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This review discusses demographics, survival, and risks in kidney transplantation since the mid-1990s. It addresses postoperative events that impede long-term survival, as well as factors relevant to racial or ethnic minority recipients and health care coverage for immunosuppressive agents.

Patients in the US in need of a life-saving organ transplant must complete a long process of medical decisions, and a first step is to identify a transplant center to complete an evaluation. This study describes a patient-centered process of testing and refinement of a new website ( www.transplantcentersearch.org ) that was developed to provide data to patients who are seeking a transplant center. Mixed methods, including online surveys and structured usability testing, were conducted to inform changes in an iterative process. Survey data from 684 participants indicated the effects of different icon styles on user decisions. Qualitative feedback from 38 usability testing participants informed improvements to the website interface. The mixed methods approach was feasible and well suited to the need to address multiple development steps of a patient-facing tool. The combined methods allowed for large survey sample sizes and also allowed interaction with a functioning website and in-depth qualitative discussions. The approach is applicable for a broad range of target user groups who are faced with challenging decisions and a need for information tailored to individual users. The survey and usability testing concluded with a functioning website that is positively received by users and meets the objective to support patient decisions when seeking an organ transplant.

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.

We performed RNA sequencing (RNAseq) on peripheral blood mononuclear cells (PBMCs) to identify differentially expressed gene transcripts (DEGs) after kidney transplantation and after the start of immunosuppressive drugs. RNAseq is superior to microarray to determine DEGs because it's not limited to available probes, has increased sensitivity, and detects alternative and previously unknown transcripts. DEGs were determined in 32 adult kidney recipients, without clinical acute rejection (AR), treated with antibody induction, calcineurin inhibitor, mycophenolate, with and without steroids. Blood was obtained pre-transplant (baseline), week 1, months 3 and 6 post-transplant. PBMCs were isolated, RNA extracted and gene expression measured using RNAseq. Principal components (PCs) were computed using a surrogate variable approach. DEGs post-transplant were identified by controlling false discovery rate (FDR) at < 0.01 with at least a 2 fold change in expression from pre-transplant. The top 5 DEGs with higher levels of transcripts in blood at week 1 were TOMM40L, TMEM205, OLFM4, MMP8, and OSBPL9 compared to baseline. The top 5 DEGs with lower levels at week 1 post-transplant were IL7R, KLRC3, CD3E, CD3D, and KLRC2 (Striking Image) compared to baseline. The top pathways from genes with lower levels at 1 week post-transplant compared to baseline, were T cell receptor signaling and iCOS-iCOSL signaling while the top pathways from genes with higher levels than baseline were axonal guidance signaling and LXR/RXR activation. Gene expression signatures at month 3 were similar to week 1. DEGs at 6 months post-transplant create a different gene signature than week 1 or month 3 post-transplant. RNAseq analysis identified more DEGs with lower than higher levels in blood compared to baseline at week 1 and month 3. The number of DEGs decreased with time post-transplant. Further investigations to determine the specific lymphocyte(s) responsible for differential gene expression may be important in selecting and personalizing immune suppressant drugs and may lead to targeted therapies.

Determine the effect of the genetic variants beyond CYP3A5*3 on tacrolimus disposition. We studied genetic correlates of tacrolimus trough concentrations with POR*28, CYP3A4*22 and ABCC2 haplotypes in a large, ethnically diverse kidney transplant cohort (n = 2008). Subjects carrying one or more CYP3A5*1 alleles had lower tacrolimus trough concentrations (p = 9.2 × 10 ). The presence of one or two POR*28 alleles was associated with a 4.63% reduction in tacrolimus trough concentrations after adjusting for CYP3A5*1 and clinical factors (p = 0.037). In subset analyses, POR*28 was significant only in CYP3A5*3/*3 carriers (p = 0.03). The CYP3A4*22 variant and the ABBC2 haplotypes were not associated. This study confirmed that CYP3A5*1 was associated with lower tacrolimus trough concentrations. POR*28 was associated with decreased tacrolimus trough concentrations although the effect was small possibly through enhanced CYP3A4 enzyme activity. CYP3A4*22 and ABCC2 haplotypes did not influence tacrolimus trough concentrations. Original submitted 19 December 2014; Revision submitted 2 April 2015

Background African American (AA) recipients of deceased-donor (DD) kidney transplants (KT) have shorter allograft survival than recipients of other ethnic groups. Reasons for this disparity encompass complex interactions between donors and recipients characteristics. Methods Outcomes from 3872 AA and 19,719 European American (EA) DDs who had one kidney transplanted in an AA recipient and one in an EA recipient were analyzed. Four donor/recipient pair groups (DRP) were studied, AA/AA, AA/EA, EA/AA, and EA/EA. Survival random forests and Cox proportional hazard models were fitted to rank and evaluate modifying effects of DRP on variables associated with allograft survival. These analyses sought to identify factors contributing to the observed disparities in transplant outcomes among AA and EA DDKT recipients. Results Transplant era, discharge serum creatinine, delayed graft function, and DRP were among the top predictors of allograft survival and mortality among DDKT recipients. Interaction effects between DRP with the kidney donor risk index and transplant era showed significant improvement in allograft survival over time in EA recipients. However, AA recipients appeared to have similar or poorer outcomes for DDKT performed after 2010 versus before 2001; allograft survival hazard ratios (95% CI) were 1.15 (0.74, 1.76) and 1.07 (0.8, 1.45) for AA/AA and EA/AA, compared to 0.62 (0.54, 0.71) and 0.5 (0.41, 0.62) for EA/EA and AA/EA DRP, respectively. Recipient mortality improved over time among all DRP, except unemployed AA/AAs. Relative to DDKT performed pre-2001, employed AA/AAs had HR = 0.37 (0.2, 0.69) versus 0.59 (0.31, 1.11) for unemployed AA/AA after 2010. Conclusion Relative to DDKT performed before 2001, similar or worse overall DCAS was observed among AA/AAs, while EA/EAs experienced considerable improvement regardless of employment status, KDRI, and EPTS. AA recipients of an AA DDKT, especially if unemployed, had worse allograft survival and mortality and did not appear to benefit from advances in care over the past 20 years.

Apolipoprotein L1 gene (APOL1) G1 and G2 renal-risk variants, common in populations with recent African ancestry, are strongly associated with non-diabetic nephropathy, end-stage kidney disease, and shorter allograft survival in deceased-donor kidneys (autosomal recessive inheritance). Circulating APOL1 protein is synthesized primarily in the liver and hydrodynamic gene delivery of APOL1 G1 and G2 risk variants has caused hepatic necrosis in a murine model. To evaluate the impact of these variants in liver transplantation, this multicenter study investigated the association of APOL1 G1 and G2 alleles in deceased African American liver donors with allograft survival. Transplant recipients were followed for liver allograft survival using data from the Scientific Registry of Transplant Recipients. Of the 639 liver donors evaluated, 247 had no APOL1 risk allele, 300 had 1 risk allele, and 92 had 2 risk alleles. Graft failure assessed at 15 days, 6 months, 1 year and total was not significantly associated with donor APOL1 genotype (p-values = 0.25, 0.19, 0.67 and 0.89, respectively). In contrast to kidney transplantation, deceased-donor APOL1 G1 and G2 risk variants do not significantly impact outcomes in liver transplantation.

Post-transplant diabetes mellitus (PTDM) reduces allograft and recipient life span. Polygenic risk scores (PRSs) show robust association with greater risk of developing type 2 diabetes (T2D). We examined the association of PTDM with T2D PRS in liver recipients ( n  = 1,581) and their donors ( n  = 1,555), and kidney recipients ( n  = 2,062) and their donors ( n  = 533). Recipient T2D PRS was associated with pre-transplant T2D and the development of PTDM. T2D PRS in liver donors, but not in kidney donors, was an independent risk factor for PTDM development. The inclusion of a combined liver donor and recipient T2D PRS significantly improved PTDM prediction compared with a model that included only clinical characteristics: the area under the curve (AUC) was 67.6% (95% confidence interval (CI) 64.1–71.1%) for the combined T2D PRS versus 62.3% (95% CI 58.8–65.8%) for the clinical characteristics model ( P  = 0.0001). Liver recipients in the highest quintile of combined donor and recipient T2D PRS had the greatest risk of PTDM, with an odds ratio of 3.22 (95% CI 2.07–5.00) (P  = 1.92 × 10 −7 ) compared with those in the lowest quintile. In conclusion, T2D PRS identifies transplant candidates with high risk of PTDM for which pre-emptive diabetes management and donor selection may be warranted. The analysis of large transplant cohorts reveals that in the context of liver transplant, but not kidney transplant, both the donor and the recipient type 2 diabetes polygenic risk scores influence the risk of developing post-transplant diabetes.

OBJECTIVES/GOALS: AA are over-represented on the waitlist for kidney transplant and are often unaware of how waitlist acceptance practices differ across transplant programs and influence access to transplant. We will develop a culturally sensitive transplant program report card to communicate these variations. METHODS/STUDY POPULATION: Scientific Registry of Transplant Recipients (SRTR) data will be used to identity clinical factors strongly associated with AA access to transplant. Interviews and focus groups with AA kidney transplant candidates and their families will collect feedback on the SRTR report card and inform the development of the culturally sensitive report card. Additional focus groups will evaluate its effect on knowledge and medical decision making. We will collaborate with the stakeholders, including AA transplant candidates and their families, transplant programs, SRTR, and providers, to identify strategies to disseminate the report card in the AA community RESULTS/ANTICIPATED RESULTS: To date, no investigation has systematically collected feedback on the SRTR transplant program report card from AA candidates to ensure that the tool is accessible and effective in the AA community. We hypothesize that a culturally sensitive report card will improve AA candidates’ knowledge of program factors that impact access to transplant and enable informed decisions about where they pursue a transplant evaluation. The results of this study have the potential to change how AA patients are counselled while seeking transplantation. DISCUSSION/SIGNIFICANCE OF IMPACT: A culturally sensitive report card can reach more AA patients and enable more informed decision making by providing education about differences in transplant programs that may impact their access to transplant. In the future, we will design a trial to evaluate the prototype.