Biomedical subjects

M R First

Publications and source records attributed to M R First.

At least 19 recordsLinked to original sources

PubMed1998

Results of the double-blind, randomized, multicenter, phase III clinical trial of Thymoglobulin versus Atgam in the treatment of acute graft rejection episodes after renal transplantation.

BACKGROUND: Thymoglobulin, a rabbit anti-human thymocyte globulin, was compared with Atgam, a horse anti-human thymocyte globulin for the treatment of acute rejection after renal transplantation. METHODS: A multicenter, double-blind, randomized trial with enrollment stratification based on standardized histology (Banff grading) was conducted. Subjects received 7-14 days of Thymoglobulin (1.5 mg/kg/ day) or Atgam (15 mg/kg/day). The primary end point was rejection reversal (return of serum creatinine level to or below the day 0 baseline value). RESULTS: A total of 163 patients were enrolled at 25 transplant centers in the United States. No differences in demographics or transplant characteristics were noted. Intent-to-treat analysis demonstrated that Thymoglobulin had a higher rejection reversal rate than Atgam (88% versus 76%, P=0.027, primary end point). Day 30 graft survival rates (Thymoglobulin 94% and Atgam 90%, P=0.17), day 30 serum creatinine levels as a percentage of baseline (Thymoglobulin 72% and Atgam 80%; P=0.43), and improvement in posttreatment biopsy results (Thymoglobulin 65% and Atgam 50%; P=0.15) were not statistically different. T-cell depletion was maintained more effectively with Thymoglobulin than Atgam both at the end of therapy (P=0.001) and at day 30 (P=0.016). Recurrent rejection, at 90 days after therapy, occurred less frequently with Thymoglobulin (17%) versus Atgam (36%) (P=0.011). A similar incidence of adverse events, post-therapy infections, and 1-year patient and graft survival rates were observed with both treatments. CONCLUSIONS: Thymoglobulin was found to be superior to Atgam in reversing acute rejection and preventing recurrent rejection after therapy in renal transplant recipients.

Acute Disease↗

PubMed1998

Utility of standardized histological classification in the management of acute rejection. 1995 Efficacy Endpoints Conference.

BACKGROUND: Standardized histological grading of transplant kidney biopsies has become a primary criterion for diagnosis of rejection in immunosuppression clinical trials. METHODS: A consortium of 19 transplant centers from North America, Europe, and Australia convened in 1995 to examine kidney transplant rejection. Data from the 1995 Efficacy Endpoints Conference were examined for frequency of adoption of Banff schema. Biopsy grading was correlated with clinical parameters of rejection and therapy response. RESULTS: Histological confirmation of rejection episodes occurred in 73% of 953 cases, with Banff criteria adoption increasing in frequency between 1992 and 1995. Banff grading significantly correlated with clinical rejection severity (rejection creatinine: grade I, 2.8+/-0.2 mg/dl; grade II, 3.5+/-0.2 mg/dl; grade III, 4.1+/-0.3 mg/dl; P < 0.001), although nadir creatinines were similar. Response rates of Banff grades I and II to steroid therapy were not different, but only 42% of grade III rejections responded to steroids (P < 0.003. Banff grading also correlated with postrejection creatinine, day 15: grade I, 2.2+/-0.2 mg/dl; grade II, 3.0+/-0.2 mg/dl; grade III, 3.8+/-0.4 mg/dl (P < 0.001), and day 30: grade I, 2.1+/-0.1 mg/dl; grade II, 2.2+/-0.2 mg/dl; grade III, 2.7+/-0.2 mg/dl (P < 0.06). Banff grade III correlated with reduced graft survival at 1 year: grade I, 86%; grade II, 88%; grade III, 70% (P < 0.01). CONCLUSIONS: This multicenter review of rejection severity confirms that standardized histologic classifications such as the Banff schema provide a reliable means for stratifying patient risk of treatment success or failure. These data support the use of Banff criteria in clinical trial design.

Acute Disease↗

PubMed1998

Economic costs of expanded criteria donors in renal transplantation.

BACKGROUND: The organ shortage has increased interest in the use of "expanded criteria" donors (ECDs). Although much has been written concerning the clinical outcomes associated with the use of such donors, little has been published concerning the financial results associated with their use. METHODS: A retrospective cost identification study of recipients of kidneys from expanded criteria cadaveric donors was used. RESULTS: Of a total of 78 cadaveric renal transplants in fiscal year 1995, there were 38 kidneys (49%) transplanted from ECDs. Graft survival at 1 year was not statistically different between patients who received kidneys from ECDs and those who received non-ECD kidneys (84% vs. 85%, respectively). Length of stay (P < 0.05), serum creatinine at 1 year after transplantation (P < 0.01), and the percentage of patients requiring hemodialysis (P < 0.05) were all higher among patients who received kidneys from ECDs. Cold ischemic time was significantly longer in patients who received kidneys from ECDs (31.4+/-12 hr vs. 24.0+/-9 hr; P < 0.05). The total average and median costs were $12,190 and $10,911 higher in recipients of kidneys from ECDs as compared with non-ECD controls (P < 0.01). Stepwise linear regression demonstrated that length of stay was the major clinical determinant of total costs; only the use of antilymphocyte induction was otherwise significantly associated. When kidneys from ECDs were transplanted into "high-risk" recipients (age > 60 or retransplant patient), the average total costs were $15,311 more than when kidneys from ECDs were transplanted into non-high-risk patients (n=16 and 21, respectively; P < 0.05) and $20,680 more than when a non-ECD, non-high-risk pairing was undertaken (n=26; P < 0.05). CONCLUSIONS: Kidney transplantation with organs from ECDs is significantly more expensive than with organs from non-ECDs, even in the face of similar graft survival rates. Further study is needed to determine the cost-effectiveness of renal transplantation utilizing kidneys from ECDs vis-a-vis hemodialysis.

Adult↗

PubMed1998

Improved cyclosporine pharmacokinetics in maintenance renal transplant recipients converted to cyclosporine for microemulsion.

BACKGROUND: Variability in cyclosporine drug exposure of > or = 20% has been shown to be a risk factor for the development of chronic renal allograft rejection. We tested the hypothesis that a cyclosporine microemulsion (CsA-ME) would result in reduced variability in stable maintenance renal transplant patients when compared with the original formulation of cyclosporine (CsA). METHODS: The 31 maintenance renal transplant recipients were part of a multicenter, randomized, double-blind, prospective study comparing the CsA formulation with the CsA-ME formulation. Pharmacokinetics analyses were performed at two centers 1, 4, 12, and 52 weeks after patients were randomized to continue receiving CsA or to convert to CsA-ME. RESULTS: The means of the week 1-, 4-, and 12-week areas under the concentration-time curves (AUC), and Cmax were significantly higher and the Tmax was significantly shorter in those patients converted to CsA-ME than in those remaining on CsA. There was no correlation between change in AUC after conversion and change in serum creatinine. The coefficient of variation values for dose-adjusted AUC, expressed as a percentage (%CVAUC), were lower in CsA-ME patients than CsA patients after both 12 and 52 weeks. Over the initial 12 weeks. %CVAUC values of < or = 20% were seen in a significantly greater proportion of CsA-ME patients than CsA patients. CONCLUSIONS: Conversion of maintenance renal transplant recipients from CsA to CsA-ME resulted in improved absorption of cyclosporine. The CsA-ME formulation resulted in long-term reduction in the variability of cyclosporine exposure and more consistent pharmacokinetics.

Adult↗

PubMed1998

Early operative intervention for urologic complications of kidney-pancreas transplantation.

Bladder drainage of exocrine secretions during pancreas transplantation can be associated with significant complications. We present a proactive approach to these complications consisting of early cystoenteric conversion (CEC). Although 81 patients underwent pancreas transplant between March 1985 and May 1995; 26 (32%) required CEC. Complications presented as urine leaks, other complications, and refractory metabolic acidosis. There were 13 patients who presented with a urine leak: 12 with acute abdominal pain, and 1 asymptomatic. Serum amylase and creatinine rose a mean of 823 IU and 0.61 mg/dl, respectively. The interval to CEC ranged from 2 to 45 months. One patient died of fungal sepsis. Postoperative complications included duodenojejunal anastomotic bleed (n = 1), negative relaparotomy (n = 1), myocardial infarction (n = 1), graft pancreatitis (n = 1), and wound infection (n = 1). Twelve patients presented with other complications: three women with cystitis (n = 2) or hematuria (n = 1), and nine men with urethritis (n = 6), scrotal edema (n = 2), or dysuria (n = 1), The interval to conversion ranged from 1 to 108 months. There were no deaths. One patient required relaparotomy for anastomotic bleed. One patient was converted because of refractory metabolic acidosis. Admissions and inpatient days were significantly reduced. Overall mortality was 3.8%, morbidity 23.1%, and graft salvage rate 96.1%. Leak-associated mortality was 7.7%, morbidity 38.5%, and graft salvage rate 92.3%. For other complications the mortality was 0, morbidity 7.7%, and graft salvage rate 100%. CEC is a safe, effective treatment for urologic complications of pancreas transplantation. Morbidity and mortality were acceptable; admissions and hospital days were decreased. Early CEC results in superior outcomes and improved quality of life. It is preferable to nondefinitive measures for management of urologic complications of pancreatic transplantation.

Adult↗

PubMed1998

Clinical application of immunosuppressive agents in renal transplantation.

The availability of a number of new immunosuppressive drugs has resulted in significant improvements in the outcome of kidney transplantation. Currently 1-year graft survival rate for cadaver kidney transplants is approximately 85%. A number of new agents are presently in clinical studies. This article reviews the currently available agents and examines various aspects of induction and maintenance immunosuppressive therapy, and the treatment of acute rejection episodes. In addition, the agents currently in clinical trials and future directions in immunosuppressive therapy are discussed.

Acute Disease↗

PubMed1998