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D M Canafax

Publications and source records attributed to D M Canafax.

At least 91 records · Page 5Linked to original sources
PubMed1987

Recent advances in solid organ transplantation.

Advances in organ transplantation have come rapidly and consistently in recent years as the result of improved surgical techniques and immunosuppressive drug therapies. Experience gained in renal transplantation over the past 30 years has made this a standard therapeutic approach for treating chronic renal failure. This knowledge has been successfully applied to the transplantation of other organs to produce steadily increasing survival rates and improved quality of life. This article reviews the advances that have been made in solid organ transplantation and immunosuppressive drug therapy.

Heart Transplantation↗
PubMed1987

Monoclonal antilymphocyte antibody (OKT3) treatment of acute renal allograft rejection.

Recent advances in immunosuppressive therapy have dramatically improved the survival rates for recipients of organ allografts by reducing the frequency of rejection. Cyclosporine, azathioprine, and prednisone for immunoprophylaxis are especially effective. When rejection occurs, the treatment usually includes high doses of oral or intravenous corticosteroids, antilymphocyte globulin, or antithymocyte globulin. A new monoclonal antilymphocyte antibody, OKT3, promises to improve allograft survival rates further.

Antibodies, Monoclonal↗
PubMed1987

The therapeutic use of azathioprine in renal transplantation.

This review discusses the pharmacokinetics, mechanism of action, clinical use, toxicities, drug interactions, and possible approaches for therapeutic monitoring of azathioprine (AZA). The drug has been used extensively in posttransplant immunosuppressive protocols. Its therapeutic use is hampered by the development of toxicities, however, especially leukopenia, which is a common criterion for dosage adjustment. Azathioprine is rapidly converted in the liver and erythrocytes to 6-mercaptopurine (6MP), which is eventually metabolized to inactive 6-thiouric acid (6TU). The terminal half-lives of AZA and 6MP are 50 and 74 minutes, respectively. While renal dysfunction does not alter the disposition of AZA, hepatic insufficiency attenuates the pharmacologic activity. Immunosuppression depends on the formation of active intracellular thiopurine ribonucleotides, although AZA itself may block antigen recognition. Individualization of AZA regimens by determining tissue concentrations of thioguanine nucleotides, and plasma concentrations of AZA, 6MP, or 6TU may improve the risk:benefit ratio.

Azathioprine↗
PubMed1987

The impact of cyclosporine and combination immunosuppression on the incidence of posttransplant diabetes in renal allograft recipients.

The incidence of posttransplant diabetes mellitus (PTDM) was compared in three groups of renal transplant recipients: nondiabetic patients who had been randomized between 1980 and 1983 to receive antilymphoblast globulin (ALG), azathioprine (AZA), and prednisone (P) (group 1) or cyclosporine (CsA) plus prednisone (group 2). Group 3 consisted of a more recent (1984-85) cohort who were given a combination of azathioprine, cyclosporine, and prednisone (+/- ALG). PTDM developed in 20 of 173 previously nondiabetic 18-55-year-old patients. Three of 47 patients (6.4%) in group 1, 4 of 58 patients (6.9%) in group 2, and 13 of 68 patients in group 3 (19.1%) developed PTDM. Thus in the two groups composing the concurrent prospective randomized trial (groups 1 and 2) the incidence of PTDM did not differ. The subsequent patients who were given a combination of ALG, azathioprine, cyclosporine, and prednisone developed a significantly greater incidence of PTDM even though the total dose of cyclosporine and prednisone were lower than in groups 1 and 2. PTDM usually occurred within two months of transplantation, and 11 of 17 patients who initially required insulin are still dependent upon exogenous insulin. The incidence of PTDM was not significantly affected by sex of the recipient, HLA-type, primary renal disease, rejection episodes, primary vs. secondary transplant, or prior splenectomy. The incidence of PTDM is greater in patients older than 45 (34.2% vs. 5.2%), and heavier than 70 kg (21.1% vs. 5.1%); in recipients of cadaveric allografts (15.7% vs. 4.6%); and in patients who were hospitalized for infections (22.4% vs. 4.7%). CsA levels tended to be higher in the group 2 and 3 patients who developed PTDM than in those who remained nondiabetic. One-year actuarial patient survival in those with PTDM was 83.3% vs. 98% (P less than .01) in the nondiabetic and graft survival was 77.1% vs. 87.1% (NS). The combination of Minnesota ALG, azathioprine, cyclosporine, and prednisone appears to predispose older, heavier recipients of cadaver allografts to the development of PTDM. The risk of PTDM must be weighed against the more usual results of improved patient and graft survival using this combination of immunosuppression.

Adult↗
PubMed1987

Renal transplantation at the University of Minnesota during the 1980s.

1. There have been 1,225 renal allografts performed at the University of Minnesota between January 1, 1980 and May 31, 1987. Significant risk factors for graft survival include donor type, retransplantation, and age at time of transplant. In addition, diabetes is a significant risk factor in patient survival. 2. Three immunosuppressive regimens have been used during this time period: AZA + P + ALG, CsA + P, and CsA + AZA + P (+ ALG for CAD grafts). The 3 protocols have been received by 411, 205, and 356 primary renal allograft recipients, respectively. No overall differences between the therapies exist with respect to graft or patient survival. However, females, recipients of CAD organs (especially the recipient with diabetes), and patients 18-50 years of age at transplant have improved graft survival results using CsA + AZA + P (+ ALG). Females and the 18-50-year-old recipients also have improved results with respect to patient survival. 3. The 3 protocols [AZA + P + ALG; CsA + P; and CsA + AZA + P + ALG] have been used for 125, 112, and 174 primary recipients of CAD organs, respectively. Recipients of CsA + AZA + P + ALG have significantly better graft survival overall in the diabetic and poorly matched subgroups. Other high-risk (but small sample size) subgroups show statistically nonsignificant, but clinically important, improvements. These groups include patients over 50 years of age, patients with preformed antibodies, as well as those with compatible ABO blood types. Similar trends exist with respect to patient survival. 4. Risk factor analysis of all patients receiving CsA + AZA + P (+ ALG) indicates that donor type, retransplantation, and age at the time of transplant are still serious risk factors for graft survival. Only age at transplant influences patient survival significantly. 5. The failure to find any significant risk factors in primary recipients of CAD organs in the CsA + AZA + P(+ ALG) era, combined with the generally consistent good graft and patient survival rates, suggest that the traditionally high-risk patient can be successfully transplanted with excellent results. 6. Pediatric patients can be successfully transplanted with results equivalent to 18-50-year-old patients and better than those recipients over 50 years of age at the time of transplant. Random transfusions and combination therapy are at least as good as DST and AZA + P + ALG.

Adolescent↗
PubMed1986

The effects of delayed function on recipients of cadaver renal allografts. A study of 158 patients randomized to cyclosporine or ALG-azathioprine.

We randomized 158 recipients of cadaver renal allografts to cyclosporine-prednisone (83) or antilymphocyte globulin-azathioprine-prednisone (75) to evaluate: the effects of immunosuppression and pretransplant risk factors on the incidence of delayed graft function, the effects of immunosuppression on the resolution of delayed graft function, and the effects of delayed graft function and pretransplanted risk factors on patient and graft survival. Cyclosporine did not increase the incidence of delayed graft function, compared with ALG-azathioprine-treated patients (33% versus 27%, P = 0.550) but doubled the mean (+/- SD) duration of oliguria (11.8 +/- 11.0 versus 5.9 +/- 3.2 days, P = 0.002) and the number of required dialyses (6.6 +/- 7.6 versus 3.2 +/- 1.3, P = 0.031). Retransplanted patients had a higher incidence of delayed graft function that recipients of primary grafts in both the cyclosporine (82% versus 25%, P = 0.001) and ALG-azathioprine (55% versus 22%, P = 0.025) treatment groups. The presence of delayed function reduced one-year graft survival from 89% in all patients without delayed function to 72% (P = 0.011) in all patients with delayed function. Cyclosporine-treated patients had a slightly, but not significantly better one-year graft survival rate than ALG-azathioprine treated patients both with (73% versus 68%, P = 0.750) and without (92% versus 82%, P = 0.069) delayed graft function. A preservation time longer than 24 hr did not increase the incidence of delayed graft function in cyclosporine-treated patients (34% versus 32%, P = 0.811) or ALG-azathioprine-treated patients (27% versus 27%, P = 0.902). Cyclosporine-treated patients given kidneys with greater than 24 hr of preservation time had reduced graft survival only when delayed graft function occurred (67% versus 92%, P = 0.009). In conclusion, (1) cyclosporine did not increase the incidence of delayed graft function over ALG-azathioprine treatment; (2) cyclosporine did significantly slow recovery of kidneys with delayed function; (3) delayed graft function correlated with poorer graft survival rate in both treatment groups; but (4) prolonged preservation time did not increase the incidence of delayed graft function or reduce graft survival.

Actuarial Analysis↗
PubMed1986

Cyclosporine monitoring.

Cyclosporine is an important immunosuppressive agent in organ and bone marrow transplantation. The pharmacokinetics of cyclosporine are quite complex and are complicated by the availability of two assay systems that yield differing results. This article summarizes the views from two major solid organ transplant centers and one bone marrow transplant center on important cyclosporine monitoring questions. A general consensus exists in the four areas discussed that: cyclosporine concentrations must be monitored due in part to the extreme variability in kinetics, either blood or plasma can be used in monitoring programs, the radioimmunoassay or high pressure liquid chromatography can be used in routine monitoring, and the interpretation of cyclosporine concentrations must be performed in relation to patient variables that affect drug response and toxicity.

Cyclosporins↗
PubMed1985

Results of the Minnesota randomized prospective trial of cyclosporine versus azathioprine-antilymphocyte globulin for immunosuppression in renal allograft recipients.

Between September 26, 1980 and June 8, 1984, 246 splenectomized, transfused renal allograft recipients were randomized to treatment with either cyclosporine (CsA)-prednisone (n = 131) or azathioprine (Aza)-prednisone-antilymphocyte globulin (n = 115). On December 31, 1984, actuarial patient survival rates at three years were 89% in the CsA group and 90% in the Aza group, and the corresponding graft survival rates were 82% and 79% (statistically insignificant differences). The results were also compared separately in diabetic and nondiabetic patients and in recipients of related and cadaver donor grafts; only in the subgroup of diabetic recipients of cadaver kidneys were the differences in graft survival rates significantly different between CsA- and Aza-treated patients. The incidence of posttransplant acute tubular necrosis was similar in CsA- and Aza-treated patients (33% v 27%), but the duration was significantly longer in CsA- than in Aza-treated recipients (15.7 +/- 18.4 v 7.7 +/- 3.0 days). Rejection episodes and infections (particularly CMV) occurred significantly less frequently in CsA- than in Aza-treated patients. Mean serum creatinine levels were significantly higher in CsA- than in Aza-treated recipients (2.0 +/- 0.6 v 1.5 +/- 0.5 mg/dl). Treatment of hypertension and hyperkalemia was required significantly more frequently in the CsA-treated patients than in the Aza-treated patients. Initial mean hospitalization time was significantly shorter in the CsA group than in the Aza group (15.6 +/- 9.5 v 19.8 +/- 10.7 days). In the CsA group, 19% of the patients were switched to Aza and 35% had Aza added to their regimen with a concomitant lowering of the CsA dose because of nephrotoxicity. The results of our randomized trial are at variance with those of others in that the graft survival rates in our trial were not different between CsA and Aza-treated patients, primarily because our conventionally-treated patients had a higher graft survival rate than in the other trials. The advantages of CsA (fewer rejection episodes, fewer infections, shorter hospitalization) outweigh the disadvantages (higher serum creatinine, more hypertension), and thus we believe it should be used in most renal allograft recipients, perhaps in combination with Aza so that a lower dose of CsA can be used and the side effects minimized--a regimen that we are currently evaluating.

Adolescent↗