Ron Wald

University of Toronto, Toronto, Ontario, Canada

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Publications (88)528.56 Total impact

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    ABSTRACT: IntroductionPatients with severe acute kidney injury (AKI) who are hospitalized at centres that do not provide renal replacement therapy (RRT) are frequently subjected to inter-hospital transfer for the provision of RRT. It is unclear whether such transfers are associated with worse patient outcomes as compared to the receipt of initial care in a centre that provides RRT. This study examined the relationship between inter-hospital transfer and 30-day mortality among critically ill patients with AKI who received RRT.Methods We conducted a retrospective cohort study of all critically ill patients who commenced RRT for AKI at two academic hospitals in Toronto, Canada. The exposure of interest was inter-hospital transfer for the administration of RRT. We evaluated the relationship between transfer status and 30-day mortality (primary outcome) and RRT dependence at 30 days following RRT initiation (secondary outcome) respectively, using multivariate logistic regression with adjustment for patient demographics, clinical factors, biochemical indices and severity of illness.ResultsOf 370 patients who underwent RRT for AKI, 82 (22.2%) were transferred for this purpose from another hospital. Compared to non-transferred patients who started RRT, transferred patients were younger (61¿±¿15 versus 65¿±¿15 years, P¿=¿0.03) and had a higher serum creatinine concentration at RRT initiation (474¿±¿295 versus 365¿±¿169 ¿mol/L, P¿=¿0.002). Inter-hospital transfer was not associated with mortality (adjusted OR 0.61, 95% CI 0.33 to 1.12) or RRT-dependence (adjusted OR 1.64, 95% CI 0.70 to 3.81) at 30 days.Conclusions Within the limitations of this observational study and the potential for residual confounding, inter-hospital transfer of critically ill patients with AKI was not associated with a higher risk of death or dialysis dependence 30 days after the initiation of acute RRT.
    Critical care (London, England) 09/2014; 18(5):513. · 4.72 Impact Factor
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    ABSTRACT: Several adverse outcomes attributed to atypical antipsychotic drugs, specifically quetiapine, risperidone, and olanzapine, are known to cause acute kidney injury (AKI). Such outcomes include hypotension, acute urinary retention, and the neuroleptic malignant syndrome or rhabdomyolysis.
    Annals of internal medicine 08/2014; 161(4):242-248. · 13.98 Impact Factor
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    ABSTRACT: Background and objectives No data on the development of conventional indications for RRT (refractory acidosis, hyperkalemia, uremia, oliguria/anuria, and volume overload) related to timing of RRT exist. The prevalence of conventional indications among critically ill patients on RRT for AKI was evaluated, and patients manifesting indications versus patients without indications were compared in terms of crude and adjusted 90-day mortality. Design, setting, participants, & measurements In this substudy of the Finnish Acute Kidney Injury study conducted in 2011 and 2012 in 17 intensive care units with 2901 patients, patients were classified as pre-emptive (no conventional indications) and classic (one or more indications) RRT recipients. Patients with classic RRT were divided into classic-urgent (RRT initiated #12 hours from manifesting indications) and classic-delayed (RRT .12 hours from first indication). Additionally, 2450 patients treated without RRT were matched to patients with pre-emptive RRT. Results Of 239 patients treated with RRT, 134 (56.1%; 95% confidence interval [95% CI], 49.8% to 62.4%) fulfilled at least one conventional indication before commencing RRT. Crude 90-day mortality of 134 patients with classic RRT was 48.5% (95% CI, 40.0% to 57.0%), and it was 29.5% (95% CI, 20.8% to 38.2%) for the 105 patients with pre-emptive RRT. Classic RRT was associated with a higher risk for mortality (adjusted odds ratio, 2.05; 95% CI, 1.03 to 4.09). Forty-four patients with classic–delayed RRT showed higher crude mortality (68.2%; 95% CI, 54.4% to 82.0%) compared with patients with classic–urgent RRT, and this association persisted after adjustment for known confounders (odds ratio, 3.85; 95% CI, 1.48 to 10.22). Crude 90-day mortality of 67 1:1 matched patients with pre-emptive RRT was 26.9% (95% CI, 6.3% to 37.5%), and it was 49.3% (95% CI, 37.3% to 61.2%; P=0.01) for their non-RRT matches. Conclusions Patients on RRT after one or more conventional indications had both higher crude and adjusted 90-day mortality compared with patients without conventional indications. These findings require confirmation in an adequately powered, multicenter, randomized controlled trial.
    Clinical Journal of the American Society of Nephrology 08/2014; 9:1577-1585. · 5.07 Impact Factor
  • Ron Wald, Sean M Bagshaw
    Critical care medicine. 08/2014; 42(8):1933-1934.
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    ABSTRACT: Survivors of acute kidney injury are at an increased risk of developing irreversible deterioration in kidney function and in some cases, the need for chronic dialysis. We aimed to determine predictors of chronic dialysis and death among survivors of dialysis-requiring acute kidney injury.
    BMC Nephrology 07/2014; 15(1):114. · 1.64 Impact Factor
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    ABSTRACT: Some studies but not others suggest angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) use prior to major surgery associates with a higher risk of postoperative acute kidney injury (AKI) and death. We conducted a large population-based retrospective cohort study of patients aged 66 years or older who received major elective surgery in 118 hospitals in Ontario, Canada from 1995 to 2010 (n = 237,208). We grouped the cohort into ACEi/ARB users (n = 101,494) and non-users (n = 135,714) according to whether the patient filled at least one prescription for an ACEi or ARB (or not) in the 120 days prior to surgery. Our study outcomes were acute kidney injury treated with dialysis (AKI-D) within 14 days of surgery and all-cause mortality within 90 days of surgery. After adjusting for potential confounders, preoperative ACEi/ARB use versus non-use was associated with 17% lower risk of post-operative AKI-D (adjusted relative risk (RR): 0.83; 95% confidence interval (CI): 0.71 to 0.98) and 9% lower risk of all-cause mortality (adjusted RR: 0.91; 95% CI: 0.87 to 0.95). Propensity score matched analyses provided similar results. The association between ACEi/ARB and AKI-D was significantly modified by the presence of preoperative chronic kidney disease (CKD) (P value for interaction < 0.001) with the observed association evident only in patients with CKD (CKD - adjusted RR: 0.62; 95% CI: 0.50 to 0.78 versus No CKD: adjusted RR: 1.00; 95% CI: 0.81 to 1.24). In this cohort study, preoperative ACEi/ARB use versus non-use was associated with a lower risk of AKI-D, and the association was primarily evident in patients with CKD. Large, multi-centre randomized trials are needed to inform optimal ACEi/ARB use in the peri-operative setting.
    BMC Nephrology 04/2014; 15(1):53. · 1.64 Impact Factor
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    ABSTRACT: Dialysis intensification from conventional regimens (typically thrice weekly, 4 hours per session) is increasingly utilized with the intent of improving the cardiovascular health and quality of life of chronic dialysis recipients. While home nocturnal hemodialysis offers the opportunity for maximal intensification of dialysis, it is inaccessible to the majority of dialysis recipients who are unable to self-administer hemodialysis in their own homes. In-center nocturnal hemodialysis (INHD) permits the intensification of conventional hemodialysis with the benefits of nursing support and supervision in addition to freedom from dialysis during productive daytime hours. Although no randomized trials have evaluated the relative merits of INHD, preliminary data indicate that INHD is a viable option that may confer a variety of benefits for chronic dialysis recipients.
    Seminars in Dialysis 03/2014; 27(2):179-87. · 2.25 Impact Factor
  • Matthew T James, Ron Wald
    Clinical Journal of the American Society of Nephrology 02/2014; · 5.07 Impact Factor
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    ABSTRACT: Novel oral anticoagulants (NOACs) (rivaroxaban, dabigatran, apixaban) have been approved by international regulatory agencies to treat atrial fibrillation and venous thromboembolism in patients with kidney dysfunction. However, altered metabolism of these drugs in the setting of impaired kidney function may subject patients with CKD to alterations in their efficacy and a higher risk of bleeding. This article examined the efficacy and safety of the NOACs versus vitamin K antagonists (VKAs) for atrial fibrillation and venous thromboembolism in patients with CKD. A systematic review and meta-analyses of randomized controlled trials were conducted to estimate relative risk (RR) with 95% confidence interval (95% CIs) using a random-effects model. MEDLINE, Embase, and the Cochrane Library were searched to identify articles published up to March 2013. We selected published randomized controlled trials of NOACs compared with VKAs of at least 4 weeks' duration that enrolled patients with CKD (defined as creatinine clearance of 30-50 ml/min) and reported data on comparative efficacy and bleeding events. Eight randomized controlled trials were eligible. There was no significant difference in the primary efficacy outcomes of stroke and systemic thromboembolism (four trials, 9693 participants; RR, 0.64 [95% CI, 0.39 to 1.04]) and recurrent thromboembolism or thromboembolism-related death (four trials, 891 participants; RR, 0.97 [95% CI, 0.43 to 2.15]) with NOACs versus VKAs. The risk of major bleeding or the combined endpoint of major bleeding or clinically relevant nonmajor bleeding (primary safety outcome) (eight trials, 10,616 participants; RR 0.89 [95% CI, 0.68 to 1.16]) was similar between the groups. The use of NOACs in select patients with CKD demonstrates efficacy and safety similar to those with VKAs. Proactive postmarketing surveillance and further studies are pivotal to further define the rational use of these agents.
    Journal of the American Society of Nephrology 01/2014; · 8.99 Impact Factor
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    ABSTRACT: IMPORTANCE Calcium-channel blockers are metabolized by the cytochrome P450 3A4 (CYP3A4; EC 1.14.13.97) enzyme. Blood concentrations of these drugs may rise to harmful levels when CYP3A4 activity is inhibited. Clarithromycin is an inhibitor of CYP3A4 and azithromycin is not, which makes comparisons between these 2 macrolide antibiotics useful in assessing clinically important drug interactions. OBJECTIVE To characterize the risk of acute adverse events following coprescription of clarithromycin compared with azithromycin in older adults taking a calcium-channel blocker. DESIGN, SETTING, AND PARTICIPANTS Population-based retrospective cohort study in Ontario, Canada, from 2003 through 2012 of older adults (mean age, 76 years) who were newly coprescribed clarithromycin (n = 96 226) or azithromycin (n = 94 083) while taking a calcium-channel blocker (amlodipine, felodipine, nifedipine, diltiazem, or verapamil). MAIN OUTCOMES AND MEASURES Hospitalization with acute kidney injury (primary outcome) and hospitalization with hypotension and all-cause mortality (secondary outcomes examined separately). Outcomes were assessed within 30 days of a new coprescription. RESULTS There were no differences in measured baseline characteristics between the clarithromycin and azithromycin groups. Amlodipine was the most commonly prescribed calcium-channel blocker (more than 50% of patients). Coprescribing clarithromycin vs azithromycin with a calcium-channel blocker was associated with a higher risk of hospitalization with acute kidney injury (420 patients of 96 226 taking clarithromycin [0.44%] vs 208 patients of 94 083 taking azithromycin [0.22%]; absolute risk increase, 0.22% [95% CI, 0.16%-0.27%]; odds ratio [OR], 1.98 [95% CI, 1.68-2.34]). In a subgroup analysis, the risk was highest with dihydropyridines, particularly nifedipine (OR, 5.33 [95% CI, 3.39-8.38]; absolute risk increase, 0.63% [95% CI, 0.49%-0.78%]). Coprescription with clarithromycin was also associated with a higher risk of hospitalization with hypotension (111 patients of 96 226 taking clarithromycin [0.12%] vs 68 patients of 94 083 taking azithromycin [0.07%]; absolute risk increase, 0.04% [95% CI, 0.02%-0.07%]; OR, 1.60 [95% CI, 1.18-2.16]) and all-cause mortality (984 patients of 96 226 taking clarithromycin [1.02%] vs 555 patients of 94 083 taking azithromycin [0.59%]; absolute risk increase, 0.43% [95% CI, 0.35%-0.51%]; OR, 1.74 [95% CI, 1.57-1.93]). CONCLUSIONS AND RELEVANCE Among older adults taking a calcium-channel blocker, concurrent use of clarithromycin compared with azithromycin was associated with a small but statistically significant greater 30-day risk of hospitalization with acute kidney injury. These findings support current safety warnings regarding concurrent use of CYP3A4 inhibitors and calcium-channel blockers.
    JAMA The Journal of the American Medical Association 12/2013; 310(23):2544-2553. · 29.98 Impact Factor
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    ABSTRACT: We aimed to clarify the correlates of left ventricular mass and secondarily, left ventricular volume, in a cohort of prevalent hemodialysis recipients. Left ventricular hypertrophy is common and left ventricular mass is a widely-accepted surrogate for clinical outcomes in dialysis recipients, who are often subjected to chronic pressure and volume overload. However, the precise pathophysiologic mechanisms of left ventricular hypertrophy in this unique population have not been well understood. This was a cross-sectional study of patients receiving conventional thrice-weekly dialysis in Toronto, Canada. Left ventricular mass and volume were assessed with cardiac magnetic resonance and indexed to the patient's height to the power of 2.7. Fibroblast growth factor-23 concentration was measured using a C-terminal enzyme-linked immunosorbent assay. Patient demographics, comorbidities, dialysis-associated blood pressures and ultrafiltration volumes, biochemical and hematologic parameters, vascular access and medications were extracted from clinical records. Multivariable linear regression was used to identify independent correlates of left ventricular mass index (LVMI) and the left ventricular end diastolic volume index (LVEDVI). We enrolled 56 patients, of whom 23 (41.1 %) were women with mean age 54 ± 12 years. Mean LVMI was 31.1 ± 6.8 g/m(2.7). In multivariable analyses, systolic blood pressure and LVEDVI were the only factors significantly associated with LVMI. Post-dialysis weight, percent reduction in urea and the presence of a permanent form of vascular access were associated with LVEDVI. Fibroblast growth factor-23 was not associated with either LVMI or LVEDVI. Blood pressure and left ventricular dilatation are independent determinants of elevated left ventricular mass. Aggressive blood pressure reduction and avoidance of volume overload may confer LVM regression and improve clinical outcomes.
    The international journal of cardiovascular imaging 11/2013; · 2.15 Impact Factor
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    ABSTRACT: Among critically ill patients with acute kidney injury, the impact of renal replacement therapy modality on long-term kidney function is unknown. Compared with conventional intermittent hemodialysis, continuous renal replacement therapy may promote kidney recovery by conferring greater hemodynamic stability; yet continuous renal replacement therapy may not enhance patient survival and is resource intense. Our objective was to determine whether continuous renal replacement therapy was associated with a lower risk of chronic dialysis as compared with intermittent hemodialysis, among survivors of acute kidney injury. Retrospective cohort study. Linked population-wide administrative databases in Ontario, Canada. Critically ill adults who initiated dialysis for acute kidney injury between July 1996 and December 2009. In the primary analysis, we considered those who survived to at least 90 days after renal replacement therapy initiation. Initial receipt of continuous renal replacement therapy versus intermittent hemodialysis. Continuous renal replacement therapy recipients were matched 1:1 to intermittent hemodialysis recipients based on a history of chronic kidney disease, receipt of mechanical ventilation, and a propensity score for the likelihood of receiving continuous renal replacement therapy. Cox proportional hazards were used to evaluate the relationship between initial renal replacement therapy modality and the primary outcome of chronic dialysis, defined as the need for dialysis for a consecutive period of 90 days. We identified 2,315 continuous renal replacement therapy recipients of whom 2,004 (87%) were successfully matched to 2,004 intermittent hemodialysis recipients. Participants were followed over a median duration of 3 years. The risk of chronic dialysis was significantly lower among patients who initially received continuous renal replacement therapy versus intermittent hemodialysis (hazard ratio, 0.75; 95% CI, 0.65-0.87). This relation was more prominent among those with preexisting chronic kidney disease (p value for interaction term = 0.065) and heart failure (p value for interaction term = 0.035). Compared with intermittent hemodialysis, initiation of continuous renal replacement therapy in critically ill adults with acute kidney injury is associated with a lower likelihood of chronic dialysis.
    Critical care medicine 11/2013; · 6.37 Impact Factor
  • Ziv Harel, Chaim M Bell, Ron Wald
    Kidney International 11/2013; 84(5):1054. · 8.52 Impact Factor
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    ABSTRACT: Acute kidney injury is a common and devastating complication of critical illness, for which renal replacement therapy is frequently needed to manage severe cases. While a recent systematic review suggested that "earlier" initiation of renal replacement therapy improves survival, completed trials are limited due to small size, single-centre status, and use of variable definitions to define "early" renal replacement therapy initiation.Methods/designThis is an open-label pilot randomized controlled trial. One hundred critically ill patients with severe acute kidney injury will be randomly allocated 1:1 to receive "accelerated" initiation of renal replacement therapy or "standard" initiation at 12 centers across Canada. In the accelerated arm, participants will have a venous catheter placed and renal replacement therapy will be initiated within 12 hours of fulfilling eligibility. In the standard initiation arm, participants will be monitored over 7 days to identify indications for renal replacement therapy. For participants in the standard arm with persistent acute kidney injury, defined as a serum creatinine not declining >50% from the value at the time of eligibility, the initiation of RRT will be discouraged unless one or more of the following criteria are fulfilled: serum potassium >=6.0 mmol/L; serum bicarbonate <=10 mmol/L; severe respiratory failure (PaO2/FiO2<200) or persisting acute kidney injury for >=72 hours after fulfilling eligibility. The inclusion criteria are designed to identify a population of critically ill adults with severe acute kidney injury who are likely to need renal replacement therapy during their hospitalization, but not immediately. The primary outcome is protocol adherence (>90%). Secondary outcomes include measures of feasibility (proportion of eligible patients enrolled in the trial, proportion of enrolled patients followed to 90 days for assessment of vital status and the need for renal replacement therapy) and safety (occurrence of adverse events). The optimal timing of renal replacement therapy initiation in patients with severe acute kidney injury remains uncertain, representing an important knowledge gap and a priority for high-quality research. This pilot trial is necessary to establish protocol feasibility, confirm the safety of participants and obtain estimated events rates for design of a large definitive trial.Trial registration numberNCT01557361.
    Trials 10/2013; 14(1):320. · 2.21 Impact Factor
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    ABSTRACT: IgA nephropathy (IgAN) accounts for a far higher proportion of end-stage renal disease (ESRD) in Asia compared with North America. It is not known whether this is entirely because of differences in disease prevalence or a higher risk of disease progression. The lack of a racially diverse population cohort followed longitudinally has previously precluded the ability to address this question. To determine whether Asians in North America with IgAN are at higher risk for ESRD, we analyzed a cohort of 202 patients of self-reported Pacific Asian origin and 467 of other origin from the Toronto GN Registry followed up for a median of 46.4 months. The primary outcome of ESRD (dialysis, transplantation, or eGFR below 15) was analyzed using Cox regression analysis. Baseline eGFR was 59.6 ml/min/1.73 m(2), and median proteinuria was 1.8 g/day. ESRD occurred in 213 patients. By univariable analysis, the risk of ESRD was similar between the two groups (hazard ratio 0.98, 95% CI 0.73, 1.31); however, after adjusting for age, gender, eGFR, medication use, blood pressure, and proteinuria, the risk of ESRD was significantly higher in Pacific Asian individuals (hazard ratio 1.56, 95% CI 1.10, 2.22). This was supported by a significant 1.62 ml/min/1.73 m(2)/year faster rate of eGFR decline (95% CI -3.19, -0.5) and an increased risk of a reduction in eGFR by half (hazard ratio 1.81, 95% CI 1.25, 2.62). Thus, in a large multiracial cohort of patients with IgAN, individuals of Pacific Asian origin have a higher risk of progression to ESRD.Kidney International advance online publication, 5 June 2013; doi:10.1038/ki.2013.210.
    Kidney International 06/2013; · 8.52 Impact Factor
  • JAMA Internal Medicine 04/2013; · 10.58 Impact Factor
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    ABSTRACT: BACKGROUND: Some evidence suggests that the direct renin inhibitor aliskiren may increase the risk of severe hyperkalemia, stroke, or acute kidney injury (AKI) when prescribed with angiotensin-converting enzyme inhibitors (ACEi's) or angiotensin-receptor blockers (ARBs). The extent to which concomitant treatment increases the risk of these outcomes in routine clinical practice is unknown. We addressed this issue with the use of administrative databases. METHODS: We established a cohort of Ontarians treated with an ACEi or an ARB. Within this cohort, we conducted 3 case-control studies. Cases were patients hospitalized with 1 of 3 outcomes (hyperkalemia, AKI, or stroke). In each analysis, we identified up to 5 matched control subjects for each case. Conditional logistic regression was used to examine the association between hospitalization for each outcome and the use of aliskiren in the preceding 60 days. RESULTS: Among 903,346 patients aged 66 years and older treated with an ACEi or ARB during the 28-month study period, we identified 4235 hospitalized with hyperkalemia, 18,231 hospitalized with AKI, and 8283 hospitalized with stroke. After extensive multivariable adjustment, aliskiren therapy was not associated with a significant increase in the risk of hospitalization for hyperkalemia, AKI, or stroke. We found similar results in stratified analyses of patients with and without a history of chronic kidney disease, diabetes, or heart failure. CONCLUSIONS: Among community-dwelling patients aged 66 years and older receiving therapy with an ACEi or an ARB, aliskiren use was not associated with hospitalization for hyperkalemia, AKI, or stroke.
    The Canadian journal of cardiology 03/2013; · 3.12 Impact Factor
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    American Journal of Kidney Diseases 03/2013; · 5.29 Impact Factor
  • Critical Care 03/2013; 17(2). · 4.93 Impact Factor
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    ABSTRACT: Survivors of severe acute kidney injury remain at high risk of death well after apparent recovery from the initial insult. Here we determine whether early nephrology follow-up after a hospitalization complicated by severe acute kidney injury associates with patient survival. This consisted of a cohort study of all hospitalized adults in Ontario from 1996 to 2008 with acute kidney injury who received temporary inpatient dialysis and survived for 90 days following discharge independent from dialysis. Propensity scores were used to match individuals with early nephrology follow-up, defined as a visit with a nephrologist within 90 days of discharge, to those without. The outcome was time to all-cause mortality of 3877 patients who met the eligibility criteria within a maximum follow-up of 2 years. A total of 1583 patients had early nephrology follow-up of whom 1184 were successfully matched 1:1 to those not receiving early follow-up. The incidence of all-cause mortality was lower in those patients with early nephrology follow-up compared with those without (8.4 compared with 10.6 per 100-patient years, hazard ratio 0.76 (95% CI: 0.62-0.93)). Thus, early nephrology follow-up after hospitalization with acute kidney injury and temporary dialysis was associated with improved survival. This finding requires definitive testing in a randomized controlled trial.Kidney International advance online publication, 16 January 2013; doi:10.1038/ki.2012.451.
    Kidney International 01/2013; · 8.52 Impact Factor

Publication Stats

2k Citations
528.56 Total Impact Points

Institutions

  • 2005–2014
    • University of Toronto
      • • Department of Medicine
      • • Division of Neurology
      • • Division of Critical Care Medicine
      • • Saint Michael's Hospital
      • • Division of Cardiology
      Toronto, Ontario, Canada
  • 2011–2013
    • The University of Western Ontario
      • • Division of Nephrology
      • • Department of Medicine
      London, Ontario, Canada
    • University of Alberta
      • Division of Critical Care Medicine
      Edmonton, Alberta, Canada
  • 2009–2013
    • St. Michael's Hospital
      Toronto, Ontario, Canada
  • 2012
    • Tufts University
      • Department of Medicine
      Medford, MA, United States
    • Indiana University-Purdue University Indianapolis
      • Department of Medicine
      Indianapolis, IN, United States
    • Yale-New Haven Hospital
      New Haven, Connecticut, United States
    • Sunnybrook Health Sciences Centre
      • Division of Nephrology
      Toronto, Ontario, Canada
  • 2011–2012
    • University of Ottawa
      Ottawa, Ontario, Canada
  • 2007–2009
    • St. Elizabeth's Medical Center
      Boston, Massachusetts, United States
  • 2006
    • Brigham and Women's Hospital
      • Department of Medicine
      Boston, MA, United States
    • Tufts Medical Center
      • Division of Nephrology
      Boston, Massachusetts, United States