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  1. Article ; Online: Immune monitoring of allograft status in kidney transplant recipients.

    Han, Hwarang S / Lubetzky, Michelle L

    Frontiers in nephrology

    2023  Volume 3, Page(s) 1293907

    Abstract: Kidney transplant patients require careful management of immunosuppression to avoid rejection while minimizing the risk of infection and malignancy for the best long-term outcome. The gold standard for monitoring allograft status and immunosuppression ... ...

    Abstract Kidney transplant patients require careful management of immunosuppression to avoid rejection while minimizing the risk of infection and malignancy for the best long-term outcome. The gold standard for monitoring allograft status and immunosuppression adequacy is a kidney biopsy, but this is invasive and costly. Conventional methods of allograft monitoring, such as serum creatinine level, are non-specific. Although they alert physicians to the need to evaluate graft dysfunction, by the time there is a clinical abnormality, allograft damage may have already occurred. The development of novel and non-invasive methods of evaluating allograft status are important to improving graft outcomes. This review summarizes the available conventional and novel methods for monitoring allograft status after kidney transplant. Novel and less invasive methods include gene expression, cell-free DNA, urinary biomarkers, and the use of artificial intelligence. The optimal method to manage patients after kidney transplant is still being investigated. The development of less invasive methods to assess allograft function has the potential to improve patient outcomes and allow for a more personalized approach to immunosuppression management.
    Language English
    Publishing date 2023-11-08
    Publishing country Switzerland
    Document type Journal Article ; Review
    ISSN 2813-0626
    ISSN (online) 2813-0626
    DOI 10.3389/fneph.2023.1293907
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  2. Article ; Online: Do we need to treat chronic active T cell-mediated rejection?

    Mengel, Michael / Lubetzky, Michelle

    Kidney international

    2021  Volume 100, Issue 2, Page(s) 275–277

    Abstract: Chronic active T cell-mediated rejection, demonstrated by the presence of inflammation in areas of fibrosis, is associated with long-term allograft loss. Kung et al., in this issue of Kidney International, describe a series of cases of CA TCMR and ... ...

    Abstract Chronic active T cell-mediated rejection, demonstrated by the presence of inflammation in areas of fibrosis, is associated with long-term allograft loss. Kung et al., in this issue of Kidney International, describe a series of cases of CA TCMR and analyze their clinical, molecular, and pathologic features as well as their response to therapy. Their translational study aids in understanding this diverse phenotype and provides future direction for managing these patients.
    MeSH term(s) Graft Rejection/prevention & control ; Humans ; Inflammation ; Kidney ; Kidney Transplantation/adverse effects ; T-Lymphocytes
    Language English
    Publishing date 2021-07-22
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 120573-0
    ISSN 1523-1755 ; 0085-2538
    ISSN (online) 1523-1755
    ISSN 0085-2538
    DOI 10.1016/j.kint.2021.04.031
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  3. Article ; Online: Urinary Cell mRNA Profiles Predictive of Human Kidney Allograft Status.

    Lubetzky, Michelle L / Salinas, Thalia / Schwartz, Joseph E / Suthanthiran, Manikkam

    Clinical journal of the American Society of Nephrology : CJASN

    2021  Volume 16, Issue 10, Page(s) 1565–1577

    Abstract: Immune monitoring of kidney allograft recipients and personalized therapeutics may help reach the aspirational goal of "one transplant for life." The invasive kidney biopsy procedure, the diagnostic tool of choice, has become safer and the biopsy ... ...

    Abstract Immune monitoring of kidney allograft recipients and personalized therapeutics may help reach the aspirational goal of "one transplant for life." The invasive kidney biopsy procedure, the diagnostic tool of choice, has become safer and the biopsy classification more refined. Nevertheless, biopsy-associated complications, interobserver variability in biopsy specimen scoring, and costs continue to be significant concerns. The dynamics of the immune repertoire make frequent assessments of allograft status necessary, but repeat biopsies of the kidney are neither practical nor safe. To address the existing challenges, we developed urinary cell mRNA profiling and investigated the diagnostic, prognostic, and predictive accuracy of absolute levels of a hypothesis-based panel of mRNAs encoding immunoregulatory proteins. Enabled by our refinements of the PCR assay and by investigating mechanistic hypotheses, our single-center studies identified urinary cell mRNAs associated with T cell-mediated rejection, antibody-mediated rejection, interstitial fibrosis and tubular atrophy, and BK virus nephropathy. In the multicenter National Institutes of Health Clinical Trials in Organ Transplantation-04, we discovered and validated a urinary cell three-gene signature of T-cell CD3
    MeSH term(s) Acute Disease ; Animals ; Biomarkers/urine ; Biopsy ; CD3 Complex/genetics ; CD3 Complex/urine ; Chemokine CXCL10/genetics ; Chemokine CXCL10/urine ; Gene Expression Profiling ; Graft Rejection/diagnosis ; Graft Rejection/genetics ; Graft Rejection/immunology ; Graft Rejection/urine ; Graft Survival ; Humans ; Kidney Transplantation/adverse effects ; Predictive Value of Tests ; RNA, Messenger/genetics ; RNA, Messenger/urine ; RNA, Ribosomal, 18S/genetics ; RNA, Ribosomal, 18S/urine ; Time Factors ; Transcriptome ; Treatment Outcome ; Urinalysis
    Chemical Substances Biomarkers ; CD3 Complex ; CD3E protein, human ; CXCL10 protein, human ; Chemokine CXCL10 ; RNA, Messenger ; RNA, Ribosomal, 18S
    Language English
    Publishing date 2021-04-27
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2226665-3
    ISSN 1555-905X ; 1555-9041
    ISSN (online) 1555-905X
    ISSN 1555-9041
    DOI 10.2215/CJN.14010820
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  4. Article ; Online: Facilitating Medical Care for Latinx Individuals at Risk for CKD: A Pilot Intervention.

    Novick, Tessa K / Barrios, Francisco / Osuna, Michelle / Emery, Caroline / Ramirez, Daniel / Palau, Laura / Ravi, Sanjana / Lubetzky, Michelle / Cruz, Evelyn / Crews, Deidra C / Cervantes, Lilia

    Kidney medicine

    2023  Volume 5, Issue 8, Page(s) 100679

    Abstract: Rationale and objective: Latinx individuals are at a higher risk for kidney failure than non-Latinx White individuals; however, they are less likely to receive pre-kidney failure medical care. The objective of this study was to determine the feasibility ...

    Abstract Rationale and objective: Latinx individuals are at a higher risk for kidney failure than non-Latinx White individuals; however, they are less likely to receive pre-kidney failure medical care. The objective of this study was to determine the feasibility and acceptability of a community health worker (CHW) intervention that facilitated access to medical care for Latinx individuals.
    Study design: Single-arm prospective study.
    Setting and participants: Latinx adults were found to have albuminuria or risk factors for kidney disease at community screening events in Austin, Texas.
    Intervention: A 6-month CHW intervention that facilitated the following: (1) obtaining medical insurance; (2) medical care coordination with primary and nephrology care; (3) kidney disease education; and (4) connection with local resources to address health-related social needs.
    Outcomes: Recruitment, retention, medical care linkage, and participant and CHW-reported satisfaction with the intervention.
    Results: Of the 173 individuals who attended the 2 community screening events, 49 agreed to participate in the study, of whom, 51% were men with a mean ± standard deviation (SD) age of 45 ± 14 years, and all self-identified as Mexican or Chicano. The mean ± SD estimated glomerular filtration rate (eGFR) was 110 ± 21 mL/min/1.73 m
    Limitations: Small sample size and a single community may limit generalizability.
    Conclusions: We reported the acceptability of a CHW intervention. We encountered challenges with feasibility and identified strategies to overcome them. Studies are needed to test the effect of CHW interventions on outcomes and kidney health disparities.
    Funding: National Kidney Foundation young investigator research grant to Dr Novick.
    Plain language summary: Latinx individuals are at a higher risk for kidney failure than non-Latinx White individuals; however, they are less likely to receive pre-kidney failure medical care. We piloted a community health worker intervention that connected people with risk factors or showed evidence of kidney dysfunction at community screening events with medical care. Our findings indicate the acceptability of the intervention. We encountered challenges with feasibility and identified strategies to overcome them.
    Language English
    Publishing date 2023-05-25
    Publishing country United States
    Document type Journal Article
    ISSN 2590-0595
    ISSN (online) 2590-0595
    DOI 10.1016/j.xkme.2023.100679
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  5. Article: Posttransplant Lymphoproliferative Disorder Presenting as Testicular Lymphoma in a Kidney Transplant Recipient: A Case Report and Review of the Literature.

    Obanor, Steve Omoruyi / Gruttadauria, Michelle / Applebaum, Kayla / Eskandari, Mohammad / Lieberman Lubetzky, Michelle / Greenstein, Stuart

    Case reports in nephrology

    2018  Volume 2018, Page(s) 9787093

    Abstract: Posttransplant lymphoproliferative disorder (PTLD) is a malignancy caused by the immunosuppression that occurs after transplantation. It is primarily a nodal lesion but frequently it involves extranodal masses. Treatment is usually by reducing ... ...

    Abstract Posttransplant lymphoproliferative disorder (PTLD) is a malignancy caused by the immunosuppression that occurs after transplantation. It is primarily a nodal lesion but frequently it involves extranodal masses. Treatment is usually by reducing immunosuppressive therapy. Testicular lymphoma as PTLD is notably rare in documented literature and there is limited evidence of definitive treatment guidelines. This manuscript describes a patient who developed diffuse large B-cell lymphoma of his right testis one year following kidney transplantation. A diagnosis of PTLD was made and treatment with rituximab, locoregional radiotherapy, and intrathecal methotrexate in addition to the standard reduction of immunosuppression resulted in complete remission until now. We submit this case along with literature review of similar cases in the past and a review of specific peculiarities of our case with emphasis on our treatment plan to further the understanding of this diversiform disease.
    Language English
    Publishing date 2018-02-14
    Publishing country United States
    Document type Case Reports
    ZDB-ID 2627652-5
    ISSN 2090-665X ; 2090-6641
    ISSN (online) 2090-665X
    ISSN 2090-6641
    DOI 10.1155/2018/9787093
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  6. Article ; Online: Hospital readmissions in diabetic kidney transplant recipients with peripheral vascular disease.

    Lubetzky, Michelle / Kamal, Layla / Ajaimy, Maria / Akalin, Enver / Kayler, Liise

    Clinical transplantation

    2018  Volume 32, Issue 6, Page(s) e13271

    Abstract: Background: The benefits of kidney transplantation in diabetic patients with peripheral vascular disease (PVD) are unclear. While patients may have improved survival compared to dialysis, the burden of care after transplant has not been assessed.: ... ...

    Abstract Background: The benefits of kidney transplantation in diabetic patients with peripheral vascular disease (PVD) are unclear. While patients may have improved survival compared to dialysis, the burden of care after transplant has not been assessed.
    Methods: We performed a retrospective review of adult diabetic kidney-only transplant recipients with and without PVD transplanted from January 2012 until June 30, 2015.
    Results: Of 203 diabetic kidney transplant recipients, 56 (27.6%) had PVD and 147 (72.4%) had no PVD. At a median of 3.14 years follow-up, there were no significant differences in 30-, 90-, or 1-year readmission rates. At 1 year after transplant, PVD patients were significantly more likely to have a greater sum of unplanned inpatient days (44.6% vs 27.9% with ≥10 inpatient days, P = .03) and at least 1 reoperation (28.6% vs. 8.7%, P < .01). At 1 year post-transplant, there were similar rates of graft-related reoperations; however, patients with PVD had significantly increased rates of non-graft-related operations of which 31.2% were PVD-related.
    Conclusions: Diabetic patients with PVD utilize more resources after kidney transplant, spending more time in the hospital and undergoing more post-transplant operations. The causes of readmission are predominantly related to progression of PVD rather than allograft complications.
    MeSH term(s) Diabetes Mellitus/physiopathology ; Diabetic Neuropathies/etiology ; Diabetic Neuropathies/pathology ; Diabetic Neuropathies/surgery ; Female ; Follow-Up Studies ; Glomerular Filtration Rate ; Graft Survival ; Humans ; Kidney Function Tests ; Kidney Transplantation/methods ; Male ; Middle Aged ; Patient Readmission/statistics & numerical data ; Peripheral Vascular Diseases/complications ; Postoperative Complications ; Prognosis ; Retrospective Studies ; Risk Factors ; Survival Rate ; Transplant Recipients
    Language English
    Publishing date 2018-05-22
    Publishing country Denmark
    Document type Clinical Trial ; Journal Article
    ZDB-ID 639001-8
    ISSN 1399-0012 ; 0902-0063
    ISSN (online) 1399-0012
    ISSN 0902-0063
    DOI 10.1111/ctr.13271
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    Zs.A 2204: Show issues Location:
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  7. Article ; Online: Urine biomarkers informative of human kidney allograft rejection and tolerance.

    Nissaisorakarn, Voravech / Lee, John Richard / Lubetzky, Michelle / Suthanthiran, Manikkam

    Human immunology

    2018  Volume 79, Issue 5, Page(s) 343–355

    Abstract: We developed urinary cell messenger RNA (mRNA) profiling to monitor in vivo status of human kidney allografts based on our conceptualization that the kidney allograft may function as an in vivo flow cell sorter allowing access of graft infiltrating cells ...

    Abstract We developed urinary cell messenger RNA (mRNA) profiling to monitor in vivo status of human kidney allografts based on our conceptualization that the kidney allograft may function as an in vivo flow cell sorter allowing access of graft infiltrating cells to the glomerular ultrafiltrate and that interrogation of urinary cells is informative of allograft status. For the profiling urinary cells, we developed a two-step preamplification enhanced real-time quantitative PCR (RT-QPCR) assays with a customized amplicon; preamplification compensating for the low RNA yield from urine and the customized amplicon facilitating absolute quantification of mRNA and overcoming the inherent limitations of relative quantification widely used in RT-QPCR assays. Herein, we review our discovery and validation of urinary cell mRNAs as noninvasive biomarkers prognostic and diagnostic of acute cellular rejection (ACR) in kidney allografts. We summarize our results reflecting the utility of urinary cell mRNA profiling for predicting reversal of ACR with anti-rejection therapy; differential diagnosis of kidney allograft dysfunction; and noninvasive diagnosis and prognosis of BK virus nephropathy. Messenger RNA profiles associated with human kidney allograft tolerance are also summarized in this review. Altogether, data supporting the idea that urinary cell mRNA profiles are informative of kidney allograft status and tolerance are reviewed in this report.
    MeSH term(s) Allografts/cytology ; Allografts/immunology ; Biomarkers/urine ; Gene Expression Profiling ; Graft Rejection/diagnosis ; Graft Rejection/genetics ; Graft Rejection/immunology ; Graft Rejection/urine ; Humans ; Immune Tolerance/genetics ; Immune Tolerance/immunology ; Kidney/cytology ; Kidney/immunology ; Kidney Transplantation ; Monitoring, Immunologic ; RNA, Messenger/genetics ; RNA, Messenger/immunology ; RNA, Messenger/urine ; Transplantation, Homologous
    Chemical Substances Biomarkers ; RNA, Messenger
    Language English
    Publishing date 2018-01-31
    Publishing country United States
    Document type Journal Article ; Review ; Validation Studies
    ZDB-ID 801524-7
    ISSN 1879-1166 ; 0198-8859
    ISSN (online) 1879-1166
    ISSN 0198-8859
    DOI 10.1016/j.humimm.2018.01.006
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  8. Article ; Online: Characteristics of natural immunity to SARS-CoV-2 over time in wait-listed dialysis patients and recent kidney transplant recipients.

    Lubetzky, Michelle / Zhao, Zhen / Sukhu, Ashley / Sharma, Vijay / Sultan, Samuel / Kapur, Zoe / Albakry, Shady / Craig-Schapiro, Rebecca / Lee, John R / Salinas, Thalia / Aull, Meredith / Kapur, Sandip / Cushing, Melissa / Dadhania, Darshana M

    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

    2022  Volume 37, Issue 8, Page(s) 1585–1587

    MeSH term(s) COVID-19 ; Humans ; Immunity, Innate ; Kidney Transplantation ; Renal Dialysis ; SARS-CoV-2 ; Transplant Recipients
    Language English
    Publishing date 2022-03-22
    Publishing country England
    Document type Letter
    ZDB-ID 90594-x
    ISSN 1460-2385 ; 0931-0509
    ISSN (online) 1460-2385
    ISSN 0931-0509
    DOI 10.1093/ndt/gfac132
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  9. Article ; Online: Complications of rabbit anti-thymocyte globulin induction immunosuppression in HIV-infected kidney transplant recipients.

    Al Jurdi, Ayman / Liu, Esther C / Salinas, Thalia / Aull, Meredith J / Lubetzky, Michelle / Drelick, Alexander L / Small, Catherine B / Kapur, Sandip / Hartono, Choli / Muthukumar, Thangamani

    Frontiers in nephrology

    2022  Volume 2, Page(s) 1047170

    Abstract: Background: Kidney transplantation in HIV-infected individuals with end-stage kidney disease is associated with improved survival compared to dialysis. Rabbit anti-thymocyte globulin (rATG) induction in HIV-infected kidney transplant recipients has been ...

    Abstract Background: Kidney transplantation in HIV-infected individuals with end-stage kidney disease is associated with improved survival compared to dialysis. Rabbit anti-thymocyte globulin (rATG) induction in HIV-infected kidney transplant recipients has been associated with a lower risk of acute rejection, but data on the rates of
    Methods: We performed a single-center retrospective cohort study of adult HIV-infected individuals who underwent kidney transplantation with rATG induction between January 2006 and December 2016. The primary outcome was the development of
    Results: Twenty-seven HIV-infected individuals with end-stage kidney disease received deceased (n=23) or living (n=4) donor kidney transplants. The cumulative rate of malignancy at five years was 29%, of whom 29% died because of advanced malignancy. BK viremia was detected in six participants (22%), of whom one had biopsy-proven BK virus-associated nephropathy and all of whom cleared the BK viremia. Five-year acute rejection rates, patient survival and death-censored allograft survival were 17%, 85% and 80% respectively.
    Conclusion: rATG induction in HIV-infected kidney transplant recipients was associated with a low risk of acute rejection, but a potentially higher risk of
    Language English
    Publishing date 2022-12-14
    Publishing country Switzerland
    Document type Journal Article
    ISSN 2813-0626
    ISSN (online) 2813-0626
    DOI 10.3389/fneph.2022.1047170
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  10. Article: Impact of Cold Ischemia Time in Kidney Transplants From Donation After Circulatory Death Donors.

    Kayler, Liise / Yu, Xia / Cortes, Carlos / Lubetzky, Michelle / Friedmann, Patricia

    Transplantation direct

    2017  Volume 3, Issue 7, Page(s) e177

    Abstract: Background: Deceased-donor kidneys are exposed to ischemic events from donor instability during the process of donation after circulatory death (DCD). Clinicians may be reluctant to transplant DCD kidneys with prolonged cold ischemia time (CIT) for fear ...

    Abstract Background: Deceased-donor kidneys are exposed to ischemic events from donor instability during the process of donation after circulatory death (DCD). Clinicians may be reluctant to transplant DCD kidneys with prolonged cold ischemia time (CIT) for fear of an additional deleterious effect.
    Methods: We performed a retrospective cohort study examining US registry data between 1998 and 2013 of adult first-time kidney-only recipients of paired kidneys (derived from the same donor transplanted into different recipients) from DCD donors.
    Results: On multivariable analysis, death-censored graft survival (DCGS) was comparable between recipients of kidneys with higher CIT relative to paired donor recipients with lower CIT when the CIT difference was 1 hour or longer (adjusted hazard ratio, [aHR], 1.02; 95% confidence interval [CI], 0.88-1.17; n = 6276), 5 hours or longer (aHR, 0.98; 95% CI, 0.80-1.19; n = 3130), 10 hours or longer (aHR, 1.15; 95% CI, 0.82-1.60; n = 1124) or 15 hours (aHR, 1.15; 95% CI, 0.66-1.99; n = 498). There was a higher rate of primary non function in the long CIT groups for delta 1 hour or longer (0.89% vs 1.63%;
    Conclusions: These results suggest that in the setting of a prior ischemic donor event, prolonged CIT has limited bearing on long-term outcomes.
    Language English
    Publishing date 2017-06-23
    Publishing country United States
    Document type Journal Article
    ISSN 2373-8731
    ISSN 2373-8731
    DOI 10.1097/TXD.0000000000000680
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