Michael Zappitelli

McGill University Health Centre, Montréal, Quebec, Canada

Are you Michael Zappitelli?

Claim your profile

Publications (60)243.65 Total impact

  • Kelly Benisty, Michael Zappitelli
    [Show abstract] [Hide abstract]
    ABSTRACT: Glomerular filtration rate (GFR) is the most important measure of kidney function used for chronic kidney disease screening, dosing medications, and following kidney disease progression. Gold standard GFR measurement is inulin clearance; however, GFR is most commonly measured by plasma disappearance of exogenously administered substances. Recent improvements in GFR measurement have been made, and understanding the limitations of different methods is important. In clinical practice, GFR is typically estimated using equations. Most equations are based on serum creatinine, but other markers, in particular Cystatin C have been investigated as well. In the last 10 years, several GFR estimation equations have been published, each associated with strengths and limitations. Understanding how these equations were derived and considering individual patient characteristics is helpful to determine what equations are most likely to estimate GFR most accurately. This review will address each of these issues, highlighting recent literature and focusing on clinical application.
    Current Pediatrics Reports. 12/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Early acute kidney injury (AKI) diagnosis is needed to pursue treatment trials. We evaluated cystatin C (CysC) as an early biomarker of serum creatinine (SCr)-AKI and an alternative to define AKI. We studied 160 non-cardiac children in the intensive care unit (ICU). We measured daily CysC and SCr. AKI was staged by KDIGO (Kidney Disease: Improving Global Outcomes) guidelines using SCr and CysC (CysC-AKI). We calculated area under the curve (AUC) for (1) neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1) and urine CysC to diagnose SCr- and CysC-AKI; and (2) for CysC to diagnose SCr-AKI. We evaluated AKI associations with length of stay and ventilation duration. We found that 44 % of patients developed SCr-AKI; 32 % developed CysC-AKI. Early ICU NGAL was most diagnostic of CysC-AKI (AUC 0.69, 95% CI 0.54-0.84); IL-18 was most diagnostic for SCr-AKI (AUC 0.69 95% CI 0.55-0.82). Combining SCr and CysC-AKI definition led to higher biomarker diagnostic AUC's. CysC-AKI was not more strongly associated with clinical outcomes. Early ICU CysC predicted SCr-AKI development (AUC 0.70, 95 % CI 0.53-0.89). Our findings do not support replacing SCr by CysC to define AKI. Early ICU CysC predicts SCr-AKI development and combined SCr-CysC-AKI definition leads to stronger AKI biomarker associations.
    Pediatric nephrology (Berlin, Germany). 12/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: The relative influence of facilities and regions on the timing of dialysis initiation remains unknown. The purpose of the study is to determine the variation in eGFR at dialysis initiation across dialysis facilities and geographic regions in Canada after accounting for patient-level factors (case mix).
    Clinical journal of the American Society of Nephrology : CJASN. 09/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: This paper proposes a new statistical approach for predicting postoperative morbidity such as intensive care unit length of stay and number of complications after cardiac surgery in children. In a recent multi-center study sponsored by the National Institutes of Health, 311 children undergoing cardiac surgery were enrolled. Morbidity data are count data in which the observations take only nonnegative integer values. Often, the number of zeros in the sample cannot be accommodated properly by a simple model, thus requiring a more complex model such as the zero-inflated Poisson regression model. We are interested in identifying important risk factors for postoperative morbidity among many candidate predictors. There is only limited methodological work on variable selection for the zero-inflated regression models. In this paper, we consider regularized zero-inflated Poisson models through penalized likelihood function and develop a new expectation–maximization algorithm for numerical optimization. Simulation studies show that the proposed method has better performance than some competing methods. Using the proposed methods, we analyzed the postoperative morbidity, which improved the model fitting and identified important clinical and biomarker risk factors. Copyright © 2014 John Wiley & Sons, Ltd.
    Statistics in Medicine 09/2014; · 2.04 Impact Factor
  • [Show abstract] [Hide abstract]
    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; · 6.12 Impact Factor
  • Source
    Canadian Journal of Kidney Health and Disease. 07/2014; 1:17.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Physicians' perceptions and opinions may influence when to initiate dialysis. Objective: To examine providers' perspectives and opinions regarding the timing of dialysis initiation.
    The Canadian Journal of Kidney Health and Disease. 05/2014;
  • [Show abstract] [Hide abstract]
    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
  • [Show abstract] [Hide abstract]
    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
  • Source
    [Show abstract] [Hide abstract]
    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.
  • [Show abstract] [Hide abstract]
    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
  • Canadian Journal of Kidney Health and Disease. 01/2014; 1(1):2.
  • [Show abstract] [Hide abstract]
    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.
  • Canadian Journal of Kidney Health and Disease. 01/2014; 1(1):3.
  • Source
    [Show abstract] [Hide abstract]
    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
  • Source
    [Show abstract] [Hide abstract]
    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
  • [Show abstract] [Hide abstract]
    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
  • Source
    American Journal of Kidney Diseases 03/2013; · 5.29 Impact Factor
  • Sean M Bagshaw, Michael Zappitelli, Lakhmir S Chawla
    [Show abstract] [Hide abstract]
    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
  • [Show abstract] [Hide abstract]
    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

Publication Stats

2k Citations
243.65 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