Michael Zappitelli

McGill University Health Centre, Montréal, Quebec, Canada

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Publications (53)235.48 Total impact

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    ABSTRACT: Fluid overload is associated with poor PICU outcomes in different populations. Little is known about fluid overload in children undergoing cardiac surgery. We described fluid overload after cardiac surgery, identified risk factors of worse fluid overload and also determined if fluid overload predicts longer length of PICU stay, prolonged mechanical ventilation (length of ventilation) and worse lung function as estimated by the oxygenation index.
    Critical care medicine. 07/2014;
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    Canadian Journal of Kidney Health and Disease. 07/2014; 1:17.
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    ABSTRACT: Pediatric cardiac surgery may lead to poor outcomes such as acute kidney injury (AKI) and prolonged hospital length of stay (LOS). Plasma and urine biomarkers may help with early identification and prediction of these adverse clinical outcomes. In a recent multi-center study, 311 children undergoing cardiac surgery were enrolled to evaluate multiple biomarkers for diagnosis and prognosis of AKI and other clinical outcomes. LOS is often analyzed as count data, thus Poisson regression and negative binomial (NB) regression are common choices for developing predictive models. With many correlated prognostic factors and biomarkers, variable selection is an important step. The present paper proposes new variable selection methods for Poisson and NB regression. We evaluated regularized regression through penalized likelihood function. We first extend the elastic net (Enet) Poisson to two penalized Poisson regression: Mnet, a combination of minimax concave and ridge penalties; and Snet, a combination of smoothly clipped absolute deviation (SCAD) and ridge penalties. Furthermore, we extend the above methods to the penalized NB regression. For the Enet, Mnet, and Snet penalties (EMSnet), we develop a unified algorithm to estimate the parameters and conduct variable selection simultaneously. Simulation studies show that the proposed methods have advantages with highly correlated predictors, against some of the competing methods. Applying the proposed methods to the aforementioned data, it is discovered that early postoperative urine biomarkers including NGAL, IL18, and KIM-1 independently predict LOS, after adjusting for risk and biomarker variables.
    Statistical Methods in Medical Research 04/2014; · 2.36 Impact Factor
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    ABSTRACT: Acute kidney injury (AKI) after pediatric cardiac operations is associated with poor outcomes and is difficult to predict. We conducted a prospective study to evaluate whether preoperative brain natriuretic peptide (BNP) levels predict postoperative AKI among children undergoing cardiac operations. This was a three-center, prospective study (2007-2009) of 277 children undergoing cardiac operations (n = 121, aged <2 years) with available preoperative BNP values. Preoperative BNP was measured and categorized into tertiles. The performance of BNP was evaluated alone and in combination with clinical factors. AKI was defined as doubling of serum creatinine or need for acute dialysis. Postoperative AKI occurred in 165 children (60%), with 118 cases (43%) being mild and 47 cases (17%) severe. Preoperative BNP was not associated with increased risk of mild or severe postoperative AKI and did not significantly improve AKI risk prediction when added to clinical models. Preoperative BNP was, however, associated with several clinical outcomes, including length of stay and mechanical ventilation. The results were similar when the analysis was repeated in the subset of children younger than 2 years of age or when the association of postoperative BNP and AKI was evaluated. Preoperative BNP levels did not predict postoperative AKI in this cohort of children undergoing cardiac operations. Both preoperative and postoperative BNP levels are associated with postoperative outcomes. Clinical Trial Registration at Clinicaltrials.gov as NCT00774137.
    The Annals of thoracic surgery 04/2014; · 3.45 Impact Factor
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    ABSTRACT: Derivation and validation of the renal angina index to improve the prediction of acute kidney injury in critically ill children Reliable prediction of severe acute kidney injury (AKI) has the potential to optimize treatment. Here we operationalized the empiric concept of renal angina with a renal angina index (RAI) and determined the predictive performance of RAI. This was assessed on admission to the pediatric intensive care unit, for subsequent severe AKI (over 200% rise in serum creatinine) 72 h later (Day-3 AKI). In a multicenter four cohort appraisal (one derivation and three validation), incidence rates for a Day 0 RAI of 8 or more were 15–68% and Day-3 AKI was 13–21%. In all cohorts, Day-3 AKI rates were higher in patients with an RAI of 8 or more with the area under the curve of RAI for predicting Day-3 AKI of 0.74–0.81. An RAI under 8 had high negative predictive values (92–99%) for Day-3 AKI. RAI outperformed traditional markers of pediatric severity of illness (Pediatric Risk of Mortality-II) and AKI risk factors alone for prediction of Day-3 AKI. Additionally, the RAI outperformed all KDIGO stages for prediction of Day-3 AKI. Thus, we operationalized the renal angina concept by deriving and validating the RAI for prediction of subsequent severe AKI. The RAI provides a clinically feasible and applicable methodology to identify critically ill children at risk of severe AKI lasting beyond functional injury. The RAI may potentially reduce capricious AKI biomarker use by identifying patients in whom further testing would be most beneficial.
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    ABSTRACT: The KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice guideline for management of glomerulonephritis was recently released. The Canadian Society of Nephrology convened a working group to review the recommendations and comment on their relevancy and applicability to the Canadian context. A subgroup of pediatric nephrologists reviewed the guideline statements for management of childhood nephrotic syndrome and agreed with most of the guideline statements developed by KDIGO. This commentary highlights areas in which there is lack of evidence and areas in need of translation of evidence into clinical practice. Areas of controversy or uncertainty, including the length of corticosteroid therapy for the initial presentation and relapses, definitions of steroid resistance, and choice of second-line agents, are discussed in more detail. Existing practice variation is also addressed.
    American Journal of Kidney Diseases 01/2014; · 5.29 Impact Factor
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    ABSTRACT: Peritoneal dialysis is associated with similar survival and similar improvement in quality of life and is less costly compared with in-centre hemodialysis. We examined facility and geographic variation in the use of peritoneal dialysis in Canada.
    CMAJ open. 01/2014; 2(1):E36-44.
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    ABSTRACT: Reliable prediction of severe acute kidney injury (AKI) has the potential to optimize treatment. Here we operationalized the empiric concept of renal angina with a renal angina index (RAI) and determined the predictive performance of RAI. This was assessed on admission to the pediatric intensive care unit, for subsequent severe AKI (over 200% rise in serum creatinine) 72 h later (Day-3 AKI). In a multicenter four cohort appraisal (one derivation and three validation), incidence rates for a Day 0 RAI of 8 or more were 15-68% and Day-3 AKI was 13-21%. In all cohorts, Day-3 AKI rates were higher in patients with an RAI of 8 or more with the area under the curve of RAI for predicting Day-3 AKI of 0.74-0.81. An RAI under 8 had high negative predictive values (92-99%) for Day-3 AKI. RAI outperformed traditional markers of pediatric severity of illness (Pediatric Risk of Mortality-II) and AKI risk factors alone for prediction of Day-3 AKI. Additionally, the RAI outperformed all KDIGO stages for prediction of Day-3 AKI. Thus, we operationalized the renal angina concept by deriving and validating the RAI for prediction of subsequent severe AKI. The RAI provides a clinically feasible and applicable methodology to identify critically ill children at risk of severe AKI lasting beyond functional injury. The RAI may potentially reduce capricious AKI biomarker use by identifying patients in whom further testing would be most beneficial.Kidney International advance online publication, 18 September 2013; doi:10.1038/ki.2013.349.
    Kidney International 09/2013; · 8.52 Impact Factor
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    ABSTRACT: Practice variation is common for nephrotic syndrome (NS) treatment. A cross-sectional, web-based survey on NS treatment was administered to 58 Canadian pediatric nephrologists with the aim to document existing practice variation and compare practice with the recommendations of the Kidney Disease Improving Global Outcomes Clinical Practice Guideline for NS. Of the 58 nephrologists asked to participate in the survey, 40 (69 %) responded. Among these, 62 % prescribed initial daily glucocorticoid (GC) therapy for 6 weeks, 26 % for 4 weeks by 26 %, and 10 % prescribed 'other'. Alternate-day GC was continued for 6 weeks by 63 % of respondents and for >6 and <6 weeks by 32 and 6 %, respectively. For biopsy-confirmed minimal change disease, 65 and 46 % of respondents chose oral cyclophosphamide for frequently relapsing and steroid-dependent phenotypes, respectively; calcineurin inhibitors or mycophenolate were the second most popular choices. Kidney biopsy was 'always' performed by 16, 39, and 97 % of respondents for frequently relapsing, steroid-dependent, and steroid-resistant patients, respectively. Rituximab had been administered by 60 % of respondents; 22, 56, and 72 % reported that they would consider rituximab for frequently relapsing, steroid-dependent, and steroid-resistant patients, respectively. Most notable differences between practice and Guideline recommendations were first presentation GC duration, GC-sparing agent choices in frequently relapsing and steroid-dependent patients, and biopsy practices. There is substantial Canadian practice variation in NS treatment. Assessment of factors driving variation and strategies to implement Guideline recommendations are needed.
    Pediatric Nephrology 08/2013; · 2.94 Impact Factor
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    ABSTRACT: BACKGROUND AND OBJECTIVES: AKI is common and novel biomarkers may help provide earlier diagnosis and prognosis of AKI in the postoperative period. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a prospective, multicenter cohort study involving 1219 adults and 311 children consecutively enrolled at eight academic medical centers. Performance of two urine biomarkers, kidney injury molecule-1 (KIM-1) and liver fatty acid-binding protein (L-FABP), alone or in combination with other injury biomarkers during the perioperative period was evaluated. AKI was defined as doubling of serum creatinine or need for acute dialysis. RESULTS: KIM-1 peaked 2 days after surgery in adults and 1 day after surgery in children, whereas L-FABP peaked within 6 hours after surgery in both age groups. In multivariable analyses, the highest quintile of the first postoperative KIM-1 level was associated with AKI compared with the lowest quintile in adults, whereas the first postoperative L-FABP was not associated with AKI. Both KIM-1 and L-FABP were not significantly associated with AKI in adults or children after adjusting for other kidney injury biomarkers (neutrophil gelatinase-associated lipocalin and IL-18). The highest area under the curves achievable for discrimination for AKI were 0.78 in adults using urine KIM-1 from 6 to 12 hours, urine IL-18 from day 2, and plasma neutrophil gelatinase-associated lipocalin from day 2 and 0.78 in children using urine IL-18 from 0 to 6 hours and urine L-FABP from day 2. CONCLUSIONS: Postoperative elevations of KIM-1 associate with AKI and adverse outcmes in adults but were not independent of other AKI biomarkers. A panel of multiple biomarkers provided moderate discrimination for AKI.
    Clinical Journal of the American Society of Nephrology 04/2013; · 5.07 Impact Factor
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    American Journal of Kidney Diseases 03/2013; · 5.29 Impact Factor
  • Sean M Bagshaw, Michael Zappitelli, Lakhmir S Chawla
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    ABSTRACT: The clinical integration of novel biomarkers specific for kidney damage have brought the promise of a new era in our understanding of and care for those patients susceptible to or suffering from acute kidney injury (AKI) and has consistently been viewed as a top research priority. The expectations are clearly high; however, as with many promises, there are often accompanying challenges and a degree of pessimism. In this issue of Nephrology Dialysis Transplantation, Van Massenhove et al. offer their 'Devil's advocacy' view in a narrative review focused on the state of novel biomarkers for the diagnosis of AKI. While AKI biomarkers would appear to clearly have value, in particular for informing on the pathobiology of AKI, the question of how to optimally utilize them remains unresolved. Their performance is influenced by patient case-mix, comorbid illness, inciting kidney injury event, timing of measurement, the specific biomarker being investigated and the selected thresholds for diagnosis, not to mention factors related to study design, methodology and how to best translate to the bedside. The challenge as the field moves forward is to fully and appropriately utilize and interpret information from AKI biomarker studies in order to understand and evaluate how to optimally utilize these novel biomarkers (or panel of biomarkers) in the susceptible patient across a spectrum of clinical settings to improve and better inform our clinical decision-making.
    Nephrology Dialysis Transplantation 02/2013; 28(2):235-8. · 3.37 Impact Factor
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    ABSTRACT: BACKGROUND: Acute kidney injury (AKI) is common after cardiac surgery and is associated with adverse patient outcomes. Urinary cystatin C (CysC) level is a biomarker of proximal tubule function and may increase earlier in AKI than serum creatinine level. STUDY DESIGN: Prospective cohort study. SETTINGS & PARTICIPANTS: The TRIBE AKI (Translational Research Investigating Biomarker Endpoints in AKI) Consortium prospectively enrolled 1,203 adults and 299 children and adolescents at 8 institutions in 2007-2009. INDEX TEST: Urinary CysC (in milligrams per liter) within the first 12 hours after surgery. OUTCOME: Serum creatinine-based AKI was defined as AKI Network stage 1 (mild AKI) and doubling of serum creatinine from the preoperative value or need for dialysis during hospitalization (severe AKI). OTHER MEASUREMENTS: Analyses were adjusted for characteristics used clinically for AKI risk stratification, including age, sex, race, estimated glomerular filtration rate, diabetes, hypertension, heart failure, nonelective surgery, cardiac catheterization within 72 hours, type of surgery, myocardial infarction, and cardiopulmonary bypass time longer than 120 minutes. RESULTS: Urinary CysC level measured in the early postoperative period (0-6 and 6-12 hours postoperatively) correlated with both mild and severe AKI in adults and children. However, after analyses were adjusted for other factors, the effect was attenuated for both forms of AKI in both cohorts. LIMITATIONS: Limited numbers of patients with severe AKI and in-hospital dialysis treatment. CONCLUSIONS: Urinary CysC values are not associated significantly with the development of AKI after cardiac surgery in adults and children.
    American Journal of Kidney Diseases 01/2013; · 5.29 Impact Factor
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    Michael Zappitelli, David T Selewski, David J Askenazi
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    ABSTRACT: Nephrotoxic medication use is common in neonates. In older children, the use of nephrotoxic medication is known to be one of the most common causes of acute kidney injury (AKI) and to be associated with increased morbidity. In critically ill neonates, AKI significantly complicates fluid and electrolyte management and may be an important risk factor for mortality. Better understanding of methods to avoid and detect the presence of nephrotoxicity may lead to more intelligent use of these medications, which could ultimately reduce the incidence of AKI and improve outcomes. In this work, we summarize why neonates are predisposed to drug nephrotoxicity, review the mechanisms and clinical picture of the most common nephrotoxic medications used in neonates (aminoglycosides, vancomycin, amphotericin B, acyclovir, nonsteroidal anti-inflammatory drugs, and radiocontrast agents), and discuss the roles of angiotensin-converting enzyme inhibitors and diuretics in nephrotoxicity. We also suggest ways to avoid and reduce the incidence and complications of neonatal nephrotoxicity.
    NeoReviews 12/2012; 13(7):e421-427.
  • Michael Zappitelli
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    ABSTRACT: Early acute kidney injury (AKI) diagnosis in critically ill children has been an important recent research focus because of the known association of AKI with poor outcomes and the requirement of early intervention to mitigate negative effects of AKI. In children having surgery, the preoperative period offers a unique opportunity to predict postoperative acute kidney injury (AKI), well before AKI occurs. Pediatric AKI epidemiologic studies have begun to identify which preoperative factors may predict development of postoperative cardiac surgery. Using these clinical risk factors, it may be possible to derive preoperative clinical risk scores and improve upon our ability to risk-stratify children into AKI treatment trials, pre-emptively provide conservative renal injury prevention strategies, and ultimately improve patient outcomes. Developing risk scores requires rigorous methodology and validation before widespread use. There is little information currently on the use of preoperative biological or physiological biomarkers to predict postoperative AKI, representing an important area of future research. This review will provide an overview of methodology of preoperative risk score development, discuss pediatric-specific issues around deriving such risk scores, including the combination of preoperative clinical and biologic biomarkers for AKI prediction, and suggest future research avenues.
    Pediatric Nephrology 11/2012; · 2.94 Impact Factor
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    ABSTRACT: BACKGROUND AND OBJECTIVES: This study determined if preoperative and postoperative urine albumin/creatinine ratios (ACRs) predict postoperative AKI in children undergoing cardiac surgery (CS). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a three-center, prospective study (2007-2009) of 294 children undergoing CS (n=145 aged <2 years). Urine ACR was measured preoperatively and 0-6 hours after intensive care unit arrival. AKI outcomes were based on the Acute Kidney Injury Network serum creatinine (SCr) criteria (stage 1 AKI, ≥50% or 0.3 mg/dl SCr rise from baseline; and stage 2 or worse AKI, ≥SCr doubling or dialysis). AKI was predicted using preoperative and postoperative ACRs and postoperative ACR performance was compared with other AKI biomarkers. RESULTS: Preoperative ACR did not predict AKI in younger or older children. In children aged <2 years, first postoperative ACR ≥908 mg/g (103 mg/mmol) predicted stage 2 AKI development (adjusted relative risk, 3.4; 95% confidence interval, 1.2-9.4). In children aged ≥2 years, postoperative ACR ≥169 mg/g (19.1 mg/mmol) predicted stage 1 AKI (adjusted relative risk, 2.1; 95% confidence interval, 1.1-4.1). In children aged ≥2 years, first postoperative ACR improved AKI prediction from other biomarker and clinical prediction models, estimated by net reclassification improvement (P≤0.03), but only when serum cystatin C was also included in the model. CONCLUSIONS: Postoperative ACR is a readily available early diagnostic test for AKI after pediatric CS that performs similarly to other AKI biomarkers; however, its use is enhanced in children aged ≥2 years and in combination with serum cystatin C.
    Clinical Journal of the American Society of Nephrology 08/2012; · 5.07 Impact Factor
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    ABSTRACT: OBJECTIVE: To characterize the epidemiology of and identify risk factors for neonatal cardiac surgery-associated acute kidney injury (CS-AKI) and determine its impact on clinical outcomes. STUDY DESIGN: Using secondary analysis of data from an ongoing multiprovincial prospective cohort study, we studied 264 neonates undergoing complex cardiac repair. CS-AKI was defined based on the Acute Kidney Injury Network (AKIN) definition. We used regression modeling and survival analysis (adjusting for covariates) to evaluate associations. RESULTS: CS-AKI occurred in 64% of the neonates in our study cohort. Lower age, longer cardiopulmonary bypass time, hypothermic circulatory arrest, type of repair, lower preoperative serum creatinine (SCr) level, lower gestational age, and preoperative ventilation were independent risk factors for developing CS-AKI. Neonates with CS-AKI had longer times to extubation, intensive care discharge, and hospital discharge, after adjusting for covariates. Mortality was significantly increased in neonates with AKIN stage 2 or higher CS-AKI. The neonates with CS-AKI had a lower z-score for height at 2-year follow-up and were seen by more specialists. CONCLUSION: Neonatal CS-AKI is common and independently predicts important clinical outcomes, including mortality. Many risk factors are similar to those in older children, but some are unique to neonates. The observation that lower baseline SCr predicts CS-AKI merits further study. The AKIN definition, based on preoperative SCr value, is a reasonable method for defining CS-AKI in neonates. Many previous studies of CS-AKI have excluded neonates; we suggest that future intervention studies on approaches to reducing CS-AKI incidence and improving outcomes should include neonates.
    The Journal of pediatrics 08/2012; · 4.02 Impact Factor
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    ABSTRACT: Acute kidney injury and fluid overload (FO) are associated with increased mortality in critically ill patients, including the subset supported with extracorporeal membrane oxygenation (ECMO). The indication for and method of application of renal support therapy (RST) during ECMO is largely unknown beyond single-center experiences. The current study uses a survey design to document practice variation regarding RST, including indication, method of interface with the ECMO circuit, and prescribing practices. Sixty-five international ECMO centers (31%) responded to an online electronic survey regarding RST during ECMO. Nearly a quarter of centers (23%) reported using no RST during ECMO. Among those using the therapy, the predominant mode of therapy applied was convection and included slow continuous ultrafiltration and continuous venovenous hemofiltration. The predominant indication for RST was the treatment (43%) or prevention (16%) of FO. Nephrology rather than critical care medicine is reported as the prescribing service in a majority of centers with a significant difference between US centers and non-US centers. The results of this study identify a wide variation in practice regarding RST during ECMO that will offer multiple important avenues for further research by this group and others regarding the interface of RST and ECMO.
    ASAIO journal (American Society for Artificial Internal Organs: 1992) 05/2012; 58(4):407-14. · 1.39 Impact Factor
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    ABSTRACT: Extracorporeal membrane oxygenation (ECMO) is a lifesaving procedure used in neonates, children, and adults with severe, reversible, cardiopulmonary failure. On the basis of single-center studies, the incidence of AKI occurs in 70%-85% of ECMO patients. Those with AKI and those who require renal replacement therapy (RRT) are at high risk for mortality, independent of potentially confounding variables. Fluid overload is common in ECMO patients, and is one of the main indications for RRT. RRT to maintain fluid balance and metabolic control is common in some but not all centers. RRT on ECMO can be performed via an in-line hemofilter or by incorporating a standard continuous renal replacement machine into the ECMO circuit. Both of these methods require specific technical considerations to provide safe and effective RRT. This review summarizes available epidemiologic data and how they apply to our understanding of AKI pathophysiology during ECMO, identifies indications for RRT while on ECMO, reviews technical elements for RRT application in the setting of ECMO, and finally identifies specific research-focused questions that need to be addressed to improve outcomes in this at-risk population.
    Clinical Journal of the American Society of Nephrology 04/2012; 7(8):1328-36. · 5.07 Impact Factor
  • Michael Zappitelli, Chirag R Parikh
    Kidney International 03/2012; 81(6):598-9. · 8.52 Impact Factor

Publication Stats

1k Citations
235.48 Total Impact Points

Institutions

  • 2004–2014
    • McGill University Health Centre
      Montréal, Quebec, Canada
    • McGill University
      • • Department of Pediatrics
      • • Division of Nephrology
      Montréal, Quebec, Canada
  • 2013
    • University of Chicago
      • Section of Nephrology
      Chicago, IL, United States
    • Cincinnati Children's Hospital Medical Center
      Cincinnati, Ohio, United States
  • 2012
    • Vanderbilt University
      • Department of Pediatrics
      Nashville, MI, United States
  • 2011
    • Yale University
      • Department of Pediatrics
      New Haven, CT, United States
  • 2010
    • Stanford University
      • Department of Pediatrics
      Stanford, CA, United States
  • 2007–2010
    • Baylor College of Medicine
      • Department of Pediatrics
      Houston, Texas, United States
    • Texas Children's Hospital
      Houston, Texas, United States