Michelle Lubetzky

Montefiore Medical Center, New York, New York, United States

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Publications (16)53.23 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Severe systemic hypertension (HTN) is a risk factor for perioperative cardiovascular complications; however its' impact at the time of kidney transplantation (KTX) is not well defined. A retrospective cohort study of adult kidney-only transplant recipients between 10/09-12/12 was performed to examine outcomes between patients with (n=111) and without (n=98) severe preoperative HTN defined as SBP >180 or DBP> 110 mmHg. Recipients with severe HTN were older (56.7+/- 13.0 vs. 53.5+/- 12.4 years,p=0.07) and significantly more likely to receive an expanded criteria donor kidney (32.7% vs. 12.2%,p=0.02). No patients developed hypertensive crisis, intracranial hemorrhage, or life treating ventricular arrhythmias within 30 days post-transplantation; however, 3 patients with severe HTN had cardiac events; 2 with demand ischemia and 1 with decompensate heart failure. Two patients in the control group had decompensated heart failure. There were no differences between the groups in terms of cardiac event (2.7% vs. 2.0%, p=0.75), 1-year patient survival (98.2% vs. 98.0%;p=0.90) or graft survival (90.1% vs. 92.9%;p=0.48). Nadir creatinine > 2 mg/dl (4.6% vs. 6.2%, p=0.62), length of stay>6 days (37.8%vs. 35.7%, p=0.75) and DGF (52.3% vs. 63.3%, p=0.11). Our results suggest that severe preoperative hypertension should not be considered an absolute contraindication to kidney transplant in patients who are otherwise clinically stable. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Clinical Transplantation 06/2015; DOI:10.1111/ctr.12579 · 1.49 Impact Factor
  • Yu Xia · Patricia Friedmann · Carlos M. Cortes · Michelle L. Lubetzky · Liise K. Kayler
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    ABSTRACT: Deceased-donor kidneys are often exposed to ischemic events from donor instability, as evidenced by acute kidney injury (AKI). Clinicians may be reluctant to transplant kidneys with AKI that also have prolonged cold ischemia time (CIT) for fear of an additional deleterious effect. We evaluated national data between 1998 and 2013 of adult first-time kidney-only recipients of paired kidneys from donors with AKI (terminal serum creatinine ≥ 2 mg/dL), in which the CIT difference between recipients was ≥1, 5, 10, or 15 hours. On multivariate analysis of AKI kidney recipients, overall death-censored graft survival (DCGS) was comparable between recipients with higher CIT relative to paired donor recipients with lower CIT when the CIT difference was at least 1 hour (adjusted hazard ratio [aHR] 0.98, 95% CI 0.85 to 1.13, n = 4,458), 5 hours (aHR 0.97, 95% CI 0.79 to 1.18, n = 2,412), 10 hours (aHR 0.82, 95% CI 0.59 to 1.15, n = 922), or 15 hours (aHR 0.94, 95% CI 0.57 to 1.58, n = 442). Overall patient survival of the longer CIT groups was comparable or protective with delta CIT of ≥1 (aHR 0.94, 95% CI 0.83 to 1.06), 5 (aHR 0.80, 95% CI 0.68 to 0.94), 10 (aHR 0.70, 95% CI 0.53 to 0.91), and 15 (aHR 0.64, 95%CI 0.43 to 0.95) hours. Between each of the 4 delta-CIT levels of shorter and longer CIT, there were no statistically significant differences in the proportion of acute rejection at delta ≥1, 5, 10, or 15 hours. These results suggest that in the setting of a previous ischemic donor event, prolonged CIT has limited bearing on long-term outcomes. This may be important evidence that despite the occurrence of other ischemic events, kidneys with prolonged CIT offer acceptable outcomes to recipients and are a potential source to expand the donor pool. Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.
    Journal of the American College of Surgeons 05/2015; 221(2). DOI:10.1016/j.jamcollsurg.2015.05.003 · 4.45 Impact Factor
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    ABSTRACT: Background It is estimated that approximately 50% of males over 50 have benign prostatic hypertrophy (BPH). BPH is under appreciated in anuric patients with end stage renal disease and failure of diagnosis in this population can lead to complications after kidney transplantation.MethodsA single center retrospective review of male patients over 50 years of age transplanted from January 1, 2010 until September 30, 2013 was performed. Outcomes assessed were: graft survival, urinary retention, discharge with Foley catheter, and urinary tract infection (UTI).ResultsOf 147 patients, 17.0% were diagnosed with BPH before transplant, 19.0% received a BPH diagnosis after transplant and 64% did not have BPH. Compared to those without BPH, a post-transplant BPH diagnosis was associated with urinary retention during the transplant admission (0% vs. 46.4%, p <0.01), discharge with Foley catheter (0% vs. 21.4%, p<0.01), readmission related to urinary retention (0% vs. 46.4%, p <0.01), and UTI (18.0% vs. 64.3%, p <0.01). Patients with prior diagnosis of BPH and on therapy had similar outcomes to those without BPH.Conclusions Following kidney transplant, urinary tract complications are more common in patients with BPH, however, being on medical therapy prior to transplantation diminishes the incidence of these complications significantly.This article is protected by copyright. All rights reserved.
    Clinical Transplantation 03/2015; 29(6). DOI:10.1111/ctr.12548 · 1.49 Impact Factor
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    ABSTRACT: We aimed to investigate the clinical, histopathological, and molecular factors associated with allograft loss in transplant glomerulopathy (TGP) patients. Of the 525 patients who underwent clinically indicated kidney biopsies, 52 (10%) had diagnosis of TGP. Gene expression profiles of 28 TGP and 11 normal transplant kidney biopsy samples were analyzed by Affymetrix HuGene 1.0 ST expression arrays. Over a median follow up of 23 months (1-46 months) after the diagnosis of TGP by biopsy, 17 patients (32%) lost their allografts at a median of 16 months (1-44 months). There was no difference between the 2 groups in terms of any demographic variables, serum creatinine, panel reactive antibody levels, donor-specific antibody frequency, or mean fluorescence intensity values. Patients who lost their allograft had a significantly higher median spot protein to creatinine ratio 2.81 (1.20-6.00) compared to no graft loss patients 1.16 (0.15-2.53), (P < 0.01), and a trends toward a higher mean chronic glomerulopathy (cg) score (1.65 ± 0.93 vs 1.11 ± 0.93) (P = 0.05). There was also no difference in microvascular inflammation or any other Banff injury scores between the 2 groups. Although 117 gene transcripts were upregulated in both groups, 86 and 57 were upregulated in graft loss and functioning allograft groups, respectively. There were significantly increased levels of intragraft endothelial cell-associated transcripts, gene transcripts associated with complement cascade, interleukins and their receptors and granulysin in graft loss patients compared to patients with a functioning allograft. Our results demonstrate differential intragraft gene expression profiles in TGP patients with allograft loss.
    Transplantation 02/2015; Online First. DOI:10.1097/TP.0000000000000598 · 3.78 Impact Factor
  • 15th Annual State of the Art Winter Symposium of the; 01/2015
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    ABSTRACT: Abstract Affymetrix Human Gene 1.0-ST arrays were used to assess the gene expression profiles of kidney transplant patients who presented with donor-specific antibodies (DSAs) but showed normal biopsy histopathology and did not develop antibody-mediated rejection (AMR). Biopsy and whole-blood profiles for these DSA-positive, AMR-negative (DSA +/AMR−) patients were compared to both DSA-positive, AMR-positive (DSA +/AMR +) patients as well as DSA-negative (DSA −) controls. While individual gene expression changes across sample groups were relatively subtle, gene-set enrichment analysis using previously identified pathogenesis-based transcripts (PBTs) identified a clear molecular signature involving increased rejection-associated transcripts in AMR − patients. Results from this study have been published in Kidney International (Hayde et al., 2014 [1]) and the associated data have been deposited in the GEO archive and are accessible via the following link: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE50084
    Genomics Data 12/2014; 2:357 - 360. DOI:10.1016/j.gdata.2014.10.005
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    ABSTRACT: Background: Patients with pretransplantation strong donor-specific anti–human leukocyte antigen (HLA) antibodies (DSA) are at higher risk for rejection. We aimed to study the safety of kidney transplantation in patients with lower strength DSAs in a prospective cohort study. Methods: Three hundred and seventy-three consecutive adult kidney transplant recipients with (DSA+; n=66) and without (DSA−; n=307) DSA were evaluated. Anti-HLA antibodies with mean fluorescence intensity values over 5,000 for HLA-A, HLA-B, and HLA-DR and more than 10,000 for HLA-DQ were reported as unacceptable antigens. Patients received transplant if flow cytometry T-cell and B-cell cross-match channel shift values were less than 150 and 250, respectively, with antithymocyte globulin and intravenous immunoglobulin induction treatment. Results: Patients had a mean number of 1.6±0.8 DSAs with a mean fluorescence intensity value of 2,815±2,550. Twenty-seven percent were flow cytometry cross-match positive with T-cell and B-cell channel shift values of 129±49 and 159±52, respectively. During a median follow-up of 24 months (range, 6–50), there were no statistically significant differences in patient (99% vs. 95%) and graft survival (88% vs. 90%) rates between DSA+ and DSA− groups, respectively. Cumulative acute rejection rates of 11% in the DSA+ group and 12% in the DSA− group were similar. Two DSA+ (3%) and five DSA− (2%) patients developed chronic antibody-mediated rejection (3%). The mean serum creatinine levels were identical between the two groups (1.4±0.6 mg/dL). Conclusion: Similar patient and graft survival, and acute rejection rates can be achieved in DSA+ patients compared to DSA− patients with pretransplantation immunologic risk assessment.
    Transplantation 05/2014; 98(10). DOI:10.1097/TP.0000000000000191 · 3.78 Impact Factor
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    ABSTRACT: We investigated why some donor-specific antibody-positive patients do not develop antibody-mediated rejection. Of 71 donor-specific antibody-positive patients, 46 had diagnosis of antibody-mediated rejection and 25 had normal biopsies. Fifty donor-specific antibody-negative patients with normal biopsies were used as a control group. A subgroup of 61 patients with available biopsy and 64 with blood samples were analyzed by microarrays. Both donor-specific antibody-positive/antibody-mediated rejection-positive and negative biopsies showed increased expression of gene transcripts associated with cytotoxic T cells, natural killer cells, macrophages, interferon-gamma, and rejection compared to donor-specific antibody-negative biopsies. Regulatory T-cell transcripts were upregulated in donor-specific antibody-positive/antibody-mediated rejection-positive and B-cell transcripts in donor-specific antibody-positive/antibody-mediated rejection-negative biopsies. Whole-blood gene expression analysis showed increased immune activity in only donor-specific antibody-positive/antibody-mediated rejection-positive but not negative patients. During a median follow-up of 36 months, 4 donor-specific antibody-positive/antibody-mediated rejection-negative patients developed antibody-mediated rejection, 12 continued to have donor-specific antibody, but 9 lost their donor-specific antibody. Gene expression profiles did not predict the development of antibody-mediated rejection or the persistence of donor-specific antibody. Thus, donor-specific antibody-positive/antibody-mediated rejection-negative patients had increased rejection-associated gene transcripts in their allografts despite no histologic findings of rejection but not in their blood. This was found in both biopsy and blood samples of donor-specific antibody-positive/antibody-mediated rejection-positive patients.Kidney International advance online publication, 26 March 2014; doi:10.1038/ki.2014.75.
    Kidney International 03/2014; 86(3). DOI:10.1038/ki.2014.75 · 8.52 Impact Factor
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    ABSTRACT: This study aimed to investigate global gene expression profiles of BK viremia and nephropathy (BKVN) samples using microarrays to investigate the immunologic response to BK virus. Patients were monitored for BK viremia in the blood monthly for 6 months, then at 9 and 12 months after kidney transplantation. BKVN and normal transplant kidney biopsy samples, and whole blood samples of patients with and without BK viremia were analyzed by Affymetrix Human Gene 1.0 ST Arrays. During a mean follow-up of 917±325 days, 61 of the 289 patients (21%) developed BK viremia at a median 149 (27, 1,113) days after transplantation with a median peak PCR titers of 35,900 (1,000, 2,677,000). The only significant risk factor for development of BK viremia was induction with anti-thymocyte globulin (P=0.03). Only four patients developed BKVN (1.3%). Pathogenesis-based transcript analysis revealed a significant increased expression of interferon-gamma and rejection induced (GRIT), quantitative cytotoxic T-cell (QCAT), quantitative constitutive and alternate macrophage, B-cell and natural killer cell-associated transcripts (NKAT), indicating an active inflammatory immune response in BKVN biopsies (n=3) compared to normal transplant kidney biopsies with (n=3) and without BK viremia (n=11). The whole blood gene expression profiles of 19 BK viremia patients revealed significant increased expression of GRIT, QCAT, and NKAT compared to 14 patients without viremia. The results showed increased activity of cytotoxic T cells and natural killer cells in BKVN and viremia samples resembling acute rejection and suggested the involvement of both adaptive and innate immunity.
    Transplantation 12/2013; 97(4). DOI:10.1097/01.TP.0000437432.35227.3e · 3.78 Impact Factor
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    ABSTRACT: This study investigated the mechanisms involved in development of donor-specific antibody (DSA) and/or C4d-negative transplant glomerulopathy (TGP) by allograft gene expression profiles using microarrays. This cohort study was conducted in kidney transplant recipients. Patients were eligible for inclusion if they required a clinically indicated biopsy at any time point after their transplant. They were then classified according to their histopathology findings and DSA and C4d results. Eighteen chronic antibody-mediated rejection (CAMR), 14 DSA+/C4d- TGP, 25 DSA-/C4d- TGP, and 47 nonspecific interstitial fibrosis/tubular atrophy (IFTA) biopsy specimens were identified. In a subset of patients from the study population, biopsy specimens in each group and normal transplant kidney specimens were analyzed with Affymetrix Human Gene 1.0 ST Arrays. The mean sum score of glomerulitis and peritubular capillaritis increased from 0.28±0.78 in IFTA specimens to 0.75±0.85 in DSA-/C4d- TGP specimens, 1.71±1.49 in DSA+/C4d-/TGP specimens, and 2.11±1.74 in CAMR specimens (P<0.001). During a median follow-up time of 2 (interquartile range, 1.4-2.8) years after biopsy, graft loss was highest in CAMR specimens (27.8%) compared to IFTA specimens (8.5%), DSA+/C4d- TGP specimens (14.3%), and DSA-/C4d- TGP specimens (16%) (P=0.01). With use of microarrays, comparison of the gene expression profiles of DSA-/C4d- TGP specimens with glomerulitis + peritubular capillaritis scores > 0 to normal and IFTA biopsy specimens revealed higher expression of quantitative cytotoxic T cell-associated transcripts (QCAT). However, both CAMR and DSA+/C4d- TGP specimens had higher expression of not only QCAT but also IFN-γ and rejection-induced, constitutive macrophage-associated, natural killer cell-associated, and DSA-selective transcripts. Endothelial cell-associated transcript expression was upregulated only in CAMR biopsy specimens. These results suggested that DSA+/C4d- TGP biopsy specimens may be classified as CAMR. In contrast, DSA-/C4d- TGP specimens showed increased cytotoxic T cell-associated transcripts, suggesting T cell activation as a mechanism of injury.
    Clinical Journal of the American Society of Nephrology 09/2013; 8(12). DOI:10.2215/CJN.04240413 · 5.25 Impact Factor
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    ABSTRACT: Alemtuzumab (AZ) induction in hepatitis C-seropositive (HCV+) kidney transplant (KTX) recipients may negatively affect patient survival; however, available information is scant. Using US registry data from 2003 to 2010 of adult HCV+ deceased-donor KTXs (n = 4910), we examined outcomes by induction agent - AZ (n = 294), other T cell-depleting agents, (n = 2033; T cell), IL-2 receptor blockade (n = 1135; IL-2RAb), and no induction (n = 1448). On multivariate analysis, induction therapy was associated with significantly better overall patient survival with AZ [adjusted hazards ratio (aHR) 0.64, 95% confidence interval (CI) 0.45, 0.92], T cell (aHR 0.52, 95% CI 0.41, 0.65) or IL-2RAb (aHR 0.67, 95% CI 0.53, 0.87), compared to no induction. A significant protective effect was also seen with AZ (aHR 0.63, 95% CI 0.40, 0.99), T cell (aHR 0.62, 95% CI 0.49, 0.78), and IL2R-Ab (aHR 0.62, 95% CI 0.47, 0.82) in terms of death-censored graft survival relative to no induction. There were 88 HIV+/HCV+ coinfected recipients. Compared to noninduction, any induction (i.e. three induction groups combined) was associated with similar overall patient survival (P = 0.2255) on univariate analysis. Induction therapy with AZ, other T cell-depleting agents, or IL-2RAb in HCV+ KTX is associated with better patient and death-censored graft survival compared to noninduction. In HCV/HIV coinfected patients, induction is not contraindicated.
    Transplant International 07/2013; 26. DOI:10.1111/tri.12167 · 3.16 Impact Factor
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    ABSTRACT: BACKGROUND: The outcome of HIV-infected kidney transplant recipients managed with an early corticosteroid withdrawal protocol is not known. METHODS: Eleven consecutive HIV-infected patients with undetectable plasma HIV RNA and more than 200/mm CD4 T cells underwent deceased-donor (n=8) or living-donor (n=3) kidney transplantation at our center. All were managed with an early corticosteroid withdrawal protocol; 9 of 11 received antithymocyte globulin and 2 received basiliximab induction. We analyzed patient and graft outcomes, acute rejection rate, HIV progression, BKV replication, infections, and urinary cell mRNA profiles. RESULTS: The median (range) follow-up was 44.5 (26-73) months. The incidence of acute rejection was 9% at 1 year and the patient and allograft survival rates were 100% and 91%, respectively. Estimated glomerular filtration rate at 1 year (mean±SD) was 78±39 mL/min/1.73 m. Plasma HIV RNA was undetectable at 24 months and none had BKV replication. Six of the 11 kidney recipients developed eight infections requiring hospitalization. Urinary cell levels of mRNA for complement components and complement regulatory proteins, cell lineage-specific proteins CD3, CD4, CD8, CTLA4, Foxp3, chemokine IP-10, cytotoxic perforin and granzyme B, and BKV VP1 mRNA were not different (P>0.05) between HIV-infected patients and HIV-negative recipients (n=22) with stable graft function and normal biopsy results. CONCLUSION: An early steroid withdrawal regimen with antithymocyte globulin induction was associated with excellent graft and patient outcomes in HIV-infected recipients of kidney allografts. Their urinary cell mRNA profiles are indistinguishable from those of HIV-negative patients with stable graft function and normal biopsy results.
    Transplantation 03/2013; 95(5):711-720. DOI:10.1097/TP.0b013e31827ac322 · 3.78 Impact Factor
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    ABSTRACT: The positive costimulatory proteins OX40 and OX40L and negative regulatory proteins programmed death (PD)-1, PD ligand 1, and PD ligand 2 have emerged as significant regulators of acute rejection in experimental transplantation models. We obtained 21 urine specimens from 21 renal allograft recipients with graft dysfunction and biopsy-confirmed acute rejection and 25 specimens from 25 recipients with stable graft function and normal biopsy results (stable). Urinary cell levels of mRNAs were measured using real-time quantitative polymerase chain reaction assays, and the levels were correlated with allograft status and outcomes. Levels of OX40 mRNA (P<0.0001, Mann-Whitney test), OX40L mRNA (P=0.0004), and PD-1 mRNA (P=0.004), but not the mRNA levels of PD ligand 1 (P=0.08) or PD ligand 2 (P=0.20), were significantly higher in the urinary cells from the acute rejection group than the stable group. Receiver operating characteristic curve analysis demonstrated that acute rejection is predicted with a sensitivity of 95% and a specificity of 92% (area under the curve=0.98, 95% confidence interval 0.96-1.0, P<0.0001) using a combination of levels of mRNA for OX40, OX40L, PD-1, and levels of mRNA for the previously identified biomarker Foxp3. Within the acute rejection group, levels of mRNA for OX40 (P=0.0002), OX40L (P=0.0004), and Foxp3 (P=0.04) predicted acute rejection reversal, whereas only OX40 mRNA levels (P=0.04) predicted graft loss after acute rejection. A linear combination of urinary cell levels of mRNA for OX40, OX40L, PD-1, and Foxp3 was a strong predictor of acute rejection in human renal allograft biopsies. This prediction model should be validated using an independent cohort of renal allograft recipients.
    Transplantation 11/2010; 90(12):1381-7. DOI:10.1097/TP.0b013e3181ffbadd · 3.78 Impact Factor
  • Transplantation 07/2010; 90. DOI:10.1097/00007890-201007272-00460 · 3.78 Impact Factor
  • Clinical transplants 01/2010;
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    ABSTRACT: We report 2 cases of sensitized patients who were successfully treated with bortezomib therapy resulting in reduction of donor-specific antibodies (DSA). Our cases illustrate the synergistic effects of combination therapy that includes bortezomib on prevention and treatment of AMR in highly sensitized patients. Moving forward, long-term data on sensitized patients treated with bortezomib are needed to fully evaluate the impact of this therapy.
    Clinical transplants 01/2009;

Publication Stats

45 Citations
53.23 Total Impact Points

Institutions

  • 2013–2015
    • Montefiore Medical Center
      • Department of Surgery
      New York, New York, United States
    • Albert Einstein College of Medicine
      • Department of Surgery
      New York, New York, United States
  • 2010
    • New York Presbyterian Hospital
      • Department of Pain Medicine
      New York, New York, United States
    • Weill Cornell Medical College
      New York City, New York, United States