The effect of Share 35 on biliary complications: An interrupted time series analysis.

The purpose of the Share 35 allocation policy was to improve liver transplant waitlist mortality, targeting high MELD waitlisted patients. However, policy changes may also have unintended consequences that must be balanced with the primary desired outcome. We performed an interrupted time series assessing the impact of Share 35 on biliary complications in a select national liver transplant population using the Vizient CDB/RM database. Liver transplants that occurred between October 2012 and September 2015 were included. There was a significant change in the incident-rate of biliary complications between Pre-Share 35 (n = 3018) and Post-Share 35 (n = 9984) cohorts over time (P = .023, r2  = .44). As a control, a subanalysis was performed throughout the same time period in Region 9 transplant centers, where a broad sharing agreement had previously been implemented. In the subanalysis, there was no change in the incident-rate of biliary complications between the two time periods. Length of stay and mean direct cost demonstrated a change after implementation of Share 35, although they did not meet statistical difference. While the target of improved waitlist mortality is of utmost importance for the equitable allocation of organs, unintended consequences of policy changes should be studied for a full assessment of a policy's impact.

Metformin use in the first year after kidney transplant, correlates, and associated outcomes in diabetic transplant recipients: A retrospective analysis of integrated registry and pharmacy claims data.

While guidelines support metformin as a therapeutic option for diabetic patients with mild-to-moderate renal insufficiency, the frequency and outcomes of metformin use in kidney transplant recipients are not well described. We integrated national U.S. transplant registry data with records from a large pharmaceutical claims clearinghouse (2008-2015). Associations (adjusted hazard ratio, 95% LCL aHR95% UCL ) of diabetes regimens (with and excluding metformin) in the first year post-transplant with patient and graft survival over the subsequent year were quantified by multivariate Cox regression, adjusted for recipient, donor, and transplant factors and propensity for metformin use. Among 14 144 recipients with pretransplant type 2 diabetes mellitus, 4.7% filled metformin in the first year post-transplant; most also received diabetes comedications. Compared to those who received insulin-based regimens without metformin, patients who received metformin were more likely to be female, have higher estimated glomerular filtration rates, and have undergone transplant more recently. Metformin-based regimens were associated with significantly lower adjusted all-cause (aHR 0.18 0.410.91 ), malignancy-related (aHR 0.45 0.450.99 ), and infection-related (aHR 0.12 0.320.85 ) mortality, and nonsignificant trends toward lower cardiovascular mortality, graft failure, and acute rejection. No evidence of increased adverse graft or patient outcomes was noted. Use of metformin-based diabetes treatment regimens may be safe in carefully selected kidney transplant recipients.

The impact of direct-acting antiviral agents on liver and kidney transplant costs and outcomes.

Direct-acting antiviral medications (DAAs) have revolutionized care for hepatitis C positive (HCV+) liver (LT) and kidney (KT) transplant recipients. Scientific Registry of Transplant Recipients registry data were integrated with national pharmaceutical claims (2007-2016) to identify HCV treatments before January 2014 (pre-DAA) and after (post-DAA), stratified by donor (D) and recipient (R) serostatus and payer. Pre-DAA, 18% of HCV+ LT recipients were treated within 3 years and without differences by donor serostatus or payer. Post-DAA, only 6% of D-/R+ recipients, 19.8% of D+/R+ recipients with public insurance, and 11.3% with private insurance were treated within 3 years (P < .0001). LT recipients treated for HCV pre-DAA experienced higher rates of graft loss (adjusted hazard ratio [aHR] 1.34 1.852.10 , P < .0001) and death (aHR 1.47 1.681.91 , P < .0001). Post-DAA, HCV treatment was not associated with death (aHR 0.34 0.671.32 , P = .25) or graft failure (aHR 0.32 0.641.26 , P = .20) in D+R+ LT recipients. Treatment increased in D+R+ KT recipients (5.5% pre-DAA vs 12.9% post-DAA), but did not differ by payer status. DAAs reduced the risk of death after D+/R+ KT by 57% (0.19 0.430.95 , P = .04) and graft loss by 46% (0.27 0.541.07 , P = .08). HCV treatment with DAAs appears to improve HCV+ LT and KT outcomes; however, access to these medications appears limited in both LT and KT recipients.

Prescription opioid use before and after kidney transplant: Implications for posttransplant outcomes.

Evolving literature suggests that the epidemic of prescription opioid use affects the transplant population. We examined a novel database wherein national U.S. transplant registry records were linked to a large pharmaceutical claims warehouse (2007-2015) to characterize prescription opioid use before and after kidney transplant, and associations (adjusted hazard ratio, 95%LCL aHR95%UCL ) with death and graft loss. Among 75 430 eligible patients, 43.1% filled opioids in the year before transplant. Use was more common among recipients who were women, white, unemployed, publicly insured, and with longer pretransplant dialysis. Of those with the highest level of pretransplant opioid use, 60% continued high-level use posttransplant. Pretransplant opioid use had graded associations with one-year posttransplant outcomes; the highest-level use predicted 46% increased risk of death (aHR 1.28 1.461.66 ) and 28% increased risk of all-cause graft failure (aHR 1.17 1.281.41 ). Effects of high-level opioid use in the first year after transplant were stronger, predicting twice the risk of death (aHR 1.93 2.242.60 ) and 68% higher all-cause graft failure risk (aHR 1.50 1.681.89 ) over the subsequent year; increased risk persisted over five years. While associations may, in part, reflect underlying conditions or behaviors, opioid use history is relevant in assessing and providing care to transplant candidates and recipients.

OPTN/SRTR 2016 Annual Data Report: Economics.

Medicare costs vary for solid organ transplant recipients by outcome: survival with graft function, survival with graft failure, and death. Average per-person per-year reimbursement was $75 thousand for kidney recipients who survived the first year posttransplant with a functioning graft, $171 thousand for those who required a return to dialysis or retransplant, and $350 thousand for those who died with function. For pancreas recipients: $105 thousand for those who survived the first year with a functioning graft, $120 thousand for those who survived pancreas failure, and $443 thousand for those who died with function. For liver recipients: $154 thousand for those who survived with a functioning graft, $388 thousand for those who required retransplant, and $740 thousand who died with function. For intestine recipients: $301 thousand for those who survived with a functioning graft and $1 million for those who died with function. For heart recipients: $272 thousand for those who survived with a functioning graft and $1.2 million for those who died with function. For lung recipients: $196 thousand for those who survived with a functioning graft, $642 thousand for those who required retransplant, and $761 thousand for those who died with function.

The Incremental Cost of Incompatible Living Donor Kidney Transplantation: A National Cohort Analysis.

Incompatible living donor kidney transplantation (ILDKT) has been established as an effective option for end-stage renal disease patients with willing but HLA-incompatible living donors, reducing mortality and improving quality of life. Depending on antibody titer, ILDKT can require highly resource-intensive procedures, including intravenous immunoglobulin, plasma exchange, and/or cell-depleting antibody treatment, as well as protocol biopsies and donor-specific antibody testing. This study sought to compare the cost and Medicare reimbursement, exclusive of organ acquisition payment, for ILDKT (n = 926) with varying antibody titers to matched compatible transplants (n = 2762) performed between 2002 and 2011. Data were assembled from a national cohort study of ILDKT and a unique data set linking hospital cost accounting data and Medicare claims. ILDKT was more expensive than matched compatible transplantation, ranging from 20% higher adjusted costs for positive on Luminex assay but negative flow cytometric crossmatch, 26% higher for positive flow cytometric crossmatch but negative cytotoxic crossmatch, and 39% higher for positive cytotoxic crossmatch (p < 0.0001 for all). ILDKT was associated with longer median length of stay (12.9 vs. 7.8 days), higher Medicare payments ($91 330 vs. $63 782 p < 0.0001), and greater outlier payments. In conclusion, ILDKT increases the cost of and payments for kidney transplantation.

OPTN/SRTR 2015 Annual Data Report: Economics.

While the costs to Medicare of solid organ transplants are varied and considerable, the total Medicare expenditure of $4.4 billion for solid organ transplant recipients in 2014 remained less than 1% of all Medicare expenditures. For patients covered by Medicare, the ratio of pre- to posttransplant cost of care varied widely by organ and within some organ categories by patient characteristics. This chapter reports pretransplant costs for all solid organ candidates covered by Medicare to allow investigators to further explore the relative cost of transplant compared with alternative management.

The Changing Financial Landscape of Renal Transplant Practice: A National Cohort Analysis.

Kidney transplantation has become more resource intensive as recipient complexity has increased and average donor quality has diminished over time. A national retrospective cohort study was performed to assess the impact of kidney donor and recipient characteristics on transplant center cost (exclusive of organ acquisition) and Medicare reimbursement. Data from the national transplant registry, University HealthSystem Consortium hospital costs, and Medicare payments for deceased donor (N = 53 862) and living donor (N = 36 715) transplants from 2002 to 2013 were linked and analyzed using multivariate linear regression modeling. Deceased donor kidney transplant costs were correlated with recipient (Expected Post Transplant Survival Score, degree of allosensitization, obesity, cause of renal failure), donor (age, cause of death, donation after cardiac death, terminal creatinine), and transplant (histocompatibility matching) characteristics. Living donor costs rose sharply with higher degrees of allosensitization, and were also associated with obesity, cause of renal failure, recipient work status, and 0-ABDR mismatching. Analysis of Medicare payments for a subsample of 24 809 transplants demonstrated minimal correlation with patient and donor characteristics. In conclusion, the complexity in the landscape of kidney transplantation increases center costs, posing financial disincentives that may reduce organ utilization and limit access for higher-risk populations.

Predonation Prescription Opioid Use: A Novel Risk Factor for Readmission After Living Kidney Donation.

Implications of opioid use in living kidney donors for key outcomes, including readmission rates after nephrectomy, are unknown. We integrated Scientific Registry of Transplant Recipients data with records from a nationwide pharmacy claims warehouse and administrative records from an academic hospital consortium to quantify predonation prescription opioid use and postdonation readmission events. Associations of predonation opioid use (adjusted odds ratio [aOR]) in the year before donation and other baseline clinical, procedural, and center factors with readmission within 90 days postdonation were examined by using multivariate logistic regression. Among 14 959 living donors, 11.3% filled one or more opioid prescriptions in the year before donation. Donors with the highest level of predonation opioid use (>305 mg/year) were more than twice as likely as nonusers to be readmitted (6.8% vs. 2.6%; aOR 2.49, 95% confidence interval 1.74-3.58). Adjusted readmission risk was also significantly (p < 0.05) higher for women (aOR = 1.25), African Americans (aOR = 1.45), spouses (aOR = 1.42), exchange participants (aOR = 1.46), uninsured donors (aOR = 1.40), donors with predonation estimated glomerular filtration rate <60 mL/min/1.73 m2 (aOR = 2.68), donors with predonation pulmonary conditions (aOR = 1.54), and after robotic nephrectomy (aOR = 1.68). Predonation opioid use is independently associated with readmission after donor nephrectomy. Future research should examine underlying mechanisms and approaches to reducing risks of postdonation complications.

Variation in Comedication Use According to Kidney Transplant Immunosuppressive Regimens: Application of Integrated Registry and Pharmacy Claims Data.

BACKGROUND: Modern immunosuppression therapies (ISx) have many side effects, and transplant recipients must take an array of "comedications" to help mitigate complications. Comedication use patterns are not well described in large, representative samples because of lack of data. METHODS: We integrated national U.S. transplant registry data with pharmacy records (2005-2010) from a large pharmaceutical claims clearinghouse to examine treatments for anemia, metabolic disorders, and infections in relation to ISx regimens in months 6-12 post-transplantation (N = 22,453). Associations of ISx with comedication use (adjusted odds ratio [aOR]) were quantified with multivariate logistic regression including adjustment for recipient, donor, and transplant factors. RESULTS: Compared to a reference regimen of tacrolimus, mycophenolic acid, and prednisone, sirolimus-based ISx was associated with significantly more common use of erythropoiesis-stimulating agents (aOR 2.52, 95% confidence interval [CI] 2.06-3.09), iron (aOR 2.26, 95% CI 1.92-2.65), statins (aOR 1.47, 95% CI 1.33-1.63), fibrates (aOR 2.35, 95% CI 1.90-2.90), and phosphorous binders (aOR 2.85, 95% CI 1.80-4.50). Patterns were similar after adjustment for first-year estimated glomerular filtration rate, except the association with phosphorous binders was no longer significant. Cyclosporine-based ISx was associated with more common erythropoiesis-stimulating agent use, including after estimated glomerular filtration rate adjustment (aOR 1.61, 95% CI 1.24-2.10). Compared to those who were being administered triple ISx, recipients receiving tacrolimus-based dual and monotherapies had lower use of statins, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEi/ARBs), and antibacterial agents. Recipients of steroid-free ISx were less commonly treated for post-transplantation diabetes. CONCLUSIONS: Alternate ISx regimens are associated with varying treatment requirements for hematologic, metabolic. and infectious complications. Comedication use should be considered in the cost-effectiveness and individualization of ISx regimens.

National Variation in Use of Immunosuppression for Kidney Transplantation: A Call for Evidence-Based Regimen Selection.

Immunosuppression management in kidney transplantation has evolved to include an increasingly diverse choice of medications. Although informed by patient and donor characteristics, choice of immunosuppression regimen varies widely across transplant programs. Using a novel database integrating national transplant registry and pharmacy fill records, immunosuppression use at 6-12 and 12-24 mo after transplant was evaluated for 22 453 patients transplanted in 249 U.S. programs in 2005-2010. Use of triple immunosuppression comprising tacrolimus, mycophenolic acid or azathioprine, and steroids varied widely (0-100% of patients per program), as did use of steroid-sparing regimens (0-77%), sirolimus-based regimens (0-100%) and cyclosporine-based regimens (0-78%). Use of triple therapy was more common in highly sensitized patients, women and recipients with dialysis duration >5 years. Sirolimus use appeared to diminish over the study period. Patient and donor characteristics explained only a limited amount of the observed variation in regimen use, whereas center choice explained 30-46% of the use of non-triple-therapy immunosuppression. The majority of patients who received triple-therapy (79%), cyclosporine-based (87.6%) and sirolimus-based (84.3%) regimens continued them in the second year after transplant. This population-based study of immunosuppression practice demonstrates substantial variation in center practice beyond that explained by differences in patient and donor characteristics.

The Impact of Redistricting Proposals on Health Care Expenditures for Liver Transplant Candidates and Recipients.

Redistricting, which means sharing organs in novel districts developed through mathematical optimization, has been proposed to reduce pervasive geographic disparities in access to liver transplantation. The economic impact of redistricting was evaluated with two distinct data sources, Medicare claims and the University HealthSystem Consortium (UHC). We estimated total Medicare payments under (i) the current allocation system (Share 35), (ii) full regional sharing, (iii) an eight-district plan, and (iv) a four-district plan for a simulated population of patients listed for liver transplant over 5 years, using the liver simulated allocation model. The model predicted 5-year transplant volumes (Share 35, 29,267; regional sharing, 29,005; eight districts, 29,034; four districts, 28,265) and a reduction in overall mortality, including listed and posttransplant patients, of up to 676 lives. Compared with current allocation, the eight-district plan was estimated to reduce payments for pretransplant care ($1638 million to $1506 million, p < 0.001), transplant episode ($5607 million to $5569 million, p < 0.03) and posttransplant care ($479 million to $488 million, p < 0.001). The eight-district plan was estimated to increase per-patient transportation costs for organs ($8988 to $11,874 per patient, p < 0.001) and UHC estimated hospital costs ($4699 per case). In summary, redistricting appears to be potentially cost saving for the health care system but will increase the cost of performing liver transplants for some transplant centers.

Economics.

While the costs to Medicare of solid organ transplants are varied and considerable, the total Medicare expenditure of $4.2 billion for solid organ transplant recipients in 2013 remains less than 1% of all Medicare expenditures. Kidney transplant remains one of the most cost-effective surgical interventions in medicine and exhibits a rare feature in that it is generally known to be cost-saving in the long term. For patients covered by Medicare, lung transplant is one of the more costly solid organ transplants performed. This chapter reports pretransplant costs for lung candidates to allow investigators to further explore the relative cost of lung transplant compared with alternative management.

Economic Impacts of ABO-Incompatible Live Donor Kidney Transplantation: A National Study of Medicare-Insured Recipients.

The infrequent use of ABO-incompatible (ABOi) kidney transplantation in the United States may reflect concern about the costs of necessary preconditioning and posttransplant care. Medicare data for 26 500 live donor kidney transplant recipients (2000 to March 2011), including 271 ABOi and 62 A2-incompatible (A2i) recipients, were analyzed to assess the impact of pretransplant, transplant episode and 3-year posttransplant costs. The marginal costs of ABOi and A2i versus ABO-compatible (ABOc) transplants were quantified by multivariate linear regression including adjustment for recipient, donor and transplant factors. Compared with ABOc transplantation, patient survival (93.2% vs. 88.15%, p = 0.0009) and death-censored graft survival (85.4% vs. 76.1%, p < 0.05) at 3 years were lower after ABOi transplant. The average overall cost of the transplant episode was significantly higher for ABOi ($65 080) compared with A2i ($36 752) and ABOc ($32 039) transplantation (p < 0.001), excluding organ acquisition. ABOi transplant was associated with high adjusted posttransplant spending (marginal costs compared to ABOc - year 1: $25 044; year 2: $10 496; year 3: $7307; p < 0.01). ABOi transplantation provides a clinically effective method to expand access to transplantation. Although more expensive, the modest increases in total spending are easily justified by avoiding long-term dialysis and its associated morbidity and cost.

Perioperative Complications After Living Kidney Donation: A National Study.

We integrated the US transplant registry with administrative records from an academic hospital consortium (97 centers, 2008-2012) to identify predonation comorbidity and perioperative complications captured in diagnostic, procedure, and registry sources. Correlates (adjusted odds ratio, aOR) of perioperative complications were examined with multivariate logistic regression. Among 14 964 living kidney donors, 11.6% were African American. Nephrectomies were predominantly laparoscopic (93.8%); 2.4% were robotic and 3.7% were planned open procedures. Overall, 16.8% of donors experienced a perioperative complication, most commonly gastrointestinal (4.4%), bleeding (3.0%), respiratory (2.5%), surgical/anesthesia-related injuries (2.4%), and "other" complications (6.6%). Major Clavien Classification of Surgical Complications grade IV or higher affected 2.5% of donors. After adjustment for demographic, clinical (including comorbidities), procedure, and center factors, African Americans had increased risk of any complication (aOR 1.26, p = 0.001) and of Clavien grade II or higher (aOR 1.39, p = 0.0002), grade III or higher (aOR 1.56, p < 0.0001), and grade IV or higher (aOR 1.56, p = 0.004) events. Other significant correlates of Clavien grade IV or higher events included obesity (aOR 1.55, p = 0.0005), predonation hematologic (aOR 2.78, p = 0.0002) and psychiatric (aOR 1.45, p = 0.04) conditions, and robotic nephrectomy (aOR 2.07, p = 0.002), while annual center volume >50 (aOR 0.55, p < 0.0001) was associated with lower risk. Complications after live donor nephrectomy vary with baseline demographic, clinical, procedure, and center factors, but the most serious complications are infrequent. Future work should examine underlying mechanisms and approaches to minimizing the risk of perioperative complications in all donors.