Polygenic risk score for acute rejection based on donor-recipient non-HLA genotype mismatch.

BACKGROUND: Acute rejection (AR) after kidney transplantation is an important allograft complication. To reduce the risk of post-transplant AR, determination of kidney transplant donor-recipient mismatching focuses on blood type and human leukocyte antigens (HLA), while it remains unclear whether non-HLA genetic mismatching is related to post-transplant complications. METHODS: We carried out a genome-wide scan (HLA and non-HLA regions) on AR with a large kidney transplant cohort of 784 living donor-recipient pairs of European ancestry. An AR polygenic risk score (PRS) was constructed with the non-HLA single nucleotide polymorphisms (SNPs) filtered by independence (r2 < 0.2) and P-value (< 1×10-3) criteria. The PRS was validated in an independent cohort of 352 living donor-recipient pairs. RESULTS: By the genome-wide scan, we identified one significant SNP rs6749137 with HR = 2.49 and P-value = 2.15×10-8. 1,307 non-HLA PRS SNPs passed the clumping plus thresholding and the PRS exhibited significant association with the AR in the validation cohort (HR = 1.54, 95% CI = (1.07, 2.22), p = 0.019). Further pathway analysis attributed the PRS genes into 13 categories, and the over-representation test identified 42 significant biological processes, the most significant of which is the cell morphogenesis (GO:0000902), with 4.08 fold of the percentage from homo species reference and FDR-adjusted P-value = 8.6×10-4. CONCLUSIONS: Our results show the importance of donor-recipient mismatching in non-HLA regions. Additional work will be needed to understand the role of SNPs included in the PRS and to further improve donor-recipient genetic matching algorithms. Trial registry: Deterioration of Kidney Allograft Function Genomics (NCT00270712) and Genomics of Kidney Transplantation (NCT01714440) are registered on ClinicalTrials.gov.

Extreme Phenotype Sampling and Next Generation Sequencing to Identify Genetic Variants Associated with Tacrolimus in African American Kidney Transplant Recipients.

African American (AA) kidney transplant recipients (KTRs) have poor outcomes, which may in-part be due to tacrolimus (TAC) sub-optimal immunosuppression. We previously determined the common genetic regulators of TAC pharmacokinetics in AAs which were CYP3A5 *3, *6, and *7. To identify low-frequency variants that impact TAC pharmacokinetics, we used extreme phenotype sampling and compared individuals with extreme high (n=58) and low (n=60) TAC troughs (N=515 AA KTRs). Targeted next generation sequencing was conducted in these two groups. Median TAC troughs in the high group were 7.7 ng/ml compared with 6.3 ng/ml in the low group, despite lower daily doses of 5 versus 12mg, respectively. Of 34,542 identified variants across 99 genes, 1,406 variants were suggestively associated with TAC troughs in univariate models (p-value <0.05), however none were significant after multiple testing correction. We suggest future studies investigate additional sources of TAC pharmacokinetic variability such as drug-drug-gene interactions and pharmacomicrobiome.

OPTN/SRTR 2022 Annual Data Report: Introduction.

The OPTN/SRTR 2022 Annual Data Report presents the status of the solid organ transplant system in the United States from 2011 through 2022. Organ-specific chapters are presented for kidney, pancreas, liver, intestine, heart, and lung transplant. Each organ-specific chapter is organized to present waitlist information, donor information (both deceased and living, as appropriate), transplant information, and patient outcomes. Data pertaining to pediatric patients are generally presented separately from the adult data. In addition to the organ-specific chapters, the reader will find chapters dedicated to deceased organ donation, vascularized composite allografts, and the COVID-19 pandemic. The data presented in the Annual Data Report are descriptive in nature. In other words, most tables and figures present raw data without statistical adjustment for possible confounding or changes over time. Therefore, the reader should keep in mind the observational nature of the data when attempting to draw inferences before trying to ascribe a cause to any observed patterns or trends. This introduction provides a brief overview of trends in waitlist and transplant activity from 2012 through 2022. More detailed descriptions can be found in the respective organ-specific chapters.

OPTN/SRTR 2022 Annual Data Report: Lung.

For the first time since the COVID-19 pandemic, the annual number of lung transplants performed in the United States increased. The year 2022, encompassed in this report, marks the last full calendar year where the Lung Allocation Score was used for ranking transplant candidates based on their estimated transplant benefit and donor lung allocation in the United States. In March 2023, a major change in transplant allocation policy occurred with the implementation of the Composite Allocation Score. Transplant rates have increased over the past decade, although there is variability among age, diagnosis, racial and ethnic, and blood groups. Over half of candidates received a lung transplant within 3 months of placement on the waiting list, with nearly 75% of candidates accessing transplant by 1 year. Pretransplant mortality rates remained stable, with approximately 13% of lung transplant candidates dying or being removed from the waiting list within a year of listing. Posttransplant survival remained stable; however, variability exists by age, diagnosis, and racial and ethnic groups.

OPTN/SRTR 2022 Annual Data Report: Liver.

In 2022, liver transplant activity continued to increase in the United States, with an all-time high of 9,527 transplants performed, representing a 52% increase over the past decade (2012-2022). Of these transplants, 8,924 (93.7%) were from deceased donors and 603 (6.3%) were from living donors. Liver transplant recipients were 94.5% adult and 5.5% pediatric. The overall size of the liver transplant waiting list contracted, with more patients being removed than added, although 10,548 adult patients still remained on the waiting list at the end of 2022. Alcohol-associated liver disease continued to be the leading diagnosis among both candidates and recipients, followed by metabolic dysfunction-associated steatohepatitis. Simultaneous liver-kidney transplant was the most common multiorgan combination, with 800 liver-kidney transplants performed in 2022; in addition, there were 303 new listings for kidney transplant via the safety net mechanism. Among adults added to the liver waiting list in 2021, 39.9% received a deceased donor liver transplant within 3 months; 45.7%, within 6 months; and 54.5%, within 1 year. Pretransplant mortality decreased to 12.3 deaths per 100 patient-years in 2022, although still 15.6% of removals from the waiting list were for death or being too sick for transplant. Graft and patient survival outcomes after deceased donor liver transplant improved, approximating pre-COVID-19 pandemic levels, with 5.1% mortality observed at 6 months; 6.8%, at 1 year; 12.7%, at 3 years; 19.8%, at 5 years; and 35.7%, at 10 years. Five-year graft and patient survival rates after living donor liver transplant exceeded those of deceased donor liver transplant. Candidates receiving model for end-stage liver disease exception points for hepatocellular carcinoma constituted 15.5% of transplants performed in 2022, with similar transplant rates and posttransplant outcomes compared to cases without hepatocellular carcinoma exception. In 2022, more pediatric liver transplant candidates were added to the waiting list and underwent transplant compared with either of the preceding 2 years, with an uptick in living donor liver transplant volume. Although pretransplant mortality has improved after the recent policy change prioritizing pediatric donors for pediatric recipients, still, in 2022, 50 children died or were removed from the waiting list for being too sick to undergo transplant. Posttransplant mortality among pediatric liver transplant recipients remained notable, with death occurring in 4.0% at 6 months, 6.0% at 1 year, 8.2% at 3 years, 9.8% at 5 years, and 13.9% at 10 years. Similar to adult living donor recipients, pediatric living donor recipients had better 5-year patient survival compared with deceased donor recipients.

OPTN/SRTR 2022 Annual Data Report: COVID-19.

This chapter updates the COVID-19 chapter from the 2021 Annual Data Report with trends through November 12, 2022, and introduces trends in recovery and use of organs from donors with a positive COVID-19 test. Posttransplant mortality and graft failure, which remained a concern in all organs at the last report due to the Omicron variant wave, have returned to lower levels in the most recent available data through November 2022. Use of organs from donors with a positive COVID-19 test has grown, particularly after the first year of the pandemic. Mortality due to COVID-19 should continue to be monitored, but most other measures have sustained their recovery and may now be responding more to changes in policy than to ongoing concerns with COVID-19.

Pediatric Lung Transplant Outcomes Based on Immunosuppressive Regimen at Discharge: Retrospective Cohort Study Using Real-World Evidence From the US Scientific Registry of Transplant Recipients.

BACKGROUND: This retrospective analysis of the US Scientific Registry of Transplant Recipients was undertaken to obtain real-world evidence concerning the efficacy and safety of tacrolimus-based immunosuppression in pediatric lung transplant recipients to support a supplemental New Drug Application. METHODS: Overall, 725 pediatric recipients of a primary deceased-donor lung transplant between January 1, 1999, and December 31, 2017, were followed for up to 3 years post-transplant based on an immunosuppressive regimen at hospital discharge: immediate-release tacrolimus (TAC)+mycophenolate mofetil (MMF), TAC+azathioprine (AZA), cyclosporine (CsA)+MMF, or CsA+AZA. The primary outcome was the composite endpoint of graft failure or death (all-cause) at 1 year post-transplant, calculated by Kaplan-Meier analysis. RESULTS: The use of TAC+MMF increased over time. During 2010 to 2017, 91.7% of pediatric lung transplant recipients were receiving TAC+MMF at the time of discharge. The proportion of recipients continuing their discharge regimen at 1 year post-transplant was 83.7% with TAC+MMF and 40.4% to 59.7% with the other regimens. Cumulative incidence of the composite endpoint of graft failure or death at 1 year post-transplant was 7.7% with TAC+MMF, 13.9% with TAC+AZA, 8.9% with CsA+MMF, and 9.1% with CsA+AZA. There was no significant difference in the risk of graft failure or death at 1 year post-transplant between groups from 1999 to 2005 (the only era when adequate numbers on each regimen allowed statistical comparison). No increase in hospitalization for infection or malignancy was seen with TAC+MMF. CONCLUSION: The real-world evidence from the US database of transplant recipients supported the Food and Drug Administration's approval of tacrolimus-based maintenance immunosuppression in pediatric lung transplant recipients.

OPTN/SRTR 2021 Annual Data Report: Lung.

The number of lung transplants has continued to decline since 2020, a period that coincides with the onset of the COVID-19 pandemic. Lung allocation policy continues to undergo considerable change in preparation for adoption of the Composite Allocation Score system in 2023, beginning with multiple adaptations to the calculation of the Lung Allocation Score that occurred in 2021. The number of candidates added to the waiting list increased after a decline in 2020, while waitlist mortality has increased slightly with a decreased number of transplants. Time to transplant continues to improve, with 38.0% of candidates waiting fewer than 90 days for a transplant. Posttransplant survival remains stable, with 85.3% of transplant recipients surviving to 1 year; 67%, to 3 years; and 54.3%, to 5 years.

OPTN/SRTR 2021 Annual Data Report: Liver.

In 2021, liver transplant volume continued to grow, with a record 9,234 transplants performed in the United States, 8,665 (93.8%) from deceased donors and 569 (6.2%) from living donors. There were 8,733 (94.6%) adult and 501 (5.4%) pediatric liver transplant recipients. An increase in the number of deceased donor livers corresponded to an increase in the overall transplant rate and shorter waiting times, although still 10.0% of livers that were recovered were not transplanted. Alcohol-associated liver disease was the leading indication for both waitlist registration and liver transplant in adults, outpacing nonalcoholic steatohepatitis, while biliary atresia remained the leading indication for children. Related to allocation policy changes implemented in 2019, the proportion of liver transplants performed for hepatocellular carcinoma has decreased. Among adult candidates listed for liver transplant in 2020, 37.7% received a deceased donor liver transplant within 3 months, 43.8% within 6 months, and 53.3% within 1 year. Pretransplant mortality improved for children following implementation of acuity circle-based distribution. Short-term graft and patient survival outcomes up to 1 year worsened for adult deceased and living donor liver transplant recipients, which is a reversal of previous trends and coincided with the onset of the COVID-19 pandemic in early 2020. Longer-term outcomes among adult deceased donor liver transplant recipients were unaffected, with overall posttransplant mortality rates of 13.3% at 3 years, 18.6% at 5 years, and 35.9% at 10 years. Pretransplant mortality improved for children following implementation of acuity circle-based distribution and prioritization of pediatric donors to pediatric recipients in 2020. Pediatric living donor recipients had superior graft and patient survival outcomes compared with deceased donor recipients at all time points.

OPTN/SRTR 2021 Annual Data Report: Introduction.

The OPTN/SRTR 2021 Annual Data Report presents the status of the solid organ transplantation system in the United States from 2010 through 2021. Organ-specific chapters are presented for kidney, pancreas, liver, intestine, heart, and lung transplant. Each organ-specific chapter is organized to present waitlist information, donor information (both deceased and living, as appropriate), transplant information, and patient outcomes. Data pertaining to pediatric patients are generally presented separately from the adult data. In addition to the organ-specific chapters, you will find chapters dedicated to deceased organ donation, vascularized composite allograft, and the COVID-19 pandemic. The data presented in the Annual Data Report are descriptive in nature. In other words, most tables and figures present raw data without statistical adjustment for possible confounding or changes over time. Therefore, the reader should keep in mind the observational nature of the data when attempting to draw inferences before trying to ascribe a cause to any observed patterns or trends. This introduction provides a brief overview of trends in waitlist and transplant activity. More detailed descriptions can be found in the respective organ-specific chapters.

Higher number of tacrolimus dose adjustments in kidney transplant recipients who are extensive and intermediate CYP3A5 metabolizers.

Kidney transplant recipients carrying the CYP3A5*1 allele have lower tacrolimus troughs, and higher dose requirements compared to those with the CYP3A5*3/*3 genotype. However, data on the effect of CYP3A5 alleles on post-transplant tacrolimus management are lacking. The effect of CYP3A5 metabolism phenotypes on the number of tacrolimus dose adjustments and troughs in the first 6 months post-transplant was evaluated in 78 recipients (64% Caucasians). Time to first therapeutic concentration, percentage of time in therapeutic range (TTR), and estimated glomerular filtration rate (eGFR) were also evaluated. Fifty-five kidney transplant recipients were CYP3A5 poor metabolizers (PM), 17 were intermediate metabolizers (IM), and 6 were extensive metabolizers (EM). Compared to PMs, EMs/IMs had significantly more dose adjustments (6.1 vs. 8.1, p = .015). Overall, 33.82% of trough measurements resulted in a dose change. There was no difference in the number of tacrolimus trough measurements between PMs and EM/IMs. The total daily tacrolimus dose requirements were higher in EMs and IMs compared to PMs (<.001). TTR was ∼50% in the PMs and EMs/IMs groups. CYP3A5 EM/IM metabolizers have more tacrolimus dose changes and higher dose requirements which increases clinical management complexity. Larger studies are needed to assess the cost and benefits of including genotyping data to improve clinical management.

Lung Transplant Outcomes in Adults in the United States: Retrospective Cohort Study Using Real-world Evidence from the SRTR.

BACKGROUND: The Scientific Registry of Transplant Recipients was retrospectively analyzed to provide real-world evidence of the efficacy and safety of tacrolimus-based immunosuppressive regimens in adult lung transplant recipients in the United States. METHODS: Adult recipients (N = 25 355; ≥18 y) of a primary deceased-donor lung transplant between January 1, 1999, and December 31, 2017, were followed for 3 y posttransplant based on immunosuppressive regimen at discharge: immediate-release tacrolimus (TAC) + mycophenolate mofetil (MMF), TAC + azathioprine (AZA), cyclosporine (CsA) + MMF, or CsA + AZA. The primary outcome was the composite endpoint of graft failure or death (all-cause) at 1 y posttransplant (calculated via a modified Kaplan-Meier method). RESULTS: Discharge immunosuppressive regimens in lung transplant recipients changed over time, with a substantial increase in the use of TAC + MMF. TAC + MMF was the most common immunosuppressive regimen (received by 61.0% of individuals at discharge). The cumulative incidence of graft failure or death at 1 y posttransplant in adult lung transplant patients receiving TAC + MMF was 8.6% (95% confidence interval 8.1-9.1). Risk of graft failure or death was significantly higher in adults receiving CsA + MMF or CsA + AZA compared with TAC + MMF, with no significant difference seen between TAC + MMF and TAC + AZA. TAC + MMF had the highest continued use at 1 y posttransplant (72.0% versus 35.4%-51.5% for the other regimens). There was no increase in the rate of infection or malignancy in the TAC + MMF group. CONCLUSIONS: Real-world evidence from the most comprehensive database of transplant recipients in the United States supports the use of TAC in combination with MMF or AZA as maintenance immunosuppression in adult lung transplant recipients.

Cost, healthcare utilization, and outcomes of antibody-mediated rejection in kidney transplant recipients in the US.

BACKGROUND: Antibody-mediated rejection (AMR) is one of the leading causes of graft loss in kidney transplant recipients but little is known about the associated cost and healthcare burden of AMR. METHODS: We developed an algorithm to detect AMR using the 2006-2011 Centers for Medicare & Medicaid Services (CMS) using ICD-10 and billing codes as there is no specific ICD-10 or procedure code for AMR. We then compared healthcare utilization, cost, and risk of graft failure or death in AMR. patients versus matched controls. RESULTS: The algorithm had a 39.4% true-positive rate (69/175) and a 4.1% false-positive rate (110/2,655). We identified 5,679/101,554 (5.6%) with AMR, who had a nearly 3-fold higher risk of graft failure (hazard ratio [HR], 2.75, 95% confidence interval [CI], 2.50 to 3.03; p < .0001) and death (HR, 2.59; 95% CI, 2.35 to 2.86; p < .0001) at 2 years, nearly 5 times the hospitalizations in the 60 d before AMR diagnosis, and increased nephrology and emergency department visits. Mean AMR attributable healthcare costs were 4 times higher than matched controls, at $13,066 more per patient in the 60 d before AMR diagnosis and $35,740 per patient per year higher in the 2 years after AMR diagnosis. CONCLUSIONS: US kidney transplant recipients with AMR have substantially greater healthcare utilization and higher costs and risk of graft loss and mortality.

Incidence, risk factors, and long-term outcomes associated with antibody-mediated rejection - The long-term Deterioration of Kidney Allograft Function (DeKAF) prospective cohort study.

Major gaps remain in our understanding of antibody-mediated rejection (AMR) after kidney transplant. We examined the incidence, risk factors, response to treatment, and effects on outcomes of AMR at seven transplant programs in the long-term Deterioration of Kidney Allograft Function prospective study cohort. Among 3131 kidney recipients, there were 194 observed AMR cases (6.2%) during (mean ± SD) 4.85 ± 1.86 years of follow-up. Time to AMR was 0.97 ± 1.17 (median, 0.48) years. Risk factors for AMR included younger recipient age, human leukocyte antigen DR mismatches, panel-reactive antibody >0%, positive T- or B-cell cross-match, and delayed graft function. Compared with no AMR, the adjusted time-dependent hazard ratio for death-censored graft failure is 10.1 (95% confidence interval, 6.5-15.7) for all AMR patients, 4.0 (2.5, 9.1) for early AMR (<90 days after transplant), and 24.0 (14.0-41.1) for late AMR (≥90 days after transplant). Patients were treated with different therapeutic combinations. Of 194 kidney transplant recipients with AMR, 50 (25.8%) did not respond to treatment, defined as second AMR within 100 days or no improvement in estimated glomerular filtration rate by 42 days. Long-term outcomes after AMR are poor, regardless of the initial response to treatment. Better prevention and new therapeutic strategies are needed to improve long-term allograft survival.

Designing a patient-specific search of transplant program performance and outcomes: Feedback from heart transplant candidates and recipients.

BACKGROUND: The Scientific Registry of Transplant Recipients provides transplant program-specific information, but it is unclear what patients and stakeholders need to know. Acceptance criteria for the candidate waitlist and donor organs vary by program and region, but there is no means to search for programs by the clinical profiles of recipients and donors. METHODS: We examined variability in program-specific characteristics that could influence access to transplantation. We also conducted three interviews and three focus groups with heart transplant candidates and recipients. Participants evaluated prototypes of a patient-specific search tool and its capacity to identify programs tailored to specific patient needs. Patient experiences and feedback influenced the development of tools. RESULTS: The distribution of recipient and donor characteristics influenced access to transplantation, as age and body mass index varied across programs (all with p < .01). Several themes emerged related to decision-making and the perceived usability of the patient-specific search. Perceptions of the prototypes varied, but were positive overall and support making the patient-specific search publicly available. Participants revealed barriers to evaluating transplant programs and suggest that patient-specific search results may optimize the process. CONCLUSIONS: The patient-specific tool (http://transplantcentersearch.org/) is valued by heart transplant patients and is important to maximizing access to transplant.

Precision Dosing for Tacrolimus Using Genotypes and Clinical Factors in Kidney Transplant Recipients of European Ancestry.

Genetic variation in the CYP3A4 and CYP3A5 (CYP3A4/5) genes, which encode the key enzymes in tacrolimus metabolism, is associated with tacrolimus clearance and dose requirements. Tacrolimus has a narrow therapeutic index with high intra- and intersubject variability, in part because of genetic variation. High tacrolimus clearance and low trough concentration are associated with a greater risk for rejection, whereas high troughs are associated with calcineurin-induced toxicity. The objective of this study was to develop a model of tacrolimus clearance with a dosing equation accounting for genotypes and clinical factors in adult kidney transplant recipients of European ancestry that could preemptively guide dosing. Recipients receiving immediate-release tacrolimus for maintenance immunosuppression from 2 multicenter studies were included. Participants in the GEN03 study were used for tacrolimus model development (n = 608 recipients) and was validated by prediction performance in the DeKAF Genomics study (n = 1361 recipients). Nonlinear mixed-effects modeling was used to develop the apparent oral tacrolimus clearance (CL/F) model. CYP3A4/5 genotypes and clinical covariates were tested for their influence on CL/F. The predictive performance of the model was determined by assessing the bias (median prediction error [ME] and median percentage error [MPE]) and the precision (root median squared error [RMSE]) of the model. CYP3A5*3, CYP3A4*22, corticosteroids, calcium channel blocker and antiviral drug use, age, and diabetes significantly contributed to the interindividual variability of oral tacrolimus apparent clearance. The bias (ME, MPE) and precision (RMSE) of the final model was good, 0.49 ng/mL, 6.5%, and 3.09 ng/mL, respectively. Prospective testing of this equation is warranted.

Improving the predictive ability of the pediatric end-stage liver disease score for young children awaiting liver transplant.

The current pediatric end-stage liver disease (PELD) score underestimates pediatric waitlist mortality. Children frequently require PELD exception points to achieve appropriate priority ranking. We developed a new PELD score using serum sodium, creatinine, and updated original PELD components to more accurately rank children and equalize children's mortality risk with the age-standardized mortality rate of adults. We included children aged younger than 12 years with chronic liver disease, listed for deceased donor livers January 1, 2005-December 31, 2017. Pediatric candidates (n = 5111) were followed from listing to the earliest of waitlist mortality (death or removal from the list due to being too sick to undergo transplant, n = 339) or 180 days. We incorporated linear splines for the current components of PELD and added sodium and creatinine to the equation. The updated PELD-Na-Cr had a cross-validated AUC ROC of 0.854, vs 0.799 for the original PELD. PELD-Na-Cr required 9.44 additional points to equalize children's mortality risk with the age-standardized mortality rate of adults. PELD-Na-Cr better ordered the sickest children and should better prioritize children relative to adults. As a result, PELD-Na-Cr could increase pediatric transplant rates and reduce pediatric liver transplant waitlist mortality.

Development of a Patient-specific Search of Transplant Program Outcomes and Characteristics: Feedback From Kidney Transplant Patients.

BACKGROUND: Patients face obstacles in finding a transplant program that meets their healthcare needs. Acceptance criteria and waiting times vary by region and program. The Scientific Registry of Transplant Recipients provides program-specific information, but it is unclear what patients and referring physicians need to know. METHODS: We examined variability in program-specific characteristics that could influence access to transplantation. We also conducted 20 interviews and 16 focus groups with transplant candidates, recipients, and their family members. Participants were shown prototypes of a patient-specific search tool and evaluated its capacity to identify programs tailored to the needs of individual patients. RESULTS: The distribution of recipient and donor characteristics that may impact access to transplantation, such as recipients on Medicaid, varied across programs (all with P < 0.01). Several themes emerged related to impressions of access to transplantation and the usability of patient-specific search functions. Perceptions of the prototypes and results varied, but were positive overall and support providing an individualized search of program level data. Participants revealed significant barriers to identifying and evaluating transplant programs and suggest that patient-specific search results reduce the anxiety associated with selecting a program. CONCLUSIONS: Providing patient-specific tools is valued by patients and important to maximizing access to transplant.

Pharmacogenomics in kidney transplant recipients and potential for integration into practice.

WHAT IS KNOWN AND OBJECTIVE: Pharmacogenomic biomarkers are now used in many clinical care settings and represent one of the successes of precision medicine. Genetic variants are associated with pharmacokinetic and pharmacodynamic changes leading to medication adverse effects and changes in clinical response. Actionable pharmacogenomic variants are common in transplant recipients and have implications for medications used in transplant, but yet are not broadly incorporated into practice. METHODS: From the Clinical Pharmacogenetics Implementation Consortium and Dutch Pharmacogenetics Working Group guidelines, and PharmGKB databases, 12 pharmacogenomic genes with 30 variants were selected and used to create diplotypes and actionable pharmacogenomic phenotypes. A total of 853 kidney allograft recipients who had genomic information available from a genome-wide association study were included. RESULTS: Each recipient had at least one actionable pharmacogenomic diplotype/phenotype, whereas the majority (58%) had three or four actionable diplotypes/phenotypes and 17.4% had five or more among the 12 genes. The participants carried actionable diplotypes/phenotypes for multiple medications, including tacrolimus, azathioprine, clopidogrel, warfarin, simvastatin, voriconazole, antidepressants and proton-pump inhibitors. WHAT IS NEW AND CONCLUSION: Pharmacogenomic variants are common in transplant recipients, and transplant recipients receive medications that have actionable variants. CLINICAL TRIAL: Genomics of Transplantation, clinicaltrials.gov (NCT01714440).