Publications by authors named "Mark A Schnitzler"

144 Publications

Incidence, Clinical Correlates, and Outcomes of Pulmonary Hypertension after Kidney Transplantation: Analysis of Linked U.S. Registry and Medicare Billing Claims.

Transplantation 2021 Apr 9. Epub 2021 Apr 9.

Saint Louis University, St. Louis, MO, USA University of Calgary, Calgary, AB, Canada University of Iowa, Iowa City, IA, USA Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA UT Health, San Antonio, TX, USA University of Wisconsin, Madison, WI, USA University of Chicago, Chicago, IL, USA Einstein Medical Center, Philadelphia, PA, USA Weill Cornell Medicine, New York, NY, USA Hennepin County Medical Center, Minneapolis, MN, USA University Virginia, Charlottesville, VA, USA.

Background: The incidence, risks, and outcomes associated with pulmonary hypertension (P-HTN) in the kidney transplant (KTx) population are not well described.

Methods: We linked U.S. transplant registry data with Medicare claims (2006-2016) to investigate P-HTN diagnoses among Medicare-insured KTx recipients (N=35,512) using billing claims. Cox regression was applied to identify independent correlates and outcomes of P-HTN (adjusted hazard ratio, aHR, 95%LCLaHR95%UCL), and to examine P-HTN diagnoses as time-dependent mortality predictors.

Results: Overall, 8.2% of recipients had a diagnostic code for P-HTN within 2 years preceding transplant. By 3 years posttransplant, P-HTN was diagnosed in 10.310.6%11.0 of the study cohort. After adjustment, posttransplant P-HTN was more likely in KTx recipients who were older (aHR for age >60 vs. 18-30 years: 1.912.403.01) or female (aHR, 1.151.241.34), who had pretransplant P-HTN (aHR, 4.384.795.24), coronary artery disease (aHR, 1.051.151.27), valvular heart disease (aHR, 1.221.321.43), peripheral vascular disease (aHR, 1.051.181.33), chronic pulmonary disease (aHR, 1.201.311.43), obstructive sleep apnea (aHR, 1.151.281.43), longer dialysis duration, pretransplant hemodialysis (aHR, 1.171.371.59), or who underwent transplant in the more recent era (2012-2016 vs. 2006-2011: aHR, 1.291.391.51). Posttransplant P-HTN was associated with >2.5-fold increased risk of mortality (aHR, 2.572.843.14) and all-cause graft failure (aHR, 2.422.642.88) within 3 years posttransplant. Outcome associations of newly-diagnosed posttransplant P-HTN were similar.

Conclusions: Posttransplant P-HTN is diagnosed in 1 in 10 KTx recipients and is associated with an increased risk of death and graft failure. Future research is needed to refine diagnostic, classification, and management strategies to improve outcomes in KTx recipients who develop P-HTN.
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http://dx.doi.org/10.1097/TP.0000000000003783DOI Listing
April 2021

Survival implications of prescription opioid and benzodiazepine use in lung transplant recipients: Analysis of linked transplant registry and pharmacy fill records.

J Heart Lung Transplant 2021 Feb 17. Epub 2021 Feb 17.

Saint Louis Transplant Center, St. Louis, Missouri, USA.

Background: Prescription opioid and benzodiazepine use have been associated with morbidity and mortality among some groups of solid organ transplant recipients, but implications for outcomes among lung transplant patients are not well described.

Methods: We conducted a retrospective cohort study using linked national transplant registry and pharmaceutical records to characterize the associations between benzodiazepine and opioid prescription fills in the years before and after lung transplant (2006-2017), with risk-adjusted posttransplant survival (adjusted hazard ratio, aHR).

Results: Among 11,568 recipients, 33.7% filled an opioid prescription, and 25.8% filled a benzodiazepine prescription before transplant. Compared to patients without prescriptions, those who filled both short- and long-acting benzodiazepine prescriptions before transplant had 2-fold higher mortality in the first year posttransplant (aHR, 2.12), after adjustment for baseline factors and opioid fills, while pretransplant opioid fills were not associated with posttransplant mortality after adjustment for benzodiazepine fills. Pretransplant opioid and benzodiazepine use strongly predicted more use after transplant. Fills of both short- and long-acting benzodiazepines in the first year posttransplant were associated with 77% increased mortality >1-to-2 years posttransplant (aHR, 1.77). Compared with no posttransplant opioid fills, there was a dose-dependent association between first-year opioid fills and subsequent adjusted mortality risk (level 2: aHR, 1.50 to level 4: aHR, 2.01). These effects were independent, and interactions were not detected.

Conclusions: Benzodiazepine prescription fills before and after lung transplant, and opioid fills after transplant, are independently associated with posttransplant mortality. Review of benzodiazepine and opioid use history is relevant to risk-stratifying patients before and after lung transplant.
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http://dx.doi.org/10.1016/j.healun.2021.02.004DOI Listing
February 2021

COVID-19 test result reporting for deceased donors: Emergent policies, logistical challenges, and future directions.

Clin Transplant 2021 Mar 10:e14280. Epub 2021 Mar 10.

University of Iowa, Iowa City, IA, USA.

The coronavirus disease 2019 (COVID-19) pandemic poses unprecedented challenges to the transplant community, including organ procurement organizations (OPOs), transplant centers, regulatory agencies, and recipient candidates. Access to timely, accurate information on the status of deceased donor viral infection is essential in determining organ acceptance. The Organ Procurement and Transplantation Network expeditiously added fields to collect these data; however, use of the data collection fields was not uniform nationally. Standardized, field-defined data capture and reporting are vital to ensure optimal organ utilization during this pandemic, and to prepare the community for subsequent challenges.
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http://dx.doi.org/10.1111/ctr.14280DOI Listing
March 2021

Trends in Discard of Kidneys from Hepatitis C Viremic Donors in the United States.

Clin J Am Soc Nephrol 2021 Feb 15;16(2):251-261. Epub 2021 Jan 15.

Division of Nephrology, Washington University School of Medicine, St. Louis, Missouri

Background And Objectives: Kidneys from hepatitis C virus (HCV) viremic donors have become more commonly accepted for transplant, especially after effective direct-acting antiviral therapy became available in 2014. We examined the contemporary trend of kidney discard from donors with HCV seropositivity and viremia.

Design, Setting, Participants, & Measurements: Data from the Organ Procurement and Transplantation Network were used to identify deceased donor kidneys recovered for transplant. The exposure was donor HCV antibody status in the first analyses, and donor HCV antibody and viremia status in the second analyses. Multilevel, multivariable logistic regression was used to assess the association of these HCV exposure measures with kidney discard, adjusted for donor characteristics. Multilevel analyses were conducted to account for similar kidney discard pattern within clusters of organ procurement organizations and regions.

Results: Among 225,479 kidneys recovered from 2005 to 2019, 5% were from HCV seropositive donors. Compared with HCV seronegative kidneys, the odds of HCV seropositive kidney discard gradually declined, from a multivariable-adjusted odds ratio (aOR) of 7.06 (95% confidence interval [95% CI], 5.65 to 8.81) in 2014, to 1.20 (95% CI, 1.02 to 1.42) in 2019. Among 82,090 kidneys with nucleic acid amplification test results in 2015-2019, 4% were from HCV viremic donors and 2% were from aviremic seropositive donors. Compared with HCV aviremic seronegative kidneys, the odds of HCV viremic kidney discard decreased from an aOR of 4.89 (95% CI, 4.03 to 5.92) in 2018, to 1.48 (95% CI, 1.22 to 1.81) in 2019. By 2018 and 2019, aviremic seropositive status was not associated with higher odds of discard (2018: aOR, 1.13; 95% CI, 0.88 to 1.45; and 2019: aOR, 0.97; 95% CI, 0.76 to 1.23).

Conclusions: Despite the decrease in kidney discard in recent years, kidneys from viremic (compared with aviremic seronegative) donors still had 48% higher odds of discard in 2019. The potential of these discarded organs to provide successful transplantation should be explored.
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http://dx.doi.org/10.2215/CJN.10960720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863640PMC
February 2021

An International survey on living kidney donation and transplant practices during the COVID-19 pandemic.

Transpl Infect Dis 2021 Apr 19;23(2):e13526. Epub 2020 Dec 19.

Saint Louis University Center for Abdominal Transplantation, Saint Louis University, St. Louis, MO, USA.

The scope of the impact of the Coronavirus disease 19 (COVID-19) pandemic on living donor kidney transplantation (LDKT) practices across the world is not well-defined. We received survey responses from 204 transplant centers internationally from May to June 2020 regarding the impact of the COVID-19 pandemic on LDKT practices. Respondents represented 16 countries on five continents. Overall, 75% of responding centers reported that LDKT surgery was on hold (from 67% of North American centers to 91% of European centers). The majority (59%) of centers reported that new donor evaluations were stopped (from 46% of North American centers to 86% of European centers), with additional 23% of centers reporting important decrease in evaluations. Only 10% of centers reported slight variations on their evaluations. For the centers that continued donor evaluations, 40% performed in-person visits, 68% by video, and 42% by telephone. Center concerns for donor (82%) and recipient (76%) safety were the leading barriers to LDKT during the pandemic, followed by patients concerns (48%), and government restrictions (46%). European centers reported more barriers related to staff limitations while North and Latin American centers were more concerned with testing capacity and insufficient resources including protective equipment. As LDKT resumes, 96% of the programs intend to screen donor and recipient pairs for coronavirus infection, most of them with polymerase chain reaction testing of nasopharyngeal swab samples. The COVID-19 pandemic has had broad impact on all aspects of LDKT practice. Ongoing research and consensus-building are needed to guide safe reopening of LDKT programs.
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http://dx.doi.org/10.1111/tid.13526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744917PMC
April 2021

Immunosuppression Regimen Use and Outcomes in Older and Younger Adult Kidney Transplant Recipients: A National Registry Analysis.

Transplantation 2020 Nov 18. Epub 2020 Nov 18.

University of Iowa, Iowa City, IA, USA.

Background: Although the population of older transplant recipients has increased dramatically, there are limited data describing the impact of immunosuppression regimen choice on outcomes in this recipient group.

Methods: National data for U.S. Medicare-insured adult kidney recipients (N=67,362; 2005-2016) were examined to determine early immunosuppression regimen and associations with acute rejection, death-censored graft failure and mortality using multivariable regression analysis in younger (18-64 years) and older (>65 years) adults.

Results: The use of anti-thymocyte globulin (TMG) or alemtuzumab (ALEM) induction with triple maintenance immunosuppression (reference) was less common in older compared with younger (36.9% vs 47.0%) recipients, as was TMG/ALEM + steroid avoidance (19.2% vs 20.1%) and mTORi-based (6.7% vs 7.7%) treatments. Conversely, older patients were more likely to receive IL2-receptor antibody (IL2rAb) + triple maintenance (21.1% vs 14.7%), IL2rAb + steroid avoidance (4.1% vs 1.8%), and cyclosporine-based (8.3% vs 6.6%) immunosuppression. Compared to older recipients treated with TMG/ALEM + triple maintenance (reference regimen), those managed with TMG/ALEM + steroid avoidance (adjusted odds ratio (aOR), 0.440.520.61) and IL2rAb + steroid-avoidance (aOR, 0.390.550.79) had lower risk of acute rejection. Older patients experienced more death censored graft failure when managed with Tac+ antimetabolite avoidance (adjusted hazard (aHR), 1.411.782.25), mTORi-based (aHR, 1.702.142.71), and cyclosporine-based (aHR, 1.411.782.25) regimens, versus the reference regimen. mTORi-based and cyclosporine-based regimens were associated with increased mortality in both older and younger patients.

Conclusions: Lower-intensity immunosuppression regimens (e.g. steroid-sparing) appear beneficial for older kidney transplant recipients, while mTORi and cyclosporine-based maintenance immunosuppression are associated with higher risk of adverse outcomes.
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http://dx.doi.org/10.1097/TP.0000000000003547DOI Listing
November 2020

Financial Evaluation of Kidney Transplant With Hepatitis C Viremic Donors to Uninfected Recipients.

Transplant Direct 2020 Dec 10;6(12):e627. Epub 2020 Nov 10.

Department of Medicine, Saint Louis University, St. Louis, MO.

Kidney transplantation with hepatitis C viremic (dHCV+) donors appears safe for recipients without HCV when accompanied by direct acting antiviral (DAA) treatment. However, US programs have been reluctant to embrace this approach due to concern about insurance coverage. While the cost of DAA treatment is currently offset by the reduction in waiting time, increased competition for dHCV+ organs may reduce this advantage. This analysis sought to demonstrate the financial benefit of dHCV+ transplant for third-party health insurers to expand coverage availability.

Methods: An economic analysis was developed using a Markov model for 2 decisions: first, to accept a dHCV+ organ versus wait for a dHCV uninfected organ; or second, accept a high kidney donor profile index (KDPI) (>85) organ versus wait for a better quality dHCV+ organ. The analysis used Medicare payments, historical survival data, cost report data, and an estimated cost of DAA of $29 874.

Results: In the first analysis, using dHCV+ kidneys reduced the cost of end-stage kidney disease care if the wait for a dHCV uninfected organ exceeded 11.5 months. The financial breakeven point differed according to the cost of DAA treatment. In the second analysis, declining a high-KDPI organ in favor of a waiting dHCV+ organ was marginally clinically beneficial if waiting times were <12 months but not cost effective.

Conclusions: dHCV+ transplant appears to be economically and clinically advantageous compared with waiting for dHCV-uninfected transplant but should not replace high-KDPI transplant when appropriate. Despite the high cost of DAA therapy, health insurers benefit financially from dHCV+ transplant within 1 year.
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http://dx.doi.org/10.1097/TXD.0000000000001056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665247PMC
December 2020

Induction immunosuppression and the risk of incident malignancies among older and younger kidney transplant recipients: A prospective cohort study.

Clin Transplant 2020 12 20;34(12):e14121. Epub 2020 Nov 20.

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Background: Older (≥65) KT recipients differ from their younger counterparts in their immune response to immunosuppression (IS) and may have a different risk of malignancy after receiving induction.

Methods: We identified 66 700 adult KT recipients treated with anti-thymocyte globulin (ATG) (n = 40 443) or interleukin-2 receptor antagonist (IL-2RA) (n = 26 327) induction (1/1/1999-12/31/2014) using USRDS/Medicare data. We estimated the risk of first-diagnosed post-KT malignancy associated with induction (ATG vs. IL-2RA) using Cox proportional hazard models. We then tested whether these risks differed between older and younger recipients (Wald test for interaction). Models incorporated inverse probability of treatment weights to adjust for confounders.

Results: The 3-year cumulative incidences of any diagnosed malignancy were 11.5%. ATG was associated with a higher malignancy risk (HR = 1.12, 95%CI:1.06-1.18). This association differed (p  = 0.04) between younger (HR = 1.12, 95%CI:1.06-1.18) and older recipients (HR = 1.03, 95%CI:0.96-1.09). ATG was also associated with higher risk of skin (HR = 1.18, 95%CI:1.08-1.29), lung (HR = 1.24, 95%CI:1.05-1.47), and ovary malignancies (HR = 1.94, 95%CI:1.08-3.48). However, only the association of ATG with post-KT skin malignancy differed (p  = 0.01) between younger (HR = 1.18; 95%CI:1.08-1.29) and older (HR = 1.01; 95%CI:0.93-1.09) recipients.

Conclusions: Compared with IL-2RA induction, ATG was associated with elevated post-KT malignancy risk but only among younger recipients. Transplant centers may need to tailor induction IS for younger recipients to mitigate malignancy risk.
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http://dx.doi.org/10.1111/ctr.14121DOI Listing
December 2020

Hydroxychloroquine and maintenance immunosuppression use in kidney transplant recipients: Analysis of linked US registry and claims data.

Clin Transplant 2020 12 22;34(12):e14118. Epub 2020 Nov 22.

Johns Hopkins University, Baltimore, MD, USA.

Hydroxychloroquine (HCQ) is an antimalarial drug with immunomodulatory effects used to treat systemic lupus erythematosus (SLE) and scleroderma. The antiviral effects of HCQ have raised attention in the context of the COVID-19 pandemic, although safety is controversial. We examined linkages of national transplant registry data with pharmaceutical claims and Medicare billing claims to study HCQ use among Medicare-insured kidney transplant recipients with SLE or scleroderma (2008-2017; N = 1820). We compared three groups based on immunosuppression regimen 7 months-to-1 year post transplant: (a) tacrolimus (Tac) + mycophenolic acid (MPA) + prednisone (Pred) (referent group, 77.7%); (b) Tac + MPA + Pred + HCQ (16.5%); or (c) other immunosuppression + HCQ (5.7%). Compared to the referent group, recipients treated with other immunosuppression + HCQ had a 2-fold increased risk of abnormal ECG or QT prolongation (18.9% vs. 10.7%; aHR, 1.96 , p = .02) and ventricular arrhythmias (15.2% vs. 11.4%; aHR, 1.81 , p = .05) in the >1-to-3 years post-transplant. Tac + MPA + Pred + HCQ was associated with increased risk of ventricular arrhythmias (13.5% vs. 11.4%; aHR, 1.54 , p = .04) and pancytopenia (35.9% vs. 31.4%; aHR, 1.31 , p = .03) compared to triple immunosuppression without HCQ. However, HCQ-containing regimens were not associated with an increased risk of death or graft failure. HCQ may be used safely in selected kidney transplant recipients in addition to their maintenance immunosuppression, although attention to arrhythmias is warranted.
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http://dx.doi.org/10.1111/ctr.14118DOI Listing
December 2020

Impact of Functional Status on Outcomes of Simultaneous Pancreas-kidney Transplantation: Risks and Opportunities for Patient Benefit.

Transplant Direct 2020 Sep 21;6(9):e599. Epub 2020 Aug 21.

Emory University, Atlanta, GA.

Background: The impact of functional status on survival among simultaneous pancreas-kidney transplant (SPKT) candidates and recipients is not well described.

Methods: We examined national Scientific Registry of Transplant Recipients (SRTR) data for patients listed for SPKT in the United States (2006-2019). Functional status was categorized by center-reported Karnofsky Performance Score (KPS). We used Cox regression to quantify associations of KPS at listing and transplant with subsequent patient survival, adjusted for baseline patient and transplant factors (adjusted hazard ratio, aHR). We also explored time-dependent associations of SPKT with survival risk after listing compared with continued waiting in each functional status group.

Results: KPS distributions among candidates (N = 16 822) and recipients (N = 10 316), respectively, were normal (KPS 80-100), 62.0% and 57.8%; capable of self-care (KPS 70), 23.5% and 24.7%; requires assistance (KPS 50-60), 12.4% and 14.2%; and disabled (KPS 10-40), 2.1% and 3.3%. There was a graded increase in mortality after listing and after transplant with lower functional levels. Compared with normal functioning, mortality after SPKT rose progressively for patients capable of self-care (aHR, 1.18), requiring assistance (aHR, 1.31), and disabled (aHR, 1.55). In time-dependent regression, compared with waiting, SPKT was associated with 2-fold mortality risk within 30 days of transplant. However, beyond 30 days, SPKT was associated with reduced mortality, from 52% for disabled patients (aHR, 0.48) to 70% for patients with normal functioning (aHR, 0.30).

Conclusions: While lower functional status is associated with increased mortality risk among SPKT candidates and recipients, SPKT can provide long-term survival benefit across functional status levels in those selected for transplant.
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http://dx.doi.org/10.1097/TXD.0000000000001043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447442PMC
September 2020

Survey of US Living Kidney Donation and Transplantation Practices in the COVID-19 Era.

Kidney Int Rep 2020 Nov 25;5(11):1894-1905. Epub 2020 Aug 25.

Organ Transplant Center, University of Iowa, Iowa City, Iowa, USA.

Introduction: The scope of the impact of the coronavirus disease 2019 (COVID-19) pandemic on living donor kidney transplantation (LDKT) practices is not well defined.

Methods: We surveyed US transplant programs to assess practices, strategies, and barriers to living LDKT during the COVID-19 pandemic. After institutional review board approval, the survey was distributed from 9 May 2020 to 30 May 2020 by e-mail and postings to professional society list-servs. Responses were stratified based on state COVID-19 cumulative incidence levels.

Results: Staff at 118 unique centers responded, representing 61% of US living donor recovery programs and 75% of LKDT volume in the prepandemic year. Overall, 66% reported that LDKT surgery was on hold (81% in "high" vs. 49% in "low" COVID-19 cumulative incidence states). A total of 36% reported that evaluation of new donor candidates had paused, 27% reported that evaluations were very much decreased (>0% to <25% typical), and 23% reported that evaluations were moderately decreased (25% to <50% typical). Barriers to LDKT surgery included program concerns for donor (85%) and recipient (75%) safety, patient concerns (56%), elective case restrictions (47%), and hospital administrative restrictions (48%). Programs with higher local COVID-19 cumulative incidence reported more barriers related to staff and resource diversion. Most centers continuing donor evaluations used remote strategies (video, 82%; telephone, 43%). As LDKT resumes, all programs will screen for COVID-19, although timeframe and modalities will vary. Recommendations for presurgical self-quarantine are also variable.

Conclusion: The COVID-19 pandemic has had broad impacts on LDKT practice. Ongoing research and consensus building are needed to reduce barriers, to guide optimal practices, and to support safe restoration of LDKT across centers.
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http://dx.doi.org/10.1016/j.ekir.2020.08.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445484PMC
November 2020

A simple risk-based reimbursement system for kidney transplant.

Clin Transplant 2021 Jan 24;35(1):e14068. Epub 2020 Sep 24.

University of Iowa, Iowa City, IA, USA.

Transplant centers were challenged by the Executive Order on Advancing Kidney health to increase access to kidney transplant (KTx) by accepting higher risk patients and organs. However, Medicare reimbursement for KTx does not include adjustment for major complicating comorbidities (MCCs) like other transplants. The prevalence of MCCs was assessed for KTx performed from 10/15 to 10/19 at a single academic center, using Medicare ICD10 MCC criteria exclusive of end-stage kidney disease. KTx hospital resource utilization and estimated margin, assuming Medicare reimbursement, were determined for cases with and without MCC. Among 260 KTx recipients, 49 (19%) had an MCC. Patients with MCCs had longer wait times (1121 days vs 703 days, P < .001); however, there were no differences in age, gender, race, or diagnosis. Donor characteristics associated with an MCC included greater cold ischemic time (1042 vs 670 minutes, P < .001) and fewer living donor KTx (9% vs 32%, P < .001). KTx cost, exclusive of organ acquisition, was 31% higher (MCC: $38 293 vs No MCC: $29 132) and estimated margin was markedly lower (-$7750 vs -$1001, P = .001). In conclusion, KTx with qualifying MCCs resulted in significant financial losses and modification of KTx payment methodology to align with other organ transplants is needed.
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http://dx.doi.org/10.1111/ctr.14068DOI Listing
January 2021

Outcome implications of benzodiazepine and opioid co-prescription in kidney transplant recipients.

Clin Transplant 2020 09 3;34(9):e14005. Epub 2020 Aug 3.

Center for Abdominal Transplantation, Saint Louis University School of Medicine, St. Louis, MO, USA.

The outcomes of benzodiazepine and opioid co-prescription are not well-defined in transplant populations. We examined linked national transplant registry and pharmaceutical records to characterize benzodiazepine and opioid use in the years before and after transplant in large US cohort of kidney transplant recipients (2007-2016; N = 98 620), and associations (adjusted hazard ratio, aHR ) with death and graft failure. Among the cohort, 15.6% filled benzodiazepine prescriptions in the year before transplant, and 14.0% filled benzodiazepine prescriptions in the year after transplant (short-acting, 9.5%; long-acting, 3.3%; both 1.1%). Use of short-acting benzodiazepines in the year before transplant was associated with a 22% increased risk of death in the year after transplant (aHR, 1.22 ), while use of all classes in the year after transplant was associated with increased risk of death from >1 to 5 years (aHR: short-acting 1.39 ; long-acting 1.25 ; both 1.74 ). Recipients who used benzodiazepines were also more likely to fill opioid prescriptions. Recipients who filled both classes of benzodiazepine and the highest level of opioids had a 2.9-fold increased risk of death compared to recipients who did not use either. Co-prescription of benzodiazepines and opioids in kidney transplant recipients is associated with increased mortality. Ongoing research is needed to understand mechanisms of risk relationships.
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http://dx.doi.org/10.1111/ctr.14005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722087PMC
September 2020

Prescription patterns of opioids and non-steroidal anti-inflammatory drugs in the first year after living kidney donation: An analysis of U.S. Registry and Pharmacy fill records.

Clin Transplant 2020 08 29;34(8):e14000. Epub 2020 Jun 29.

Center for Abdominal Transplantation, Saint Louis University School of Medicine, St. Louis, MO, USA.

We examined a novel database linking national donor registry identifiers to records from a US pharmaceutical claims warehouse (2007-2015) to describe opioid and NSAID prescription patterns among LKDs during the first year postdonation, divided into three periods: 0-14 days, 15-182 days, and 183-365 days. Associations of opioid and NSAID prescription fills with baseline factors were examined by logistic regression (adjusted odds ratio, aOR ). Among 23,565 donors, opioid prescriptions were highest during days 0-14 (36.6%), but 12.6% of donors filled opioids during days 183-365. NSAID prescriptions rose from 0.5% during days 0-14 to 3.3% during days 183-365. Women filled opioids more commonly than men, and black donors filled both opioids and NSAIDs more commonly than white donors. After covariate adjustment, significant correlates of opioid prescription fills during days 183-365 included obesity (aOR, 1.38 ), less than college education (aOR, 1.31 ), smoking (aOR, 1.45 ), and nephrectomy complications (aOR, 1.29 ). NSAID prescription fills in year 1 were not associated with differences in estimated glomerular filtration rate, incidence of proteinuria or new-onset hypertension at the first and second year postdonation. Prescription fills for opioids and NSAIDs for LKDs varied with demographic and clinic traits. Future work should examine longer-term outcome implications to help inform safe analgesic regimen choices after donation.
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http://dx.doi.org/10.1111/ctr.14000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449599PMC
August 2020

Economic impacts of alternative kidney transplant immunosuppression: A national cohort study.

Clin Transplant 2020 04 11;34(4):e13813. Epub 2020 Mar 11.

Saint Louis University Center for Abdominal Transplantation, St. Louis, Missouri.

Understanding the economic implications of induction and maintenance immunosuppression (ISx) is important in developing personalized kidney transplant (KTx) care. Using data from a novel integrated data set including financial records from the University Health System Consortium, Medicare, and pharmacy claims (2007-2014), we estimated the differences in the impact of induction and maintenance ISx regimens on transplant hospitalization costs and Medicare payments from KTx to 3 years. Use of thymoglobulin (TMG) significantly increased transplant hospitalization costs ($12 006; P = .02), compared with alemtuzumab and basiliximab. TMG resulted in lower Medicare payments in posttransplant years 1 (-$2058; P = .05) and 2 (-$1784; P = .048). Patients on steroid-sparing ISx incurred relatively lower total Medicare spending (-$10 880; P = .01) compared with patients on triple therapy (tacrolimus, antimetabolite, and steroids). MPA/AZA-sparing, mammalian target of rapamycin inhibitors-based, and cyclosporine-based maintenance ISx regimens were associated with significantly higher payments. Alternative ISx regimens were associated with different KTx hospitalization costs and longer-term payments. Future studies of clinical efficacy should also consider cost impacts to define the economic effectiveness of alternative ISx regimens.
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http://dx.doi.org/10.1111/ctr.13813DOI Listing
April 2020

Impacts of center and clinical factors in antihypertensive medication use after kidney transplantation.

Clin Transplant 2020 03 29;34(3):e13803. Epub 2020 Feb 29.

Division of Nephrology, Department of Medicine, Saint Louis University, St. Louis, MO, USA.

Hypertension guidelines recommend calcium channel blockers (CCBs), thiazide diuretics, and angiotensin-converting-enzyme inhibitors/angiotensin receptor blockers (ACEi/ARBs) as first-line agents to treat hypertension. Hypertension is common among kidney transplant (KTx) recipients, but data are limited regarding patterns of antihypertensive medication (AHM) use in this population. We examined a novel database that links national registry data for adult KTx recipients (age > 18 years) with AHM fill records from a pharmaceutical claims warehouse (2007-2016) to describe use and correlates of AHM use during months 7-12 post-transplant. For patients filling AHMs, individual agents used included: dihydropyridine (DHP) CCBs, 55.6%; beta-blockers (BBs), 52.8%; diuretics, 30.0%; ACEi/ARBs, 21.1%; non-DHP CCBs, 3.0%; and others, 20.1%. Both BB and ACEi/ARB use were significantly lower in the time period following the 2014 Eighth Joint National Committee (JNC-8) guidelines (2014-2016), compared with an earlier period (2007-2013). The median odds ratios generated from case-factor adjusted models supported variation in use of ACEi/ARBs (1.51) and BBs (1.55) across transplant centers. Contrary to hypertension guidelines for the general population, KTx recipients are prescribed relatively more BBs and fewer ACEi/ARBs. The clinical impact of this AHM prescribing pattern warrants further study.
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http://dx.doi.org/10.1111/ctr.13803DOI Listing
March 2020

Postdonation eGFR and New-Onset Antihypertensive Medication Use After Living Kidney Donation.

Transplant Direct 2019 Aug 25;5(8):e474. Epub 2019 Jul 25.

Saint Louis University, St. Louis, MO.

Background: Limited data are available regarding clinical implications of lower renal function after living kidney donation. We examined a novel integrated database to study associations between postdonation estimated glomerular filtration rate (eGFR) and use of antihypertensive medication (AHM) treatment after living kidney donation.

Methods: Study data were assembled by linking national U.S. transplant registry identifiers, serum creatinine (SCr) values from electronic medical records, and pharmacy fill records for 3222 living donors (1989-2016) without predonation hypertension. Estimated GFR (mL/min per 1.73 m) was computed from SCr values by the CKD-EPI equation. Repeated measures multivariable mixed effects modeling examined the associations (adjusted odds ratio, aOR) between AHM use and postdonation eGFR levels (random effect) with fixed effects for baseline donor factors.

Results: The linked database identified an average of 3 postdonation SCr values per donor (range: 1-38). Lower postdonation eGFR (vs ≥75) bore graded associations with higher odds of AHM use (eGFR 30-44: aOR 1.47; <30: aOR 2.52). Other independent correlates of postdonation AHM use included older age at donation (aOR per decade: 1.23), black race (aOR 1.51), body mass index > 30 kg/m (aOR 1.45), first-degree donor-recipient relationship (aOR 1.38), "prehypertension" at donation (systolic blood pressure 120-139: aOR 1.46; diastolic blood pressure 80-89: aOR 1.45).

Conclusions: This novel linkage illustrates the ability to identify postdonation kidney function and associate it with clinically meaningful outcomes; lower eGFR after living kidney donation is a correlate of AHM treatment requirements. Further work should define relationships of postdonation renal function, hypertension, and other morbidity measures.
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http://dx.doi.org/10.1097/TXD.0000000000000913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6708633PMC
August 2019

Three-month pancreas graft function significantly influences survival following simultaneous pancreas-kidney transplantation in type 2 diabetes patients.

Am J Transplant 2020 03 1;20(3):788-796. Epub 2019 Nov 1.

Center for Abdominal Transplantation, Saint Louis University School of Medicine, St. Louis, Missouri, USA.

Successful simultaneous pancreas-kidney transplantation (SPK) improves quality-of-life and prolongs kidney allograft and patient survival in type-1 diabetic (T1DM) patients. However, the use of SPK in type-2 diabetic (T2DM) patients remains limited. We examined a national transplant registry for 35 849 T2DM kidney disease patients who received transplant between 2000 and 2016 and survived the first 3 months with a functioning kidney, and categorized as: deceased-donor kidney transplant alone (DD-KA, 68%), living-donor kidney transplant alone (LD-KA, 30%), or SPK (2%). Among SPK recipients, 6% had pancreas allograft failure within 3 months (SPK,P-) and 94% had a functional pancreas (SPK,P+). Associations of transplant type with kidney allograft failure and death (multivariable-adjusted hazard ratio, aHR ), over follow-up through December 2018, were quantified by multivariable inverse probability of treatment weighted survival analyses. SPK recipients had better kidney graft and patient survival than LD-KA or DD-KA recipients. Compared to SPK,P+, DD-KA, or LD-KA recipients had significantly higher risk of kidney allograft failure (DD-KA: aHR 2.20 ; LD-KA: aHR 1.87 ) and death (DD-KA: aHR 3.25 ; LD-KA: aHR 2.35 ). SPK,P- recipients had significantly higher risk of death (aHR 3.30 ). Similar to T1DM, T2DM patients with SPK have a survival benefit compared to those with kidney transplant alone, but this benefit depends upon successful early pancreas function.
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http://dx.doi.org/10.1111/ajt.15615DOI Listing
March 2020

Associations of obesity with antidiabetic medication use after living kidney donation: An analysis of linked national registry and pharmacy fill records.

Clin Transplant 2019 10 8;33(10):e13696. Epub 2019 Sep 8.

Center for Abdominal Transplantation, Saint Louis University School of Medicine, St. Louis, MO, USA.

We examined a novel linkage of national US donor registry data with records from a pharmacy claims warehouse (2007-2016) to examine associations (adjusted hazard ratio, aHR ) of post-donation fills of antidiabetic medications (ADM, insulin or non-insulin agents) with body mass index (BMI) at donation and other demographic and clinical factors. In 28 515 living kidney donors (LKDs), incidence of ADM use at 9 years rose in a graded manner with higher baseline BMI: underweight, 0.9%; normal weight, 2.1%; overweight, 3.5%; obese, 8.5%. Obesity was associated with higher risk of ADM use compared with normal BMI (aHR, 4.59 ). Metformin was the most commonly used ADM and was filled more often by obese than by normal weight donors (9-year incidence, 6.87% vs 1.85%, aHR, 5.00 ). Insulin use was uncommon and did not differ significantly by BMI. Among a subgroup with BMI data at the 1-year post-donation anniversary (n = 19 528), compared with stable BMI, BMI increase >0.5 kg/m by year 1 was associated with increased risk of subsequent ADM use (aHR, 1.48 P = .04). While this study did not assess the impact of donation on the development of obesity, these data support that among LKD, obesity is a strong correlate of ADM use.
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http://dx.doi.org/10.1111/ctr.13696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153560PMC
October 2019

Prescription opioid use before and after heart transplant: Associations with posttransplant outcomes.

Am J Transplant 2019 12 12;19(12):3405-3414. Epub 2019 Sep 12.

Center for Abdominal Transplantation, Saint Louis University School of Medicine, St. Louis, Missouri.

Impacts of the prescription opioid epidemic have not yet been examined in the context of heart transplantation. We examined a novel database in which national U.S. transplant registry records were linked to a large pharmaceutical claims warehouse (2007-2016) to characterize prescription opioid use before and after heart transplant, and associations (adjusted hazard ratio, aHR ) with death and graft loss. Among 13 958 eligible patients, 40% filled opioids in the year before transplant. Use was more common among recipients who were female, white, or unemployed, or who underwent transplant in more recent years. Of those with the highest level of pretransplant opioid use, 71% continued opioid use posttransplant. Pretransplant use had graded associations with 1-year posttransplant outcomes; compared with no use, the highest-level use (>1000 mg morphine equivalents) predicted 33% increased risk of death (aHR 1.33 ) in the year after transplant. Risk relationships with opioid use in the first year posttransplant were stronger, with highest level use predicting 70% higher mortality (aHR 1.70 ) over the subsequent 4 years (from >1 to 5 years posttransplant). 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.
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http://dx.doi.org/10.1111/ajt.15565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883129PMC
December 2019

Variation in use of procurement biopsies and its implications for discard of deceased donor kidneys recovered for transplantation.

Am J Transplant 2019 08 12;19(8):2241-2251. Epub 2019 Apr 12.

University of Iowa Transplant Institute, Iowa City, Iowa.

The use of procurement biopsies in deceased donor kidney acceptance is controversial. We analyzed Scientific Registry of Transplant Recipients data (n = 59 328 allografts, 2014-2018) to describe biopsy practices across US organ procurement organizations (OPOs) and examine relationships with discards, using hierarchical modeling to account for OPO and donor factors. Median odds ratios (MORs) provide the median of the odds that allografts with identical reported traits would be biopsied or discarded from 2 randomly drawn OPOs. Biopsies were obtained for 52.7% of kidneys. Biopsy use rose in a graded manner with kidney donor profile index (KDPI). Biopsy rates differed significantly among OPOs (22.8% to 77.5%), even after adjustment for KDPI and other donor factors. Discard rates also varied from 6.6% to 32.1% across OPOs. After adjustment for donor factors and OPO, biopsy was associated with more than 3 times the likelihood of discard (adjusted odds ratio [ aOR ], 3.51 ). This association was most pronounced for low-risk (KDPI <20) kidneys (aOR, 6.47 ), with minimal impact at KDPI >85 (aOR, 1.15 ). Adjusted MORs for kidney discard and biopsy were greatest for low-risk kidneys. Reducing the rate of unnecessary biopsy and improving the accuracy of histologic assessments in higher KDPI organs may help reduce graft discard rates.
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http://dx.doi.org/10.1111/ajt.15325DOI Listing
August 2019

Cannabis Dependence or Abuse in Kidney Transplantation: Implications for Posttransplant Outcomes.

Transplantation 2019 11;103(11):2373-2382

Division of Nephrology, Saint Louis University School of Medicine, St. Louis, MO.

Background: Cannabis is categorized as an illicit drug in most US states, but legalization for medical indications is increasing. Policies and guidance on cannabis use in transplant patients remain controversial.

Methods: We examined a database linking national kidney transplant records (n = 52 689) with Medicare claims to identify diagnoses of cannabis dependence or abuse (CDOA) and associations [adjusted hazard ratio (aHR) with 95% upper and lower confidence limits (CLs)] with graft, patient, and other clinical outcomes.

Results: CDOA was diagnosed in only 0.5% (n = 254) and 0.3% (n = 163) of kidney transplant recipients in the years before and after transplant, respectively. Patients with pretransplant CDOA were more likely to be 19 to 30 years of age and of black race, and less likely to be obese, college-educated, and employed. After multivariate and propensity adjustment, CDOA in the year before transplant was not associated with death or graft failure in the year after transplant, but was associated with posttransplant psychosocial problems such as alcohol abuse, other drug abuse, noncompliance, schizophrenia, and depression. Furthermore, CDOA in the first year posttransplant was associated with an approximately 2-fold increased risk of death-censored graft failure (aHR, 2.29; 95% CL, 1.59-3.32), all-cause graft loss (aHR, 2.09; 95% CL, 1.50-2.91), and death (aHR, 1.79; 95% CL, 1.06-3.04) in the subsequent 2 years. Posttransplant CDOA was also associated with cardiovascular, pulmonary, and psychosocial problems, and with events such as accidents and fractures.

Conclusions: Although associations likely, in part, reflect associated conditions or behaviors, clinical diagnosis of CDOA in the year after transplant appears to have prognostic implications for allograft and patient outcomes. Recipients with posttransplant CDOA warrant focused monitoring and support.
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http://dx.doi.org/10.1097/TP.0000000000002599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679817PMC
November 2019

Racial/Ethnic Disparities in Access and Outcomes of Simultaneous Liver-Kidney Transplant Among Liver Transplant Candidates With Renal Dysfunction in the United States.

Transplantation 2019 08;103(8):1663-1674

Section of Abdominal Transplantation, Department of Surgery, Washington University School of Medicine, St Louis, MO.

Background: Since the Model for End-stage Liver Disease (MELD) allocation system was implemented, the proportion of simultaneous liver-kidney transplantation (SLKT) has increased significantly. However, whether racial/ethnic disparities exist in access to SLKT and post-SLKT survival remains understudied.

Methods: A retrospective cohort of patients aged ≥18 years with renal dysfunction on the liver transplant (LT) waiting list was obtained from Organ Procurement and Transplantation Network. Renal dysfunction was defined as estimated glomerular filtration rate <60 mL/min/1.73 m at listing for LT. Multilevel time-to-competing-events regression adjusting for center effect was used to examine the likelihood of receiving SLKT. Inverse probability of treatment weighted survival analyses were used to analyze posttransplant mortality outcomes.

Results: For patients with renal dysfunction at listing for LT, not listed for simultaneous kidney transplant, non-Hispanic black (NHB) and Hispanic patients were more likely to receive SLKT than non-Hispanic white (NHW) patients (NHB: multivariable-adjusted hazard ratio [aHR] 2.57; 95% confidence interval [CI], 1.42-4.65; Hispanic: aHR, 2.03; 95% CI, 1.14-3.60). For post-SLKT outcomes, compared to NHW patients, NHB patients had a lower mortality risk before 24 months (aHR, 0.80; 95% CI, 0.65-0.97) but had a higher mortality risk (aHR, 2.00; 95% CI, 1.59-2.55) afterward; in contrast, Hispanic patients had a lower overall mortality risk than NHW patients (aHR, 0.61; 95% CI, 0.51-0.74).

Conclusions: In the MELD era, racial/ethnic differences exist in access and survival of SLKT for patients with renal dysfunction at listing for LT. Future studies are warranted to examine whether these differences remain in the post-SLK allocation policy era.
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http://dx.doi.org/10.1097/TP.0000000000002574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779036PMC
August 2019

Center-driven and Clinically Driven Variation in US Liver Transplant Maintenance Immunosuppression Therapy: A National Practice Patterns Analysis.

Transplant Direct 2018 Jul 13;4(7):e364. Epub 2018 Jun 13.

Division of Transplantation, Department of Surgery, Lahey Clinic, Burlington, MA.

Background: Variation in the use of immunosuppression regimens after liver transplant has not been well described.

Methods: Immunosuppression regimens used after liver transplant were identified in a novel database integrating national transplant registry and pharmacy fill records for 24 238 recipients (2006-2014). Bilevel hierarchical models were developed to quantify the effects of transplant program, recipient, and donor characteristics on regimen choice.

Results: In the first 6 months after transplant, triple immunosuppression (tacrolimus, antimetabolite, corticosteroids) was the most common regimen (42.9%). By months 7 to 12, immunosuppression regimens were more commonly antimetabolite sparing (33.7%) or steroid sparing (26.9%), followed by triple (14.4%), mammalian target of rapamycin inhibitor (mTORi)-based (12.1%), or cyclosporine-based (9.2%). Based on intraclass correlation analysis, clinical characteristics explained less than 10% of the variation in immunosuppression choice, whereas program preference/practice explained 23% of steroid sparing, 26% of antimetabolite sparing, 28% of mTORi, and 21% of cyclosporine-based regimen use. Although case factors were not dominant practice drivers, triple immunosuppression in months 7 to 12 was more common among retransplant recipients and those with prior acute rejection. Hepatocellular carcinoma as cause of liver failure (adjusted odds ratio [aOR], 2.15; <0.001), cancer within 6 months (aOR, 6.07; <0.001), and 6-month estimated glomerular filtration rate less than 30 mL/min per 1.3 m (aOR, 1.98; <0.001) were associated with mTORi use compared with triple immunosuppression in months 7 to 12, whereas acute rejection predicted lower use (aOR, 0.72; =0.003).

Conclusions: Liver transplant immunosuppression is dominantly driven by program preference, but case factors also affect regimen choice. This variation frames a natural experiment for future evaluations of comparative efficacy.
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http://dx.doi.org/10.1097/TXD.0000000000000800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6056277PMC
July 2018

An economic assessment of contemporary kidney transplant practice.

Am J Transplant 2018 05 31;18(5):1168-1176. Epub 2018 Mar 31.

Center for Abdominal Transplantation, Saint Louis University School of Medicine, St. Louis, MO, USA.

Kidney transplantation is the optimal therapy for end-stage renal disease, prolonging survival and reducing spending. Prior economic analyses of kidney transplantation, using Markov models, have generally assumed compatible, low-risk donors. The economic implications of transplantation with high Kidney Donor Profile Index (KDPI) deceased donors, ABO incompatible living donors, and HLA incompatible living donors have not been assessed. The costs of transplantation and dialysis were compared with the use of discrete event simulation over a 10-year period, with data from the United States Renal Data System, University HealthSystem Consortium, and literature review. Graft failure rates and expenditures were adjusted for donor characteristics. All transplantation options were associated with improved survival compared with dialysis (transplantation: 5.20-6.34 quality-adjusted life-years [QALYs] vs dialysis: 4.03 QALYs). Living donor and low-KDPI deceased donor transplantations were cost-saving compared with dialysis, while transplantations using high-KDPI deceased donor, ABO-incompatible or HLA-incompatible living donors were cost-effective (<$100 000 per QALY). Predicted costs per QALY range from $39 939 for HLA-compatible living donor transplantation to $80 486 for HLA-incompatible donors compared with $72 476 for dialysis. In conclusion, kidney transplantation is cost-effective across all donor types despite higher costs for marginal organs and innovative living donor practices.
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http://dx.doi.org/10.1111/ajt.14702DOI Listing
May 2018

Transplant recipients are vulnerable to coverage denial under Medicare Part D.

Am J Transplant 2018 06 30;18(6):1502-1509. Epub 2018 Mar 30.

Transplant and Hepatobiliary Surgery, Lahey Clinic, Burlington, MA, USA.

Transplant immunosuppressants are often used off-label because of insufficient randomized prospective trial data to achieve organ-specific US Food and Drug Administration (FDA) approval. Transplant recipients who rely on Medicare Part D for immunosuppressant drug coverage are vulnerable to coverage denial for off-label prescriptions, unless use is supported by Centers for Medicare & Medicaid Services (CMS)-approved compendia. An integrated dataset including national transplant registry data and 3 years of dispensed pharmacy records was used to identify the prevalence of immunosuppression use that is both off-label and not supported by CMS-approved compendia. Numbers of potentially vulnerable transplant recipients were identified. Off-label and off-compendia immunosuppression regimens are frequently prescribed (3-year mean: lung 66.5%, intestine 34.2%, pancreas 33.4%, heart 21.8%, liver 16.5%, kidney 0%). The annual retail cost of these at-risk medications exceeds $30 million. This population-based study of transplant immunosuppressants vulnerable to claim denials under Medicare Part D coverage demonstrates a substantial gap between clinical practice, current FDA approval processes, and policy mandates for pharmaceutical coverage. This coverage barrier reduces access to life-saving medications for patients without alternative resources and may increase the risk of graft loss and death from medication nonadherence.
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http://dx.doi.org/10.1111/ajt.14703DOI Listing
June 2018

Center practice drives variation in choice of US kidney transplant induction therapy: a retrospective analysis of contemporary practice.

Transpl Int 2018 02 2;31(2):198-211. Epub 2017 Nov 2.

Center for Abdominal Transplantation, Saint Louis University School of Medicine, St. Louis, MO, USA.

To assess factors that influence the choice of induction regimen in contemporary kidney transplantation, we examined center-identified, national transplant registry data for 166 776 US recipients (2005-2014). Bilevel hierarchical models were constructed, wherein use of each regimen was compared pairwise with use of interleukin-2 receptor blocking antibodies (IL2rAb). Overall, 82% of patients received induction, including thymoglobulin (TMG, 46%), IL2rAb (22%), alemtuzumab (ALEM, 13%), and other agents (1%). However, proportions of patients receiving induction varied widely across centers (0-100%). Recipients of living donor transplants and self-pay patients were less likely to receive induction treatment. Clinical factors associated with use of TMG or ALEM (vs. IL2rAb) included age, black race, sensitization, retransplant status, nonstandard deceased donor, and delayed graft function. However, these characteristics explained only 10-33% of observed variation. Based on intraclass correlation analysis, "center effect" explained most of the variation in TMG (58%), ALEM (66%), other (51%), and no induction (58%) use. Median odds ratios generated from case-factor adjusted models (7.66-11.19) also supported large differences in the likelihood of induction choices between centers. The wide variation in induction therapy choice across US transplant centers is not dominantly explained by differences in patient or donor characteristics; rather, it reflects center choice and practice.
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http://dx.doi.org/10.1111/tri.13079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5862637PMC
February 2018

Temporal trends, center-level variation, and the impact of prevalent state obesity rates on acceptance of obese living kidney donors.

Am J Transplant 2018 03 30;18(3):642-649. Epub 2017 Oct 30.

Saint Louis University Center for Abdominal Transplantation, St. Louis, MO, USA.

The impact of pre-donation obesity on long-term outcomes of living kidney donors remains controversial. Published guidelines offer varying recommendations regarding BMI (kg/m ) thresholds for donor acceptance. We examined temporal and center-level variation in BMI of accepted donors across US transplant centers. Using national transplant registry data, we performed multivariate hierarchical logistic regression modeling using pairwise comparisons (overweight, BMI: 25-29.9; mildly obese, BMI: 30-34.9; very obese, BMI: ≥35; versus normal BMI: 18.5-24.9). Metrics of heterogeneity, including median odds ratio (MOR), were calculated. Among 90 013 living kidney donors, 2001-2016, proportions who were very obese decreased and proportions who were mildly obese or overweight increased. Significant center-level heterogeneity was noted in BMI of accepted donors; the MOR varied from 1.10 for overweight to 1.93 for very obese donors. At centers located in the 10 states with the highest general population obesity rates, adjusted odds of very obese donor status were 185% higher (reference: normal BMI) than in states with the lowest obesity rates. Although there is a declining trend in acceptance of very obese living kidney donors, variation across centers is significant. Furthermore, local population obesity rates may affect the decision to accept obese individuals as donors.
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http://dx.doi.org/10.1111/ajt.14519DOI Listing
March 2018

Antidepressant medication use before and after kidney transplant: implications for outcomes - a retrospective study.

Transpl Int 2018 01 3;31(1):20-31. Epub 2017 Aug 3.

Center for Abdominal Transplantation, Saint Louis University School of Medicine, St. Louis, MO, USA.

We examined a novel database wherein national US transplant registry identifiers were linked to records from a large pharmaceutical claims warehouse (2008-2015) to characterize antidepressant use before and after kidney transplantation, and associations [adjusted hazard ratio (aHR) 95% CI] with death and graft failure. Among 72 054 recipients, 12.6% filled antidepressant medications in the year before transplant, and use was more common among women and patients who were white, unemployed, and had limited functional status. Pre-transplant antidepressant use was associated with 39% higher 1-year mortality (aHR 1.39, 95% CI 1.18-1.64) and 15% higher all-cause graft loss risk (aHR 1.15, 95% CI 1.02-1.30). More than 50% of patients who filled antidepressants pre-transplant continued fill post-transplant. Antidepressant use in the first year after transplant was associated with twofold higher risk of death (aHR 1.94, 95% CI 1.60-2.35), 38% higher risk of death-censored graft failure, and 61% higher risk of all-cause graft failure in the subsequent year. Pre-listing antidepressant use was also associated with increased mortality, but transplantation conferred a survival benefit regardless of prelisting antidepressant use status. While associations may in part reflect underlying behaviors or comorbidities, kidney transplant candidates and recipients treated with antidepressant medications should be monitored and supported to reduce the risk of adverse outcomes.
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http://dx.doi.org/10.1111/tri.13006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334638PMC
January 2018

Survival implications of opioid use before and after liver transplantation.

Liver Transpl 2017 03;23(3):305-314

Center for Abdominal Transplantation, Saint Louis University School of Medicine, St. Louis, MO.

Implications of prescription opioid use for outcomes after liver transplantation (LT) have not been described. We integrated national transplant registry data with records from a large pharmaceutical claims clearinghouse (2008-2014; n = 29,673). Opioid fills on the waiting list were normalized to morphine equivalents (MEs), and exposure was categorized as follows: > 0-2 ME/day (level 1), > 2-10 ME/day (level 2), > 10-70 ME/day (level 3), and >70 ME/day (level 4). Associations (adjusted hazard ratio [aHR], aHR ) of pretransplant ME level with patient and graft survival over 5 years after transplant were quantified by multivariate Cox regression including adjustment for recipient, donor, and transplant factors, as well as propensity adjustment for opioid use. Overall, 9.3% of recipients filled opioids on the waiting list. Compared with no use, level 3 (aHR 1.28 ) and 4 (aHR 1.52 ) opioid use during listing were associated with increased mortality over 5 years after transplant. These associations were driven by risk after the first transplant anniversary, such that mortality >1-5 years increased in a graded manner with higher use on the waiting list (level 2, aHR, 1.27 ; level 3, aHR, 1.38 ; level 4, aHR, 2.01 ). Similar patterns occurred for graft failure. Of recipients with the highest level of opioids on the waiting list, 65% had level 3 or 4 use in the first year after transplant, including 55% with use at these levels from day 90-365 after transplant. Opioid use in the first year after transplant also bore graded associations with subsequent death and graft loss >1-5 years after transplant. Opioid use history may be relevant in assessing and providing care to LT candidates. Liver Transplantation 23 305-314 2017 AASLD.
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http://dx.doi.org/10.1002/lt.24714DOI Listing
March 2017