Publications by authors named "Huiling Xiao"

50 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

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

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

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

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

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

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

Education Strategies in Dialysis Centers Associated With Increased Transplant Wait-listing Rates.

Transplantation 2020 02;104(2):335-342

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

Background: Transplant education in dialysis centers can increase access to kidney transplant; however, dialysis center transplant barriers are common, and limited research identifies the most effective transplant education approaches.

Methods: We surveyed transplant educators in 1694 US dialysis centers about their transplant knowledge, use of 12 education practices, and 8 identified education barriers. Transplant wait-listing rates were calculated using US Renal Data System data.

Results: Fifty-two percent of educators orally recommended transplant to patients, 31% had in-center transplant discussions with patients, 17% distributed print educational resources, and 3% used intensive education approaches. Distribution of print education (incident rate ratio: 1.021.151.30) and using >1 intensive education practice (1.001.111.23) within dialysis centers were associated with increased wait-listing rates. Several dialysis center characteristics were associated with reduced odds of using education strategies leading to increased wait-listing. Centers with greater percentages of uninsured patients (odds ratio [OR]: 0.960.970.99), in rural locations (OR: 0.660.790.95), with for-profit ownership (OR: 0.640.770.91), and with more patients older than 65 years (OR: 0.050.110.23) had lower odds of recommending transplant, while centers with a higher patient-to-staff ratio were more likely to do so (OR: 1.011.031.04). Language barriers (OR: 0.480.640.86) and having competing work priorities (OR: 0.400.530.70) reduced the odds of distributing print education. Providers with greater transplant knowledge were more likely to use >1 intensive educational strategy (OR: 1.011.271.60) while providers who reported competing work priorities (OR: 0.510.660.84) and poor communication with transplant centers (OR: 0.580.760.98) were less likely to do so.

Conclusions: Educators should prioritize transplant education strategies shown to be associated with increasing wait-listing rates.
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http://dx.doi.org/10.1097/TP.0000000000002781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933099PMC
February 2020

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

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

Clinical and Economic Consequences of Early Cancer After Kidney Transplantation in Contemporary Practice.

Transplantation 2017 04;101(4):858-866

1 Division of Nephrology, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO. 2 Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI. 3 Division of Abdominal Transplantation, Department of Surgery, Brody School of Medicine, Greenville, NC. 4 Saint Louis University Abdominal Transplantation Center, Saint Louis University School of Medicine, St. Louis, MO. 5 Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, MO. 6 Division of Abdominal Transplantation, Department of Surgery, Johns Hopkins University, Baltimore, MD. 7 Center for Outcomes Research, Saint Louis University School of Medicine, St. Louis, MO. 8 Division of Nephrology, Department of Medicine, Hennepin County Medical Center, Minneapolis, MN.

Background: Current clinical and economic consequences of cancer after kidney transplantation are incompletely defined.

Methods: We examined United States Renal Data System records of Medicare-insured kidney transplant recipients in 2000 to 2011 to determine clinical and economic impacts of cancer diagnosed within the first 3 years posttransplantation. Cancer diagnoses were identified using Medicare billing codes and categorized as nonmelanoma skin cancer (NMSC), viral-linked and "other" cancers. Associations of cancers with mortality and graft loss were estimated by time-varying Cox regression. Impacts of cancer diagnoses on inpatient and outpatient costs within each year were quantified by multivariate linear regression modeling.

Results: Among 67 157 recipients, by 3 years posttransplant, NMSC was diagnosed in 5.7%, viral-linked cancer in 1.9%, and "other" cancers in 6.3%. Viral-linked cancer was associated with more than 3-fold increased risk in subsequent mortality until the third transplant anniversary, and nearly twice the mortality risk after year 3. "Other" cancers had similar associations with death and graft loss, whereas NMSC was associated with 33% higher mortality beyond the third year posttransplant. Viral-linked cancer had the largest inpatient and outpatient cost impacts per case, followed by "other" cancer, whereas NMSC impacted only outpatient costs. Care of new cancer diagnoses was generally more costly than care of previously established diagnoses. Cancer accounted for 3% to 5.5% of total inpatient Medicare expenditures and 1.5% to 3.3% of outpatient expenditures in the first 3 years posttransplant.

Conclusions: Early posttransplant malignancy is an expensive and morbid condition that warrants attention in efforts to improve pretransplant screening and management protocols before and after transplant.
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http://dx.doi.org/10.1097/TP.0000000000001385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346345PMC
April 2017

Diabetes Mellitus in Living Pancreas Donors: Use of Integrated National Registry and Pharmacy Claims Data to Characterize Donation-Related Health Outcomes.

Transplantation 2017 06;101(6):1276-1281

1 Division of Nephrology, University of Alberta, Edmonton, AB, Canada. 2 Center for Abdominal Transplantation, Saint Louis University School of Medicine, St. Louis, MO. 3 Division of Transplantation, Department of Surgery, Johns Hopkins School of Medicine, Baltimore, MD. 4 Symphony Health Solutions, Leonard Davis Institute for Health Economics, Philadelphia, PA. 5 Leonard Davis Institute for Health Economics, University of Pennsylvania, Philadelphia, PA. 6 Division of Nephrology, Department of Medicine, Hennepin County Medical Center, Minneapolis, MN. 7 Scientific Registry of Transplant Recipients, Minneapolis Medical Research Foundation, Minneapolis, MN. 8 Division of Abdominal Transplantation, Department of Surgery, Brody School of Medicine, Greenville, NC. 9 Division of Nephrology, Western University, London, ON, Canada. 10 Transplant Nephrology, Washington University School of Medicine, St. Louis, MO.

Background: Living donor pancreas transplant is a potential treatment for diabetic patients with end-organ complications. Although early surgical risks of donation have been reported, long-term medical outcomes in living pancreas donors are not known.

Methods: We integrated national Scientific Registry of Transplant Recipients data (1987-2015) with records from a nationwide pharmacy claims warehouse (2005-2015) to examine prescriptions for diabetes medications and supplies as a measure of postdonation diabetes mellitus. To compare outcomes in controls with baseline good health, we matched living pancreas donors to living kidney donors (1:3) by demographic traits and year of donation.

Results: Among 73 pancreas donors in the study period, 45 were identified in the pharmacy database: 62% women, 84% white, and 80% relatives of the recipient. Over a mean postdonation follow-up period of 16.3 years, 26.7% of pancreas donors filled prescriptions for diabetes treatments, compared with 5.9% of kidney donors (odds ratio, 4.13; 95% confidence interval, 1.91-8.93; P = 0.0003). Use of insulin (11.1% vs 0%) and oral agents (20.0% vs 5.9%; odds ratio, 4.50, 95% confidence interval, 2.09-9.68; P = 0.0001) was also higher in pancreas donors.

Conclusions: Diabetes is more common after living pancreas donation than after living kidney donation, supporting clinical consequences from reduced endocrine reserve.
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http://dx.doi.org/10.1097/TP.0000000000001375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5288378PMC
June 2017

Pretransplant Midodrine Use: A Newly Identified Risk Marker for Complications After Kidney Transplantation.

Transplantation 2016 05;100(5):1086-93

1 Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, MO. 2 Transplant Epidemiology Research Collaboration (TERC), Institute of Public Health, Washington University School of Medicine, St. Louis, MO. 3 Center for Abdominal Transplantation, Saint Louis University School of Medicine, St. Louis, MO. 4 Division of Nephrology, Department of Medicine, Saint Louis University School of Medicine, St. Louis, MO. 5 Division of Abdominal Transplantation, Department of Surgery, Dartmouth Hitchcock Medical Center, Hanover, NH. 6 Division of Abdominal Transplantation, Department of Surgery, Johns Hopkins University, Baltimore, MD. 7 Division of Nephrology, Department of Medicine, Saint Louis University School of Medicine, St. Louis, MO.

Background: Midodrine is prescribed to prevent symptomatic hypotension and decrease complications associated with hypotension during dialysis. We hypothesized that midodrine use before kidney transplantation may be a novel marker for posttransplant risk.

Methods: We analyzed integrated national US transplant registry, pharmacy records, and Medicare claims data for 16 308 kidney transplant recipients transplanted 2006 to 2008, of whom 308 (1.9%) had filled midodrine prescriptions in the year before transplantation. Delayed graft function (DGF), graft failure, and patient death were ascertained from the registry. Posttransplant cardiovascular complications were identified using diagnosis codes on Medicare billing claims. Adjusted associations of pretransplant midodrine use with complications at 3 and 12 months posttransplant were quantified by multivariate Cox or logistic regression, including propensity for midodrine exposure.

Results: At 3 months, patients who used midodrine pretransplant had significantly (P < 0.05) higher rates of DGF, 32% versus 19%; hypotension, 14% versus 4%; acute myocardial infarction, 4% versus 2%; cardiac arrest, 2% versus 0.9%, graft failure, 5% versus 2%; and death, 4% versus 1% than nonusers. After multivariate adjustment including recipient and donor factors, as well as for the propensity of midodrine exposure, pretransplant midodrine use was independently associated with risks of DGF (adjusted odds ratio, 1.78; 95% confidence interval [CI], 1.36-2.32), and 3 month death-censored graft failure (adjusted hazard ratio, 2.0; 95% CI, 1.18-3.39), and death (adjusted hazard ratio, 3.49; 95% CI, 1.95-6.24). Patterns were similar at 12 months.

Conclusions: Although associations may in part reflect underlying conditions, the need for midodrine before kidney transplantation is a risk marker for complications including DGF, graft failure, and death.
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http://dx.doi.org/10.1097/TP.0000000000001113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4846474PMC
May 2016

Clinical and economic consequences of first-year urinary tract infections, sepsis, and pneumonia in contemporary kidney transplantation practice.

Transpl Int 2016 Feb 9;29(2):241-52. Epub 2015 Dec 9.

Saint Louis University Center for Transplant Research, Saint Louis University Hospital, St. Louis, MO, USA.

We examined United States Renal Data System registry records for Medicare-insured kidney transplant recipients in 2000-2011 to study the clinical and cost impacts of urinary tract infections (UTI), pneumonia, and sepsis in the first year post-transplant among a contemporary, national cohort. Infections were identified by billing diagnostic codes. Among 60 702 recipients, 45% experienced at least one study infection in the first year post-transplant, including UTI in 32%, pneumonia in 13%, and sepsis in 12%. Older recipient age, female sex, diabetic kidney failure, nonstandard criteria organs, sirolimus-based immunosuppression, and steroids at discharge were associated with increased risk of first-year infections. By time-varying, multivariate Cox regression, all study infections predicted increased first-year mortality, ranging from 41% (aHR 1.41, 95% CI 1.25-1.56) for UTI alone, 6- to 12-fold risk for pneumonia or sepsis alone, to 34-fold risk (aHR 34.38, 95% CI 30.35-38.95) for those with all three infections. Infections also significantly increased first-year costs, from $17 691 (standard error (SE) $591) marginal cost increase for UTI alone, to approximately $40 000-$50 000 (SE $1054-1238) for pneumonia or sepsis alone, to $134 773 (SE $1876) for those with UTI, pneumonia, and sepsis. Clinical and economic impacts persisted in years 2-3 post-transplant. Early infections reflect important targets for management protocols to improve post-transplant outcomes and reduce costs of care.
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http://dx.doi.org/10.1111/tri.12711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4805426PMC
February 2016

Assessing Transplant Education Practices in Dialysis Centers: Comparing Educator Reported and Medicare Data.

Clin J Am Soc Nephrol 2015 Sep 20;10(9):1617-25. Epub 2015 Aug 20.

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

Background And Objectives: The Centers for Medicare & Medicaid Services (CMS) requires that dialysis centers inform new patients of their transplant options and document compliance using the CMS-2728 Medical Evidence Form (Form-2728). This study compared reports of transplant education for new dialysis patients reported to CMS with descriptions from transplant educators (predominantly dialysis nurses and social workers) of their centers' quantity of and specific educational practices. The goal was to determine what specific transplant education occurred and whether provision of transplant education was associated with center-level variation in transplant wait-listing rates.

Design, Setting, Participants, & Measurements: Form-2728 data were drawn for 1558 incident dialysis patients at 170 centers in the Heartland Kidney Network (Iowa, Kansas, Missouri, and Nebraska) in 2009-2011; educators at these centers completed a survey describing their transplant educational practices. Educators' own survey responses were compared with Form-2728 reports for patients at each corresponding center. The association of quantity of transplant education practices used with wait-listing rates across dialysis centers was examined using multivariable negative binomial regression.

Results: According to Form-2728, 77% of patients (n=1203) were informed of their transplant options within 45 days. Educators, who reported low levels of transplant knowledge themselves (six of 12 questions answered correctly), most commonly reported giving oral recommendations to begin transplant evaluation (988 informed patients educated, 81% of centers) and referrals to external transplant education programs (959 informed patients educated, 81% of centers). Only 18% reported having detailed discussions about transplant with their patients. Compared with others, centers that used more than three educational activities (incident rate ratio, 1.36; 95% confidence interval, 1.07 to 1.73) had higher transplant wait-listing rates.

Conclusions: While most educators inform new patients that transplant is an option, dialysis centers with higher wait-listing rates use multiple transplant education strategies.
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http://dx.doi.org/10.2215/CJN.09851014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4559519PMC
September 2015

Long-term safety and efficacy of antithymocyte globulin induction: use of integrated national registry data to achieve ten-year follow-up of 10-10 Study participants.

Trials 2015 Aug 19;16:365. Epub 2015 Aug 19.

Transplant Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.

Background: Rabbit antithymocyte globulin (rATG, Thymoglobulin®) is the most common induction immunosuppression therapy in kidney transplantation. We applied a database integration strategy to capture and compare long-term (10-year) outcome data for US participants in a clinical trial of rATG versus FDA-approved basiliximab.

Methods: Records for US participants in an international, 1-year, randomized clinical trial comparing rATG and basiliximab induction in deceased donor kidney transplantation were integrated with records from the US national Organ Procurement and Transplantation (OPTN) registry using center, transplant dates, recipient sex, and birthdates. The OPTN captures center-reported acute rejection, graft failure, death, and cancer events, and incorporates comprehensive death records from the Social Security Death Master File. Ten-year outcomes according to randomized induction regimen were compared by Kaplan-Meier analysis (two-sided P). Non-inferiority of rATG was assessed using a one-tailed equivalence test (a-priori equivalence margins of 0-10 %).

Results: Of 183 US trial participants, 89 % (n = 163) matched OPTN records exactly; the remainder were matched by extending agreement windows for transplant and birthdates. Matches were validated by donor and recipient blood types. By Kaplan-Meier analysis, 10 years post-transplant, freedom from acute rejection, graft failure, or death was 32.6 % and 24.0 % in the rATG and basiliximab arms, respectively (P = 0.09). The incidence of acute rejection with rATG versus basiliximab induction was 21.0 % versus 32.8 % (P = 0.07). Patient survival (52.8 % [Corrected] versus 52.2 %, P = 0.92) and graft survival (34.3 % versus 30.9 %, P = 0.56) rates were numerically and statistically similar for both arms. Comparison of the composite outcome meets non-inferiority criteria even with a 0 % equivalence margin (one-sided P = 0.04). With a 10 % equivalence margin, the odds that rATG is no worse than basiliximab for 10-year risk of the composite endpoint are >99 %.

Conclusions: Ten years post-transplant, rATG induction has comparable efficacy and safety to FDA-approved basiliximab. Integration of clinical trial records with national registry data can enable long-term monitoring of trial participants in transplantation, circumventing logistical and cost barriers of extended follow-up.

Trial Registration: ClinicalTrials.gov NCT00235300.
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http://dx.doi.org/10.1186/s13063-015-0891-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4545548PMC
August 2015

Gender differences in use of prescription narcotic medications among living kidney donors.

Clin Transplant 2015 Oct 18;29(10):927-37. Epub 2015 Sep 18.

Division of Abdominal Transplantation, Department of Surgery, Johns Hopkins School of Medicine, Baltimore, MD, USA.

Prescription narcotic use among living kidney donors is not well described. Using a unique database that integrates national registry identifiers for living kidney donors (1987-2007) in the United States with billing claims from a private health insurer (2000-2007), we identified pharmacy fills for prescription narcotic medications in periods 1-4 and >4 yr post-donation and estimated relative likelihoods of post-donation narcotic use by Cox regression. We also compared narcotic fill rates and medication possession ratios (MPRs, defined as (days of medication supplied)/(days observed)), between donors and age- and sex-matched non-donors. Overall, rates of narcotic medication fills were 32.3 and 32.4 per 100 person-years in periods 1-4 and >4 yr post-donation. After age and race adjustment, women were approximately twice as likely as men to fill a narcotic prescription in years 1-4 (adjusted hazard ratio, aHR, 2.28; 95% confidence interval, CI, 1.86-2.79) and >4 yr (aHR 1.70; 95% CI 1.50-1.93). MPRs in donors were low (<2.5% days exposed), and lower than among age- and sex-matched non-donors. Prescription narcotic medication use is more common among women than men in the intermediate term after live kidney donation. Overall, total narcotic exposure is low, and lower than among non-donors from the general population.
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http://dx.doi.org/10.1111/ctr.12599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4805522PMC
October 2015

Race, Relationship and Renal Diagnoses After Living Kidney Donation.

Transplantation 2015 Aug;99(8):1723-9

1 Center for Outcomes Research, Saint Louis University School of Medicine, St. Louis, MO. 2 Division of Abdominal Transplantation, Department of Surgery, Saint Louis University School of Medicine, St. Louis, MO. 3 Division of Nephrology, Western University, London, ON, Canada. 4 Division of Abdominal Transplantation, Department of Surgery, Dartmouth Hitchcock Medical Center, Hanover, NH. 5 Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, MO. 6 Division of Abdominal Transplantation, Department of Surgery, Johns Hopkins University, Baltimore, MD.

Background: In response to recent studies, a better understanding of the risks of renal complications among African American and biologically related living kidney donors is needed.

Methods: We examined a database linking U.S. registry identifiers for living kidney donors (1987-2007) to billing claims from a private health insurer (2000-2007 claims) to identify renal condition diagnoses categorized by International Classification of Diseases 9th Revision coding. Cox regression with left and right censoring was used to estimate cumulative incidence of diagnoses after donation and associations (adjusted hazards ratios, aHR) with donor traits.

Results: Among 4650 living donors, 13.1% were African American and 76.3% were white; 76.1% were first-degree relatives of their recipient. By 7 years post-donation, after adjustment for age and sex, greater proportions of African American compared with white donors had renal condition diagnoses: chronic kidney disease (12.6% vs 5.6%; aHR, 2.32; 95% confidence interval [95% CI], 1.48-3.62), proteinuria (5.7% vs 2.6%; aHR, 2.27; 95% CI, 1.32-3.89), nephrotic syndrome (1.3% vs 0.1%; aHR, 15.7; 95% CI, 2.97-83.0), and any renal condition (14.9% vs 9.0%; aHR, 1.72; 95% CI, 1.23-2.41). Although first-degree biological relationship to the recipient was not associated with renal risk, associations of African American race persisted for these conditions and included unspecified renal failure and reported disorders of kidney dysfunction after adjustment for biological donor-recipient relationship.

Conclusions: African Americans more commonly develop renal conditions after living kidney donation, independent of donor-recipient relationship. Continued research is needed to improve risk stratification for renal outcomes among African American living donors.
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http://dx.doi.org/10.1097/TP.0000000000000733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4663050PMC
August 2015

Gout after living kidney donation: correlations with demographic traits and renal complications.

Am J Nephrol 2015 17;41(3):231-40. Epub 2015 Apr 17.

Division of Nephrology, Western University, London, Ont., Canada.

Background: The demographic and clinical correlates of gout after living kidney donation are not well described.

Methods: Using a unique database that integrates national registry identifiers of U.S. living kidney donors (1987-2007) with billing claims from a private health insurer (2000-2007), we identified post-donation gout based on medical diagnosis codes or pharmacy fills for gout therapies. The frequencies and demographic correlates of gout after donation were estimated by Cox regression with left- and right-censoring. We also compared the rates of renal diagnoses among donors with and without gout, matched in the ratio 1:3 by age, sex, and race.

Results: The study sample of 4,650 donors included 13.1% African Americans. By seven years, African Americans were almost twice as likely to develop gout as Caucasian donors (4.4 vs. 2.4%; adjusted hazard ratio, aHR, 1.8; 95% confidence interval (CI) 1.0-3.2). Post-donation gout risk also increased with older age at donation (aHR per year 1.05) and was higher in men (aHR 2.80). Gout rates were similar in donors and age- and sex-matched general non-donors (rate ratio 0.86; 95% CI 0.66-1.13). Compared to matched donors without gout, donors with gout had more frequent renal diagnoses, reaching significance for acute kidney failure (rate ratio 12.5; 95% CI 1.5-107.0), chronic kidney disease (rate ratio 5.0; 95% CI 2.1-11.7), and other disorders of the kidney (rate ratio 2.2; 95% CI 1.2-4.2).

Conclusion: Donor subgroups at increased risk of gout include African Americans, older donors, and men. Donors with gout have a higher burden of renal complications after demographic adjustment.
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http://dx.doi.org/10.1159/000381291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4522163PMC
May 2016

Associations of pre-transplant prescription narcotic use with clinical complications after kidney transplantation.

Am J Nephrol 2015 27;41(2):165-76. Epub 2015 Mar 27.

Center for Outcomes Research, Saint Louis University School of Medicine, St. Louis, Mo., USA.

Background: The impact of narcotic use before kidney transplantation on post-transplant clinical outcomes is not well described.

Methods: We examined integrated national transplant registry, pharmacy records, and Medicare billing claims to follow 16,322 kidney transplant recipients, of whom 28.3% filled a narcotic prescription in the year before transplantation. Opioid analgesic fills were normalized to morphine equivalents (ME) and expressed as mg/kg exposures (approximate quartiles: 0.1-1.7, 1.8-5.4, 5.5-23.7, and ≥ 23.8 mg/kg, respectively). Post-transplant cardiovascular, respiratory, neurological, accidents, substance abuse, and noncompliance events were identified using diagnosis codes on Medicare billing claims. Adjusted associations of ME level with post-transplant complications were quantified by multivariate Cox regression.

Results: The incidence of complications at 3 years post-transplant among those with the highest pre-transplant ME exposure compared to no use included: ventricular arrhythmias, 1.1 vs. 0.2% (p < 0.001); cardiac arrest, 4.7 vs. 2.7% (p < 0.05); hypotension, 14 vs. 8% (p < 0.0001); hypercapnia, 1.6 vs. 0.9% (p < 0.05); mental status changes, 5.3 vs. 2.7% (p < 0.001); drug abuse/dependence, 7.0 vs. 1.7% (p < 0.0001); alcohol abuse, 1.8 vs. 0.6% (p = 0.0001); accidents, 0.9 vs. 0.3% (p < 0.05); and noncompliance, 3.5 vs. 2.3% (p < 0.05). In multivariate analyses, transplant recipients with the highest level of pre-transplant narcotic use had approximately 2 to 4 times the risks of post-transplant ventricular arrhythmias, mental status changes, drug abuse, alcohol abuse, and accidents compared with non-users, and 35-45% higher risks of cardiac arrest and hypotension.

Conclusion: Although associations may reflect underlying conditions or behaviors, high-level prescription narcotic use before kidney transplantation predicts increased risk of clinical complications after transplantation.
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http://dx.doi.org/10.1159/000377685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4522162PMC
January 2016

Quantifying prognostic impact of prescription opioid use before kidney transplantation through linked registry and pharmaceutical claims data.

Transplantation 2015 Jan;99(1):187-96

1 Center for Outcomes Research, Saint Louis University School of Medicine, St. Louis, MO. 2 Division of Abdominal Transplantation, Department of Surgery, Saint Louis University School of Medicine, St. Louis, MO. 3 Department of Anesthesia, Saint Louis University School of Medicine, St. Louis, MO. 4 Division of Abdominal Transplantation, Department of Surgery, Dartmouth Hitchcock Medical Center, Hanover, NH. 5 Transplant Nephrology, Washington University School of Medicine, St. Louis, MO.

Background: Limited data are available on the outcome implications of prescription narcotic use before kidney transplantation.

Methods: We examined a novel database wherein national transplant registry identifiers for kidney transplant recipients were linked to records from a large U.S. pharmaceutical claims clearinghouse (2005-2010). We selected recipients with 1 year of captured pretransplant pharmaceutical fill records (N=31,197). Opioid analgesic fills in the year before transplantation were normalized to morphine equivalents (ME) and expressed as mg/kg exposures. Adjusted associations of ME level with posttransplant graft and patient survival (adjusted hazards ratio, aHR) were quantified by multivariate Cox regression.

Results: Among the 29% of the sample who filled opioid prescriptions in the year before transplantation, the 25th, 50th, and 75th percentiles of annual ME were 1.8, 5.5, and 23.7 mg/kg, respectively. Three-year graft survival was 88.0% and 84.4% in live donor recipients with upper quartiles of ME use, compared with 92.0% among those who did not receive prescription narcotics (P<0.0001). Adjusted risks of posttransplant death and all-cause graft loss in live donor recipients with the highest quartile of narcotic use were 2.3 times (aHR, 2.27; 95% confidence interval, 1.66-3.10) and 1.8 times (aHR, 1.75; 95% confidence interval, 1.37-2.26), respectively, that of narcotic nonusers. Graded associations of pretransplant opioid exposure level with death and graft loss after deceased donor transplantation were also observed.

Conclusions: Although associations may in part reflect underlying conditions or behaviors, high levels of prescription opioid use before kidney transplantation predict increased risk of posttransplant death and graft loss.
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http://dx.doi.org/10.1097/TP.0000000000000248DOI Listing
January 2015

Clopidogrel use as a risk factor for poor outcomes after kidney transplantation.

Am J Surg 2014 Oct 18;208(4):556-62. Epub 2014 Jul 18.

Division of Abdominal Organ Transplantation, Department of Surgery, Saint Louis University Medical Center, St. Louis, MO, USA; Center for Outcomes Research, Saint Louis University School of Medicine, St. Louis, MO, USA; Division of Nephrology, Saint Louis University School of Medicine, St. Louis, MO, USA.

Background: Limited data are available on outcome implications of clopidogrel use before kidney transplantation.

Methods: A novel dataset linking national transplant registry data with records from a large pharmacy claims clearinghouse (2005 to 2010) was examined to estimate risks of post-transplant death and graft failure associated with clopidogrel fills within 90 or more than 90 days before transplant.

Results: Clopidogrel fills within 90 days of transplant were associated with 61% of increased relative mortality risk and 23% of increased graft failure risk. Risks were higher in those whose last clopidogrel fill was more than 90 days before transplantation (111% for death, 59% for graft loss). Adverse prognostic associations persisted among recipients of live and deceased donor allografts, older recipients, and those with diabetes or reported cardiovascular disease.

Conclusions: Clopidogrel use before kidney transplantation portends increased risks of post-transplant death and graft loss. Pharmacy claims may identify novel prognostic markers not currently captured in the transplant registry.
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http://dx.doi.org/10.1016/j.amjsurg.2014.06.007DOI Listing
October 2014

Understanding antihypertensive medication use after living kidney donation through linked national registry and pharmacy claims data.

Am J Nephrol 2014 2;40(2):174-83. Epub 2014 Sep 2.

Center for Outcomes Research, Saint Louis University School of Medicine, St. Louis, Mo., USA.

Background: Use of antihypertensive medications (AHM) after living kidney donation is not well described.

Methods: We examined a database wherein national transplant registry data for 4,650 living kidney donors in 1987-2007 were linked to pharmacy claims from a US private health insurer (2000-2007 claims) to identify post-donation AHM fills. Cox regression with left- and right-censoring was used to estimate the frequencies and relative likelihood (adjusted hazards ratios, aHR) of post-donation AHM fills according to donor demographic traits. Medication possession ratio (MPRs), defined as (days of AHM dispensed)/(days observed), were also compared among donors and non-donor general beneficiaries.

Results: Overall, 17.8% of the sample filled at least one AHM by 5 years post-donation. As compared with White living donors, African-Americans had 37% higher relative likelihood of any AHM use after donation (aHR 1.37, p < 0.0007), including significantly higher likelihoods of filling diuretics (aHR 2.25, p < 0.0001), ACEi/ARBs (aHR 1.46, p < 0.01), calcium channel blockers (aHR 1.56, p = 0.03), and vasodilators/other agents (aHR 2.17, p = 0.03). MPRs for any AHM and subcategories were lower among donors compared with age- and sex-matched non-donors. However, AHM MPRs rose in donors with multiple hypertension diagnoses, and prescription fill exposure for all AHM classes except diuretics was similar among donors and general non-donors with ≥ 3 hypertension diagnoses.

Conclusions: While AHM requirements are lower after kidney donation than among unscreened general persons, racial variation in AHM use occurs in privately insured donors. Demonstration of pharmaceutical care needs of insured donors supports the need for long-term follow-up and healthcare access for all donors.
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http://dx.doi.org/10.1159/000365157DOI Listing
June 2015

Prognostic impact of mechanical ventilation after liver transplantation: a national database study.

Am J Surg 2014 Oct 18;208(4):582-90. Epub 2014 Jul 18.

Department of Surgery, Saint Louis University School of Medicine, St. Louis, MO, USA; Department of Surgery, Dartmouth Hitchcock Medical Center, Hanover, NH, USA. Electronic address:

Background: The impact of mechanical ventilatory support (MCVS) on mortality and graft loss after liver transplantation (LT) is not well described.

Methods: Multivariate analysis of a novel database linking national transplant registry and Medicare claims data was used to assess the impact of early MCVS on mortality and graft survival following LTs performed between 2002 and 2008.

Results: Among 10,517 LT recipients, 6.9% (n = 726) required postoperative MCVS, 25.6% of whom required less than 96 hours, 24.2% required 96 hours or longer, and 50.1% received an unspecified duration. Significant predictors of prolonged MCVS included older age, female sex, pretransplant dialysis requirement, and ascites. After multivariate adjustment, MCVS of 96 hours or longer was associated with nearly 3 times the adjusted hazard ratio of mortality (2.95, P < .001), while MCVS less than 96 hours was not significantly associated with mortality (adjusted hazard ratio .88, P = .55).

Conclusions: Recognition of LT patients at risk for prolonged MCVS may help to reduce the incidence and consequences of this complication.
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http://dx.doi.org/10.1016/j.amjsurg.2014.06.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4457441PMC
October 2014

National assessment of early biliary complications after liver transplantation: economic implications.

Transplantation 2014 Dec;98(11):1226-35

1 Section of Transplant Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, NH. 2 Center for Outcome Research, St. Louis University, St. Louis, MO. 3 Department of Surgery, St. Louis University, St. Louis, MO. 4 Department of Surgery, Johns Hopkins School of Medicine, Baltimore, MD. 5 Address correspondence to: David A. Axelrod, M.D., MBA, Dartmouth-Hitchcock Medical Center, 1 Medical Center Drive, Lebanon, NH 03756.

Background: Despite improvement in surgical technique and medical management of liver transplant recipients, biliary complications remain a frequent cause of posttransplant morbidity and graft loss. Biliary complications require potentially expensive interventions including radiologic procedures and surgical revisions.

Methods: A national data set linking transplant registry and Medicare claims data for 12,803 liver transplant recipients was developed to capture information on complications, treatments, and associated direct medical costs up to 3 years after transplantation.

Results: Biliary complications were more common in recipients of donation after cardiac death compared to donation after brain death allografts (23% vs. 19% P<0.001). Among donation after brain death recipients, biliary complications were associated with $54,699 (95% confidence interval [CI], $49,102 to $60,295) of incremental spending in the first year after transplantation and $7,327 in years 2 and 3 (95% CI, $4,419-$10,236). Biliary complications in donation after cardiac death recipients independently increased spending by $94,093 (95% CI, $64,643-$124,542) in the first year and $12,012 (95% CI, $-1,991 to $26,016) in years 2 and 3.

Conclusion: This national study of biliary complications demonstrates the significant economic impact of this common perioperative complication and suggests a potential target for quality of care improvements.
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http://dx.doi.org/10.1097/TP.0000000000000197DOI Listing
December 2014

Early clinical complications after ABO-incompatible live-donor kidney transplantation: a national study of Medicare-insured recipients.

Transplantation 2014 Jul;98(1):54-65

1 Center for Outcomes Research, Saint Louis University School of Medicine, St. Louis, MO. 2 Division of Abdominal Transplantation, Department of Surgery, Saint Louis University School of Medicine, St. Louis, MO. 3 Division of Abdominal Transplantation, Department of Surgery, Dartmouth Hitchcock Medical Center, Hanover, NH. 4 Transplant Nephrology, Washington University School of Medicine, St. Louis, MO. 5 Division of Abdominal Transplantation, Department of Surgery, Johns Hopkins University, Baltimore, MD. 6 Address correspondence to: Krista L. Lentine, M.D., Ph.D., Saint Louis University Center for Outcomes Research, Salus Center 4th Floor, 3545 Lafayette Ave, St. Louis, MO 63104.

Background: Descriptions of the sequelae of ABO-incompatible (ABOi) kidney transplantation are limited to single-center reports, which may lack power to detect important effects.

Methods: We examined U.S. Renal Data System registry data to study associations of ABOi live-donor kidney transplantation with clinical complications in a national cohort. Among 14,041 Medicare-insured transplants in 2000 to 2007, 119 non-donor-A2 ABOi transplants were identified. A2-incompatible (n=35) transplants were categorized separately. Infection and hemorrhage events were identified by diagnosis codes on billing claims. Associations of ABO incompatibility with complications were assessed by multivariate Cox regression.

Results: Recipients of ABOi transplants experienced significantly (P<0.05) higher incidence of wound infections (12.7% vs. 7.3%), pneumonia (7.6% vs. 3.8%), and urinary tract infections (UTIs) or pyelonephritis (24.5% vs. 15.3%) in the first 90 days compared with ABO-compatible recipients. In adjusted models, ABO incompatibility was associated with twice the risk of pneumonia (adjusted hazard ratio [aHR], 2.22; 95% confidence interval [CI], 1.14-4.33) and 56% higher risk of UTIs or pyelonephritis (aHR, 1.56; 95% CI, 1.05-2.30) in the first 90 posttransplantation days, and 3.5 times the relative risk of wound infections in days 91 to 365 (aHR, 3.55; 95% CI, 1.92-6.57). ABOi recipients, 19% of whom underwent pre- or peritransplant splenectomy, experienced twice the adjusted risk of early hemorrhage (aHR, 1.96; 95% CI, 1.19-3.24). A2-incompatible transplantation was associated only with early risk of UTIs or pyelonephritis.

Conclusion: ABOi transplantation offers patients with potential live donors an additional transplant option but with higher risks of infectious and hemorrhagic complications. Awareness of these complications may help improve protocols for the management of ABOi transplantation.
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http://dx.doi.org/10.1097/TP.0000000000000029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4411309PMC
July 2014

Brain areas involved in the acupuncture treatment of AD model rats: a PET study.

BMC Complement Altern Med 2014 May 31;14:178. Epub 2014 May 31.

School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.

Background: Acupuncture may effectively treat certain symptoms of Alzheimer's disease (AD). Although several studies have used functional brain imaging to investigate the mechanisms of acupuncture treatment on AD, these mechanisms are still poorly understood. We therefore further explored the mechanism by which needling at ST36 may have a therapeutic effect in a rat AD model.

Methods: A total of 80 healthy Wistar rats were divided into healthy control (n = 15) and pre-model (n = 65) groups. After inducing AD-like disease, a total of 45 AD model rats were randomly divided into three groups: the model group (n = 15), the sham-point group (n = 15), and the ST36 group (n = 15). The above three groups underwent PET scanning. PET images were processed with SPM2.

Results: The brain areas that were activated in the sham-point group relative to the model group were primarily centred on the bilateral limbic system, the right frontal lobe, and the striatum, whereas the activated areas in the ST36 group were primarily centred on the bilateral limbic system (pyriform cortex), the bilateral temporal lobe (olfactory cortex), the right amygdala and the right hippocampus. Compared with the sham-point group, the ST36 group showed greater activation in the bilateral amygdalae and the left temporal lobe.

Conclusion: We concluded that needling at a sham point or ST36 can increase blood perfusion and glycol metabolism in certain brain areas, and thus may have a positive influence on the cognition of AD patients.
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http://dx.doi.org/10.1186/1472-6882-14-178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4107978PMC
May 2014