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1.
Clin Transplant ; 38(4): e15257, 2024 04.
Article in English | MEDLINE | ID: mdl-38563475

ABSTRACT

BACKGROUND: Recent clinical trials demonstrate benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with chronic kidney disease, but data on use in kidney transplant (KTx) recipients are limited. METHODS: We examined a novel database linking SRTR registry data for KTx recipients (2000-2021) with outpatient fill records from a large pharmaceutical claims warehouse (2015-2021). Adult (≥18 years) KTx recipients treated with SGLT2i were compared to those who received other noninsulin diabetes medications without SGLT2i. Characteristics associated with SGLT2i use were quantified by multivariable logistic regression (adjusted odds ratio, 95%LCLaOR95%UCL). RESULTS: Among 18 988 KTx recipients treated with noninsulin diabetes agents in the study period, 2224 filled an SGLT2i. Mean time from KTx to prescription was 6.7 years for SGLT2i versus 4.7 years for non-SGLT2i medications. SGLT2i use was more common in Asian adults (aOR, 1.091.311.58) and those aged > 30-59 years (compared with 18-30 years) or with BMI > 35 kg/m2 (aOR, 1.191.411.67), and trended higher with self-pay status. SGLT2i use was lower among KTx recipients who were women (aOR, .79.87.96), Black (aOR, .77.881.00) and other (aOR, .52.751.07) race, publicly insured (aOR, .82.921.03), or with less than college education (aOR, .78.87.96), and trended lower in those age 75 years and older. SGLT2i use in KTx patients increased dramatically in 2019-2021 (aOR, 5.015.636.33 vs. prior years). CONCLUSION: SGLT2i use is increasing in KTx recipients but varies with factors including race, education, and insurance. While ongoing study is needed to define risks and benefits of SGLT2i use in KTx patients, attention should also focus on reducing treatment disparities related to sociodemographic traits.


Subject(s)
Diabetes Mellitus, Type 2 , Kidney Transplantation , Pharmacy , Sodium-Glucose Transporter 2 Inhibitors , Adult , Humans , Female , Male , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Kidney Transplantation/adverse effects , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/etiology , Glucose , Sodium/therapeutic use , Hypoglycemic Agents/therapeutic use
2.
Clin Transplant ; 38(1): e15161, 2024 01.
Article in English | MEDLINE | ID: mdl-37842872

ABSTRACT

BACKGROUND: With the introduction of direct-acting antiviral therapies (DAAs), the non-use rate of hepatitis C virus (HCV)-positive donor organs (D+) has decreased significantly. We present the donor, recipient, and transplant allograft characteristics, along with recipient outcomes, in one of the largest cohorts of HCV-D+ transplants into HCV-naïve recipients (R-). METHODS: Charts of HCV D+/R- kidney (KT), liver (LT), and simultaneous liver-kidney (SLKT) transplant recipients between January 2019 and July 2022 were reviewed. Primary outcomes of interest included waitlist times and 1-year graft failure. Secondary outcomes included hospital and intensive care unit length of stay, post-transplant complications, effectiveness of DAA therapy, and characteristics of patients who relapsed from initial DAA therapy. RESULTS: Fifty-five HCV D+/R- transplants at our center [42 KT (26 nucleic acid testing positive [NAT+], 16 NAT-), 12 LT (eight NAT+, four NAT-), and one SLKT (NAT+)] had a median waitlist time of 69 days for KT, 87 days for LT, and 15 days for SLKT. There were no graft failures at 1 year. All viremic recipients were treated with a 12-week course of DAAs, of which 100% achieved end of treatment response (EOTR)-85.7% (n = 30) achieved sustained virologic response (SVR) and 14.3% relapsed (n = 5; four KT, one LT). All relapsed recipients were retreated and achieved SVR. The most common post-transplantation complications include BK virus infection (n = 9) for KT and non-allograft infections (n = 4) for LT. CONCLUSIONS: Our study has demonstrated no graft failures or recipient deaths at 1 year, and despite a 14.3% relapse rate, we achieved 100% SVR. Complications rates of D+/R- appeared comparable to national D-/R- complication rates. Further studies comparing D+/R- to D-/R- outcomes are needed.


Subject(s)
Hepatitis C, Chronic , Hepatitis C , Kidney Transplantation , Humans , Hepacivirus , Antiviral Agents/therapeutic use , Kidney Transplantation/adverse effects , Hepatitis C, Chronic/drug therapy , Hepatitis C/drug therapy , Hepatitis C/surgery , Hepatitis C/etiology , Tissue Donors , Kidney
3.
J Am Soc Nephrol ; 34(6): 1069-1077, 2023 06 01.
Article in English | MEDLINE | ID: mdl-36890643

ABSTRACT

SIGNIFICANCE STATEMENT: Cardiovascular diseases account for 32% of deaths among kidney transplant recipients. Statin therapy is common in this population. However, its effect on mortality prevention remains unclear among kidney transplant recipients, whose clinical risk profile might be unique because of concomitant immunosuppressive therapy. In this national study of 58,264 single-kidney transplant recipients, statin use was associated with a 5% decrease in mortality. More importantly, this protective association was stronger among those who used a mammalian target of rapamycin (mTOR) inhibitor for immunosuppression (27% decrease in mTOR inhibitor users versus 5% in nonusers). Our results suggest that statin therapy may reduce mortality in kidney transplant recipients and that the strength of this protective association may vary by immunosuppression regimen. BACKGROUND: Cardiovascular diseases are the leading cause of mortality in kidney transplant (KT) recipients, accounting for 32% of deaths. Statins are widely used in KT recipients, but effectiveness for preventing mortality remains unclear in this population, especially because of interaction between statins and immunosuppressive agents. We analyzed a national cohort to assess the real-world effectiveness of statins for reducing all-cause mortality in KT recipients. METHODS: We studied statin use and mortality among 58,264 adults (18 years or older) who received single kidneys between 2006 and 2016 and had Medicare part A/B/D. Statin use was ascertained from Medicare prescription drug claims and deaths from Center for Medicare and Medicaid Services records. We estimated the association of statin use with mortality using multivariable Cox models, with statin use as a time-varying exposure and immunosuppression regimen as effect modifiers. RESULTS: Statin use increased from 45.5% at KT to 58.2% at 1-year post-KT to 70.9% at 5-year post-KT. We observed 9785 deaths over 236,944 person-years. Overall, statin use was significantly associated with lower mortality (adjusted hazard ratio [aHR], 0.95; 95% confidence interval [CI], 0.90 to 0.99). The strength of this protective association varied by calcineurin inhibitor use (among tacrolimus users, aHR, 0.97; 95% CI, 0.92 to 1.03 versus among calcineurin nonusers, aHR, 0.72; 95% CI, 0.60 to 0.87; interaction P =0.002), mammalian target of rapamycin (mTOR) inhibitor use (among mTOR inhibitor users, aHR, 0.73; 95% CI, 0.57 to 0.92 versus among nonusers, aHR, 0.95; 95% CI, 0.91 to 1.00; interaction P =0.03), and mycophenolate use (among mycophenolate users, aHR, 0.96; 95% CI, 0.91 to 1.02 versus among nonusers, aHR, 0.76; 95% CI, 0.64 to 0.89; interaction P =0.002). CONCLUSION: Real-world evidence supports statin therapy for reducing all-cause mortality in KT recipients. Effectiveness might be greater when combined with mTOR inhibitor-based immunosuppression.


Subject(s)
Cardiovascular Diseases , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Kidney Transplantation , Adult , Humans , Aged , United States/epidemiology , Immunosuppressive Agents/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Medicare , TOR Serine-Threonine Kinases , Transplant Recipients
4.
Clin Transplant ; 37(7): e14924, 2023 07.
Article in English | MEDLINE | ID: mdl-36733213

ABSTRACT

In the United States, living donor liver transplantation (LDLT) is limited to transplant centers with specific experience. However, the impact of recipient characteristics on procedure selection (LDLT vs. deceased donor liver transplant [DDLT]) within these centers has not been described. Transplant registry data for centers that performed ≥1 LDLT in 2002-2019 were analyzed using hierarchal regression modeling to quantify the impact of patient and center factors on the adjusted odds ratio (aOR) of LDLT (vs DDLT). Among 73,681 adult recipients, only 4% underwent LDLT, varying from <1% to >60% of total liver transplants. After risk adjustment, the likelihood of receiving an LDLT rose by 73% in recent years (aOR 1.73 for 2014-2019 vs. 2002-2007) but remained lower for older adults, men, racial and ethnic minorities, and obese patients. LDLT was less commonly used in patients with hepatocellular carcinoma or alcoholic cirrhosis, and more frequently in those with hepatitis C and with lower severity of illness (Model for End-Stage Liver Disease (MELD) score < 15). Patients with public insurance, lower educational achievement, and residence in the Northwest and Southeast had decreased access. While some differences in access to LDLT reflect clinical factors, further exploration into disparities in LDLT utilization based on center practice and socioeconomic determinants of health is needed.


Subject(s)
End Stage Liver Disease , Liver Neoplasms , Liver Transplantation , Male , Humans , United States , Aged , Living Donors , Liver Transplantation/methods , End Stage Liver Disease/surgery , Retrospective Studies , Severity of Illness Index , Liver Neoplasms/pathology , Treatment Outcome
5.
Am J Transplant ; 22(6): 1705-1713, 2022 06.
Article in English | MEDLINE | ID: mdl-35143100

ABSTRACT

An electronic survey canvassing current policies of transplant centers regarding a COVID-19 vaccine mandate for transplant candidates and living donors was distributed to clinicians at US solid organ transplant centers performing transplants from October 14, 2021-November 15, 2021. Responses were received from staff at 141 unique transplant centers. These respondents represented 56.4% of US transplant centers, and responding centers performed 78.5% of kidney transplants and 82.4% of liver transplants in the year prior to survey administration. Only 35.7% of centers reported implementing a vaccine mandate, while 60.7% reported that vaccination was not required. A minority (42%) of responding centers with a vaccine mandate for transplant candidates also mandated vaccination for living organ donors. Centers with a vaccine mandate most frequently cited clinical evidence supporting the efficacy of pre-transplant vaccination (82%) and stewardship obligations to ensure organs were transplanted into the lowest risk patients (64%). Centers without a vaccine mandate cited a variety of reasons including administrative, equity, and legal considerations for their decision. Transplant centers in the United States exhibit significant heterogeneity in COVID-19 vaccination mandate policies for transplant candidates. While all centers encourage vaccination, most centers have not mandated COVID-19 vaccination for candidates and living donors, citing administrative opposition, legal prohibitions, and concern about equity in access to transplants.


Subject(s)
COVID-19 Vaccines , COVID-19 , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/therapeutic use , Humans , Living Donors , SARS-CoV-2 , Surveys and Questionnaires , Transplant Recipients , United States/epidemiology
6.
Clin Transplant ; 36(12): e14817, 2022 12.
Article in English | MEDLINE | ID: mdl-36065568

ABSTRACT

INTRODUCTION: Value-based purchasing requires accurate techniques to appropriately measure both outcomes and cost with robust adjustment for differences in severity of illness. Traditional methods to adjust cost estimates have exclusively used administrative data derived from billing claims to identify comorbidity and complications. Transplantation uniquely has accurate national clinical registry data that can be used to supplement administrative data. METHODS: Administrative claims from the Vizient, Inc, Clinical Data Base (CDB) were linked with clinical records from the Scientific Registry for Transplant Recipients for 76 liver and 109 kidney transplant programs. Using either or both datasets, we fitted a regression model to the total direct cost of care for 16,649 kidney and 6058 liver transplants. RESULTS: The proportion of variation explained by these risk-adjustment models increased significantly when combined administrative and clinical data were used for kidney (administrative only R2 = .069, clinical only R2 = .047, combined R2 = .14, p < .0001) and liver (administrative only R2 = .28, clinical only R2 = .25, combined R2 = .33, p < .0001). CONCLUSION: Incorporating accurate clinical data into risk-adjustment methodologies can improve risk adjustment methodologies; however, as majority of variation in cost remains unexplained by these risk-adjustment models further work is needed to accuracy assess transplant value.


Subject(s)
Kidney Transplantation , Risk Adjustment , Humans , Registries , Comorbidity , Costs and Cost Analysis
7.
Transpl Int ; 35: 10422, 2022.
Article in English | MEDLINE | ID: mdl-35692736

ABSTRACT

Relationships between renal function and medical costs for deceased donor kidney transplant recipients are not fully quantified post-transplant. We describe these relationships with renal function measured by estimated glomerular filtration rate (eGFR) and graft failure. The United States Renal Data System identified adults receiving single-organ deceased donor kidneys 2012-2015. Inpatient, outpatient, other facility costs and eGFRs at discharge, 6 and 12 months were included. A time-history of costs was constructed for graft failures and monthly costs in the first year post-transplant were compared to those without failure. The cohort of 24,021 deceased donor recipients had a 2.4% graft failure rate in the first year. Total medical costs exhibit strong trends with eGFR. Recipients with 6-month eGFRs of 30-59 ml/min/1.73m2 have total costs 48% lower than those <30 ml/min/1.73m2. For recipients with graft failure monthly costs begin to rise 3-4 months prior to failure, with incremental costs of over $38,000 during the month of failure. Mean annual total incremental costs of graft failure are over $150,000. Total costs post-transplant are strongly correlated with eGFR. Graft failure in the first year is an expensive, months-long process. Further reductions in early graft failures could yield significant human and economic benefits.


Subject(s)
Kidney Transplantation , Adult , Glomerular Filtration Rate , Graft Survival , Humans , Kidney/physiology , Kidney/surgery , Tissue Donors , United States
8.
Transpl Infect Dis ; 24(1): e13763, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34796585

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has created unprecedented challenges for solid organ transplant programs worldwide. The aim of this study is to assess an international perspective on challenges faced by kidney transplant programs. METHODS: We administered an electronic survey instrument from January 3, 2021 to June 8, 2021 to staff at transplant programs outside the United States that comprised of 10 questions addressing the management of kidney transplant candidates with asymptomatic COVID-19 infection or unvaccinated who receive an organ offer. RESULTS: Respondents (n = 62) represented 19 countries in five continents. Overall, 90.3% of respondents encourage vaccination on the waiting list and prior to planned living donor transplant. Twelve percent of respondents reported that they have decided to inactivate unsensitized candidates (calculated panel reactive antibody, cPRA <80%) until they received the two doses of vaccination, and 7% report inactivating candidates who have received their first vaccine dose pending receipt of their second dose. The majority (88.5%) of international respondents declined organs for asymptomatic, nucleic acid testing (NAT)+ patients during admission without documented prior infection. However, 22.9% of international respondents proceeded with kidney transplant in NAT+ patients who were at least 30 days from initial diagnosis with negative chest imaging. CONCLUSIONS: Practitioners in some countries are less willing to accept deceased donor organs for waitlist candidates with incomplete COVID-19 vaccination status and to wait longer before scheduling living donor transplant, compared to United States practices. Access to vaccinations and other resources may contribute to these differences. More research is needed to guide the optimal approach to vaccination before and after transplant.


Subject(s)
COVID-19 , Kidney Transplantation , COVID-19 Vaccines , Humans , Internationality , Kidney Transplantation/adverse effects , SARS-CoV-2 , United States , Vaccination , Waiting Lists
9.
Clin Transplant ; 35(1): e14068, 2021 01.
Article in English | MEDLINE | ID: mdl-32808362

ABSTRACT

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.


Subject(s)
Kidney Failure, Chronic , Kidney Transplantation , Aged , Humans , Kidney Failure, Chronic/surgery , Living Donors , Medicare , Retrospective Studies , United States
10.
Clin Transplant ; 35(5): e14280, 2021 05.
Article in English | MEDLINE | ID: mdl-33690910

ABSTRACT

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.


Subject(s)
COVID-19 , Tissue and Organ Procurement , Humans , Policy , SARS-CoV-2 , Tissue Donors
11.
Clin Transplant ; 35(11): e14437, 2021 11.
Article in English | MEDLINE | ID: mdl-34297878

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has created unprecedented challenges for solid organ transplant programs. While transplant activity has largely recovered, appropriate management of deceased donor candidates who are asymptomatic but have positive nucleic acid testing (NAT) for SARS-CoV-2 is unclear, as this result may reflect active infection or prolonged viral shedding. Furthermore, candidates who are unvaccinated or partially vaccinated continue to receive donor offers. In the absence of robust outcomes data, transplant professionals at US adult kidney transplant centers were surveyed (February 13, 2021 to April 29, 2021) to determine community practice (N: 92 centers, capturing 41% of centers and 57% of transplants performed). The majority (97%) of responding centers declined organs for asymptomatic NAT+ patients without documented prior infection. However, 32% of centers proceed with kidney transplant in NAT+ patients who were at least 30 days from initial diagnosis with negative chest imaging. Less than 7% of programs reported inactivating patients who were unvaccinated or partially vaccinated. In conclusion, despite national recommendations to wait for negative testing, many centers are proceeding with kidney transplant in patients with positive SARS-CoV-2 NAT results due to presumed viral shedding. Furthermore, few centers are requiring COVID-19 vaccination prior to transplantation at this time.


Subject(s)
COVID-19 , Adult , Asymptomatic Infections , COVID-19 Vaccines , Humans , SARS-CoV-2 , Vaccination
12.
Transpl Infect Dis ; 23(2): e13526, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33245844

ABSTRACT

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.


Subject(s)
COVID-19/prevention & control , Kidney Transplantation , Living Donors , Tissue and Organ Harvesting , Asia , COVID-19/diagnosis , COVID-19 Nucleic Acid Testing , Delivery of Health Care , Europe , Humans , Internationality , Latin America , Mass Screening , Middle East , North America , Patient Safety , Personal Protective Equipment/supply & distribution , SARS-CoV-2 , Surveys and Questionnaires , Telemedicine , Tissue and Organ Procurement
13.
Am J Transplant ; 20(3): 788-796, 2020 03.
Article in English | MEDLINE | ID: mdl-31553823

ABSTRACT

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, 95%LCL aHR95%UCL ), 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 1.53 2.203.17 ; LD-KA: aHR 1.29 1.872.71 ) and death (DD-KA: aHR 2.12 3.255.00 ; LD-KA: aHR 1.54 2.353.59 ). SPK,P- recipients had significantly higher risk of death (aHR 1.68 3.306.50 ). 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.


Subject(s)
Diabetes Mellitus, Type 1 , Diabetes Mellitus, Type 2 , Kidney Transplantation , Pancreas Transplantation , Graft Survival , Humans , Kidney Transplantation/adverse effects , Pancreas
14.
Clin Transplant ; 34(12): e14121, 2020 12.
Article in English | MEDLINE | ID: mdl-33048385

ABSTRACT

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 (pinteraction  = 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 (pinteraction  = 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.


Subject(s)
Kidney Transplantation , Neoplasms , Adult , Aged , Antilymphocyte Serum/adverse effects , Female , Graft Rejection , Humans , Immunosuppression Therapy/adverse effects , Immunosuppressive Agents/adverse effects , Kidney Transplantation/adverse effects , Medicare , Neoplasms/epidemiology , Neoplasms/etiology , Prospective Studies , United States/epidemiology
15.
Clin Transplant ; 34(12): e14118, 2020 12.
Article in English | MEDLINE | ID: mdl-33048372

ABSTRACT

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,1.12 1.963.42 , p = .02) and ventricular arrhythmias (15.2% vs. 11.4%; aHR,1.00 1.813.29 , 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,1.02 1.542.31 , p = .04) and pancytopenia (35.9% vs. 31.4%; aHR,1.03 1.311.68 , 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.


Subject(s)
Hydroxychloroquine/therapeutic use , Immunosuppressive Agents/therapeutic use , Kidney Failure, Chronic/surgery , Kidney Transplantation , Lupus Erythematosus, Systemic/drug therapy , Maintenance Chemotherapy/methods , Scleroderma, Systemic/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Drug Therapy, Combination , Female , Graft Rejection/prevention & control , Graft Survival , Humans , Information Storage and Retrieval , Insurance, Health , Kidney Failure, Chronic/etiology , Kidney Failure, Chronic/mortality , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/mortality , Male , Middle Aged , Registries , Retrospective Studies , Scleroderma, Systemic/complications , Scleroderma, Systemic/mortality , Treatment Outcome , United States , Young Adult
16.
Clin Transplant ; 34(9): e14005, 2020 09.
Article in English | MEDLINE | ID: mdl-32510628

ABSTRACT

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, LCL aHRUCL ) 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, 1.08 1.221.38 ), 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 1.29 1.391.48 ; long-acting 1.12 1.251.40 ; both 1.46 1.742.07 ). 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.


Subject(s)
Analgesics, Opioid , Kidney Transplantation , Analgesics, Opioid/therapeutic use , Benzodiazepines/therapeutic use , Humans , Retrospective Studies , Risk Factors , Transplant Recipients
17.
Clin Transplant ; 34(8): e14000, 2020 08.
Article in English | MEDLINE | ID: mdl-32502285

ABSTRACT

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, LCL aORUCL ). 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,1.24 1.381.53 ), less than college education (aOR,1.19 1.311.43 ), smoking (aOR,1.33 1.451.58 ), and nephrectomy complications (aOR,1.11 1.291.49 ). 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.


Subject(s)
Kidney Transplantation , Pharmaceutical Preparations , Pharmacy , Analgesics, Opioid/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Female , Humans , Kidney , Living Donors , Male , Registries
18.
Clin Transplant ; 34(4): e13813, 2020 04.
Article in English | MEDLINE | ID: mdl-32027049

ABSTRACT

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.


Subject(s)
Kidney Transplantation , Aged , Cohort Studies , Graft Rejection/drug therapy , Graft Rejection/etiology , Humans , Immunosuppression Therapy , Immunosuppressive Agents/therapeutic use , Medicare , Mycophenolic Acid , United States
19.
Clin Transplant ; 34(3): e13803, 2020 03.
Article in English | MEDLINE | ID: mdl-31997429

ABSTRACT

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.


Subject(s)
Hypertension , Kidney Transplantation , Adult , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , Humans , Hypertension/drug therapy , Hypertension/epidemiology , Middle Aged
20.
Am J Transplant ; 19(12): 3405-3414, 2019 12.
Article in English | MEDLINE | ID: mdl-31397964

ABSTRACT

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, 95%LCL aHR95%UCL ) 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 1.10 1.331.61 ) 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 1.46 1.701.98 ) 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.


Subject(s)
Analgesics, Opioid/adverse effects , Drug Prescriptions/statistics & numerical data , Heart Diseases/mortality , Heart Transplantation/mortality , Opioid-Related Disorders/mortality , Postoperative Complications/mortality , Registries/statistics & numerical data , Adolescent , Adult , Aged , Female , Follow-Up Studies , Heart Diseases/surgery , Heart Transplantation/adverse effects , Humans , Male , Middle Aged , Opioid-Related Disorders/etiology , Postoperative Complications/etiology , Prognosis , Retrospective Studies , Risk Factors , Young Adult
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