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Donor characteristics such as age and cause of death influence the incidence of delayed graft function (DGF) and graft survival; however, the relative influence of donor characteristics ("nature") versus transplant center characteristics ("nurture") on deceased-donor kidney transplant outcomes is unknown. We examined the risks for DGF and allograft failure within 19,461 recipient pairs of the same donor's kidneys using data from the US Renal Data System. For the 11,894 common-donor pairs transplanted at different centers, a recipient was twice as likely to develop DGF when the recipient of the contralateral kidney developed DGF (odds ratio [OR] 2.05; 95% confidence interval [CI] 1.82 to 2.30). Similarly, for 7567 common-donor pairs transplanted at the same center, the OR for DGF was 3.02 (95% CI 2.62 to 3.48). For pairs transplanted at the same center, there was an additional 42% risk for DGF compared with pairs transplanted at different centers. After adjustment for DGF, the within-pair ORs for allograft failure by 1 yr were 1.92 (95% CI 1.33 to 2.77) and 1.77 (95% CI 1.25 to 2.52) for recipients who underwent transplantation at the same center and different centers, respectively. These data suggest that both unmeasured donor characteristics and transplant center characteristics contribute to the risk for DGF and that the former also contribute significantly to allograft failure.

The Centers for Medicare & Medicaid Services uses kidney transplant outcomes, unadjusted for standard comorbidity, to identify centers with sufficiently higher than expected rates of graft failure or patient death (underperforming centers) that they may be denied Medicare participation. To examine whether comorbidity adjustment would affect this determination, we identified centers that would have failed to meet 1-year graft survival criteria, 1992–2005, with and without adjustment using the Elixhauser Comorbidity Index. Adjustment was performed for each US center for 24 consecutive (overlapping) 30-month intervals, including 102,176 adult deceased-donor and living-donor kidney transplant patients with Medicare as primary payer 6 months pretransplant. For each interval, we determined percent positive agreement (number of centers underperforming both before and after adjustment, divided by number underperforming either before or after adjustment). Overall percent positive agreement was 80.8%, with no evidence of a trend over time. Among deceased-donor recipients, 10 of 31 comorbid conditions were predictors of graft failure in at least half of the intervals, as were 6 conditions among living-donor recipients. Lack of comorbidity adjustment may disadvantage centers willing to accept higher risk patients. Risk of jeopardizing Medicare funding may give centers incentive to deny transplantation to higher risk patients.

We studied the incidence, trends and clinical correlates of infections following kidney transplantation in the United States Renal Data System over the years 1995–2003 in 46,471 adults with Medicare primary coverage at the time of their first kidney transplant. The incidence of most infections has declined only slightly since 1995 but infection with cytomegalovirus significantly declined while that with hepatitis C significantly increased. Relative frequencies of different types of infections (bacterial, viral, fungal and parasitic) were relatively constant, both during early and late periods following transplant. Using the Cox proportional hazards analysis we found that the clinical correlates for post-transplant bacterial and viral infections included older age, female gender, diabetes as the cause of end-stage renal disease, deceased (vs. living) donor source, time on dialysis before transplant, hepatitis B and C viral pre-transplant serologic status and pre-transplant donor-recipient cytomegalovirus serology. Our study shows that despite identifiable risk factors, the incidence of most post-transplant infections has changed little since 1995.

BACKGROUND: Polymorphisms of genes such as angiotensin-converting enzyme (ACE), angiotensinogen (AGT), and angiotensin receptor type I (AGTR1) have been associated with hypertension. Hypertension, in turn, has been associated with decreased renal allograft survival. Therefore, this study investigated whether single nucleotide polymorphisms (SNPs) in these genes are associated with decline in renal function posttransplantation. METHODS: We enrolled patients from a prospective cohort of renal transplant recipients of deceased donor kidneys being conducted at 9 centers in the Delaware Valley Region. Medical records were assessed every 6 months and estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease equation. Genotypes of 10, 2, and 5 SNPs in the AGTR1, AGT, and ACE gene were analyzed, respectively. RESULTS: The G and the T alleles of the respective AGTR1 SNPs rs275704 and rs5182 were both associated with 50% decline in eGFR (HR for rs275704: CG=1.22, 95% confidence interval [CI] 0.67-2.25 and GG=2.55, 95% CI 1.22-5.32, overall P=0.03; HR for rs5182: CT=1.26, 95% CI 0.72-2.19 and TT=3.09, 95% CI 1.50-6.37, overall P=0.007) in the adjusted analysis. Similarly, haplotype analysis showed that AGTR1 SNPs were associated with 50% decline in eGFR (global P=0.010). The GG genotype of SNP rs275704 occurred more frequently in African Americans than in non-African Americans (44% vs. 7%, chi2=36.03, P

Background Delayed renal allograft survival (delayed graft function [DGF]) after deceased donor kidney transplantation is associated with an increased risk of allograft loss. Inflammatory response and apoptosis are associated with increased risk of DGF. Study Design Cross-sectional study. Setting & Participants We first recruited 616 recipients of kidneys from 512 deceased kidney donors, and donor DNA was genotyped. These recipients, who were included in a prospective cohort study of 9 transplant centers in the Delaware Valley region, had their DGF outcome obtained through medical record abstraction. We then identified the recipient (n = 349) of the contralateral deceased kidney donor, if not part of the cohort, through the US Renal Data System registry. The final cohort consisted of 965 recipients of deceased donor kidneys from 512 donors. Predictors Donor single-nucleotide polymorphisms in genes for tumor necrosis factor α ( TNF) , transforming growth factor β1 ( TGFB1) , interleukin 10 ( IL10) , p53 (TP53) , and heme oxygenase 1 ( HMOX1) . Outcomes DGF, defined as the need for dialysis therapy in the first week posttransplantation. Secondary outcomes included acute rejection and estimated glomerular filtration rate. Measurements Information for DGF, acute rejection, and estimated glomerular filtration rate for recipients in the Delaware Valley Cohort was obtained through medical record abstraction. For other recipients, information for DGF was obtained from United Network for Organ Sharing forms and Centers for Medicare & Medicaid Services claims in the US Renal Data System registry. Results No association was detected between the TGFB1, IL10, TP53 , and HMOX1 genes and DGF. The G allele of the TNF polymorphism rs3093662 was associated with DGF in an adjusted analysis (odds ratio, 1.85 compared with A allele; 95% confidence interval, 1.16 to 2.96; P = 0.01). However, this association did not achieve statistical significance after adjusting for multiple comparisons. Limitations Inadequate sample size for infrequent genotypes and multiple comparisons. Conclusion Because of the low frequency of donor single-nucleotide polymorphisms of interest, a larger sample size and replication are necessary to confirm these findings on the association of donor genotypes with DGF.

Among recipients of deceased donor kidney transplants, African-Americans experience a more rapid rate of kidney allograft loss than non–African-Americans. The purpose of this study was to characterize and quantify the HLA-A, -B, and -DRB1 allele mismatches and amino acid substitutions at antigen recognition sites among African-American and non–African-American recipients of deceased donor kidney transplants matched at the antigen level. In recipients with zero HLA antigen mismatches, the degree of one or two HLA allele mismatches for both racial groups combined was 47%, 29%, and 11% at HLA-DRB1, HLA-B, and HLA-A, respectively. There was a greater number of allele mismatches in African-Americans than non–African-Americans at HLA-A (P < .0001), -B (P = .096), and -DRB1 loci (P < .0001). For both racial groups, the HLA allele mismatches were predominantly at A2 for HLA-A; B35 and B44 for HLA-B; but multiple specificities for HLA-DRB1. The observed amino acid mismatches were concentrated at a few functional positions in the antigen binding site of HLA-A and -B and -DRB1 molecules. Future studies are ongoing to assess the impact of these HLA mismatches on kidney allograft loss.

Since 1988 over 10 000 simultaneous cadaveric pancreas–kidney transplants (SPK) have been performed in the United States among patients with end-stage renal disease due to Type 1 diabetes (T1DM). The two aims of this study were to assess the impact on kidney allograft survival of (i) SPK versus transplantation of a kidney alone (KA), and (ii) SPK prior to versus after initiation of chronic dialysis. This retrospective, non-concurrent cohort study examined registry data collected from 8323 patients waitlisted in the United States for an SPK and transplanted with either an SPK or a KA during January 1, 1990 – October 31, 2002. SPK recipients had an adjusted hazard ratio for kidney allograft loss of 0.63 (95% CI: 0.51–0.77, p < 0.001) compared to transplantation without pancreas allograft. SPK recipients who received their allografts prior to beginning chronic dialysis had a lower rate of kidney allograft loss than SPK recipients who received their transplant after initiation of chronic dialysis (adjusted hazard rates (HR) = 0.83, 95% CI: 0.69–0.99, p = 0.042). Simultaneous transplantation of pancreas–kidney compared to kidney transplantation alone and SPK prior to the initiation of chronic dialysis compared to SPK after initiation of dialysis were both associated with longer kidney allograft survival.

Purpose The Lung Allocation Score (LAS) has been used since 2005 to rank US lung transplant candidates for access to transplant. A revised LAS (LAS-R) system that will better predict outcomes for the current cohort of transplant patients has been approved and is awaiting implementation. Both the current LAS and LAS-R calculate a candidate’s wait-list mortality risk in the year post-listing and survival likelihood during first year posttransplant. We examined the impact of modifying LAS-R to use a long-term 5-year posttransplant survival model (LAS-R5). Methods and Materials SRTR standard analysis files were used to estimate posttransplant survival for lung recipients, 5/4/05-9/30/11. We calculated the LAS for all lung-only candidates aged ≥ 12 years on the waiting list 4/1/2011 using three models: current LAS, LAS-R, and LAS-R5. Using the same variables and parameter estimates for the LAS-R 5-year and 1-year models, we compared C statistics and Hosmer-Lemeshow tests to assess model fit. Results Boxplots show increased LAS-R for diagnosis group B compared with LAS, but LAS-R5 is similar to LAS-R. [ figure 1 ] C statistics for all models are comparable (LAS = 0.59, LAS-R = 0.61, LAS-R5 = 0.58), suggesting similar survival predictive power. However, the Hosmer-Lemeshow test (P = 0.0214) for the LAS-R5 indicates that observed mortality rates do not match expected event rates in subgroups of the model. Conclusions Using long-term 5-year survival with the LAS-R covariates does not improve LAS prediction of posttransplant survival likelihood. Possibly, because wait-list mortality risk is given twice the weight of posttransplant survival in LAS calculation, changes in posttransplant covariates do not significantly impact the LAS.

Context Solid organ transplant recipients have elevated cancer risk due to immunosuppression and oncogenic viral infections. Because most prior research has concerned kidney recipients, large studies that include recipients of differing organs can inform cancer etiology. Objective To describe the overall pattern of cancer following solid organ transplantion. Design, Setting, and Participants Cohort study using linked data on solid organ transplant recipients from the US Scientific Registry of Transplant Recipients (1987-2008) and 13 state and regional cancer registries. Main Outcome Measures Standardized incidence ratios (SIRs) and excess absolute risks (EARs) assessing relative and absolute cancer risk in transplant recipients compared with the general population. Results The registry linkages yielded data on 175 732 solid organ transplants (58.4% for kidney, 21.6% for liver, 10.0% for heart, and 4.0% for lung). The overall cancer risk was elevated with 10 656 cases and an incidence of 1375 per 100 000 person-years (SIR, 2.10 [95% CI, 2.06-2.14]; EAR, 719.3 [95% CI, 693.3-745.6] per 100 000 person-years). Risk was increased for 32 different malignancies, some related to known infections (eg, anal cancer, Kaposi sarcoma) and others unrelated (eg, melanoma, thyroid and lip cancers). The most common malignancies with elevated risk were non-Hodgkin lymphoma (n = 1504; incidence: 194.0 per 100 000 person-years; SIR, 7.54 [95% CI, 7.17-7.93]; EAR, 168.3 [95% CI, 158.6-178.4] per 100 000 person-years) and cancers of the lung (n = 1344; incidence: 173.4 per 100 000 person-years; SIR, 1.97 [95% CI, 1.86-2.08]; EAR, 85.3 [95% CI, 76.2-94.8] per 100 000 person-years), liver (n = 930; incidence: 120.0 per 100 000 person-years; SIR, 11.56 [95% CI, 10.83-12.33]; EAR, 109.6 [95% CI, 102.0-117.6] per 100 000 person-years), and kidney (n = 752; incidence: 97.0 per 100 000 person-years; SIR, 4.65 [95% CI, 4.32-4.99]; EAR, 76.1 [95% CI, 69.3-83.3] per 100 000 person-years). Lung cancer risk was most elevated in lung recipients (SIR, 6.13 [95% CI, 5.18-7.21]) but also increased among other recipients (kidney: SIR, 1.46 [95% CI, 1.34-1.59]; liver: SIR, 1.95 [95% CI, 1.74-2.19]; and heart: SIR, 2.67 [95% CI, 2.40-2.95]). Liver cancer risk was elevated only among liver recipients (SIR, 43.83 [95% CI, 40.90-46.91]), who manifested exceptional risk in the first 6 months (SIR, 508.97 [95% CI, 474.16-545.66]) and a 2-fold excess risk for 10 to 15 years thereafter (SIR, 2.22 [95% CI, 1.57-3.04]). Among kidney recipients, kidney cancer risk was elevated (SIR, 6.66 [95% CI, 6.12-7.23]) and bimodal in onset time. Kidney cancer risk also was increased in liver recipients (SIR, 1.80 [95% CI, 1.40-2.29]) and heart recipients (SIR, 2.90 [95% CI, 2.32-3.59]). Conclusion Compared with the general population, recipients of a kidney, liver, heart, or lung transplant have an increased risk for diverse infection-related and unrelated cancers.

Although liberalization of donor criteria could expand the donor pool, the use of certain "marginal donors," such as those who are hepatitis C virus (HCV) positive, is controversial. Little is known about the effect of donor HCV positivity on survival in cardiac transplantation.To examine the association between donor HCV positivity and survival among heart transplant recipients and to determine the effects of recipient age and recipient HCV status on this association.A multicenter cohort study was performed using the US Scientific Registry of Transplant Recipients. Adult heart transplant patients who received their transplants between April 1, 1994, and July 31, 2003, were eligible for inclusion.All-cause mortality.Of 10 915 patients meeting entry criteria, 261 received an HCV-positive donor heart. Mortality was higher among recipients of HCV-positive donor hearts at 1 year (16.9% vs 8.2%; P.001), 5 years (41.8% vs 18.5%; P.001), and 10 years (50.6% vs 24.3%; P.001). Using Kaplan-Meier methods, 1-, 5-, and 10-year survival rates were 83%, 53%, and 25%, and 92%, 77%, and 53% for recipients of HCV-positive and HCV-negative donor hearts, respectively (P.001, log-rank test). Recipients of HCV-positive donor hearts were more likely to die of liver disease and coronary vasculopathy. After propensity matching, the overall hazard ratio (HR) associated with receipt of an HCV-positive donor heart was 2.10 (95% confidence interval [CI], 1.60-2.75). Stratified analyses showed that HRs did not vary by recipient HCV status or by recipient age (for recipients aged 18-39 years: HR, 1.75 [95% CI, 0.70-4.40]; for recipients aged 40-59 years: HR, 2.23 [95% CI, 1.42-3.52]; and for recipients aged 60 years and older: HR, 2.07 [95% CI, 1.32-3.27]; overall P value for interaction,.10).Receipt of a heart from an HCV-positive donor is associated with decreased survival in heart transplant recipients. This association appears to be independent of recipient HCV status and age. Preferential allocation of HCV-positive donors to HCV-positive recipients and/or older recipients is not warranted.

Many heart transplant recipients experience nephrotoxicity caused by cyclosporine. Tacrolimus has been associated with similar efficacy and safety in heart transplant recipients compared with cyclosporine. It is unknown whether there is any benefit to switching calcineurin inhibition from cyclosporine to tacrolimus in heart transplant recipients with presumed cyclosporine nephrotoxicity. We report five such cases in which this approach was used successfully. In these cases, the heart transplant recipients had bland urine sediments, low urinary sodium concentrations, adequate cardiovascular and systemic hemodynamics, and cyclosporine levels within or below the therapeutic range as defined by heart transplant criteria. The mechanism of renal failure in these patients was believed to be consistent with renal hypoperfusion secondary to cyclosporine-induced renal vasoconstriction. Conversion to tacrolimus resulted in a prompt and significant improvement in serum creatinine concentrations in these patients ( P = 0.002). This report shows that conversion to tacrolimus may represent a useful therapeutic strategy to reduce cyclosporine-associated renal failure in recipients of orthotopic heart transplants. © 2002 by the National Kidney Foundation, Inc.

Willingness of dialysis patients to participate in a randomized controlled trial of daily dialysis. Background. The National Institutes of Health (NIH) has proposed conducting randomized controlled trials comparing short, daily, in-center hemodialysis with conventional hemodial- ysis. However, there is concern that difficulties recruiting pa- tients may prevent the successful completion of such trials if patients believe the inconveniences of daily dialysis outweigh any potential health benefits. Methods. To gauge willingness to participate in a daily dialysis trial, we described a hypothetical, randomized controlled trial comparing conventional to daily hemodialysis to 209 chronic hemodialysis patients, and assessed their motivations for and concerns about participating. Results. We found that 85 patients (41%) of 209 patients who agreed to be interviewed expressed some willingness to partic- ipate in the hypothetical trial. Patients who expressed greater willingness to participate were younger (OR for participating = 0.96 per year, 95% CI = 0.94 to 0.98, P = 0.001), less likely to smoke (OR = 0.38, 95% CI = 0.17 to 0.84, P = 0.017), more likely to have been hospitalized during the last 12 months (OR = 2.8, 95% CI = 1.5 to 5.5, P = 0.002), less likely to have reactive airway disease (OR = 0.21, 95% CI = 0.06 to 0.69, P = 0.01) or coronary artery disease (OR = 0.20, 95% CI = 0.08 to 0.53, P = 0.001), and less likely to be on the waiting list for a kidney transplant (OR = 0.23, 95% CI = 0.10 to 0.50, P < 0.0001). Conclusion. The study suggests that less than half of eligible patients would be willing to participate in the randomized con- trolled trial. Differing willingness to participate across patient subgroups suggests that certain subgroups (i.e., older patients and those with coronary artery disease) will need to be targeted to ensure that results are generalizable to most hemodialysis patients.