RESUMO
Oral administration of protein can induce antigen-specific immune hyporesponsiveness. However, the utility of oral tolerance to autoantigens in the treatment of autoimmune diseases may be limited when candidate autoantigens cannot be produced by conventional systems in quantities sufficient for clinical studies. Plants may be ideally suited for this purpose, as they can synthesize, glycosylate and assemble mammalian proteins to provide huge quantities of relatively low cost soluble proteins. Furthermore, edible transgenic plants could provide a simple and direct method of autoantigen delivery for oral tolerance. Therefore, the aim of this study was to determine whether a transgenic plant expression system was capable of synthesizing the diabetes-associated autoantigen, glutamic acid decarboxylase (GAD) in an immunogenic form and whether the oral administration of an autoantigen expressed by a plant could directly induce protective immune responses in a mouse model of diabetes. We show that a GAD-expressing transgenic plant, given as a dietary supplement, inhibits the development of diabetes in the non-obese diabetic (NOD) mouse.
Assuntos
Autoantígenos/imunologia , Diabetes Mellitus Tipo 1/prevenção & controle , Glutamato Descarboxilase/imunologia , Tolerância Imunológica , Agrobacterium tumefaciens , Animais , Autoanticorpos/sangue , Autoantígenos/administração & dosagem , Autoantígenos/genética , Células Cultivadas , Diabetes Mellitus Tipo 1/imunologia , Dieta , Feminino , Vetores Genéticos , Glutamato Descarboxilase/administração & dosagem , Glutamato Descarboxilase/genética , Interferon gama/análise , Interleucina-10/análise , Interleucina-4/análise , Camundongos , Camundongos Endogâmicos NOD , Plantas Geneticamente Modificadas , Plantas Tóxicas , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/imunologia , Solanum tuberosum , Baço/citologia , NicotianaRESUMO
Type I diabetes may be an autoimmune disorder, although the evidence is largely circumstantial. The natural history of the disease after diagnosis includes partial remission in most patients, but only about 3 percent achieve transient insulin independence. beta Cell function, as indicated by the plasma concentration of C-peptide, is lost over 6 to 30 months and islet cell antibodies disappeared over 1 to 2 years. This article describes a pilot study in which 41 patients were treated with the immunosuppressive agent cyclosporine for 2 to 12 months. Of 30 patients treated within 6 weeks of diagnosis, 16 became insulin independent with concentrations of plasma C-peptide in the normal range and decreasing titers of islet cell antibodies. Of 11 patients who entered the study 8 to 44 weeks after diagnosis, two achieved this state. These results indicate that a controlled trial of the effects of cyclosporine in type I diabetes should be conducted.
Assuntos
Ciclosporinas/uso terapêutico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Adolescente , Adulto , Autoanticorpos/análise , Peptídeo C/sangue , Criança , Creatinina/sangue , Ciclosporinas/efeitos adversos , Diabetes Mellitus Tipo 1/imunologia , Feminino , Hiperplasia Gengival/induzido quimicamente , Humanos , Hipertricose/induzido quimicamente , Insulina/uso terapêutico , Ilhotas Pancreáticas/imunologia , Rim/efeitos dos fármacos , Masculino , Pessoa de Meia-IdadeRESUMO
We have studied the endocrine-metabolic status of patients in non-insulin-receiving (NIR) remission of insulin-dependent diabetes mellitus (IDDM) within 6-60 mo of diagnosis during administration of cyclosporine, in comparison with nondiabetic subjects. IDDM patients in NIR remission were recognized when target glycemic control (plasma glucose and mean capillary blood glucose levels less than 7.8 mM before meals) was maintained without administration of insulin for at least 2 wk. In so-called isoglycemic tests, 50 g glucose was administered orally, and the glycemic curve was simulated in a subsequent study by programmed intravenous infusion of glucose. Under these conditions, the subjects with diabetes exhibited obvious glucose intolerance: acute beta-cell responses to intravenous glucose were virtually absent but significant, although subnormal responses were present after oral glucose. The responses of plasma immunoreactive gastric inhibitory polypeptide to oral glucose were normal. After bolus intravenous injections of glucose, the patients with diabetes again exhibited glucose intolerance; acute responses of immunoreactive insulin (IRI) and C-peptide were present, although grossly obtunded. On intravenous infusion of arginine (30 g in 30 min), the patients with diabetes showed substantial but subnormal increases in plasma IRI and C-peptide. Intravenous infusion of arginine elicited increments of plasma immunoreactive glucagon (IRGI) in both groups, and this response was slightly exaggerated in the patients with diabetes. On ingestion of a standard mixed meal (Sustacal) delivering 600 cal, there was a modest but significantly greater increase in plasma glucose levels in the diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Glicemia/metabolismo , Peptídeo C/sangue , Ciclosporinas/farmacologia , Diabetes Mellitus Tipo 1/fisiopatologia , Polipeptídeo Inibidor Gástrico/sangue , Adolescente , Adulto , Arginina , Criança , Diabetes Mellitus Tipo 1/sangue , Ingestão de Alimentos , Feminino , Glucagon , Teste de Tolerância a Glucose , Humanos , Masculino , Valores de ReferênciaRESUMO
The results of uncontrolled trials in immunomodulation of insulin-dependent diabetes mellitus (IDDM) led to randomized controlled trials in Canada and Europe. In the Canadian open study, the rate of clinical remissions (target control of glycemia maintained with less than or equal to 0.15 U.kg-1.day-1 insulin) was unexpectedly high among 81 subjects who had been treated with cyclosporin for at least 3 mo (mean serum trough levels approximately 125 ng/ml by radioimmunoassay). Subjects entered the study within 14 wk of onset of symptoms and received 6 wk of insulin therapy. The clinical remission rate at 1 yr was 46%; of these patients, 84% were not receiving insulin. An effect on beta-cell function was suggested by recovery of plasma glucagon-stimulated C-peptide levels into the normal range in many patients, with maintenance of levels through 1 yr in patients in remission. On the basis of these findings, the French and Canadian-European study groups conducted randomized double-blind controlled trials of cyclosporin, which confirmed the results of the open studies in terms of clinical remission. The Canadian-European study also demonstrated enhancement of beta-cell function by cyclosporin by 3 mo, which was maintained for 1 yr. In the Canadian open study, most patients relapsed within a few weeks after discontinuation of cyclosporin, indicating the need for longer-term immunomodulatory therapy for maintenance of remission. The nature and degree of structural change in kidney biopsies from patients in these studies are under assessment. The results strongly support the hypothesis that autoimmune mechanisms mediate beta-cell damage in many patients with IDDM.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Ciclosporinas/uso terapêutico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Adolescente , Peptídeo C/sangue , Ensaios Clínicos como Assunto , Ciclosporinas/sangue , Diabetes Mellitus Tipo 1/sangue , Seguimentos , Glucagon , Humanos , ImunoterapiaRESUMO
OBJECTIVE: The majority of islet transplant recipients remain insulin-requiring, although many have near-normal connecting peptide (CP) levels. Insulin resistance may be one possible cause of the continuing need for exogenous insulin in islet transplant recipients. To assess this, we have studied the insulin sensitivity index (S1) in one patient with near-normal CP levels after islet transplant who remained insulin-requiring. RESEARCH DESIGN AND METHODS: The islet transplant recipient is a 36-year-old woman with no residual CP who received a kidney transplant, followed 7 days later by an islet transplant. The islets were infused into the liver via the umbilical vein. Induction immunosuppression consisted of OKT3, prednisone, cyclosporin A, and azathioprine, with maintenance on the latter three. RESULTS: Maximum CP levels after a standardized Sustacal meal were 2.09, 1.18, 0.85, and 0.81 nmol/l at 1,6,18, and 24 months posttransplant, respectively. Insulin requirements at the same times were 0.27, 0.45, 0.49, and 0.62 U.kg(-1).d(-1), while S1 was 36.3, 53.3, and 13.2 min (-1).nmol(-1).ml at 6,18, and 24 months, respectively. This compares with S1 values of 43.3+/- 10.0 min (-1).nmol(-1).ml for normal subjects. CONCLUSIONS: This patient had near-normal S1 and CP levels, but she was unable to discontinue insulin therapy, suggesting that other factors are critical. Despite this, she maintained normal or near-normal glycated hemoglobins, indicating metabolic benefit from the islet transplant.
Assuntos
Peptídeo C/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/cirurgia , Insulina/uso terapêutico , Transplante das Ilhotas Pancreáticas , Transplante de Rim , Adulto , Glicemia/metabolismo , Nefropatias Diabéticas/cirurgia , Feminino , Seguimentos , Humanos , Terapia de Imunossupressão , Insulina/sangueRESUMO
One hundred thirty-six patients with multiple sclerosis and several control groups were studied for measles antibodies using several different antigens. Measles antibodies were higher in the multiple sclerosis population, but siblings also had higher titers than matched and random controls. The elevation in antibody titers (complement fixation) was found in female multiple sclerosis patients and male patients with HL-A types 3, 7, and W-18. Male patients not carrying these HL-A antigens had, as a group, relatively normal antibody levels. These data confirm a familial factor in elevated measles antibody titers. We suggest that HL-A antigens are linked to one of the factors that determines measles antibody titers in multiple sclerosis patients.
Assuntos
Anticorpos Antivirais/análise , Antígenos HLA/análise , Antígenos de Histocompatibilidade/análise , Sarampo/imunologia , Esclerose Múltipla/imunologia , Fatores Etários , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores SexuaisRESUMO
The effect of cyclosporine (CsA) on the in vivo cell-mediated immune response to donor antigens was examined sequentially following cadaveric renal transplantation in both immunologically naive and specifically sensitized allograft recipients. Cytotoxic T lymphocytes (CTL) exhibiting preferential specificity for donor antigens were detected in the peripheral blood of all patients receiving azathioprine (AZA) immunosuppression by two weeks posttransplant, disappearing progressively over the first three months with clinical quiescence. In contrast, the generation of donor-reactive CTL was significantly diminished in incidence (P = 0.05) and in magnitude (P = 0.004) in subjects receiving CsA. CTL were detected in only 36% of patients by two weeks posttransplant, and were not detectable in any CsA-treated patient after the sixth posttransplant week. The ability of CsA to inhibit clonal reexpansion of CTL was examined both in vitro and in vivo in subjects exhibiting prior sensitization to donor antigens. In vitro, CsA caused a dose-dependent inhibition of accelerated (72-hr MLC) CTL generation following restimulation with donor spleen cells, which was quantitatively identical to that in parallel cultures using responder PBL from non-sensitized individuals. In vivo, CsA produced a rapid disappearance of circulating CTL posttransplant in patients who exhibited specific cell-mediated sensitization to the graft donor, as evidenced by the presence of circulating donor-reactive CTL prior to transplantation. In contrast, in patients receiving AZA there was a rapid increase in donor-reactive CTL in the peripheral blood following transplantation. CTL persisted for six weeks or longer, and two of four patients lost the graft to irreversible acute rejection within the first four weeks.
Assuntos
Ciclosporinas/farmacologia , Citotoxicidade Imunológica/efeitos dos fármacos , Transplante de Rim , Ativação Linfocitária/efeitos dos fármacos , Linfócitos T Citotóxicos/imunologia , Azatioprina/farmacologia , Testes Imunológicos de Citotoxicidade , Rejeição de Enxerto/efeitos dos fármacos , Humanos , Distribuição Aleatória , Linfócitos T Citotóxicos/efeitos dos fármacosRESUMO
Cyclosporine extends kidney allograft survival in the chacma baboon, and this study explores various administration protocols to generate optimal serum concentrations of the drug, assessed by radioimmunoassay and by inhibition of lymphocyte transformation by phytohemagglutinin and allogeneic lymphocytes in culture. Serum levels commensurate with concentrations that have been shown to be immunosuppressive in humans (150-400 ng/ml) are reached after 14 days of pretreatment with 10 mg cyclosporine/kg, and after 7 days with 20 and 30 mg cyclosporine/kg. The 10-mg dose prolongs median graft survival from 11 to 21 days, which is the same as that obtained with 20 mg/kg administered after transplantation. Further increases in the pretreatment dose to 20 or 30 mg/kg result in survivals of 27 and 31 days, respectively. All the animals died from rejection during therapy and the T-cell-binding avidity, and absorptive or degradative processes may necessitate doses far in excess of those currently used in transplantation.
Assuntos
Ciclosporinas/administração & dosagem , Sobrevivência de Enxerto/efeitos dos fármacos , Transplante de Rim , Absorção , Animais , Ciclosporinas/sangue , Relação Dose-Resposta a Droga , Feminino , Terapia de Imunossupressão/métodos , Ativação Linfocitária/efeitos dos fármacos , Teste de Cultura Mista de Linfócitos , Masculino , Papio , Fito-Hemaglutininas/farmacologiaRESUMO
The effect of the new immunosuppressant cyclosporine on survival after total small intestinal allotransplantation (TSIA) was studied in a canine model. Successful TSIA was performed in 34 dogs. Eleven dogs were treated with cyclosporine, 25 mg/kg/day i.m., starting the day before the operation and continuing for four weeks. Thereafter the same dose was given orally. Thirteen dogs were given oral cyclosporine only, 25 mg/kg/day from the day after transplantation. Ten dogs served as controls. The dogs treated with intramuscular and oral cyclosporine survived a mean of 103.8 +/- 39.4 days (mean +/- S.E.M.). The longest survivor died after 432 days. Survival in this group was significantly longer than that of the control dogs, which survived 12.5 +/- 4.6 days. The orally treated dogs survived 30.4 +/- 7.6 days. All control dogs, and seven of the orally treated dogs, but only two of the intramuscularly treated dogs, died of acute rejection. It is concluded that cyclosporine is effective in prolonging survival after TSIA in the dog and reduces the incidence of acute rejection.
Assuntos
Ciclosporinas/farmacologia , Sobrevivência de Enxerto/efeitos dos fármacos , Intestino Delgado/transplante , Animais , Ciclosporinas/uso terapêutico , Cães , Doença Enxerto-Hospedeiro/prevenção & controle , Terapia de Imunossupressão , Complicações Pós-Operatórias/patologia , Fatores de TempoRESUMO
T-cell subsets in the peripheral blood were analyzed using monoclonal antibodies during the development of experimental allergic neuritis in Lewis rats. Percentages of helper and suppressor cells and ratios of helper/suppressor cells did not exceed normal limits during the development of the disease.
Assuntos
Neurite Autoimune Experimental/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Reguladores/imunologia , Animais , Modelos Animais de Doenças , Contagem de Leucócitos , Masculino , Neurite Autoimune Experimental/patologia , Ratos , Ratos Endogâmicos Lew , Fatores de TempoRESUMO
Cyclosporine (Cy) was given to BB rats in an attempt to prevent the onset of diabetes. A dose of 15 to 20 mg/kg/d given orally or subcutaneously was associated with high Cy trough serum levels and caused nephrotoxicity and severe weight loss. Ten mg/kg/d of Cy was tolerated well. Forty rats were treated with Cy starting at 34 days of age. No Cy-treated rats developed diabetes by day 121, compared with 70% of the control rats. Once Cy was discontinued on day 121, 38% of female and 13% of male rats developed diabetes by day 169. Transient, spontaneously remitting hyperglycemia developed in nine rats. This occurred both in control rats and in rats on Cy, but it was more common in females than in males. Thus, Cy prevents diabetes mellitus in the BB rat when trough Cy serum levels greater than 100 ng/mL are achieved. Diabetes occurs in some rats after Cy is discontinued. In all treatment subgroups, diabetes occurred more frequently in females than in males.
Assuntos
Ciclosporinas/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Ratos Endogâmicos/metabolismo , Animais , Ciclosporinas/toxicidade , Diabetes Mellitus Experimental/imunologia , Diabetes Mellitus Experimental/prevenção & controle , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/prevenção & controle , Feminino , Cinética , Fígado/metabolismo , Masculino , Ratos , Ratos Endogâmicos/imunologia , Fatores SexuaisRESUMO
Technological and immunological developments within the last decade have evolved a variety of therapeutic modalities by which ESRD may be satisfactorily managed. With the exception of renal transplantation between identical twins, none of these modalities provide permanent and complete correction of the uremic state, however, and the challenge now facing those involved in the management of irreversible renal failure is to devise an individualized treatment program permitting optimal long-term physical and psychological well-being and the maintenance of a valuable and productive role in society. Such a goal is most effectively achieved by an integrated approach combining both dialysis and renal transplantation. In the program proposed and utilized at our institution, all therapeutic options are presented to the patient with incipient renal failure, and a rational long-term management strategy devised based on clinical status, psychological stability, convenience, and acceptability. Dialysis is normally employed as a limited term maintenance procedure pending renal transplantation from a living or cadaver donor, thus permitting optimal correction of the uremic state. Early rehabilitation and social reintegration are actively pursued to minimize disease impact and maximize quality of life. In subjects with chronic deterioration of graft function, retransplantation may be performed prior to requirement for dialysis, thus minimizing hospitalization time, cost, and social disruption. The definition of risk factors predicting graft success has facilitated the individualization of therapy within this integrated program. While allograft survival exceeding 90% may now be anticipated in the non-sensitized first-graft recipient, predicted outcome is poor in subjects who are highly sensitized following previous transplantation or with rapid loss of a prior graft.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Falência Renal Crônica/terapia , Transplante de Rim , Diálise Renal , Sobrevivência de Enxerto , Humanos , Falência Renal Crônica/imunologia , PrognósticoRESUMO
Brequinar sodium (BQR), a substituted 4-quinoline carboxylic acid, was in clinical development in combination with cyclosporine (CsA) as a potentially effective therapy for the treatment and prophylaxis of rejection in organ transplant patients. This phase I study was performed in stable renal, hepatic, and cardiac transplant patients receiving CsA and prednisone maintenance therapy for immunosuppression. The pharmacokinetic objectives of this study were to characterize the pharmacokinetics of (a) single oral 0.5- to 4-mg/kg doses of BQR when given in combination with CsA and prednisone to stable renal, hepatic, and cardiac transplant patients and (b) steady-state oral doses of CsA, with and without single oral doses of BQR. In all three patient populations, the pharmacokinetics of BQR were characterized by a lower oral clearance (12-19 mL/min) than that seen in previous studies in patients with cancer (approximately 30 mL/min at similar doses) and a long terminal half life (13-18 hrs). This slower oral clearance for BQR could be due either to a drug interaction between BQR and CsA or to altered clearance or metabolic processes in patients with transplants. Steady-state CsA trough levels and the oral clearance of CsA were not affected by BQR coadministration. Among the three transplant populations, the cardiac transplant patients had lower oral clearance values of BQR and of CsA. The cause of this lower clearance is not known. Safety results indicate that BQR was well tolerated by this patient population.
Assuntos
Compostos de Bifenilo/farmacocinética , Transplante de Coração/fisiologia , Imunossupressores/farmacocinética , Transplante de Rim/fisiologia , Transplante de Fígado/fisiologia , Administração Oral , Adulto , Idoso , Compostos de Bifenilo/sangue , Ciclosporina/sangue , Ciclosporina/farmacocinética , Feminino , Humanos , Imunossupressores/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
In our study of multiple sclerosis (MS) patients we have found significant increases in the A3, B7, and DW2 antigens. We have also studied immune responses in these same patients. There was elevation of measles antibodies in MS patients positive for A3, B7, and B18 as compared to MS patients without those antigens. The first study of mitogen responsiveness (31 patients) showed a decreased response in A3, and B7 positive patients. Study of a second and a larger group (62 patients), at a different time, failed to confirm this deficiency. We propose that there is a genetically linked (HLA) T cell deficiency in some MS patients and that this deficiency results in high humoral responses to measles antigens and an evanescent (or cyclical) reduced T cell response to mitogen.
Assuntos
Anticorpos Antivirais/análise , Antígenos HLA/análise , Antígenos de Histocompatibilidade/análise , Vírus do Sarampo/imunologia , Mitógenos/farmacologia , Esclerose Múltipla/imunologia , HumanosRESUMO
The current status of bone marrow transplantation is reviewed. The diseases that are treatable with marrow transplantation, the basic transplant procedure, and the potential complications of marrow transplantation are discussed in detail. The future application of marrow transplantation to additional disease processes is considered.
Assuntos
Falência Renal Crônica/terapia , Transplante de Rim , Sistema ABO de Grupos Sanguíneos/imunologia , Doença Aguda , Cadáver , Doença Crônica , Rejeição de Enxerto , Antígenos HLA/imunologia , Humanos , Terapia de Imunossupressão , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/etiologia , Monitorização Fisiológica , Educação de Pacientes como Assunto , Doadores de TecidosRESUMO
The histocompatibility antigens (HL-A) have been determined in 100 multiple sclerosis (M.S.) patients and 140 randomly selected controls. In the M.S. group there was a statistically significant increase in the frequency of HL-A 7 and W 18 with an insignificant increase in HL-A 3. The variance from normal HL-A patterns in the M.S. population may play some role in establishing the substrate for this disease. Studies in experimental animals have shown that susceptibility to autoimmune disease and to virus infection is linked to the major histocompatibility locus. This has interesting implications for both the "slow virus" and the "autoimmune" theories of the etiology of multiple sclerosis.
Assuntos
Antígenos HLA , Antígenos de Histocompatibilidade , Esclerose Múltipla/imunologia , Doenças Autoimunes , Humanos , Esclerose Múltipla/etiologia , Poliomielite/complicaçõesRESUMO
Published medical and psychological evidence now available strongly supports the widening of donor sources to include the emotionally related donor. Irrespective of the benefit conferred by a living related over an unrelated donor, it now seems indefensible to refuse the donation of a kidney from an emotionally related individual to a recipient who meets the required criteria. An absence of other donor sources, the existence of preformed antibodies, or priority on the transplant list all seem to us to be compelling reasons to consider the use of the emotionally related donor. This is especially true when the psycho-social assessment reveals a true volunteer who is likely to derive psychological benefit from the donation and where "donation consensus" exists within the family.
Assuntos
Transplante de Rim , Doadores de Tecidos/psicologia , Altruísmo , Canadá , Custos e Análise de Custo , Emoções , Ética Médica , Histocompatibilidade , Humanos , Consentimento Livre e Esclarecido , Legislação Médica , RiscoRESUMO
Rejection in non-identical pairs is both antibody- and cell-mediated. Measurements of CDC and LMC specific for the donor can be useful clinical tools in confirming rejection, detecting periods of likely rejection, and helping to predict responses to therapy. In particular, the LMC assay appears to have excellent temporal correlations with graft status. Rejection in the HLA-identical sibling transplant is directed against a non-MHC antigen, is cell-mediated, and can be typed for using CTL.
Assuntos
Rejeição de Enxerto , Imunologia de Transplantes , Anticorpos , Citotoxicidade Celular Dependente de Anticorpos , Proteínas do Sistema Complemento/fisiologia , Testes Imunológicos de Citotoxicidade , Endotélio/imunologia , Antígenos HLA/análise , Humanos , Imunidade Celular , Fragmentos Fc das Imunoglobulinas , Teste de Inibição de Aderência Leucocítica , Ativação Linfocitária , Linfócitos/imunologia , Fatores Inibidores da Migração de Macrófagos/análise , Mitógenos , Formação de RosetaRESUMO
Thirty-one MS patients were studied for their in vitro response to lymphocyte mitogens. Patients with HLA antigens A3 and/or B7 had lower mean peak responses to all three mitogens compared to A3, B7-negative patients. The difference in the mean peak responses to Con A were significantly different at a level of p less than 0.05. This supports the concept of a histocompatibility-linked T-cell deficiency in many patients with MS.
Assuntos
Antígenos HLA/análise , Antígenos de Histocompatibilidade/análise , Mitógenos , Esclerose Múltipla/imunologia , Humanos , Ativação Linfocitária , Depleção Linfocítica , Linfócitos T/imunologiaRESUMO
Sixty-nine patients receiving Cs after cadaveric or LRD renal transplants were randomly allocated to receive prednisone or no prednisone beginning on the day of transplant. There were 36 in the prednisone group and 33 in the group assigned to no prednisone. Of these latter, only seven (21%) never received prednisone and an additional four had one short course for rejection episodes (11%). Of the remaining 22 who were placed on continuous steroids, only 12 met rejection criteria and either some or all of the remainder probably had Cs nephrotoxicity. The patient and graft survival were better but not statistically so in the no-prednisone group (97% v 89%) and (88% v 78%), and the number of infections was only half that of the prednisone-treated group (22% v 42%). A policy of withholding steroids except for rejection episodes does not prejudice graft or patient survival in Cs-treated patients.