Edward Cole

University Health Network, Toronto, Ontario, Canada

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Publications (144)734.71 Total impact

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    ABSTRACT: Background: Angiotensin-converting enzyme inhibitors have been shown to reduce the risk of end-stage renal disease and death in non-transplant patients with proteinuria. We examined whether ramipril would have a similar beneficial effect on important clinical outcomes in kidney transplant recipients with proteinuria. Methods: In this double-blind, placebo-controlled, randomised trial, conducted at 14 centres in Canada and New Zealand, we enrolled adult renal transplant recipients at least 3-months post-transplant with an estimated glomerular filtration rate (GFR) of 20 mL/min/1·73m(2) or greater and proteinuria 0·2 g per day or greater and randomly assigned them to receive either ramipril (5 mg orally twice daily) or placebo for up to 4 years. Patients completing the final 4-year study visit were invited to participate in a trial extension phase. Treatment was assigned by centrally generated randomisation with permuted variable blocks of 2 and 4, stratified by centre and estimated GFR (above or below 40 mL/min/1·73 m(2)). The primary outcome was a composite consisting of doubling of serum creatinine, end-stage renal disease, or death in the intention-to-treat population. The principal secondary outcome was the change in measured GFR. We ascertained whether any component of the primary outcome had occurred at each study visit (1 month and 6 months post-randomisation, then every 6 months thereafter). This trial is registered with ISRCTN, number 78129473. Findings: Between Aug 23, 2006, and March 28, 2012, 213 patients were randomised. 109 were allocated to placebo and 104 were allocated to ramipril, of whom 109 patients in the placebo group and 103 patients in the ramipril group were analysed and the trial is now complete. The intention to treat population (placebo n=109, ramipril n=103) was used for the primary analysis and the trial extension phase analysis. The primary outcome occurred in 19 (17%) of 109 patients in the placebo group and 14 (14%) of 103 patients in the ramipril group (hazard ratio [HR] 0·76 [95% CI 0·38-1·51]; absolute risk difference -3·8% [95% CI -13·6 to 6·1]). With extended follow-up (mean 48 months), the primary outcome occurred in 27 patients (25%) in the placebo group and 25 (24%) patients in the ramipril group (HR 0·96 [95% CI 0·55-1·65]); absolute risk difference: -0·5% (95% CI -12·0 to 11·1). There was no significant difference in the rate of measured GFR decline between the two groups (mean difference per 6-month interval: -0·16 mL/min/1·73m(2) (SE 0·24); p=0·49). 14 (14%) of patients died in the ramipril group and 11 (10%) in the placebo group, but the difference between groups was not statistically significant (HR 1·45 [95% CI 0·66 to 3·21]). Adverse events were more common in the ramipril group (39 [38%]) than in the placebo group (24 [22%]; p=0·02). Interpretation: Treatment with ramipril compared with placebo did not lead to a significant reduction in doubling of serum creatinine, end-stage renal disease, or death in kidney transplant recipients with proteinuria. These results do not support the use of angiotensin-converting enzyme inhibitors with the goal of improving clinical outcomes in this population. Funding: Canadian Institutes of Health Research.
    The Lancet Diabetes & Endocrinology 10/2015; DOI:10.1016/S2213-8587(15)00368-X · 9.19 Impact Factor
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    ABSTRACT: Background: Establishment of a national kidney paired donation (KPD) program represents a unique achievement in Canada's provincially organized health care system. Methods: Key factors enabling program implementation included consultation with international experts, formation of a unique organization with a mandate to facilitate interprovincial collaboration, and the volunteer efforts of members of the Canadian transplant community to overcome a variety of logistical barriers. Results: As of December 2013, the program had facilitated 240 transplantations including 10% with Calculated panel reactive antibody (cPRA) ≥97%. Unique features of the Canadian KPD program include participation of n = 55 nondirected donors, performance of only donor specific antibody negative transplants, the requirement for donor travel, and nonuse of bridge donors. Conclusion: The national KPD program has helped maintain the volume of living kidney donor transplants in Canada over the past 5 years and serves as a model of inter-provincial collaboration to improve the delivery of health care to Canadians.
    Transplantation 10/2014; 99(5). DOI:10.1097/TP.0000000000000455 · 3.83 Impact Factor
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    E Cole · K J Tinckam ·

    American Journal of Transplantation 06/2014; 14(7). DOI:10.1111/ajt.12789 · 5.68 Impact Factor
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    Shafi Malik · Edward Cole ·
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    ABSTRACT: Kidney paired donation (KPD) remains an important strategy to facilitate transplantation in patients who have a healthy and willing donor, but are unable to proceed with directed donation due to either ABO incompatibility or a positive cross-match against their intended donor. Personal knowledge, The Canadian Blood Services Database for Living Donor Exchange, published reports and personal communications. The national Living Donor Paired Exchange Programme (LDPE) in Canada was established in 2009. 235 transplants were completed of which 190 were registered recipients and 45 were from the deceased donor (DD) wait list. At 1 year, patient survival was 100%, graft survival 98%, with a biopsy proven acute rejection rate of 8%. The mean serum creatinine (Cr) at the end of one year was 109 mmol/l. Donor survival is 100%. Key to success are national standards for antibody testing and cross-matching, and for evaluating donors and recipients, as well infrastructure (software and personnel) to run the program. The structure of the Canadian program is compared with that of other programs in the United Kingdom, Australia, the Netherlands, and the United States. This review does not include information on travel distances and difficulties, or patient satisfaction. National collaboration and acceptance of common standards is possible and leads to substantial benefits, especially for those patients who are hardest to match. What was known before: Kidney paired donation is considered ethically acceptable. National and regional programs have been created in a number of countries. Key to the success of the Canadian national program are acceptance of standardized procedures and national and provincial support and oversight.
    05/2014; 1(1):6. DOI:10.1186/2054-3581-1-6
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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; 63(1). DOI:10.1053/j.ajkd.2013.08.029 · 5.90 Impact Factor
  • 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.
    03/2013; 1(1). DOI:10.1007/s40472-013-0002-5
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    ABSTRACT: New onset diabetes mellitus (NODM) and acute rejection (AR) are important causes of morbidity and risk factors for allograft failure after kidney transplantation. 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® (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. 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%. 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: http://NCT00706680
    01/2013; 2(1):1. DOI:10.1186/2047-1440-2-1
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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. · 0.69 Impact Factor
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    Canadian Anaesthetists? Society Journal 05/2012; 59(7):729. DOI:10.1007/s12630-012-9715-7 · 2.53 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. DOI:10.2215/CJN.09990911 · 4.61 Impact Factor
  • H. Holdaas · L. Rostaing · D. Seron · E. Cole · J. Chapman ·

    Transplantation 11/2011; 92(10):E61-E61. DOI:10.1097/TP.0b013e31823e5197 · 3.83 Impact Factor
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    Transplantation 08/2011; 92(4):410-418. · 3.83 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. DOI:10.1007/s12630-011-9511-9 · 2.53 Impact Factor
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    ABSTRACT: Benefits of conversion from calcineurin inhibitor (CNI) to mammalian target of rapamycin inhibitor-based immunosuppression in long-term kidney transplant patients remain uncertain. ASCERTAIN was a 24-month, open-label, multicenter study. Kidney transplant patients more than 6 months posttransplant receiving CNI (baseline glomerular filtration rate [GFR] 30-70 mL/min/1.73 m) were randomized to everolimus with CNI elimination (n=127) or CNI minimization (n=144), or continued CNI unchanged (controls, n=123) to assess the effect on measured GFR at month 24 after randomization. Renal function was stable in all groups to month 24. Mean measured GFR at month 24, the primary endpoint, was 48.0±22.0 mL/min/1.73 m, 46.6±21.1 mL/min/1.73 m, and 46.0±20.4 mL/min/1.73 m in the CNI elimination, CNI minimization, and control groups, respectively. Differences between CNI elimination (1.12 mL/min/1.73 m, 95% confidence interval [CI] -3.51 to 5.76, P=0.63) and CNI minimization (0.59 mL/min/1.73 m, 95% CI -3.88 to 5.07, P=0.79) versus controls at month 24 were nonsignificant that is, the primary endpoint was not met. No efficacy endpoint differed significantly between groups. Post hoc analyses showed that patients with baseline creatinine clearance (CrCl) more than 50 mL/min had a significantly greater increase in measured GFR after CNI elimination versus controls (difference 11.4 mL/min/1.73 m, 95% CI 2.1 to 20.8 mL/min/1.73 m, P=0.017). Adverse events resulted in discontinuation in 36 (28.3%) CNI elimination patients, 24 (16.7%) CNI minimization patients, and 5 (4.1%) controls (P<0.001 vs. CNI elimination; P=0.020 vs. CNI minimization). Conversion to everolimus with CNI elimination or minimization a mean of 5.6 years after kidney transplantation had no overall renal benefit and was associated with more frequent adverse events and discontinuations. Patients with CrCl more than 50 mL/min may benefit from a change in therapy more than 6 months after renal transplantation.
    Transplantation 06/2011; 92(4):410-8. DOI:10.1097/TP.0b013e318224c12d · 3.83 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. DOI:10.1097/TP.0b013e3182200e5c · 3.83 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. DOI:10.1161/CIRCULATIONAHA.110.000588 · 14.43 Impact Factor

  • American Journal of Kidney Diseases 04/2011; 57(4). DOI:10.1053/j.ajkd.2011.02.055 · 5.90 Impact Factor
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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. DOI:10.1053/j.ajkd.2010.06.024 · 5.90 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. DOI:10.1097/TP.0b013e3181efd030 · 3.83 Impact Factor
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    American Journal of Kidney Diseases 08/2010; 56(2):219-46. DOI:10.1053/j.ajkd.2010.05.004 · 5.90 Impact Factor

Publication Stats

5k Citations
734.71 Total Impact Points


  • 2005-2014
    • University Health Network
      • Division of Nephrology
      Toronto, Ontario, Canada
    • University of Glasgow
      • Institute of Cardiovascular and Medical Sciences
      Glasgow, Scotland, United Kingdom
  • 1985-2014
    • University of Toronto
      • • Division of Neurology
      • • Department of Medicine
      • • Department of Surgery
      Toronto, Ontario, Canada
  • 1988-2013
    • UHN: Toronto General Hospital
      Toronto, Ontario, Canada
  • 1994-2005
    • Toronto Western Hospital
      Toronto, Ontario, Canada
  • 1991
    • University of Waterloo
      Waterloo, Ontario, Canada
  • 1990
    • Women's College Hospital
      Toronto, Ontario, Canada
  • 1989
    • St. Michael's Hospital
      Toronto, Ontario, Canada