Pretransplant Exposure to Donor HLA-DR Antigen in Random Transfusion Units and the Development of Donor Antigen-Specific Hyporeactivity

Our previous studies have shown that the in vitro assay of donor antigen-specific hyporeactivity is a useful marker for identifying solid organ transplant recipients (kidney, lung and heart) at low risk for immunologic complications (i.e., late acute rejection episodes and chronic rejection). Donor antigen-specific hyporeactivity is defined as a significantly decreased post- vs. pretransplant proliferative response to donor antigens while response to third-party controls remains unchanged. We analyzed whether exposure to the same HLA-DR antigen pretransplant via random blood transfusion and posttransplant via the transplanted organ influenced the development of hyporeactivity. Thirty previously nontransfused recipients, each receiving two 150 ml pretransplant random blood transfusions, were assessed for hyporeactivity at 1 year posttransplant. Of the 12 recipients with pretransplant exposure to kidney HLA-DR via transfusions, 6 (50%) developed hyporesponsiveness; in contrast, of the 18 recipients who were not preexposed, only 3 (15%) exhibited this form of immunomodulation. Of interest, 2 of the 3 hyporesponsive recipients who were not preexposed, received units containing HLA-DR antigens previously shown to share crossreactive epitopes with the kidney HLA-DR. In conclusion, these results suggest a increased incidence in the development of hyporeactivity in patients receiving pretransplant transfusions which share an HLA-DR antigen with the transplanted kidney.     

Examination of the role of the colloids hydroxyethylstarch, dextran, human albumin, and plasma proteins in a modified UW solution.

The delayed contralateral nephrectomy procedure (three-step) produced inconsistent results, indicating that the preserved autotransplanted kidney tends to remain unfunctional and to regenerate incompletely unless the demand for work is placed upon it. Omission of HES in UW (UW-plain) did not affect preservation success, but resulted in increased graft edema. Substitution of HES in UW with plasma (SGF-V) or albumin (MAlb) gave significantly worse results than UW-like solutions with or without synthetic colloids. Replacement of HES in UW with UMdex-70 or UMdex-500 gave nonsignificantly worse results than UW-like solutions with or without synthetic colloids. The use of UMdex-40 as the main colloid in UW cheapened the solution, equalled the preservation success of UW and UW-plain but surpassed UW-plain in edema prevention, and exceeded UW concerning recovery of graft microcirculation.     

Renal transplantation for patients 60 years of older. A single-institution experience.

OBJECTIVE: The authors reviewed renal transplant outcomes in recipients 60 years of age or older. BACKGROUND: Before cyclosporine, patients older than 45 years of age were considered to be at high risk for transplantation. With cyclosporine, the age limits for transplantation have expanded. METHODS: The authors compared patient and graft survival, hospital stay, the incidence of rejection and rehospitalization, and the cause of graft loss for primary kidney recipients 60 years of age or older versus those 18 to 59 years of age. For those patients > or = 60 years transplanted since 1985, the authors analyzed pretransplant extrarenal disease and its impact on post-transplant outcome. In addition, all surviving recipients > or = 60 years completed a medical outcome survey (SF-36). RESULTS: Patient and graft survival for those > or = 60 years of age versus those 18 to 59 years of age were similar 3 years after transplant. Subsequently, mortality increased for the older recipients. Death-censored graft survival was identical in the two groups. There were no differences in the cause of graft loss. Those 60 years of age or older had a longer initial hospitalization, but had fewer rejection episodes and fewer rehospitalizations. Quality of life for recipients 60 years of age or older was similar to the age-matched U.S. population. CONCLUSION: Renal transplantation is successful for recipients 60 years of age or older. Most of them had extrarenal disease at the time of transplantation; however, extrarenal disease was not an important predictor of outcome and should not be used as an exclusion criterion. Post-transplant quality of life is excellent.     

Improved Scoring System to Assess Adult Donors For Cadaver Renal Transplantation

We previously proposed a quantitative approach to assess donor organs for cadaver renal transplantation. To improve on our original scoring system, we studied 34 324 patients who received cadaver renal transplants from adult donors between 1994 and 1999 and were reported to the UNOS Scientific Renal Transplant Registry. A scoring system was developed from five donor variables (age, 0-25 points; history of hypertension, 0-4; creatinine clearance before procurement, 0-4; cause of death, 0-3; HLA mismatch, 0-3) that showed a significant correlation with renal function and long-term graft survival. Cadaver kidneys were stratified by cumulative donor score: grade A, 0-9 points; grade B, 10-19; grade C, 20-29; and grade D, 30-39. The influence of donor score on renal function and graft survival was most severe above 20 points, designated 'marginal' kidneys. In summary, a donor scoring system developed from a large population database was useful in predicting outcome after cadaver renal transplantation. The improved system provides a quantitative approach to evaluation of marginal kidneys and may improve allocation of these organs in cadaver renal transplantation.     

Recurrence of disease in patients retransplanted for focal segmental glomerulosclerosis.

The natural history of focal segmental glomerulosclerosis in patients retransplanted after loss of a primary allograft is not well established. We studied 14 patients with FSGS who were retransplanted between April 1964 and September 1990 to determine if recurrence in a second or subsequent allograft could be predicted. In this group, 8 of the primary allografts were lost to recurrent disease and 6 to rejection. None of the 6 patients who lost their primary allograft to rejection without evidence of recurrent FSGS suffered recurrent disease after retransplantation. In contrast, 3 of the 8 patients who lost their primary allograft rapidly to FSGS suffered recurrent disease and loss of function in all subsequent allografts. The remaining 5 patients had prolonged function of the primary allograft ranging between 4 and 10.5 years, despite recurrence of FSGS. Of these 5 patients, 2 have excellent renal function after retransplantation without recurrence of FSGS in the secondary allograft at 9 and 10.5 years posttransplant; 2 have lost their secondary allograft to recurrent FSGS, but are free of recurrence in the third allograft at 0.5 and 5.8 years postoperatively; 1 maintains a serum creatinine level of 1.9 mg% despite recurrence of FSGS in the secondary allograft at 1 year postoperatively. Our data show that, without recurrence of FSGS in the primary allograft, further renal transplants will be free of recurrent disease. Based on this finding, we advocate use of living-related donors for second transplants in these patients. With rapid recurrence of FSGS and subsequent accelerated loss of the primary allograft, further renal transplants carry a high likelihood of recurrent FSGS and graft loss. A substantial proportion of patients with recurrent FSGS in the primary allograft will have prolonged renal function, and are likely to have excellent results with subsequent allografts.     

The effect of the referring dialysis center on renal transplant results

Between 1/1/76 and 12/31/86, 448 patients underwent transplantation (360 first transplants). Of these, 286 (230 first) were referred by 5 dialysis centers, each referring more than 40 recipients. The remainder were referred by a large number of centers. Using our 5 largest referral centers, we studied the effect of dialysis center on graft and patient survival. There was no difference between dialysis centers in patient survival. Actuarial graft survival differed significantly for all cadaver transplants and for first cadaver transplants (P less than 105). Significant differences persisted when groups were subdivided by type of immunosuppression (azathioprine vs cyclosporine). Demographic (age, race, cause of renal disease) and immunologic (transfusions, PRA, matching) differences between groups did not explain the difference in graft survival. We conclude that referring dialysis center is a previously unrecognized factor affecting transplant outcome. Further studies with larger numbers will be required to determine the underlying reasons for ths phenomenon.     

Prednisone-Free Maintenance Immunosuppression—A 5-Year Experience

Concern persists that prednisone-free maintenance immunosuppression in kidney transplant recipients will be associated with an increase in late allograft dysfunction and graft loss. We herein report 5-year follow-up of a trial of prednisone-free maintenance immunosuppression. From October 1, 1999, through January 31, 2005, at our center, 589 kidney transplant recipients were treated with a protocol incorporating discontinuation of their prednisone on postoperative day 6. At 5 years, actuarial patient survival was 91%; graft survival, 84%; death-censored graft survival, 92%; acute rejection-free graft survival, 84% and chronic rejection-free graft survival, 87%. The mean serum creatinine level (+/-SD) at 1 year was 1.6 +/- 0.6; at 5 years, 1.7 +/- 0.8. In all, 86% of kidney recipients with functioning grafts remain prednisone-free as of April 30, 2005. As compared with historical controls, recipients on prednisone-free maintenance immunosuppression had a significantly lower rate of a number of complications, including cataracts (p < 0.001), posttransplant diabetes mellitus (p < 0.001), avascular necrosis (p = 0.001), and fractures (p = 0.004). We conclude that prednisone-related side effects can be minimized in a protocol incorporating prednisone-free maintenance immunosuppression. Five-year graft outcome remains good.     

Comparative evaluation of two commercial assays for direct detection ofMycobacterium tuberculosis in respiratory specimens

Two commercial systems for the amplification and detection ofMycobacterium tuberculosis directly from respiratory samples were compared. The Roche Cobas Amplicor MTB Test and the Roche manual Amplicor MTB Test (Roche Diagnostic Systems, USA) were applied to 755 decontaminated respiratory specimens collected from 470 patients. Results were compared with those of acid-fast staining and culture. A total of 251 specimens were collected from 156 patients diagnosed with pulmonary tuberculosis, including 28 specimens corresponding to 13 patients that were receiving antituberculous treatment. Given the overall positivity rate of 33.2% (251/755), the sensitivity, specificity, and positive and negative predictive values were 92.4, 100, 100, and 96.5%, respectively, for the Cobas Amplicor MTB Test and 90.8, 100, 100, and 95.8%, respectively, for the Amplicor MTB Test. For 204 (81.3%) smear positive specimens and 47 (19.7%) smear negative specimens, the sensitivity values were 100 and 59.6%, respectively, for the Cobas Amplicor MTB Test and 100 and 51%, respectively, for the Amplicor MTB Test. There were no statistically significant differences in sensitivity or specificity between the two assays and culture (p>0.05). The overall results of both assays were concordant for 99.5% of the samples. It is concluded that although both nucleic acid amplification methods are rapid and specific for the detection ofMycobacterium tuberculosis complex in respiratory specimens, the Cobas Amplicor MTB Test appears to be slightly more sensitive than the Amplicor MTB Test when smear negative specimens are investigated.     

Mental illness and the media: an assessment of attitudes and communication

Media coverage of psychiatric issues will reflect or influence public perceptions of the mentally ill. In order to explore the relationship between psychiatry and the media, an attitudinal questionnaire was administered to a systematic sample of 20 reporters, 20 psychiatrists, 20 medical outpatients with no psychiatric history, and 40 psychiatric inpatients. In addition, 4 psychiatric patients who had personal experience with media coverage were interviewed to determine the impact. Their stories are presented as clinical vignettes. The results of the questionnaire survey show that media reporters are no less accepting of mental illness than the other groups. A regression analysis of attitudinal predictors elicit education as more significant than age and media exposure. Yet low scores for the coverage by the media of mental illness were given by all groups with psychiatrists tending to be most critical. Reasons offered by reporters included "sensationalism sells" along with cost and time factors. Recommendations for both reporters and psychiatrists groups were collated, aiming at improving communication and ensuring a more positive emphasis and greater accuracy of media coverage of mental health issues.