Publications by authors named "Deirdre Sawinski"

88 Publications

Kidney injury and disease in patients with haematological malignancies.

Nat Rev Nephrol 2021 Mar 30. Epub 2021 Mar 30.

Division of Nephrology and Hypertension, Division of Hematology, Mayo Clinic, Rochester, MN, USA.

Acute kidney injury (AKI) is common in patients with cancer, especially in those with haematological malignancies. Kidney injury might be a direct consequence of the underlying haematological condition. For example, in the case of lymphoma infiltration or extramedullary haematopoiesis, it might be caused by a tumour product; in the case of cast nephropathy it might be due to the presence of monoclonal immunoglobulin; or it might result from tumour complications, such as hypercalcaemia. Kidney injury might also be caused by cancer treatment, as many chemotherapeutic agents are nephrotoxic. High-intensity treatments, such as high-dose chemotherapy followed by haematopoietic stem cell transplantation, not only increase the risk of infection but can also cause AKI through various mechanisms, including viral nephropathies, engraftment syndrome and sinusoidal obstruction syndrome. Some conditions, such as thrombotic microangiopathy, might also result directly from the haematological condition or the treatment. Novel immunotherapies, such as immune checkpoint inhibitors and chimeric antigen receptor T cell therapy, can also be nephrotoxic. As new therapies for haematological malignancies with increased anti-tumour efficacy and reduced toxicity are developed, the number of patients receiving these treatments will increase. Clinicians must gain a good understanding of the different mechanisms of kidney injury associated with cancer to better care for these patients.
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http://dx.doi.org/10.1038/s41581-021-00405-7DOI Listing
March 2021

Analysis of malignant melanoma risk and outcomes in solid organ transplant recipients: Assessment of transplant candidacy and the potential role of checkpoint inhibitors.

Clin Transplant 2021 Mar 11:e14264. Epub 2021 Mar 11.

Department of Surgery, University of Wisconsin, School of Medicine and Public Health, Madison, WI, USA.

Malignant melanoma (MM) causes tremendous morbidity and mortality in the solid organ transplant population and may arise in three different clinical scenarios: (1) pretransplant melanoma; (2) de novo melanoma post transplantation and (3) donor-derived melanoma. This manuscript primarily addresses the first two scenarios with respect to the evaluation and management of pretransplant MM, consideration of transplant candidacy and the occurrence and management of de novo MM post transplantation. The authors outline current evidence describing risks associated with pre-transplant melanoma to support recently established expert opinion for transplant candidacy.
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http://dx.doi.org/10.1111/ctr.14264DOI Listing
March 2021

Introduction to Kidney Transplantation: Long-Term Management Challenges.

Clin J Am Soc Nephrol 2021 Mar 10. Epub 2021 Mar 10.

Department of Nephrology and Hypertension, Glickman Urological and Kidney Institute, Cleveland Clinic Foundation, Cleveland, Ohio.

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http://dx.doi.org/10.2215/CJN.13440820DOI Listing
March 2021

Association of Racial/Ethnic and Gender Concordance Between Patients and Physicians With Patient Experience Ratings.

JAMA Netw Open 2020 11 2;3(11):e2024583. Epub 2020 Nov 2.

Renal-Electrolyte and Hypertension Division, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.

Importance: The Press Ganey Outpatient Medical Practice Survey is used to measure the patient experience. An understanding of the patient- and physician-related determinants of the patient experience may help identify opportunities to improve health care delivery and physician ratings.

Objective: To evaluate the associations between the patient experience as measured by scores on the Press Ganey survey and patient-physician racial/ethnic and gender concordance.

Design, Setting, And Participants: A cross-sectional analysis of Press Ganey surveys returned for outpatient visits within the University of Pennsylvania Health System between 2014 and 2017 was performed. Participants included adult patient and physician dyads for whom surveys were returned. Data analysis was performed from January to June 2019.

Exposures: Patient-physician racial/ethnic and gender concordance.

Main Outcomes And Measures: The primary outcome was receipt of the maximum score for the "likelihood of your recommending this care provider to others" question in the Care Provider domain of the Press Ganey survey. Secondary outcomes included each of the remaining 9 questions in the Care Provider domain. Generalized estimating equations clustering on physicians with exchangeable intracluster correlations and cluster-robust standard errors were used to investigate associations between the outcomes and patient-physician racial/ethnic and gender concordance.

Results: In total, 117 589 surveys were evaluated, corresponding to 92 238 unique patients (mean [SD] age, 57.7 [15.6] years; 37 002 men [40.1%]; 75 307 White patients [81.6%]) and 747 unique physicians (mean [SD] age 45.5 [10.6] years; 472 men [63.2%]; 533 White physicians [71.4%]). Compared with racially/ethnically concordant patient-physician dyads, discordance was associated with a lower likelihood of physicians receiving the maximum score (adjusted odds ratio [OR], 0.88; 95% CI, 0.82-0.94; P < .001). Black (adjusted OR, 0.73; 95% CI, 0.68-0.78; P < .001) and Asian (adjusted OR, 0.55; 95% CI, 0.50-0.60; P < .001) patient race were both associated with lower patient experience ratings. Patient-physician gender concordance was not associated with Press Ganey scores (adjusted OR, 1.00; 95% CI, 0.96-1.04; P = .90).

Conclusions And Relevance: In this study, higher Press Ganey survey scores were associated with racial/ethnic concordance between patients and their physicians. Efforts to improve physician workforce diversity are imperative. Delivery of health care in a culturally mindful manner between racially/ethnically discordant patient-physician dyads is also essential. Furthermore, Press Ganey scores may differ by a physician's patient demographic mix; thus, care must be taken when publicly reporting or using Press Ganey scores to evaluate physicians on an individual level.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.24583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653497PMC
November 2020

Preexisting melanoma and hematological malignancies, prognosis, and timing to solid organ transplantation: A consensus expert opinion statement.

Am J Transplant 2021 02 10;21(2):475-483. Epub 2020 Oct 10.

Department of Medicine, Mayo Clinic, Rochester, Minnesota.

Patients undergoing evaluation for solid organ transplantation (SOT) frequently have a history of malignancy. Only patients with treated cancer are considered for SOT but the benefits of transplantation need to be balanced against the risk of tumor recurrence, taking into consideration the potential effects of immunosuppression. Prior guidelines on timing to transplant in patients with a prior treated malignancy do not account for current staging, disease biology, or advances in cancer treatments. To update these recommendations, the American Society of Transplantation (AST) facilitated a consensus workshop to comprehensively review contemporary literature regarding cancer therapies, cancer stage specific prognosis, the kinetics of cancer recurrence, as well as the limited data on the effects of immunosuppression on cancer-specific outcomes. This document contains prognosis, treatment, and transplant recommendations for melanoma and hematological malignancies. Given the limited data regarding the risk of cancer recurrence in transplant recipients, the goal of the AST-sponsored conference and the consensus documents produced are to provide expert opinion recommendations that help in the evaluation of patients with a history of a pretransplant malignancy for transplant candidacy.
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http://dx.doi.org/10.1111/ajt.16324DOI Listing
February 2021

Pretransplant solid organ malignancy and organ transplant candidacy: A consensus expert opinion statement.

Am J Transplant 2021 02 23;21(2):460-474. Epub 2020 Oct 23.

Department of Medicine, Mayo Clinic, Rochester, Minnesota.

Patients undergoing evaluation for solid organ transplantation (SOT) often have a history of malignancy. Although the cancer has been treated in these patients, the benefits of transplantation need to be balanced against the risk of tumor recurrence, especially in the setting of immunosuppression. Prior guidelines of when to transplant patients with a prior treated malignancy do not take in to account current staging, disease biology, or advances in cancer treatments. To develop contemporary recommendations, the American Society of Transplantation held a consensus workshop to perform a comprehensive review of current literature regarding cancer therapies, cancer stage-specific prognosis, the kinetics of cancer recurrence, and the limited data on the effects of immunosuppression on cancer-specific outcomes. This document contains prognosis based on contemporary treatment and transplant recommendations for breast, colorectal, anal, urological, gynecological, and nonsmall cell lung cancers. This conference and consensus documents aim to provide recommendations to assist in the evaluation of patients for SOT given a history of a pretransplant malignancy.
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http://dx.doi.org/10.1111/ajt.16318DOI Listing
February 2021

Effect of Neighborhood Food Environment and Socioeconomic Status on Serum Phosphorus Level for Patients on Chronic Dialysis.

J Am Soc Nephrol 2020 11 11;31(11):2622-2630. Epub 2020 Sep 11.

Renal-Electrolyte and Hypertension Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

Background: Elevated blood phosphorus levels are common and associated with a greater risk of death for patients receiving chronic dialysis. Phosphorus-rich foods are prevalent in the American diet, and low-phosphorus foods, including fruits and vegetables, are often less available in areas with more poverty. The relative contributions of neighborhood food availability and socioeconomic status to phosphorus control in patients receiving dialysis are unknown.

Methods: Using longitudinal data from a national dialysis provider, we constructed hierarchical, linear mixed-effects models to evaluate the relationships between neighborhood food environment or socioeconomic status and serum phosphorus level among patients receiving incident dialysis.

Results: Our cohort included 258,510 patients receiving chronic hemodialysis in 2005-2013. Median age at dialysis initiation was 64 years, 45% were female, 32% were Black, and 15% were Hispanic. Within their residential zip code, patients had a median of 25 "less-healthy" food outlets (interquartile range, 11-40) available to them compared with a median of four "healthy" food outlets (interquartile range, 2-6). Living in a neighborhood with better availability of healthy food was not associated with a lower phosphorus level. Neighborhood income also was not associated with differences in phosphorus. Patient age, race, cause of ESKD, and mean monthly dialysis duration were most closely associated with phosphorus level.

Conclusions: Neither neighborhood availability of healthy food options nor neighborhood income was associated with phosphorus levels in patients receiving chronic dialysis. Modifying factors, such as nutrition literacy, individual-level financial resources, and adherence to diet restrictions and medications, may be more powerful contributors than food environment to elevated phosphorus.
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http://dx.doi.org/10.1681/ASN.2020030290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608959PMC
November 2020

Facilitating Patient-Centered Decision Making Around the Timing of Direct-Acting Antivirals in Patients With Hepatitis C Virus and CKD.

Kidney Med 2019 Jul-Aug;1(4):150-152. Epub 2019 Jul 13.

Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.

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http://dx.doi.org/10.1016/j.xkme.2019.07.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7380333PMC
July 2019

Current state of kidney transplantation in patients with HIV, hepatitis C, and hepatitis B infection.

Clin Transplant 2020 10 29;34(10):e14048. Epub 2020 Aug 29.

Renal Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Human immunodeficiency virus (HIV), hepatitis C (HCV), and hepatitis B (HBV) are common chronic viral infections in the end-stage kidney disease (ESKD) patient population that were once considered relative contraindications to kidney transplantation. In this review, we will summarize the current state of kidney transplantation in patients with HIV, HCV, and HBV, which is rapidly evolving. HIV+ patients enjoy excellent outcomes in the modern transplant era and may have new transplant opportunities with the use of HIV+ donors. Direct-acting antivirals for HCV have substantially changed the landscape of care for patients with HCV infection. HBV+ patients now have excellent patient and allograft survival with HBV therapy. Currently, kidney transplantation is a safe and appropriate treatment for the majority of ESKD patients with HIV, HCV, and HBV.
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http://dx.doi.org/10.1111/ctr.14048DOI Listing
October 2020

Quantifying Sex-Based Disparities in Liver Allocation.

JAMA Surg 2020 07 15;155(7):e201129. Epub 2020 Jul 15.

Division of Transplantation, Department of Surgery, University of California School of Medicine, San Francisco, San Francisco.

Importance: Differences in local organ supply and demand have introduced geographic inequities in the Model for End-stage Liver Disease (MELD) score-based liver allocation system, prompting national debate and patient-initiated lawsuits. No study to our knowledge has quantified the sex disparities in allocation associated with clinical vs geographic characteristics.

Objective: To estimate the proportion of sex disparity in wait list mortality and deceased donor liver transplant (DDLT) associated with clinical and geographic characteristics.

Design, Setting, And Participants: This retrospective cohort study used adult (age ≥18 years) liver-only transplant listings reported to the Organ Procurement and Transplantation Network from June 18, 2013, through March 1, 2018.

Exposure: Liver transplant waiting list.

Main Outcomes And Measures: Primary outcomes included wait list mortality and DDLT. Multivariate Cox proportional hazards regression models were constructed, and inverse odds ratio weighting was used to estimate the proportion of disparity across geographic location, MELD score, and candidate anthropometric and liver measurements.

Results: Among 81 357 adults wait-listed for liver transplant only, 36.1% were women (mean [SD] age, 54.7 [11.3] years; interquartile range, 49.0-63.0 years) and 63.9% were men (mean [SD] age, 55.7 [10.1] years; interquartile range, 51.0-63.0 years). Compared with men, women were 8.6% more likely to die while on the waiting list (adjusted hazard ratio [aHR], 1.11; 95% CI, 1.04-1.18) and were 14.4% less likely to receive a DDLT (aHR, 0.86; 95% CI, 0.84-0.88). In the geographic domain, organ procurement organization was the only variable that was significantly associated with increased disparity between female sex and wait list mortality (22.1% increase; aHR, 1.22; 95% CI, 1.09-1.30); no measure of the geographic domain was associated with DDLT. Laboratory and allocation MELD scores were associated with increases in disparities in wait list mortality: 1.14 (95% CI, 1.09-1.19; 50.1% increase among women) and DDLT: 0.87 (95% CI, 0.86-0.88; 10.3% increase among women). Candidate anthropometric and liver measurements had the strongest association with disparities between men and women in wait list mortality (125.8% increase among women) and DDLT (49.0% increase among women).

Conclusions And Relevance: Our findings suggest that addressing geographic disparities alone may not mitigate sex-based disparities, which were associated with the inability of the MELD score to accurately estimate disease severity in women and to account for candidate anthropometric and liver measurements in this study.
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http://dx.doi.org/10.1001/jamasurg.2020.1129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240642PMC
July 2020

Kidney transplant outcomes from donation after circulatory death donors of advanced age.

Clin Transplant 2020 07 8;34(7):e13881. Epub 2020 May 8.

Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.

Background: Continued comparison of kidney transplant outcomes between older DCD and donation after brain death (DBD) donors is needed to safely expand the deceased donor pool.

Methods: We performed a retrospective cohort study using the UNOS/OPTN transplant registry from donors >50 years old between 1994 and 2016. Donor age was stratified into 4 groups: 50-54, 55-59, 60-64, and >65 years old. Rates of delayed graft function (DGF) and primary non-function (PNF) were compared. Multivariable Cox regression models were constructed to identify factors associated with time to graft failure.

Results: The DCD donors within each age group had fewer comorbidities than the DBD donors. Graft survival for DCD kidneys was equivalent or superior to DBD kidneys in all donor age groups. DGF rates were significantly greater for DCD kidneys in all age groups. PNF rates across all groups were similar. In multivariable analysis, DCD status was not independently associated with time to all-cause graft failure in the 50-54 donor age group (HR = 1.02, 95% CI = 0.93-1.13), 55-59 donor age group (HR = 1.07, 95% CI = 0.96-1.19), or 60-64 donor age group (HR = 1.135, 95% CI = 0.97-1.32).

Conclusion: Kidneys from carefully selected older DCD donors, particularly ages 50-64, are a potential means to safely expand the deceased donor pool.
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http://dx.doi.org/10.1111/ctr.13881DOI Listing
July 2020

KDOQI US Commentary on the 2018 KDIGO Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C.

Am J Kidney Dis 2020 05 9;75(5):665-683. Epub 2020 Apr 9.

Keck School of Medicine, University of Southern California, Los Angeles, CA.

The first KDIGO (Kidney Disease: Improving Global Outcomes) guideline for the prevention, diagnosis, evaluation, and treatment of hepatitis C virus (HCV) infection was published in 2008. The ensuing decade bore witness to remarkable advances in the treatment of HCV infection following the approval of direct-acting antiviral (DAA) agents that deliver cure rates routinely >95%. In this context, the KDIGO organization correctly recognized the need for an updated HCV guideline that would be relevant to the treatment of HCV-infected patients with kidney disease in the DAA era. The current NKF-KDOQI (National Kidney Foundation-Kidney Disease Outcomes Quality Initiative) commentary provides an in-depth review and perspective on the 2018 KDIGO guideline. Of note, the KDIGO work group made significant updates to guideline chapters 2 and 4 as a direct result of the availability of DAAs. The intent of this commentary is to provide useful interpretation for nephrologists and other practitioners caring for HCV-infected patients with chronic kidney disease, including dialysis patients and kidney transplant recipients. The availability of DAA agents that are safe and highly effective has created new opportunities, such as the transplantation of kidneys from HCV-infected kidney donors. The ability to treat HCV infection in patients with kidney disease will have a significant impact on the care of our patients and should favorably influence long-term outcomes as well.
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http://dx.doi.org/10.1053/j.ajkd.2019.12.016DOI Listing
May 2020

Pregnancy in Liver Transplantation.

Liver Transpl 2020 07 6;26(7):954-955. Epub 2020 May 6.

Transplant Pregnancy Registry International, Gift of Life Institute, Philadelphia, PA.

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http://dx.doi.org/10.1002/lt.25753DOI Listing
July 2020

Long-term Kidney Transplantation Outcomes Network (APOLLO): Design and Rationale.

Kidney Int Rep 2020 Mar 13;5(3):278-288. Epub 2019 Dec 13.

Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Introduction: Much of the higher risk for end-stage kidney disease (ESKD) in African American individuals relates to ancestry-specific variation in the apolipoprotein L1 gene (). Relative to kidneys from European American deceased-donors, kidneys from African American deceased-donors have shorter allograft survival and African American living-kidney donors more often develop ESKD. The National Institutes of Health (NIH)-sponsored Long-term Kidney Transplantation Outcomes Network (APOLLO) is prospectively assessing kidney allograft survival from donors with recent African ancestry based on donor and recipient genotypes.

Methods: APOLLO will evaluate outcomes from 2614 deceased kidney donor-recipient pairs, as well as additional living-kidney donor-recipient pairs and unpaired deceased-donor kidneys.

Results: The United Network for Organ Sharing (UNOS), Association of Organ Procurement Organizations, American Society of Transplantation, American Society for Histocompatibility and Immunogenetics, and nearly all U.S. kidney transplant programs, organ procurement organizations (OPOs), and histocompatibility laboratories are participating in this observational study. APOLLO employs a central institutional review board (cIRB) and maintains voluntary partnerships with OPOs and histocompatibility laboratories. A Community Advisory Council composed of African American individuals with a personal or family history of kidney disease has advised the NIH Project Office and Steering Committee since inception. UNOS is providing data for outcome analyses.

Conclusion: This article describes unique aspects of the protocol, design, and performance of APOLLO. Results will guide use of genotypic data to improve the assessment of quality in deceased-donor kidneys and could increase numbers of transplanted kidneys, reduce rates of discard, and improve the safety of living-kidney donation.
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http://dx.doi.org/10.1016/j.ekir.2019.11.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7056919PMC
March 2020

Geographic Differences in Population Health and Expected Organ Supply in the Gulf Coast Region of the United States Compared to Non-Gulf States.

Transplantation 2020 02;104(2):421-427

Department of Surgery, Comprehensive Transplant Institute, University of Alabama at Birmingham, Birmingham, AL.

Background: The Final Rule aimed to reduce geographic disparities in access to transplantation by prioritizing the need for transplant over donor proximity. However, disparities in waiting times persist for deceased donor kidney transplantation. The kidney allocation system implemented in 2014 does not account for potential local supply based on population health characteristics within a donation service area (DSA). We hypothesized that regions with traditionally high rates of comorbid disease, such as the states located along the Gulf of Mexico (Gulf States), may be disadvantaged by limited local supply secondary to poor population health.

Methods: Using data from the Robert Wood Johnson Foundation County Health Rankings, the United States Renal Data System, and the Scientific Registry of Transplant Recipients, we compared population-level characteristics and expected kidney donation rates by Gulf States location.

Results: Prevalence of African American ethnicity, end-stage renal disease, diabetes, fair/poor self-rated health, physical inactivity, food insecurity, and uninsurance were higher among Gulf State DSAs. On unadjusted analyses, Gulf State DSAs were associated with 3.52 fewer expected kidney donors per 100 eligible deaths than non-Gulf States. After adjustment, there was no longer a statistically significant difference in expected kidney donation rate.

Conclusions: Although Gulf State DSAs have lower expected donation rates, these differences appear to be driven by the prevalence of health factors negatively associated with donation rate. These data suggest the need to discuss population health characteristics when examining kidney allocation policy, to account for potential lower supply of donors and to further address geographic disparities in access to kidney transplantation.
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http://dx.doi.org/10.1097/TP.0000000000002831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7000133PMC
February 2020

Personalizing Donor Kidney Selection: Choosing the Right Donor for the Right Recipient.

Clin J Am Soc Nephrol 2020 03 17;15(3):418-420. Epub 2019 Dec 17.

Renal Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

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http://dx.doi.org/10.2215/CJN.09180819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057303PMC
March 2020

Variation of Testing Practices for Living Kidney Donors.

Prog Transplant 2020 03 16;30(1):22-28. Epub 2019 Dec 16.

Division of General Medical Sciences, Department of Medicine, Washington University School of Medicine, St Louis, MO, USA.

Introduction: Tests exist for genetic variants to determine whether a potential donor's kidneys are at increased risk of kidney failure. Variants of the gene associated with increased risk are primarily found in people with West African ancestry. Given uncertainty about clinical implications of test results for living kidney donors and recipients and the lack of uniform guidelines for testing, transplant centers across the United States vary in testing practices.

Research Questions: (1) What approach do transplant centers take to determine whether prospective donors are of West African ancestry? (2)How do transplant centers engage potential donors during the testing process? (3) What do transplant centers identify as concerns and barriers to testing? and (4) What actions do transplant centers take when a potential donor has 2 risk variants?

Design: We explored the current practices of transplant centers by surveying nephrologists and transplant surgeons at transplant centers evaluating the majority of black living donors in the United States.

Results: About half of these transplant centers offered testing. Of those who offered testing, only half involved the donor in decision-making about donation when the donor has 2 risk variants.

Discussion: Unaddressed differences in the priorities of transplant centers and black living donors may stigmatize black donors and undermine trust in the health-care and organ donation systems. Variation in transplant center testing practices points to the critical need for further research and community engagement to inform the development of guidelines for testing.
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http://dx.doi.org/10.1177/1526924819892917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004858PMC
March 2020

New insights into the rational use of HCV+ organs worldwide.

Clin Transplant 2019 12 8;33(12):e13739. Epub 2019 Nov 8.

Renal, Electrolyte and Hypertension Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.

Hepatitis C (HCV) is a worldwide health problem. Effective therapies for HCV infection, coupled with an increase in deceased donors due to the opioid epidemic, have led to the broader availability and the use of HCV-infected donor organs, including HCV nucleic acid test-positive (NAT+) donors in HCV-negative recipients. In this review, we discuss the prevalence of HCV infection, trends in the use of HCV-infected donors, and outcomes for those who receive HCV-seropositive or HCV NAT+ donor organs. We discuss management considerations such as hepatitis B reactivation, selection of the optimal direct-acting antiviral regimen, and potential complications. We also present a framework for the rational use of HCV-infected donor organs in the future.
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http://dx.doi.org/10.1111/ctr.13739DOI Listing
December 2019

Class and Kinetics of Weakly Reactive Pretransplant Donor-specific HLA Antibodies Predict Rejection in Kidney Transplant Recipients.

Transplant Direct 2019 Aug 25;5(8):e478. Epub 2019 Jul 25.

Department of Surgery, University of Pennsylvania, Philadelphia, PA.

Background: The clinical impact of weakly reactive pretransplant donor-specific antibody (DSA) in kidney transplantation is controversial. While some evidence suggests that weakly reactive DSA can lead to rejection, it is unclear which patients are at risk for rejection and whether posttransplant changes in weakly reactive DSA are clinically meaningful.

Methods: We retrospectively studied 80 kidney transplant recipients with weakly reactive pretransplant DSA between 2007 and 2014. We performed a multivariate Cox regression analysis to identify immunologic factors most associated with risk of biopsy-proven rejection.

Results: Biopsy-proven rejection occurred in 13 of 80 (16%) patients. The presence of both class I and II DSA before transplant (hazards ratio 17.4, < 0.01) and any posttransplant increase in DSA reactivity above a mean fluorescence intensity of 3000 (hazards ratio 7.8, < 0.01) were each significantly associated with an increased risk of rejection, which primarily occurred within the first 18 months.

Conclusions: Pretransplant DSA class and DSA kinetics after transplantation are useful prognostic indicators in patients with weak DSA reactivity. These results identify a small, high-risk patient group that warrants aggressive posttransplant DSA monitoring and may benefit from alternative donor selection.
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http://dx.doi.org/10.1097/TXD.0000000000000926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6708635PMC
August 2019

Personalizing the Kidney Transplant Decision: Who Doesn't Benefit from a Kidney Transplant?

Clin J Am Soc Nephrol 2020 02 1;15(2):279-281. Epub 2019 Oct 1.

Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.

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http://dx.doi.org/10.2215/CJN.04090419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7015096PMC
February 2020

National Trends in Utilization and 1-Year Outcomes with Transplantation of HCV-Viremic Kidneys.

J Am Soc Nephrol 2019 10 12;30(10):1939-1951. Epub 2019 Sep 12.

Renal-Electrolyte and Hypertension Division, Department of Medicine,

Background: Recent pilot trials have demonstrated the safety of transplanting HCV-viremic kidneys into HCV-seronegative recipients. However, it remains unclear if allograft function is impacted by donor HCV-viremia or recipient HCV-serostatus.

Methods: We used national United States registry data to examine trends in HCV-viremic kidney use between 4/1/2015 and 3/31/2019. We applied advanced matching methods to compare eGFR for similar kidneys transplanted into highly similar recipients of kidney transplants.

Results: Over time, HCV-seronegative recipients received a rising proportion of HCV-viremic kidneys. During the first quarter of 2019, 200 HCV-viremic kidneys were transplanted into HCV-seronegative recipients, versus 69 into HCV-seropositive recipients, while 105 HCV-viremic kidneys were discarded. The probability of HCV-viremic kidney discard has declined over time. Kidney transplant candidates willing to accept a HCV-seropositive kidney increased from 2936 to 16,809 from during this time period. When transplanted into HCV-seronegative recipients, HCV-viremic kidneys matched to HCV-non-viremic kidneys on predictors of organ quality, except HCV, had similar 1-year eGFR (66.3 versus 67.1 ml/min per 1.73 m, =0.86). This was despite the much worse kidney donor profile index scores assigned to the HCV-viremic kidneys. Recipient HCV-serostatus was not associated with a clinically meaningful difference in 1-year eGFR (66.5 versus 71.1 ml/min per 1.73 m, =0.056) after transplantation of HCV-viremic kidneys.

Conclusions: By 2019, HCV-seronegative patients received the majority of kidneys transplanted from HCV-viremic donors. Widely used organ quality scores underestimated the quality of HCV-viremic kidneys based on 1-year allograft function. Recipient HCV-serostatus was also not associated with worse short-term allograft function using HCV-viremic kidneys.
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http://dx.doi.org/10.1681/ASN.2019050462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779360PMC
October 2019

Safety, Effectiveness, and Tolerability of Patiromer in Kidney Transplant Recipients.

Transplantation 2019 09;103(9):e281-e282

Renal, Electrolyte, Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.

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http://dx.doi.org/10.1097/TP.0000000000002829DOI Listing
September 2019

Center Variation and Risk Factors for Failure to Complete 6 Month Postdonation Follow-up Among Obese Living Kidney Donors.

Transplantation 2019 07;103(7):1450-1456

Comprehensive Transplant Institute, University of Alabama at Birmingham, Birmingham, AL.

Background: Living kidney donors in the United States who were obese at donation are at increased risk of end-stage renal disease and may benefit from intensive postdonation follow-up. However, they are less likely to have complete follow-up data. Center variation and risk factors for incomplete follow-up are unknown.

Methods: Adult living kidney donors with obesity (body mass index, ≥30 kg/m) at donation reported to the Scientific Registry of Transplant Recipients from January 2005 to July 2015 were included (n = 13 831). Donor characteristics were compared by recorded serum creatinine at 6 months postdonation, and multilevel logistic regression models were used to estimate odds of 6-month creatinine.

Results: After adjustment, older age, female sex, and donation after implementation of new center follow-up requirements were associated with higher odds of 6-month creatinine, with lower odds for obese donors with a history of smoking, biologically related donors, and at centers with higher total living donor volume. 23% of variation in recorded 6-month serum creatinine among obese donors was attributed to center (intraclass correlation coefficient: 0.232, P < 0.001). The adjusted probability of 6-month creatinine by center ranged from 10% to 91.5%.

Conclusions: Tremendous variation in recorded 6-month postdonation serum creatinine exists among obese living donors, with high volume centers having the lowest probability of follow-up. Moreover, individual-level characteristics such as age, sex, and relationship to recipient were associated with recorded 6-month creatinine. Given increased risk for end-stage renal disease among obese living donors, center-level efforts targeted specifically at increasing postdonation follow-up among obese donors should be developed and implemented.
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http://dx.doi.org/10.1097/TP.0000000000002508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6597173PMC
July 2019

Obesity and long-term mortality risk among living kidney donors.

Surgery 2019 08 7;166(2):205-208. Epub 2019 May 7.

Johns Hopkins University School of Medicine, Baltimore, MD.

Background: Body mass index of living kidney donors has increased substantially. Determining candidacy for live kidney donation among obese individuals is challenging because many donation-related risks among this subgroup remain unquantified, including even basic postdonation mortality.

Methods: We used data from the Scientific Registry of Transplant Recipients linked to data from the Centers for Medicare and Medicaid Services to study long-term mortality risk associated with being obese at the time of kidney donation among 119,769 live kidney donors (1987-2013). Donors were followed for a maximum of 20 years (interquartile range 6.0-16.0). Cox proportional hazards estimated the risk of postdonation mortality by obesity status at donation. Multiple imputation accounted for missing obesity data.

Results: Obese (body mass index ≥ 30) living kidney donors were more likely male, African American, and had higher blood pressure. The estimated risk of mortality 20 years after donation was 304.3/10,000 for obese and 208.9/10,000 for nonobese living kidney donors. Adjusting for age, sex, race/ethnicity, blood pressure, baseline estimated glomerular filtration rate, relationship to recipient, smoking, and year of donation, obese living kidney donors had a 30% increased risk of long-term mortality compared with their nonobese counterparts (adjusted hazard ratio: 1.32, 95% CI: 1.09-1.60, P = .006). The impact of obesity on mortality risk did not differ significantly by sex, race or ethnicity, biologic relationship, baseline estimated glomerular filtration rate, or among donors who did and did not develop postdonation kidney failure.

Conclusion: These findings may help to inform selection criteria and discussions with obese persons considering living kidney donation.
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http://dx.doi.org/10.1016/j.surg.2019.03.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6660998PMC
August 2019

APOL1 Genetic Testing in Living Kidney Transplant Donors.

Am J Kidney Dis 2019 10 11;74(4):538-543. Epub 2019 Apr 11.

Division of General Medical Sciences, Washington University School of Medicine, St. Louis, MO.

The presence of 2 apolipoprotein L1 gene (APOL1) risk variants is associated with increased risk for chronic kidney disease and end-stage kidney disease. Inferior allograft outcomes following transplantation with kidneys from donors with 2 risk variants have also been reported. These data, coupled with anecdotal case reports and a recent cohort study of living donors, raise important questions about the potential increased kidney disease risk for living donors with APOL1 risk variants and the need for testing as part of the standard living donor evaluation process. We identify a series of questions that are central to the development of clinical policy regarding APOL1 testing of potential living kidney donors given the current uncertainty over the clinical implications of having 2 risk variants. We explore the ethical challenges that arise when determining when and to whom APOL1 testing should be offered, what potential donors should be told about APOL1 testing, how test results should be used to determine suitability for donation, if and when recipients should have access to results, and how clinical policy regarding APOL1 testing should be established.
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http://dx.doi.org/10.1053/j.ajkd.2019.02.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756958PMC
October 2019

Native kidney BK virus nephropathy, a systematic review.

Transpl Infect Dis 2019 Aug 11;21(4):e13083. Epub 2019 May 11.

Division of Nephrology, University of Pennsylvania, Philadelphia, Pennsylvania.

Background: There is a growing base of literature describing BK nephropathy (BKVN) in patients outside of the setting of kidney transplant. Previous systematic reviews of the literature have been limited by methodology or by the scope of patients included.

Study Design And Methods: Systematic Review (Prospero # CRD42018088524).

Setting & Population: Patients without kidney transplant who had biopsy-proven BKVN.

Selection Criteria For Studies: Full-text articles that describe native BKVN patient cases.

Analytical Approach: Descriptive synthesis.

Results: The search identified 630 unique articles of which 51 were included in the final review. Sixty-five cases (including two new cases presented in this review) were identified, all but one occurred in the setting of known immunosuppression.

Limitations: The primary limitation was the exclusion of studies that did not fulfill the stringent review criteria. We excluded reports with only a clinical diagnosis of BKVN, such as those with viruria and/or viremia without biopsy.

Conclusions: As of May 2018, there are 65 reported cases of BKVN in native kidneys. This represents the most comprehensive description of biopsy-proven BKVN in native kidneys to date. Evaluation for BK nephropathy should be considered in immunocompromised patients who exhibit unexplained renal failure.
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http://dx.doi.org/10.1111/tid.13083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7197190PMC
August 2019

Single-center, real-world experience with granulocyte colony-stimulating factor for management of leukopenia following kidney transplantation.

Clin Transplant 2019 06 11;33(6):e13541. Epub 2019 Apr 11.

Department of Pharmacy Services, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.

Background: Leukopenia is a frequent complication following kidney transplantation. Granulocyte colony-stimulating factor (G-CSF) has been used to accelerate white blood cell (WBC) count recovery; however, published experience in kidney transplantation is limited.

Methods: We retrospectively reviewed our kidney transplant recipients from January 2012 to September 2016 with a G-CSF order to evaluate leukopenia management (defined as WBC <3000 cells/μL).

Results: Thirty-six recipients were included. On average, G-CSF treatment began at 98 ± 38 days. At G-CSF initiation, mean WBC count was 1240 ± 420 cells/μL and absolute neutrophil count (ANC) was 653 ± 368 cells/μL. Mean G-CSF dose was 4.6 ± 1.2 mcg/kg/dose (total 11.8 ± 9.0 mcg/kg), 77.8% of recipients were prescribed G-CSF as outpatients, and overall, median time to WBC count recovery was 9 (IQR 4-14) days. Changes in immunosuppression and prophylaxis regimens for leukopenia were also common. Within 1 month following leukopenia onset, no patients experienced acute rejection and 5 (14%) developed infection requiring hospitalization or opportunistic infection.

Conclusion: In kidney recipients with leukopenia, G-CSF may be helpful to achieve WBC count recovery in addition to changes in immunosuppression and prophylaxis medications. Prospective, randomized data are still needed to determine optimal G-CSF dosing in this population.
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http://dx.doi.org/10.1111/ctr.13541DOI Listing
June 2019

Kidney Transplantation in a HIV-Positive Recipient.

Clin J Am Soc Nephrol 2019 04 18;14(4):614-616. Epub 2019 Mar 18.

Comprehensive Transplant Institute, University of Alabama at Birmingham, Birmingham, Alabama.

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http://dx.doi.org/10.2215/CJN.14051118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6450335PMC
April 2019

Leveraging marginal structural modeling with Cox regression to assess the survival benefit of accepting vs declining kidney allograft offers.

Am J Transplant 2019 07 2;19(7):1999-2008. Epub 2019 Mar 2.

Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

Existing studies evaluating the survival benefit of kidney transplantation were unable to incorporate time-updated information on decisions related to each organ offer. We used national registry data, including organ turndown data, to evaluate the survival benefit of accepting vs turning down kidney offers in candidates waitlisted from 2007-2013. Among candidates who declined their first offer, only 43% ultimately received organ transplantations. Recipients who later underwent organ transplantation after declining their first offer had markedly longer wait times than recipients who accepted their first offer, and 56% received kidney transplants that were of similar or lower quality compared to their initial offer. In marginal structural modeling analyses accounting for time-updated offer characteristics (including Kidney Donor Profile Index, Public Health System risk status, and pumping), after 3 months posttransplant, there was a significant survival benefit of accepting an offer (adjusted hazard ratio 0.76, 95% confidence interval 0.66-0.89) that was similar among diabetics, candidates aged >65 years, and candidates living in donor service areas with the longest waitlist times. After carefully accounting for the effect of donor quality, we confirm that the survival benefit of accepting an organ offer is clinically meaningful and persistent beyond 3 months post-kidney transplantation, including high-risk subgroups of organ transplantation candidates.
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http://dx.doi.org/10.1111/ajt.15290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591028PMC
July 2019

Mortality and Kidney Transplantation Outcomes Among Hepatitis C Virus-Seropositive Maintenance Dialysis Patients: A Retrospective Cohort Study.

Am J Kidney Dis 2019 06 29;73(6):815-826. Epub 2019 Jan 29.

Renal Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania, Philadelphia, PA; Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA. Electronic address:

Rationale & Objective: Hepatitis C virus (HCV) infection is common among maintenance dialysis patients. Few studies have examined both dialysis survival and transplantation outcomes for HCV-seropositive patients because registry data sets lack information for HCV serostatus.

Study Design: Retrospective cohort study.

Setting & Participants: Adult long-term dialysis patients treated by a US national dialysis provider between January 1, 2004, and December 31, 2014.

Exposure: HCV antibody serostatus obtained as part of clinical data from a national dialysis provider.

Outcomes: Mortality on dialysis therapy, entry onto the kidney transplant waiting list, kidney transplantation, and estimated survival benefit from kidney transplantation versus remaining on the waitlist.

Analytical Approach: After linking clinical data with data from the Organ Procurement and Transplantation Network, Cox and cause-specific hazards regression were implemented to estimate the associations between HCV seropositivity and mortality, as well as entry onto the kidney transplant waitlist. Cox regression was also used to estimate the survival benefit from transplantation versus dialysis among HCV-seropositive individuals.

Results: Among 442,171 dialysis patients, 31,624 (7.2%) were HCV seropositive. HCV seropositivity was associated with a small elevation in the rate of death (adjusted HR [aHR], 1.09; 95% CI, 1.07-1.11) and a substantially lower rate of entry onto the kidney transplant waitlist (subdistribution HR [sHR], 0.67; 95% CI, 0.61-0.74). Once wait-listed, the kidney transplantation rate was not different for HCV-seropositive (sHR 1.10; 95% CI, 0.96-1.27) versus HCV-seronegative patients. HCV-seropositive patients lived longer with transplantation (aHR at 3 years, 0.42; 95% CI, 0.27-0.63). Receiving an HCV-seropositive donor kidney provided a survival advantage at the 2-year posttransplantation time point compared to remaining on dialysis therapy waiting for an HCV-negative kidney.

Limitations: No data for HCV viral load or liver biopsy.

Conclusions: HCV-seropositive patients experience reduced access to the kidney transplantation waitlist despite deriving a substantial survival benefit from transplantation. HCV-seropositive patients should consider foregoing HCV treatment while accepting kidneys from HCV-infected donors to facilitate transplantation and prolong survival.
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http://dx.doi.org/10.1053/j.ajkd.2018.11.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6535135PMC
June 2019