E Cole

University Health Network, Toronto, Ontario, Canada

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Publications (110)499.39 Total impact

  • E Cole, K J Tinckam
    American Journal of Transplantation 06/2014; 14(7). · 6.19 Impact Factor
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    ABSTRACT: Unlike the United States, the potential to increase organ donation in Canada may be sufficient to meet the need for transplantation. However, there has been no national coordinated effort to increase organ donation. Strategies that do not involve payment for organs, such as investment in health care resources to support deceased donor organ donation and introduction of a remuneration framework for the work of deceased organ donation, should be prioritized for implementation. Financial incentives that may be permitted under existing legislation and that pose little risk to existing donation sources should be advanced, including the following: payment of funeral expenses for potential donors who register their decision on organ donation during life (irrespective of the decision to donate or actual organ donation) and removal of disincentives for directed and paired exchange living donation, such as payment of wages, payment for pain and suffering related to the donor surgery, and payment of directed living kidney donors for participation in Canada's paired exchange program. In contrast, it would be premature to contemplate a regulated system of organ sales that would require a paradigm shift in the current approach to organ donation and legislative change to implement.
    American Journal of Kidney Diseases 11/2013; · 5.29 Impact Factor
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    ABSTRACT: BACKGROUND: New onset diabetes mellitus (NODM) and acute rejection (AR) are important causes of morbidity and risk factors for allograft failure after kidney transplantation. METHODS: In this multi-center, open label, single-arm pilot study, 49 adult (>=18 years of age), low immunologic risk, non-diabetic recipients of a first deceased or living donor kidney transplant received early steroid reduction to 5 mg/day combined with Thymoglobulin(R) (Genzyme Transplant, Cambridge, MA, USA) induction, low dose cyclosporine (2-hour post-dose (C2) target of 600 to 800 ng/ml) and mycophenolic acid (MPA) therapy. RESULTS: Six months after transplantation, two patients (4%) developed NODM and one patient (2%) developed AR. Four patients had impaired fasting glucose tolerance based on 75-g oral glucose tolerance testing (OGTT). There was one patient death. There were no episodes of cytomegalovirus (CMV) infection or BK virus nephritis. In contrast, in a historical cohort of n = 27 patients treated with Thymoglobulin induction, and conventional doses of cyclosporine and corticosteroids, the incidence of NODM and AR was 18% and 15%. CONCLUSIONS: The pilot study results suggest that Thymoglobulin induction combined with early steroid reduction, reduced cyclosporine exposure and MPA, may reduce the incidence of both NODM and AR in low immunological risk patients. A future controlled study enriched for patients at high risk for NODM is under consideration.Trial registration: ClinicalTrials.gov: NCT00706680.
    Transplantation research. 01/2013; 2(1):1.
  • Shafi Malik, Edward Cole
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    ABSTRACT: Approximately one-third of kidney transplant candidates have medically acceptable living donors, but are unable to receive transplants due to donor–recipient incompatibilities. Kidney paired donation (KPD) is a strategy that matches incompatible pairs in order to find compatible matches, thus increasing living donor transplantation. The concept was first conceived in 1986. Since then, significant strides have been made. However, the technique remains underutilized. This article describes the current advances, types of paired donation programmes, registries, worldwide experience, outcomes, barriers, and limitations.
    Current Transplantation Reports. 01/2013;
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    ABSTRACT: Immunocompromised individuals are more susceptible to complications produced by influenza infection. As a result, solid-organ transplant (SOT) recipients were targeted as a priority group to receive AS03-adjuvanted H1N1 influenza vaccine during 2009. To evaluate seroconversion after one dose of adjuvanted pandemic influenza H1N1 (pH1N1) vaccine in SOT recipients. Adult SOT recipients were enrolled to receive one 3.75 μg dose of adjuvanted pH1N1 vaccine. Serological status was tested using a hemagglutination inhibition assay before and two and four weeks postvaccination. The five SOT recipients (one liver, two kidney and two lung transplants) had a median age of 50 years (range 36 to 53 years), and three were male, who were a median time of three years (range two months to 15 years) post-transplant. All patients were on a double or triple immunosuppressive regimen. The prevaccination pH1N1 titre was 1:10 in four patients and 1:40 in one patient. Seroprotection was observed only in one patient, with a rise in titre from 1:40 at baseline to 1:320 at both two and four weeks after vaccination. This lung transplant recipient had documented previous infection with pH1N1. Results of the present small study call into question whether one dose of adjuvanted pH1N1 vaccine can provide seroprotection in SOT recipients.
    The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale / AMMI Canada 01/2013; 24(1):e7-e10. · 1.02 Impact Factor
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    Canadian Anaesthetists? Society Journal 05/2012; 59(7):729. · 2.31 Impact Factor
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    ABSTRACT: Living donor paired exchange programs assume that kidneys from living donors are of comparable quality and anticipated longevity. This study determined actual allograft t(1/2) within different recipient age groups (10-year increments) as a function of donor age (5-year increments), and juxtaposed these results against the probabilities of deceased donor transplantation, and exclusion from transplantation (death or removal from the wait-list). Data from the US Renal Data System (transplant dates 1988-2003 with follow-up through September 2007) were used to determine allograft t(1/2), whereas data from patients on the United Network for Organ Sharing waiting list between 2003 and 2005 (with follow-up through February 2010) were used to determine wait-list outcomes. With the exception of recipients aged 18-39 years, who had the best outcomes with donors aged 18-39 years, living donor age between 18 and 64 years had minimal effect on allograft t(1/2) (difference of 1-2 years with no graded association). The probability of deceased donor transplantation after 3 years of wait-listing ranged from 21% to 66% by blood type and level of sensitization, whereas the probability of being excluded from transplantation ranged from 6% to 27% by age, race, and primary renal disease. With the exception of recipients aged 18-39 years, living donor age between 18 and 64 years has minimal effect on allograft survival.
    Clinical Journal of the American Society of Nephrology 03/2012; 7(5):835-41. · 5.07 Impact Factor
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    ABSTRACT: The aim of this study was to explore donor and recipient outcomes from organ donation after cardiac death (DCD) in Ontario and to examine the impact of DCD on deceased donation rates in Ontario since its implementation. Donor data were obtained from the Trillium Gift of Life Network (TGLN) TOTAL database from June 1, 2006 until May 31, 2009. All DCDs were tracked, including unsuccessful DCD attempts during that time. For the first 36 months after DCD implementation, all Ontario solid organ transplant programs that utilized organs from DCD provided clinical outcome data at one year. Total DCD activity until December 1, 2010 was also tracked. In addition, we compared organ donation and DCD rates across all Canadian jurisdictions and the USA. For the first 36 months of DCD activity in Ontario, June 1, 2006 to May 31, 2009, there were 67 successful DCDs out of 87 attempted DCDs in 18 Ontario hospitals, resulting in 128 kidney, 41 liver, and 21 lung transplants. The one-year kidney patient and death-censored allograft survivals were 96 and 97%, respectively. Mean (SD) creatinine at 12 months was 150 (108) μmol·L(-1). In 26 (20%) extended criteria donors (ECD-DCD), the one-year creatinine was 206 (158) μmol·L(-1) vs 137 (80) μmol·L(-1) in 102 standard criteria donors (SCD-DCD) (P = 0.002). The one-year liver and lung allograft survivals were 78% and 70%, respectively. Since its implementation four and a half years ago, DCD has accounted for 10.9% of deceased donor activity in Ontario. In 2009, Ontario had a record number of organ donors. Of the 221 deceased donors, 37 (17%) donors were DCD. By December 1, 2010 there were 121 DCD Ontario donors resulting in > 300 solid organ transplants and accounting for 90% of all DCD activity in the country. The rapid update of DCD in Ontario can be attributed to strong proponents in the critical care and transplantation communities with continued support from Trillium Gift of Life Network (TGLN). Ontario is the only province to demonstrate growth in deceased donor rates over the last decade (25% over the last four years), which can be attributed primarily to the success of its DCD activity.
    Canadian Anaesthetists? Society Journal 07/2011; 58(7):599-605. · 2.31 Impact Factor
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    ABSTRACT: Pandemic H1N1 influenza has been associated with a worldwide outbreak of febrile respiratory illness. Although impaired cell mediated immunity, such as that caused by transplant immunosuppression, has been identified as a risk factor for severe infection with this virus, the course of this infection has not been adequately characterized in solid organ transplant (SOT) recipients in comparison with nontransplanted controls. We report our experience with severe pH1N1 infection in transplant recipients and compare this group with nonimmunosuppressed patients. Data were retrospectively collected on all patients admitted to our institution with proven pH1N1 infection. Clinical characteristics, treatments, and outcomes were compared between SOT recipients and nonimmunocompromised controls. Seventeen SOT recipients and 49 controls were identified. The control group had higher baseline rates of asthma (P = 0.02) and smoking (P = 0.05) at baseline. No difference in clinical features of H1N1 infection was detected except for a greater prevalence of wheeze in the non-SOT group (P = 0.02). No statistical differences in outcomes could be detected between the groups. Several markers of severity, including use of high frequency oscillatory ventilation, extracorporeal membrane oxygenation, and death were slightly more frequent in the control group. SOT recipients admitted to hospital with pH1N1 infection did not have significantly more severe outcomes of their infection compared with their nonimmunocompromised counterparts, despite their immune suppressed status.
    Transplantation 05/2011; 92(2):230-4. · 3.78 Impact Factor
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    ABSTRACT: Kidney transplant recipients, like other patients with chronic kidney disease, experience excess risk of cardiovascular disease and elevated total homocysteine concentrations. Observational studies of patients with chronic kidney disease suggest increased homocysteine is a risk factor for cardiovascular disease. The impact of lowering total homocysteine levels in kidney transplant recipients is unknown. In a double-blind controlled trial, we randomized 4110 stable kidney transplant recipients to a multivitamin that included either a high dose (n=2056) or low dose (n=2054) of folic acid, vitamin B6, and vitamin B12 to determine whether decreasing total homocysteine concentrations reduced the rate of the primary composite arteriosclerotic cardiovascular disease outcome (myocardial infarction, stroke, cardiovascular disease death, resuscitated sudden death, coronary artery or renal artery revascularization, lower-extremity arterial disease, carotid endarterectomy or angioplasty, or abdominal aortic aneurysm repair). Mean follow-up was 4.0 years. Treatment with the high-dose multivitamin reduced homocysteine but did not reduce the rates of the primary outcome (n=547 total events; hazards ratio [95 confidence interval]=0.99 [0.84 to 1.17]), secondary outcomes of all-cause mortality (n=431 deaths; 1.04 [0.86 to 1.26]), or dialysis-dependent kidney failure (n=343 events; 1.15 [0.93 to 1.43]) compared to the low-dose multivitamin. Treatment with a high-dose folic acid, B6, and B12 multivitamin in kidney transplant recipients did not reduce a composite cardiovascular disease outcome, all-cause mortality, or dialysis-dependent kidney failure despite significant reduction in homocysteine level.
    Circulation 04/2011; 123(16):1763-70. · 15.20 Impact Factor
  • American Journal of Kidney Diseases - AMER J KIDNEY DIS. 01/2011; 57(4).
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    ABSTRACT: The link between delayed graft function (DGF) and death with graft function (DWGF) in living donor kidney transplant recipients presently is unknown. Retrospective cohort study. 44,630 adult living donor kidney recipients (first transplants only) in the US Renal Data System from January 1, 1994, to December 31, 2004. DGF, defined as the need for dialysis therapy in the first week after transplant. Time to DWGF. Kaplan-Meier curves were constructed to assess the impact of DGF on DWGF. Recipients with DGF were 1:1 propensity score matched to those without DGF, and time-dependent Cox proportional hazards models were used to examine factors associated with DWGF. Subgroup and sensitivity analyses also were conducted. DWGF occurred in 3,878 patients during 3.9 years' (median) follow-up. In patients with DGF, survival with graft function at 1, 3, 5, and 10 years was 91.9%, 86.8%, 81.6%, and 61.7%, respectively (in patients without DGF, these values were 98.0%, 95.2%, 91.6%, and 80.1%, respectively; P < 0.001 compared with the DGF group). In a fully adjusted time-dependent Cox model, HRs for DWGF in patients with DGF (vs without DGF) were 6.55 (95% CI, 4.78-8.97), 3.55 (95% CI, 2.46-5.11), 2.07 (95% CI, 1.53-2.81), and 1.48 (95% CI, 1.26-1.73) at 0-1, 1-3, 3-12, and longer than 12 months posttransplant, respectively. Propensity score analysis showed similar results. Inferences were unchanged after adjustment for kidney function and acute rejection at 6 months and 1 year posttransplant. Cardiovascular and infectious causes of DWGF were more prevalent in patients with DGF. The association was more marked in female recipients and robust to various sensitivity analyses. The impact of lesser decreases in early graft function could not be evaluated. DGF is associated with an increased risk of DWGF in living donor kidney recipients. The mechanisms underlying this relation require further study.
    American Journal of Kidney Diseases 11/2010; 56(5):961-70. · 5.29 Impact Factor
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    ABSTRACT: An abstract is unavailable. This article is available as HTML full text and PDF.
    Transplantation 10/2010; 90(8):817-20. · 3.78 Impact Factor
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    American Journal of Kidney Diseases 08/2010; 56(2):219-46. · 5.29 Impact Factor
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    ABSTRACT: Delayed graft function (DGF) associates with an increased risk for graft failure, but its link with death with graft function (DWGF) is unknown. We used the US Renal Data System to assemble a cohort of all first, adult, deceased-donor kidney transplant recipients from January 1, 1998, through December 31, 2004. In total, 11,542 (23%) of 50,246 recipients required at least one dialysis session in the first week after transplantation. Compared with patients without DGF, patients with DGF were significantly more likely to die with a functioning graft (relative hazard 1.83 [95% confidence interval 1.73 to 1.93] and 1.53 [95% CI 1.45 to 1.63] for unadjusted and fully adjusted models, respectively). The risk for DWGF was slightly higher among women with DGF than among men. There was no significant heterogeneity among other subgroups, and the results were robust to sensitivity analyses. Acute rejection within the first year attenuated the DGF-DWGF association. Cardiovascular and infectious deaths were slightly more prevalent in the DGF group, but the relative hazards of cause-specific death were similar between DWGF and deaths during total follow-up. In summary, DGF associates with an increased risk for DWGF; the mechanisms underlying the negative impact of DGF require further study.
    Journal of the American Society of Nephrology 10/2009; 21(1):153-61. · 8.99 Impact Factor
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    ABSTRACT: There is a paucity of population-level data on the long-term outcomes of kidney transplants from deceased donors with a history of diabetes mellitus (DM). We examined the association of donor DM with graft and patient survival in 66,654 deceased donor kidney transplant recipients (KTR) from January 1, 1994, to December 31, 2003, in the United States. KTR receiving kidneys from DM versus non-DM donors were compared in the total study population and in a 1:1 propensity score-matched cohort. A total of 2302 KTR received kidneys from DM donors over the study period. Older and female recipients, increased donor age, longer cold ischemia time, and transplants after 2000 were associated with a greater odds of receiving a DM donor. After propensity score matching, Cox proportional hazards models revealed hazard ratios of 1.11 (95% CI: 1.02-1.22), 1.17 (95% CI: 1.04-1.33), and 1.06 (95% CI: 0.94-1.18) for graft failure, death-censored graft failure, and patient mortality, respectively. No significant effect measure modification was seen across various patient subgroups. Longer duration of donor DM was generally associated with an increased risk of adverse outcomes. The results were robust to several sensitivity analyses. The long-term graft survival of KTR with DM donors is significantly inferior to non-DM donors, but the absolute difference is small. DM donors do not adversely impact patient survival. This suggests that DM donors may be effectively used to expand the donor pool, but evidence-based guidelines on the appropriate selection of these donors are needed.
    Transplantation 08/2009; 88(2):251-60. · 3.78 Impact Factor
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    ABSTRACT: There has been no significant increase in the number of deceased organ donors in Canada over the past decade. Canada's donation and transplant system will be restructured with the formation of a new national organization to oversee activity in provincially governed donation and transplantation services. We review the current status of deceased organ donation, highlight issues contributing to the current stagnation in donation and identify changes that will enable success in a new Canadian system. Determining Canada's organ donation performance is difficult because the data required to calculate meaningful metrics of donation performance are not available. Canadians wait longer for transplantation than Americans, and Canada is falling further behind the United States primarily because of fewer donations after cardiac death. The ongoing divide between intergovernmental jurisdictional domains limits national initiatives to improve Canada's donation system. The success of a new national system will be enabled by uniform provincial legislation to ensure that all patients are offered the option to donate, commitment of resources to support organ donation by provincial governments, transparent reporting of comparable metrics of donation performance, establishment of processes to introduce and implement new initiatives and alterations to reimbursement models for organ donation and recovery.
    American Journal of Transplantation 09/2008; 8(8):1580-7. · 6.19 Impact Factor
  • Jeffrey Schiff, Edward H Cole
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    ABSTRACT: Steroids are effective immunosuppressants in renal transplantation but are associated with significant adverse effects. As a result, there has been increased interest in protocols utilizing steroid minimization. Initial trials stopped steroids at approximately 3 months, when the highest risk phase for acute rejection was over. As two randomized trials using cyclosporine and mycophenolate mofetil without induction therapy showed an unacceptably high acute rejection rate, more recent interest has focused on the cessation of steroids very early, usually within the first week after transplantation. Most protocols have used antibody induction combined with calcineurin inhibitors and mycophenolic acid derivatives. Uncontrolled studies have shown a low rate of acute rejection, but the most recent randomized controlled trials have demonstrated an increased risk of acute rejection. These trials have not shown any consistent difference in short-term patient or graft survival. Cardiovascular risk factors do not appear to be consistently improved by early steroid withdrawal. Most trials lack sufficient follow-up (5 years or more) to assess the impact of the increased acute rejection rate seen with early steroid withdrawal on long-term outcomes. Thus, the use of such protocols remains investigational.
    Pediatric Nephrology 07/2008; 24(2):243-51. · 2.94 Impact Factor
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    ABSTRACT: Development of new therapeutic strategies to improve long-term transplant outcomes requires improved understanding of the mechanisms by which these complications limit long-term transplant survival. The association of acute rejection and new-onset diabetes was determined in the first posttransplantation year with the outcomes of transplant failure from any cause, death-censored graft loss, and death with a functioning graft in 27,707 adult recipients of first kidney-only transplants, with graft survival of at least 1 yr, performed between 1995 and 2002 in the United States. In multivariate analyses, patients who developed acute rejection or new-onset diabetes had a similar risk for transplant failure from any cause, but the mechanisms of transplant failure were different: Acute rejection was associated with death-censored graft loss but only weakly associated with death with a functioning graft. In contrast new-onset diabetes was not associated with death-censored graft loss but was associated with an increased risk for death with a functioning graft. Acute rejection and new-onset diabetes have a similar impact on long-term transplant survival but lead to transplant failure through different mechanisms. The mechanisms by which new-onset diabetes leads to transplant failure should be prospectively studied. Targeted therapeutic strategies to minimize the impact of various early posttransplantation complications may lead to improved long-term outcomes.
    Clinical Journal of the American Society of Nephrology 06/2008; 3(3):814-21. · 5.07 Impact Factor
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    ABSTRACT: The calcineurin inhibitors (CNI) cyclosporine and tacrolimus remain the backbone of immunosuppression for most kidney transplant recipients. Despite many years of experience, protocols that optimize efficacy with minimal toxicity remain a subject of debate. Nevertheless, studies of the pharmacokinetic properties of the CNI, particularly cyclosporine, have led to improved dosing strategies. The purpose of this article is to review the current understanding of CNI pharmacokinetics and its relevance to proper dosing and monitoring of these medications. This article also reviews the trials that have helped to define the optimal dosages and discusses the effect of adjunctive immunosuppressive agents on CNI pharmacokinetics and dosing.
    Clinical Journal of the American Society of Nephrology 04/2007; 2(2):374-84. · 5.07 Impact Factor

Publication Stats

2k Citations
499.39 Total Impact Points

Institutions

  • 2009–2014
    • University Health Network
      • Division of Nephrology
      Toronto, Ontario, Canada
  • 2006–2013
    • UHN: Toronto General Hospital
      Toronto, Ontario, Canada
  • 1998–2013
    • University of British Columbia - Vancouver
      • Division of Nephrology
      Vancouver, British Columbia, Canada
  • 1988–2013
    • University of Toronto
      • • Division of Neurology
      • • Department of Medicine
      • • Department of Surgery
      Toronto, Ontario, Canada
  • 2007
    • McGill University Health Centre
      Montréal, Quebec, Canada
  • 2005
    • University of Ottawa
      Ottawa, Ontario, Canada
  • 1989
    • St. Michael's Hospital
      Toronto, Ontario, Canada