The artificial kidney. 1952.

In this classic article, reprinted from the March 1952 issue of the American Journal of Nursing, Barbara K. Coleman, RN, and John P. Merrill, MD, describe the early artificial kidney, which was being used experimentally to treat acute renal failure. This is the first article published in the nursing literature addressing the role of the dialysis nurse.

Immune reactivity and immunosuppressive intervention in experimental nephritis. II. Effect of TLI on the course of two models of nephritis in the inbred rat.

Fractionated high-dose (3400 rad) total lymphoid irradiation (TLI) induces a unique and prolonged state of immunologic unresponsiveness. The therapeutic efficacy of TLI in immune glomerular disease was explored in two animal models: the accelerated autologous form of nephrotoxic serum nephritis (AA-NTSN) and autologous immune complex nephritis (AICN). LEW rats with established AA-NTSN, subjected to TLI, manifest decreased levels of circulating antibody to the heterologous (sheep) immunoglobulin G (0.4 +/- 0.2 vs 1.2 +/- 0.3 mg/ml, mean +/- SE respectively, p less than 0.01) early post TLI in association with a reduction in histopathology and albuminuria (6.7 +/- 2.2 vs control 19.6 +/- 5.4 mg/24 hr, mean +/- SE, p less than 0.02). Administration of TLI to rats with established AICN effected significant (p less than 0.001) reduction in albuminuria (162 +/- 30 vs 315 +/- 27), serum creatinine (p less than 0.005), and the incidence of lipemia (p less than 0.01) vs controls. Adoptive transfer studies provided no evidence that the sustained beneficial effect of TLI in AICN was suppressor cell mediated. Thus, the observed therapeutic efficacy of TLI in the treatment of experimental nephritis, shown to be related to a reduction in the level of circulating antibody in AA-NTSN, provides a new model system for study of immunity and immunosuppression in primary glomerular disease.

Bone marrow transplantation following total lymphoid irradiation. I. Correlation with field size and suppressor cell induction.

Total lymphoid irradiation (TLI) induces a unique state of immunosuppression. Although permanent bone marrow chimerism has been obtained in rodents prepared by TLI, uniform marrow engraftment has been more difficult to obtain in larger mammals. Accordingly, studies were performed to assess the immunologic perturbations induced by TLI in inbred LEW rats, and to explore the effect of altering field size of irradiation on the induction of suppressor cells and the success of allogeneic bone marrow transplantation. Additional abdominal shielding to protect a single kidney (right) from irradiation during TLI presented successful of bone marrow engraftment (WF leads to LEW, N = 5) but chimerism was uniformly obtained (N = 3) using the full irradiation field (P less than .05) Lymphopenia and a relative monocytosis were noted in all rats subjected to TLI. Although TLI using the full irradiation field eliminated alloreactivity of nylon-wool-purified spleen cells, significant, if reduced, alloreactivity was noted in rats subjected to TLI using smaller irradiation fields. Irradiated (1500 rads) nylon-wool-purified splenic T cells of rats subjected to TLI using the full field effected significantly greater suppression (P less than .001) of a normal mixed lymphocyte culture than did cells from rats subjected to TLI with right kidney shields in place (relative response reduced to 15.2 +/- 5.7% versus 64.3 +/- 11.7%). Success of bone marrow engraftment in rats prepared by TLI was correlated, therefore, with the induction of a profound lymphopenia, elimination of alloreactivity, and the development of a potent splenic suppressor system.

Acute renal failure following cardiac operations.

The incidence and course of acute renal failure following cardiopulmonary bypass (CPB) was retrospectively analyzed. The incidence of oliguric acute renal failure was 1.5% and the mortality rate was 27%, a figure substantially lower than previously reported. Both peritoneal dialysis and hemodialysis were initiated early, with a mean of 3.6 days between the onset of acute renal failure and initiation of dialysis. Survivors had a mean duration of acute renal failure of 24 days. Deaths were caused by cardiac failure (one) and sepsis (two). Mortality rate from acute renal failure complicating CPB resembles that from acute renal failure related to other causes and may be lowered by early aggressive dialysis.

Factors contributing to the declining mortality rate in renal transplantation.

Recent modifications and refinements in the management of patients with renal allografts have diminished the mortality rate at our hospital to 2 per cent and 5 per cent at one year for patients receiving kidneys from related and cadaveric sources, respectively. Of 186 receiving transplants since 1974, seven (4 per cent) have died within one year of operation. The incidence of wound infections has been reduced from approximately 25 per cent in 1972 to 2 per cent since 1976 by the use of a single high dose of broad-spectrum antibiotics administered at the time of induction of anesthesia for any surgical procedure. Risk and limitations of immunosuppression have been better appreciated, ultrasound is used more often in the diagnosis of partial obstruction or perinephric fluid collections, and needle biopsy of the transplanted kidney has reduced the morbidity inherent in open biopsy. The contribution of sepsis as a cause of death has declined. The diminishing hazard of renal transplantation has made it an increasingly attractive treatment for end-stage kidney disease.

Vestibular toxicity of gentamicin. Incidence in patients receiving long-term hemodialysis therapy.

Twenty-three patients on long-term hemodialysis regimens who received gentamicin sulfate were reviewed retrospectively to assess the incidence of ototoxicity and to identify potential risk factors. Dosage of gentamicin sulfate was 1.0 to 1.5 mg/kg intravenously three times weekly. Serum gentamicin levels were monitored in 21 cases. Seven patients developed signs and symptoms of vestibular dysfunction. Statistically significant differences were found between the ototoxic and nonototoxic groups with respect to age (P less than .001), total dose (milligrams per kilogram) (P less than .001), and duration of therapy (P less than .001). The total dose per kilogram of body weight contributed most heavily to ototoxicity, and regression analysis suggests that the critical cumulative dose is about 17.5 mg/kg. The two groups did not differ with respect to mean peak and valley serum levels. We conclude that this population is at high risk of developing gentamicin-related vestibular dysfunction specifically when the cumulative dose exceeds 17.5 mg/kg.

Transplantation immunology 1957-1975.

Knowledge of the transplantation immunity has increased rapidly in the past twenty years. The rejection of allograft is now known to involve the interaction of several subsets of lymphocytes, as well as humoral immunity. Efforts to suppress immunity to the allograft are effective but suppress other kinds of immunity also, thus rendering the recipient susceptible to opportunistic infections. Two approaches to modification of the immune response by impairing the ability of cells sensitized specifically against allograft antigen to kill such cells are described. These agents can and have been used therapeutically in humans for other reasons and have been shown in the laboratory to actually markedly prolong the life of renal allograft, without impairing the immune response to other antigens.

Dialysis versus transplantation in the treatment of end-stage renal disease.

Both dialysis and kidney transplantation are effective techniques for prolonging life in ESRD. Because dialysis therapy does not effect replacement of the metabolic functions of the kidney, it is less tha perfect. Successful transplantation that replaces all of the aspects of renal function is the treatment of choice. Successful transplantation is highly dependent upon the availability of a suitable donor and the appropriate tissue match, which remains a problem. Present immunosuppressive therapy required to prevent the immunoresponse causing rejection of the renal allograft is a tool too dull for the job. Since all immunoresponse is suppressed, infections are common, as are the multiple complications of cortical steroid therapy. For the dialysis patient, development of more compact effective dialysis apparatus and particularly the availability of replacement therapy hold promise. New approaches to diminishing the immune response to the graft without impairing that to microorganisms may well effect improvement in graft survival as will increasing knowledge of factors other than HLA antigens in the immunologic reaction. Development of an effective method for arresting the progress of glomerulonephritis before it reaches end-stage renal failure would obviate the necessity for dialysis or transplant therapy in appoximately two thirds of ESRD patients.