Neoral-to-Gengraf conversion in renal transplant recipients.

OBJECTIVE: Our objective was to evaluate the safety, efficacy, and need for dosage adjustments when patients taking the Neoral formulation of cyclosporine are converted to the generic formulation, Gengraf. METHODS: From September 2001 through January 2002, patients receiving follow-up care in the renal transplant clinic at the VA Tennessee Valley Healthcare System were converted from Neoral to Gengraf based on a 1:1 dosing equivalency. Steady-state cyclosporine trough concentrations were obtained both prior to and following Neoral-to-Gengraf conversions. Patients were also monitored for changes in serum creatinine, hospitalization, cyclosporine toxicity, graft rejection, and need for further adjustment in cyclosporine regimen. RESULTS: Forty-one patients were included in data analysis. There were no differences in cyclosporine concentrations (P =.0853) or serum creatinine (P =.4469) following conversion to Gengraf. There were no reports of cyclosporine toxicity, no episodes of graft rejection, and no need for further dose adjustment related to the generic conversion. CONCLUSIONS: Neoral and Gengraf are therapeutically equivalent cyclosporine formulations, such that renal transplant recipients maintained on Neoral can be safely and effectively converted to the Gengraf formulation based on a 1:1 conversion ratio. The use of Gengraf over Neoral within the Veterans Affairs Healthcare System offers a reduced cost alternative but maintains equal efficacy and outcomes.

Improved flow cytometric detection of HLA alloantibodies using pronase: potential implications in renal transplantation.

BACKGROUND: Flow cytomeric crossmatch (FCXM) has grown in popularity and has become the "standard of practice" in many programs. Although FCXM is the most sensitive method for detecting alloantibody, the B cell FCXM has been problematic. Difficulties with the B cell FCXMs have been centered around high nonspecific fluorescence background owing to Fc-receptors present on the B cells and autoantibodies. To improve the specificity and sensitivity of the B cell FCXM, we utilized the proteolytic enzyme pronase to remove Fc receptors from lymphocytes before their use in FCXM. METHODS: Lymphocytes isolated from peripheral blood, spleen, or lymph nodes were treated with pronase and then used in a three-color FCXM. A total of 167 T- and B cell FCXMs using pronase-treated and untreated cells were performed. Testing used serial dilutions of HLA allosera (22 class I and 6 class II), with the titer of each antibody at one dilution past the titer at which the complement-mediated cytotoxicity anti-human globulin crossmatch became negative. RESULTS: After pronase treatment, the actual channel values of the negative control in both T cell and B cell FCXMs declined from 78+/-10 to 57+/-4 (P<0.05) and 107+/-11 to 49+/-3 (P<0.00001), respectively. Pronase treatment resulted in improved sensitivity of the T and B cell FCXM in detecting class I antibody by 20% and 80%, respectively. In no instance was a false-positive reaction observed. In this study, pronase treatment improved the specificity of B cell FCXM for detecting class II antibodies from 75% to 100% (P=0.03). In no instance was a false-negative reaction recorded. Lastly, on the basis of these observations we re-evaluated three primary transplant recipients who lost their allografts because of accelerated rejection. One of the patients was transplanted across negative T and B cell FCXM, whereas the other two patients were transplanted across a positive T cell, but negative B cell, FCXM. After pronase treatment, T and B cell FCXMs of each patient became strongly positive, and donor-specific anti-HLA class I antibody was identi. fied in each case. CONCLUSION: Utilization of pronase-treated lymphocytes improves both the sensitivity and specificity of the FCXM.

Comparison of panel-reactive antibody levels in Caucasian and African American renal transplant candidates.

PRA levels from 58 Caucasian and 70 African American ESRD patients were compared against a panel of cryopreserved lymphocytes from 60 donors (40 Caucasian, 15 African American, 5 others) to determine whether there was significant racial influence on PRA outcome. African Americans were found to have significantly higher mean PRA levels than Caucasians (27% vs. 18%, P = 0.02). Restricting this analysis to only 1 degree transplant candidates showed predictably lower mean PRAs: 6% in Caucasians and 15% in African Americans, but the difference between the two groups remained significant (P = 0.015). The percentage of patients with PRA > or = 10% was also greater among African Americans than Caucasians (43% vs. 24%, P = 0.026). For patients not previously transplanted, the difference between these frequencies remained significant: 11% in Caucasians, 30% in African Americans (P = 0.025). Untransplanted African American patients with positive PRAs (> or = 10%) had significantly higher PRA against African American cell donors (mean = 55%) than against Caucasian cell donors (mean = 44%) (mean difference = 10.6%, P = 0.0056). African Americans were more frequently transfused than Caucasians. The percentage of patients not previously transplanted receiving 0, 1-5, and > 5 transfusions were 69%, 22%, and 9% for Caucasians and 43%, 44%, and 13% for African Americans (P = 0.03). This higher transfusion rate is the most likely contributor to the elevated PRA levels observed in African Americans.

Endemic coccidioidomycosis in Northern California. An outbreak in the Capay Valley of Yolo County.

Endemicity of coccidioidomycosis in Yolo County, outside previously known endemic areas, was confirmed by occurrence of a small epidemic. Eleven cases of clinically apparent coccidioidomycosis occurred among a group of 23 archaeology students. Eight of the cases were confirmed serologically, and three by skin test conversion alone. The specific site of exposure was an ancient Indian burial ground on Cache Creek near Brooks in the Capay Valley approximately 40 miles northwest of Sacramento.