• Matsell, Douglas

    Titles

    Investigator, BC Children's Hospital
    Professor, Department of Pediatrics, University of British Columbia
    Head, Division of Nephrology, BC Children’s Hospital

    Degrees / Designations

    BSc, MDCM

    Primary Area of Research
    Healthy Starts
    Secondary Area(s) of Research
    Phone
    604-875-2272
    Fax
    604-875-3649
    Lab Phone
    604-875-5097
    Mailing Address

    BC Children's Hospital
    Room K4-150
    4480 Oak Street
    Vancouver, BC V6H 3V4

    Affiliate Websites
    Research Areas
    • Congenital urinary tract obstruction
    • Outcomes of childhood kidney injury
    • Clinical pathway development
    Summary

     

    My research focuses on defining both the mechanisms of abnormal kidney development that result in common pediatric kidney diseases such as small kidneys and renal hypodysplasia and the specific characteristics that impact on long-term outcomes.

    My areas of special interest and accomplishments include:

    Congenital urinary tract obstruction

    Urinary tract obstruction during fetal life is the most important cause of abnormal kidney development and kidney failure in children. The goal of my work has been to apply knowledge of normal and abnormal kidney development to improve the care and outcome of these children. My earlier work focused on the role of the insulin-like growth factors in mammalian nephrogenesis. Our studies demonstrated that fetal urinary tract obstruction affects the initial induction of kidney development, due to an alteration in the expression of key genes necessary for kidney maturation. In collaboration with scientists at the University of California, Davis and the California National Primate Research Center we also developed a preclinical model of human congenital urinary tract obstruction. This model is a powerful tool to explore some of the more practical issues of in utero therapy as well as providing an accurate representation of the pathogenesis of this important pediatric disease. Using a variety of other models, including transgenic mice and transformed kidney cell lines we have studied the effects of urinary tract obstruction on kidney cell biology. Kidney cells undergo extensive changes with fetal and postnatal urinary tract obstruction, including a change in phenotype that serves to attenuate injury. Our work has advanced the knowledge in this area and has implicated the kidney collecting duct as an important player in kidney injury and repair.

    Outcomes of childhood kidney injury

    Injury to the kidney as it develops in utero (developmental kidney injury) or as a result of postnatal disease (acute kidney injury) has life long consequences and impacts on long-term kidney prognosis. We have shown that the severity of in utero injury, in children born with either small kidneys or with congenital urinary tract obstruction, predicts the ultimate long-term outcome and the risk of developing end stage kidney disease requiring dialysis and transplantation. The extent of this injury is reflected in urinary biomarkers of kidney injury that associate with outcome and may have value in selecting children who may benefit from early treatment.

    With regards to postnatal kidney injury, in Walkerton, Ontario, contamination of the municipal drinking water with E. coli resulted in wide spread illness, including severe hemorrhagic colitis and hemolytic uremic syndrome (HUS), an important cause of acute kidney injury in children. We conducted a 7-year observational cohort health study on the long-term outcomes of children and adults exposed to the E. coli contaminated water. This work led to a number of important insights into the long-term complications of E. coli disease in humans, including establishing the link between AKI and the risk of developing chronic kidney disease in children with HUS, and resulted in a number of seminal publications in this area of study.

    Clinical pathway development

    The Division of Nephrology’s Clinical Pathway Development (CPD) Team was established to help transform established best practices and innovative research findings into standardized clinical care and improved patient outcomes. More specifically, the CPD: (1) critically reviews available evidence; (2) established consensus and makes evidence based-recommendations for practice in the form of clinical pathways; (3) develops the necessary tools and resources needed to support the effective education, dissemination, and evaluation of the pathways; (4) audits end-user fidelity to and satisfaction with the pathways; (5) iteratively re-evaluates and updates the pathways as new evidence becomes available, and; (6) supports ongoing research initiatives in the fields of clinical pathway theory and pediatric nephrology. The work of the CPD Team has supported ancillary research projects within clinical pathway theory. The scope of the CPD Team includes not only the Childhood Nephrotic Syndrome Pathway, but also the development of unique pathways for the other renal conditions typically seen within the scope of practice, including hypertension, childhood glomerulonephritis, and congenital kidney anomalies diagnosed in the antenatal period.

    Current Projects
    Selected Publications

    Matsell DG, Bennett T, Armstrong RA, Goodyer P, Goodyer C, Han VK.  Insulin-like growth factor (IGF) and IGF binding protein gene expression in multicystic renal dysplasia.  Journal of the American Society of Nephrology 8:85-94, 1997.

    Tarantal AF, Han VK, Cochrum KC, Mok A, daSilva M, Matsell DG.  Fetal rhesus monkey model of obstructive renal dysplasia.  Kidney International 59:446-56, 2001.

    Matsell DG, Mok A, Tarantal AF.  Altered primate glomerular development due to in utero urinary tract obstruction.  Kidney International 61:1263-9, 2002.

    Garg AX, Suri R, Barrowman N, Rehman F, Matsell D, Rosas-Arellano P, Salvadori M, Haynes RB, Clark WF. The long-term renal prognosis of diarrhea associated hemolytic uremic syndrome: A systematic review, meta-analysis and meta-regression analysis of 3476 children from 49 studies. Journal of the American Medical Association 290:1360-70, 2003.

    Bridgewater DJ, Ho J, Sauro V, Matsell DG: Insulin-like growth factors inhibit podocyte apoptosis through the PI3 kinase pathway. Kidney International 67:1308-1314, 2005.

    Garg AX, Clark WF, Salvadori M, Thiessen-Philbrook HR, Matsell D: Absence of renal sequelae after childhood E. coli O157:H7 gastroenteritis. Kidney International 70:807-12, 2006.

    Butt MJ, Tarantal AF, Matsell DG: Collecting duct epithelial mesenchymal transition in a non-human primate model of fetal obstructive nephropathy. Kidney International 72: 936-944, 2007

    Garg AX, Okell JM, Thiessen-Philbrook HR, Salvadori M, Suri RS, Moist L, Filler G, Matsell D, Clark WF: Albuminuria and estimated GFR 5 years after Escherichia coli O157 hemolytic uremic syndrome: an update. American Journal of Kidney Diseases 51:435-44, 2008

    Hiatt MJ, Ivanova L, Toran N, Tarantal AF, Matsell DG. Remodeling of the fetal collecting duct epithelium. American Journal of Pathology 176: 630-637, 2010.

    Trnka P, Ivanova L, Hiatt MJ, Milner R, Matsell DG. Urinary biomarkers in obstructive nephropathy. Clinical Journal of the American Society of Nephrology 7:1567-1575, 2012.

    Trnka P, Hiatt MJ, Tarantal AF, Matsell DG. Congenital urinary tract obstruction: defining markers of developmental kidney injury. Pediatric Research 72:446-454, 2012.

    Hiatt, MJ, Matsell DG. Urinary tract obstruction in the mouse- The kinetics of distal nephron injury. Laboratory Investigation 93:1012-23, 2013.

    Matsell DG, Cojocaru D, Matsell EW, Eddy AA. The impact of small kidneys. Pediatric Nephrology 30:1501-9, 2015

    Matsell DG, Yu S, Morrison SJ. Antenatal determinants of long-term kidney outcome in boys with posterior urethral valves. Fetal Diagnosis and Therapy 39: 214-221, 2016.

    Grants
    Honours & Awards

    Research Group Members
    • Dr. Cherry Mammen
    • Marisa Catapang- Research Co-ordinator
    • Nonnie Polderman
    • Dr. Rob Humphreys