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Kidneys from donors who are positive for hepatitis C virus (DHCV+) have recently been identified as an independent risk factor for mortality after renal transplantation. However, it has not been determined whether risk persists after adjustment for baseline cardiac comorbidity or applies in the era of modern immunosuppression. Therefore, a historical cohort study was conducted of US adult cadaveric renal transplant recipients from January 1, 1996, to May 31, 2001; followed until October 31, 2001. A total of 36,956 patients had valid donor and recipient HCV serology. Cox regression analysis was used to model adjusted hazard ratios for mortality and graft loss, respectively, adjusted for other factors, including comorbid conditions from Center for Medicare and Medicaid Studies Form 2728 and previous dialysis access-related complications. It was found that DHCV+ was independently associated with an increased risk of mortality (adjusted hazard ratio, 2.12, 95% confidence interval, 1.72 to 2.87; P < 0.001), primarily as a result of infection. Mycophenolate mofetil was associated with improved survival in DHCV+ patients, primarily related to fewer infectious deaths. Adjusted analyses limited to recipients who were HCV+, HCV negative, or age 65 and over, or by use of mycophenolate mofetil confirmed that DHCV+ was independently associated with mortality in each subgroup. It is concluded that DHCV+ is independently associated with an increased risk of mortality after renal transplantation adjusted for baseline comorbid conditions in all subgroups. Recipients of DHCV+ organs should be considered at high risk for excessive immunosuppression.

The impact of hepatitis C virus-positive donor kidneys on patient survival has not been analyzed in a national study. This study analyzed 20,111 adult (age, > or =16 yr) recipients having solitary cadaveric kidney transplants from adult donors with valid donor hepatitis C serologies from July 1, 1994, to June 30, 1998, in an historical cohort study (the 2000 United States Kidney Data System) of patient survival. Analysis was by the Cox proportional hazards models, which corrected for characteristics thought to affect outcomes. Of 484 kidneys positive for hepatitis C virus serology, 165 (34%) were given to recipients with confirmed negative hepatitis C serologies. Unadjusted 3-yr patient survival was 93% in all recipients of donor hepatitis C-negative kidneys versus 85% in all recipients of donor hepatitis C-positive kidneys (P = 0.01). Among hepatitis C-positive recipients, those who received hepatitis C-positive kidneys had worse survival than recipients of hepatitis C-negative kidneys. Among elderly hepatitis C-negative recipients, those who received hepatitis C-positive kidneys also had worse survival; in fact, all recipients of donor hepatitis C-positive kidneys had increased risk of mortality (P = 0.028). There were no significant interactions between donor hepatitis C positivity and either recipient hepatitis C positivity or older recipient age. The use of hepatitis C-positive kidneys in recipients who were hepatitis C-negative was fairly common and contrary to some current recommendations. Recipients of donor hepatitis C-positive kidneys were at independently increased risk of mortality, with no evidence that any subgroups were less affected.

Previous studies of the effect of donor factors on renal transplant outcomes have not tested the role of recipient body mass index, donor/recipient weight ratios and age matching, and other factors. We analyzed 20,309 adult (age 16 or older) recipients having solitary cadaveric renal transplants from adult donors from 1 July 1994 to 30 June 1998 in an historical cohort study (the 2000 United States Renal Data System) of death censored graft loss by the Cox proportional hazards models, which corrected for characteristics thought to affect outcomes. The only independently significant findings in Cox Regression analysis were a high donor/ recipient age ratio (> or = 1.10, e.g. a 55-year-old donor given to a recipient age 50years or younger, adjusted hazard ratio (AHR) 3.22, 95% confidence interval (CI) 2.36-4.39) and African American donor kidneys (AHR 1.64, 95% CI, 1.24-2.17). African American recipients and older donors were not at independently increased risk of graft failure in this model. Among donor factors, older donor kidneys given to younger recipients and donor African American kidneys were independently associated with graft loss in recipients of cadaver kidneys. The task for the transplant community should be to find the best means for managing all donor organs without discouraging organ donation.

Rates of and risk factors for graft loss and graft loss resulting from recurrent focal segmental glomerulosclerosis (FSGS) have not been studied in a national population. A retrospective analysis was performed on a national registry (1999 United States Renal Data System) of 101,808 renal transplant recipients (October 1, 1987, to December 31, 1996). Of these, 3,861 recipients of solitary renal transplants who had end-stage renal disease resulting from FSGS met inclusion criteria. Outcomes were graft loss and graft loss resulting from recurrent FSGS. As a percentage of all graft loss, recurrent FSGS accounted for 18.7% in living donor recipients and 7.8% in cadaveric recipients. In white recipients, the corresponding figures were 27% and 13%. In multivariate analysis, factors associated with graft loss resulting from recurrent FSGS were white recipient, donor African-American kidney in white recipient, younger recipient age, and treatment for rejection. African-American recipients had higher rates of graft loss overall. A living donor was associated with superior overall graft survival. Among renal transplant recipients with FSGS, white recipients had a higher risk of graft loss resulting from recurrent FSGS, disproportionately seen in recipients of African-American kidneys. The role of donor/recipient race pairing on graft loss resulting from recurrent FSGS should be validated. Living donor had no association with graft loss from recurrent FSGS after correction for other factors. African-American recipients with FSGS may have the most to gain from a living donor, given their improved graft survival and decreased risk of graft loss resulting from recurrent FSGS. This is a US government work. There are no restrictions on its use.

To determine if repeated HLA mismatches and other putative risk factors were predictive of second graft failure in second grafts performed at Southeastern Organ Procurement Foundation (SEOPF) members centers, we identified a cohort of 753 retransplants in which one or more HLA antigens were mismatched in primary grafts. Of this group, 158 (21.1%) received second grafts with repeated mismatches of one or more HLA-A, B, or DR antigens that were previously mismatched in the primary graft (RMMs). All regrafts were cadaveric kidneys transplanted between 1982 and 1995. Multivariate analysis of 19 covariates in 438 regrafts identified four independent factors that were predictive of graft survival frequency in second transplants. Three of the four factors were associated with a reduced risk for graft loss in retransplants: cyclosporin A (CsA) use in graft (p = 0.0001, RR = 0.26), peak PRA < 50% (p = 0.008, RR = 0.52) and white donor race (p = 0.035, RR = 0.63). One factor was associated with an increased risk of second graft failure, namely, blood transfusion prior to the first graft (p = 0.026, RR = 5.14). None of the other 15 factors exerted significant additional risk to regraft survival frequency in these SEOPF data. In multivariate analysis, RMMs were not associated with altered graft survival frequency in regrafts (p = 0.944, RR = 0.99). We than used univariate analyses to determine whether RMMs had adverse effects on GS in particular subsets of recipients that were thought to be at increased risk for the second transplant failure. Univariate analyses were performed with methods that are sensitive to early events (Wilcoxon) and late events (log-rank). The variables tested were CsA use for the regraft, duration of primary graft function, panel reactive antibody levels (PRA), immunopathologic cause of first graft failure, and HLA mismatch of the second graft. These analyses indicated that repeated HLA mismatches were not an associated risk factor in any of these subgroups. These SEOPF data indicate that RMMs are not predictive of increased frequency of graft loss in cadaveric donor second transplants. We conclude that our results do not support a policy of routine avoidance of RMMs, which may result in increased waiting time for a second donor without providing an improved graft survival rate. The available literature suggests that HLA antibody identification, the use of sensitive flow cytometric and antiglobulin-augmented cross-match tests, together with appropriate donor selection, optimal immunosuppression and patient management may be sufficient to avoid the early loss of second grafts.

Methyldopa therapy for hypertension after renal transplantation could affect graft outcome adversely, since methyldopa inhibits suppressor cells. To study effects of methyldopa on transplant outcome, we analyzed prospective data on 1,648 hypertensive, first-allograft recipients; 545 patients used methyldopa and 1,103 patients did not. One-year graft functional survival was 66% and 67% for all patients using and not using methyldopa respectively. No increased acute rejection occurred related to methyldopa. During the one to six years of follow-up, no adverse effects on graft survival could be attributed solely to methyldopa except that graft survival among white recipients using methyldopa was diminished late after transplantation (P less than .05). Patient survival was not affected by methyldopa. Azathioprine and prednisone therapy may avert the suppressor cell inhibition by methyldopa. Its effect on kidney transplant outcome is not significant except in whites late in the course of graft function; methyldopa use when clinically indicated appears safe.

This study was done to define the tolerance of ex vivo administered irradiation to intestinal allograft and to assess the effect of irradiation on the incidence and severity of rejection and graft versus host disease after intestinal transplantation in dogs. Excessive intestinal damage was produced by 2,500 rads, but 750 and 1,500 rads produced no detectable acute or chronic damage in dogs observed from 100 days to two years. Using cyclosporine for postoperative immunosuppression, 1,500 rads reduced the incidence of acute (p = 0.05) and chronic rejection (p = 0.08), yet did not impair intestinal absorption of cyclosporine. The greatest improvement in survival occurred with 750 rads (p = 0.02). Histologic evidence of graft versus host disease appeared in the native small intestine in two of four long term surviving dogs receiving a nonirradiated graft but in none of the dogs receiving irradiated grafts. Irradiation of the graft may be a promising adjunct in the search for a clinically applicable method of intestinal transplantation.