whose sole kidney had been removed following trauma. The kidney donor was his mother. The kidney functioned well for about 3 weeks and then func tion ceased abruptly. The graft showed the same morphologic pattern of rejection seen in the dog. Since all of our patients were chronically uremie, many maintained by dialysis on the artificial kidney, the suggestion was made that the delayed rejection or prolonged acceptance therefore might well repre sent an impaired immune response. Dammin et al. (4) in our group then undertook a study of the survival of skin allografts in uremie patients. In 7 patients with chronic renal failure, skin grafts were placed from multiple healthy donors and were biopsied at intervals from 32 to 115 days. In each of the re cipients, the survival of at least 1 of the skin allografts was graded fair to good. Five were listed as good, 1 as excellent, 3 as poor, 2 as fair, and 1 could not be interpreted because of infection. Further studies carried out on the immunologie potential of these recipients showed that all had normal isoagglutinin titers. In addition, 3 patients were given an injection of B blood group specific substance, and 2 of the 3 showed responses comparable to those observed in normal individuals. Six of the 7 patients gave negative reactions to Schick tests, while tuberculin tests were positive in 2 of the 7 patients. The sera of 12 patients with chronic uremia were examined by paper electrophoresis for protein patterns. No depression considered to be significant was observed in the antibodycontaining fractions. Gamma-globulin determined quantita tively by the agar diffusion method with horse antihuman gamma-globulin serum showed levels within the normal range for this method. Others have confirmed a prolonged survival of human skin allografts in chronic uremie patients (9, 11). The studies of Kirkpatrick et al. (6) are of particular interest. They reported on 28 patients with chronic renal failure, the majority of whom had chronic glomerulonephritis. The patients were candidates for renal allografting and were studied before and after this procedure. Skin tests were made with various pollens, molds, and the antigens of tricophyton and Candida albicans. In addition, tuberculin tests (PPD), histoplasmin, and mumps antigen were administered. The re sults revealed that skin reactions of the delayed hypersensitivity type were distinctly weaker in the uremie patients (22/170 positive tests) than in normal donors (73/177 positive tests). Following renal allografting each of 18 patients not on steroid therapy developed at least 1 positive test of the delayed type. The authors attributed this to the transfer of immunologically competent tissue, i.e., lymphocytes, in the renal interstitium or blood contained in the renal vasculature. In their studies