The effect of donor age, recipient age, and HLA match on immunologic graft survival in cadaver renal transplant recipients.

We retrospectively analyzed 526 primary cadaver recipients transplanted at a single center to identify pretransplant variables that predict long-term survival with multivariate analysis. All recipients received at least three random blood transfusions and were treated under a quadruple-therapy protocol consisting of ALG, azathioprine, prednisone, and cyclosporine. Of 526 consecutive transplants, 86 grafts were lost from acute or chronic rejection. Thirteen grafts were lost for nonimmunologic reasons and 35 recipients died with a functioning graft. A total of 273 patients (52%) experienced at least one episode of acute rejection. Donor age ranged from 3 to 64 years, with 62% of donors less than 30 years of age and 9% of donors over 50 years of age. Donor age was not predictive of long-term graft survival and neither was the difference between donor and recipient age. Recipient age was predictive of subsequent immunologic graft less, with younger recipients at greater risk (P = 0.011). The rate of first rejection was also inversely related to recipient age, with younger recipients rejecting earlier (P = 0.0001). The degree of DR mismatch was the only other significant predictor of long-term graft success (P = 0.013). Transplant survival correlated with the degree of DR mismatch: 2 DR mismatch was the worst, 1 DR mismatch was intermediate and 0 DR mismatch was the best (P = 0.02). A, B, AB, and BDR did not influence long-term graft outcome. In our center, donor age does not predict graft failure. Younger recipients have a higher rate of early rejection and, combined with a poor DR match, are at higher risk for long-term graft failure.     

The effect of HLA-A, -B matching on cadaver renal allograft rejection comparing public and private specificities

Data collected prospectively on 3811 cadaver renal transplants performed between June 1977 and July 1982 by the 42 member institutions of the South-Eastern Organ Procurement Foundation (SEOPF) were analyzed to determine whether donor-recipient compatibility based on public rather than private HLA-A,-B specificities influenced the beneficial effect of HLA matching on outcome. HLA compatibility was calculated considering match and mismatch based on common private or various public (crossreactive group, [CREG]) specificities. Donor-recipient compatibility using certain CREG assignments provided an equivalent means of stratifying graft outcome by the degree of HLA-A,-B match or mismatch, and other CREGs assignments did not. Multivariate Cox regression analysis of donor-recipient compatibility based on certain public antigens showed as high an association (P less than 10(-5) between good matching and decreased graft rejection as did matching for private antigens alone. Patient stratification by HLA match provided a stronger association with graft outcome than by HLA mismatch, irrespective of whether private or public antigens were considered. The likelihood of finding a better match was significantly increased using CREG assignments, and patients with at least one matched private antigen had equivalent or better graft survival when additional public antigens were matched. These findings indicate that with conventional immunosuppressive therapy: (1) matching of private or public HLA-A,-B antigens plays a highly significant role in decreasing renal allograft rejection; (2) matching based on certain public antigens can provide the same or a better association with outcome as private antigens; and (3) the association (crossreactivity) of various HLA specificities can be defined on a functional basis in terms of graft survival.     

Influence of changes in pretransplant sensitization on patient and graft survival in cadaver renal transplantation

Analysis of 2778 primary and 606 regrafted cadaveric donor renal allograft recipients transplanted between June 1977 and July 1982 as part of the South-Eastern Organ Procurement Foundation (SEOPF) Prospective Study was performed to determine the influence of changes in presensitization on graft and patient outcome. Four mutually exclusive groups of patients were identified based on the relative difference in the percentage of panel-reactive antibody (PRA) from highest ever (peak) to most recent (current) pretransplant levels as follows: group 1 (unsensitized): peak = current PRA = 0; group 2 (rising or stable PRA): (peak = current PRA) greater than 0; group 3 (small decrease): (peak - current PRA) = 1-40%;) and group 4 (large decrease): (peak - current PRA) greater than 40%. First-transplant recipients in group 4 had significantly higher mortality when compared with groups 1-3 (P less than 0.002). This decrease in patient survival was evident at 6 months (81% +/- 4 vs 91% +/- 1) and persisted to three years (68% +/- 8 vs 78% +/- 2), and it was associated with a significant (P less than 0.037) increase in death from infectious causes. This finding was even more striking when only transfused recipients were considered: at three years the difference in patient survival was 63% +/- 11 vs. 77% +/- 2. In addition, transfused patients with a decrease in pretransplant PRA of greater than 40% had significantly lower overall graft survival (P less than 0.02) and a higher incidence of irreversible graft rejection (50% +/- 8 vs 33% +/- 1 at two years). For regrafted recipients, there were no differences in patient survival among groups, but those in group 4 had significantly lower graft survival (P less than 0.0033) than groups 1-3. These findings suggest that a substantial decrease in PRA prior to transplant does not necessarily indicate a decrease in potential donor alloreactivity, and in first-graft recipients it may reflect an increased susceptibility to life-threatening infections following transplantation.     

Determining the effect of immunosuppressant adherence on graft failure risk among renal transplant recipients

The objective was to use the United States Renal Data System (USRDS) to quantify the relationship between immunosuppressant therapy (IST) adherence and risk of graft failure among adult renal transplant recipients (RTRs). A secondary objective was to examine the relationship among select patient characteristics and IST adherence. The study sample included adult RTRs who: received primary transplant between January 1, 1999 and December 31, 2005; experienced graft survival for at least 12 months post‐transplant and had at least 12 months of data in the USRDS; utilized Medicare coverage for IST; and were prescribed cyclosporine or tacrolimus. IST adherence was measured by medication possession ratio (MPR). Pearson chi‐square tests were used to examine associations between patient characteristics and MPR quartiles. Cox proportional hazards regression was used to assess relationships among time to graft failure, MPR, and patient characteristics. Thirty‐one thousand nine hundred and thirteen RTRs met inclusion criteria. Older age, female gender, white race, deceased donors, and tacrolimus were associated with greater adherence (p < 0.001). Cox proportional hazard modeling indicated greater adherence, white race, and having a living donor were significantly associated with longer graft survival (p < 0.05). Future prospective studies should further examine the clinical significance of IST nonadherence as it relates to graft failure.     

The influence of HLA-A, B, and DR matching on graft survival in primary cadaveric renal transplantation in Belfast

HLA-DR matching has been shown in a retrospective study of 72 renal transplant patients to significantly enhance graft survival at 12 months. HLA-A and -B antigen matching also increased the graft survival rate significantly. Analysis of combined HLA-A, -B and -DR matching suggested an improvement in graft survival rate with better matching, but this did not attain statistical significance. It is now our policy to use HLA-DR matching prospectively and to ensure that all recipients receive a kidney with a maximum of 1 HLA-DR incompatibility and a minimum of 2 HLA-A and -B antigens shared.     

The effect of donor age on graft survival in pediatric cadaver renal transplant recipients--a report of the North American Pediatric Renal Transplant Cooperative Study.

Data from the North American Pediatric Renal Transplant Cooperative Study were analyzed to determine the effect of donor age on graft survival for pediatric recipients of cadaver donor renal transplants. Between January 1, 1987, and November 16, 1990, 787 cadaver donor renal transplants in children less than 18 years of age were registered in the study. The ages of the donors were less than or equal to 5 years in 203 transplants, between 6 and 9 years in 87, between 10 and 39 in 389, and greater than or equal to 40 years in 108. The risk of graft loss was related to donor age by a proportional hazards analysis. The ideal donor age was 20-25 years. The risk of graft loss was increased by both young and old donor age. The risk of graft loss from a neonate donor was 2.7-fold that of the ideal donor, and the risk from a 50-year-old donor was 1.8-fold that of the ideal donor. The relationship between donor age and graft survival was not affected by the age of the recipient. Cold storage time had an added impact on graft survival: grafts with cold storage time greater than 24 hr were 1.5 times more likely to fail than grafts with shorter cold storage time for all donor ages. Analysis of the causes of graft failure revealed that 9.9% of grafts from donors less than or equal to 5 years of age were lost due to vascular thrombosis, primary nonfunction, and other technical causes, compared with 4.6% in 6-9, 4.4% in 10-39, and 2.8% in greater than or equal to 40-year-old donors. We conclude that kidneys from both young and old donors are at increased risk for graft loss, and this increased risk is seen in all recipient age groups. Many of the losses from the young donors--but not older donors--may be due to technical causes. Knowledge of these risks can be used to develop strategies for optimal utilization of kidneys from young and old donors.     

Impact of body mass index on graft failure and overall survival following liver transplant

GOALS: To assess the influence of body mass index (BMI) in the outcome of liver transplantation. BACKGROUND: Body mass index appears to affect liver transplantation, independently of several risk factors. STUDY: A review of the United Network for Organ Sharing database included 32 515 liver transplants from 1992 through 2000 with at least one follow-up visit, of which 26 920 had information for determining BMI. The overall impact of elevated BMI (>25), and the impact of increasingly elevated BMI (25-40+) on graft failure rates and overall survival rates are assessed using proportional hazards regression. RESULTS: Controlling for follow-up time, age, gender, race, number of comorbidities, and status 1 designation, the impact of BMI on survival was mixed. The risk of death was elevated for patients with low BMI (<19) and BMI values of >/=40. Compared with patients with BMI of 19-22, those with BMI > 25 had a decreased likelihood of death. This decrease was seen among patients with BMI of 25-34. CONCLUSION: BMI did not significantly affect rates of graft failure. Compared with patients with a BMI in the 'normal' range, those with moderately elevated BMI had decreased likelihood of death while patients with low BMI or extremely high BMI had increased likelihood of death.     

The effect of sirolimus on sex hormone levels of male renal transplant recipients

BACKGROUND: It is unclear whether sirolimus, a newer immunosuppressive agent, widely used in renal transplantation, affects male sex hormone levels or sexual function. METHODS: Sex hormone profiles in male renal transplant recipients were obtained and compared between a sirolimus-treated group and a group not on sirolimus in a cross-sectional study. Both groups also completed a sexual dysfunction questionnaire. RESULTS: Sixty-six subjects were evaluated, 32 in the sirolimus group and 34 in the control group. Total testosterone level was significantly lower in the sirolimus group than the control group (393.3 +/- 188 vs. 537.4 +/-232 pg/mL; p = 0.08) while follicle stimulating hormone and luteinizing hormone levels were significantly higher in the sirolimus group (12.8 +/- 14 vs. 6.0 +/- 5, p = 0.013; 10.9 +/- 14 vs. 4.7 +/- 4, p = 0.018, respectively). There was a significant negative correlation between 24-h sirolimus trough and total testosterone levels (p < 0.03). By multiple regression analysis, use of sirolimus was independently associated with decreased total testosterone level. There was no significant difference in subjective sexual dysfunction as assessed by questionnaire scores between the two groups. There was no correlation between questionnaire scores and total testosterone level. CONCLUSION: Sirolimus is associated with decreased total testosterone levels in male renal transplant recipients. It is unclear whether sirolimus may affect other aspects of sexual function.     

The impact of diabetes on vascular complications following cadaver renal transplantation

To assess the impact of diabetes on vascular complications occurring in renal transplant recipients, we compared the incidence of vascular disease in 283 non-diabetic (ND) and 99 diabetic (D) patients who received primary cadaver renal transplants at our center between 1/1/76 and 12/31/85. The median observation time in the ND patients was 31 months, and in D patients it was 20 months. Both ND and D patients were subdivided into group A if they had preexisting clinical vascular disease and group B if they had no prior disease. The vascular complications between the ND and D patients were analyzed in 3 subsets: prevalence of vascular disease prior to renal transplantation; posttransplant recurrent vascular disease in group A; and posttransplant vascular disease, new, in group B. The results showed that, prior to renal transplantation, D patients have a higher prevalence of clinical vascular disease (33%), compared with ND patients (13%) (P = .00001). In group A, the recurrence rate of vascular disease after transplantation was also higher in D patients (67%) compared with ND patients (40%) (P = .05). In group B, the incidence of posttransplant vascular disease (new) was significantly higher in D patients (33%) compared with the ND patients (13%) (P = .002). Also, the amputation rate was significantly higher in D patients (18%) compared with ND patients (0.4%) (P = .000001). Our data suggest that morbidity from vascular disease is significantly increased in diabetic renal transplant recipients compared with nondiabetic patients. Such increased morbidity from vascular disease in the diabetic patients may also be observed in the period before renal transplantation.     

The effect of ethanol on serum cyclosporine A levels in renal transplant recipients

Following an alcohol binge, cyclosporine A (CyA) levels rose by 100% in a 51-year-old transplant recipient treated with CyA. As CyA and ethanol are both metabolized by the cytochrome P-450 enzyme system, ethanol could theoretically interfere with CyA metabolism. Therefore, eight male renal transplant recipients were assessed in a crossover study to determine the effects of acute ethanol ingestion on CyA serum concentrations. CyA serum concentrations did not rise following 50 mL of 100% alcohol. We conclude that heavy alcohol intake may increase CyA levels but that acute moderate intake does not.     

Lack of influence of donor-recipient differences in subtypic HLA-A,B antigens (splits) on the outcome of cadaver renal transplantation

Data collected prospectively on 3811 cadaver renal transplants performed between June 1977 and July 1982 by the 42 member institutions of the South-Eastern Organ Procurement Foundation (SEOPF) were analyzed to determine whether donor-recipient differences in sub-typic HLA-A,B specialties (splits) influenced outcome. The number of HLA-A,B antigens matched and mismatched between each donor and recipient was calculated in three ways: (1) considering all antigens and splits as distinct (not matched); (2) considering all splits as only matched with their corresponding typic antigen (but not with each other); and (3) considering all splits as matched with both their corresponding typic antigen as well as each other. Overall graft survival, graft loss from irreversible rejection, and patient survival stratified by the level of HLA match were the same using all three methods. In addition, using multivariate Cox regression analysis, the strong association between good HLA matching and increased graft survival was the same using all three methods of matching. Patients with a given number of mismatched antigens had no significant decrease in survival when additional splits were considered mismatched with each other or their corresponding typic antigen. These results suggest that matching of typic HLA-A,B antigens plays a highly significant role in reducing graft rejection but that donor-recipient differences in splits have a negligible effect on graft outcome.     

Influence of cadaver donor age on posttransplant renal function and graft outcome

To assess the impact of cadaver donor age on posttransplant renal function and graft survival, we analyzed our clinical results in 17 recipients of younger donor kidneys (less than 10 years) and 48 recipients of older donor kidneys (greater than 50 years) and compared them with a control group of 598 patients who received kidneys from donors between 11 and 50 years of age. The 3 groups were comparable with respect to recipient age, duration of dialysis, prior transfusions, previous transplants, cold ischemia time, HLA AB mismatches, cytotoxic antibody profile, posttransplant ATN, and prophylactic ALG treatment. The cumulative patient survival at 1, 2, and 3 years was not significantly different among the 3 groups, but the graft survival in recipients of older donor kidneys was significantly lower than the control (71% vs. 62% at 2 years, P = .09 and 66% vs. 55% at 3 years, P = .0003. The short-term renal function assessed at 1 month posttransplant was significantly lower in the older donor group compared with the control (creatinine clearance 45 mL/min vs. 59 mL/min, P = .0003). Likewise, the long-term renal function assessed at the last follow-up was also lower in the older donor group than the control (creatinine clearance 40 mL/min vs. 49 mL/min, P = .07). There were no significant differences in graft survival or short- or long-term renal function between the younger donor group and the control group. These observations suggest that transplantation of a kidney from an older cadaver donor is associated with an inferior posttransplant outcome. The practical decision whether or not to use an older donor kidney should be individualized taking this as well as other factors into account.     

Prevalence of transfusion transmitted virus infection and its effect on renal graft survival in renal transplant recipients

Objective: Little is known about the prevalence of transfusion transmitted virus (TTV) infection in renal transplant recipients (RTxs) and its effects on allograft survival. We investigated the prevalence of TTV and its effects on liver injury and graft survival in RTxs. Material and Methods: The study was performed in 33 consecutive RTxs (8 females, 25 males) and 100 blood donors (35 females, 65 males). A nested polymerase chain reaction was used to detect TTV DNA in serum. Serum creatinine and alanine aminotransferase (ALT) levels and 24-h protein excretion were determined in both TTV-positive and-negative patients. The total number of blood transfusions, the duration of hemodialysis and the total duration after transplantation were recorded in RTxs. In addition, hepatitis B surface antigen (HbsAg), anti-hepatitis C virus (HCV) and hepatitis G virus DNA antibodies were determined in all patients. Results: TTV DNA was detected in 51.5% of RTxs and in 7% of the control group and this difference was statistically significant (p < 0.01). In the RTx group, 64.7% of TTV-positive and 56.2% of TTV-negative patients had undergone a previous blood transfusion. However, the blood transfusion replacement rate, total duration of dialysis therapy and posttransplant period did not differ between these two groups. Five (15.1%) patients in the RTx group had abnormal liver function tests (ALT >40 IU/l). Of these patients, 2 were anti-HCV-positive, 1 was HBsAg-positive and anti-HCV- plus TTV DNA-positive and the serologic tests of the remaining 2 patients were all negative. Among the TTV-positive patients, 2 (11.7%) were anti-HCV-positive, 1 (5.8%) was HBsAg-positive and 3 (17.6%) were HGV DNA-positive. The baseline serum creatinine levels did not differ significantly between the TTV-positive and-negative patients, being 1.5 +/- 0.6 and 1.4 +/- 0.6 mg/dl, respectively ( p > 0.05). Two of the TTV-positive patients and 1 of the TTV-negative patients had proteinuria. A 1-year follow-up of TTV-positive and-negative patients demonstrated neither acute nor chronic graft rejection. Conclusion: In RTxs, TTV infection was more prevalent than in the normal population. In our patients the virus did not have an important effect on renal graft rejection and did not cause liver injury. However, the question of whether TTV infection may affect graft survival requires further long-term investigation in larger groups.