Denis F Geary

SickKids, Toronto, Ontario, Canada

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Publications (105)

  • [Show abstract] [Hide abstract] ABSTRACT: Use of hypotonic intravenous fluids for maintenance requirements is associated with increased risk of hyponatremia that results in morbidity and mortality in children. Clinical trial data comparing isotonic and hypotonic maintenance fluids in nonsurgical hospitalized pediatric patients outside intensive care units are lacking. To compare isotonic (sodium chloride, 0.9%, and dextrose, 5%) with hypotonic (sodium chloride, 0.45%, and dextrose, 5%) intravenous maintenance fluids in a hospitalized general pediatric population. In this double-blind randomized clinical trial,we recruited 110 children admitted to a general pediatric unit of a tertiary care children's hospital from March 1, 2008, through August 31, 2012 (age range, 1 month to 18 years), with normal baseline serum sodium levels who were anticipated to require intravenous maintenance fluids for 48 hours or longer (intent-to-treat analyses). Children with diagnoses that required specific fluid tonicity and volumes were excluded. Patients were randomized to receive isotonic or hypotonic intravenous fluid at maintenance rates for 48 hours. The primary outcome was mean serum sodium level at 48 hours. The secondary outcomes were mean sodium level at 24 hours, hyponatremia and hypernatremia, weight gain, hypertension, and edema. Confounding variables were included in multiple regression models. Post hoc analyses included change from baseline sodium level at 24 and 48 hours and subgroup analysis of children with primary respiratory diagnosis. Of 110 enrolled patients, 54 received isotonic fluids and 56 received hypotonic fluids. The mean (SD) sodium level at 48 hours was 139.9 (2.7) mEq/L in the isotonic group and 139.6 (2.6) mEq/L in the hypotonic group (95% CI of the difference, -0.94 to 1.74 mEq/L; P = .60). Two patients in the hypotonic group developed hyponatremia, 1 in each group developed hypernatremia, 2 in each group developed hypertension, and 2 in the isotonic group developed edema. Mean (SD) change from baseline to 48-hour sodium level was +1.3 (2.9) vs -0.12 (2.8) mEq/L, respectively (absolute difference, 1.4 mEq/L; 95% CI of the difference, -0.01 to 2.8 mEq/L; P = .05). Our study results support the notion that isotonic maintenance fluid administration is safe in general pediatric patients and may result in fewer cases of hyponatremia. Identifier: NCT00632775.
    Article · Mar 2015 · JAMA Pediatrics
  • [Show abstract] [Hide abstract] ABSTRACT: Background and objectives: Chronic kidney disease is a persistent chronic health condition commonly seen in pediatric nephrology programs. Our study aims to evaluate the sensitivity of the Patient Reported Outcomes Measurement Information System (PROMIS) pediatric instrument to indicators of disease severity and activity in pediatric chronic kidney disease. Methods: This cross sectional study included 233 children 8-17 years old, with chronic kidney disease from 16 participating institutions in North America. Disease activity indicators, including hospitalization in the previous 6 months, edema, and number of medications consumed daily, as well as disease severity indicators of kidney function and coexisting medical conditions were captured. PROMIS domains, including depression, anxiety, social-peer relationships, pain interference, fatigue, mobility, and upper extremity function, were administered via web-based questionnaires. Absolute effect sizes (AES) were generated to demonstrate the impact of disease on domain scores. Four children were excluded because of missing glomerular filtration rate (GFR) estimations. Results: Of the 229 children included in the final analysis, 221 completed the entire PROMIS questionnaire. Unadjusted PROMIS domains were responsive to chronic kidney disease activity indicators and number of coexisting conditions. PROMIS domain scores were worse in the presence of recent hospitalizations (depression AES 0.33, anxiety AES 0.42, pain interference AES 0.46, fatigue AES 0.50, mobility AES 0.49), edema (depression AES 0.50, anxiety AES 0.60, pain interference AES 0.77, mobility AES 0.54) and coexisting medical conditions (social peer-relationships AES 0.66, fatigue AES 0.83, mobility AES 0.60, upper extremity function AES 0.48). Conclusions: The PROMIS pediatric domains of depression, anxiety, social-peer relationships, pain interference, and mobility were sensitive to the clinical status of children with chronic kidney disease in this multi-center cross sectional study. We demonstrated that a number of important clinical characteristics including recent history of hospitalization and edema, affected patient perceptions of depression, anxiety, pain interference, fatigue and mobility. The PROMIS instruments provide a potentially valuable tool to study the impact of chronic kidney disease. Additional studies will be required to assess responsiveness in PROMIS score with changes in disease status over time.
    Article · Jun 2014 · Pediatric Nephrology
  • Deepa H. Chand · Denis Geary · Hiren Patel · [...] · Rudolph P. Valentini
    [Show abstract] [Hide abstract] ABSTRACT: There has been recent emphasis on increased arteriovenous fistula (AVF) use and decreased central venous catheter use in hemodialysis (HD) patients. The International Pediatric Fistula First Initiative was founded via collaborative effort with the Midwest Pediatric Nephrology Consortium to alert nephrologists, surgeons, and dialysis staff to consider fistulae as the best access in pediatric HD patients. A multidisciplinary educational DVD outlining expectations and strategies to increase AVF placement and usage in children was created. Participants were administered a survey previewing and postviewing to identify barriers to placement and usage of AVF in children. A total of 52 surveys were subdivided as either “dialysis staff” or “proceduralist” at five centers. Thirty-three percent of respondents were unaware if their practice was following published guidelines. Sixty-five percent of respondents stated they referred to a dedicated vascular access surgeon at their respective institutions. Methods used to monitor AVF function included physical exam, venous pressure monitoring, and ultrasound dilution. Vascular access was placed within 3 months in only 35% of patients. Interdisciplinary communication problems between surgeons, interventional radiologists, and nephrologists were identified as a major barrier. Lack of AVF usage was often due to maturation failure. Routine access rounds did not occur in any centers. Regarding monitoring, 74% of the respondents use physical exam, 26% use venous pressure monitoring, and 9% use ultrasound dilution. Ninety-three percent of dialysis staff stated they would change practice patterns following the intervention; however, 12% of surgeons stated they would alter practice patterns. To our knowledge, this is the first report to identify barriers to placement of AVF in children from the perspectives of multidisciplinary team members including pediatric nephrologists, surgeons, interventional radiologists, and multidisciplinary dialysis staff.
    Article · Jun 2014 · Hemodialysis International
  • [Show abstract] [Hide abstract] ABSTRACT: Deficiency of complement factor H-related (CFHR) proteins and CFH autoantibody-positive hemolytic uremic syndrome (DEAP-HUS) represents a unique subgroup of complement-mediated atypical HUS (aHUS). Autoantibodies to the C-terminus of CFH block CFH surface recognition and mimic mutations found in the genetic form of (CFH-mediated) aHUS. CFH autoantibodies are found in 10-15 % of aHUS patients and occur-so far unexplained-almost exclusively in the background of CFHR1 or CFHR3/CFHR1 deletions. As a well-defined role for eculizumab in the treatment of complement-mediated aHUS is becoming established, its role in DEAP-HUS is less conspicuous, where a B-cell-depleting and immunosuppressive treatment strategy is being proposed in the literature. We here show eculizumab to be safe and effective in maintaining a disease-free state, without recurrence, in a previously plasma-therapy-dependent DEAP-HUS patient, and in another patient in whom, although showing a good clinical response to plasma therapy, the therapy was hampered by allergic reactions to fresh frozen plasma and contend there is a rationale for the use of eculizumab in concert with an immunosuppressive strategy in the treatment of DEAP-HUS. Considering the high rate of early relapse, the possible coexistence and contribution of both known and unknown complement-gene mutations, the probable pathogenic role of CFHR1 as a complement alternative pathway (CAP) regulator, the experimental nature of measuring and using anti-CFH autoantibodies to guide management, and until the positive reports of immunosuppression in addition to plasma therapy are confirmed in prospective studies, we feel that a complement-directed therapy should not be neglected in DEAP-HUS. Serial CFH autoantibody titer testing may become a valuable tool to monitor treatment response, and weaning patients off eculizumab may become an option once CFH autoantibody levels are depleted. A prospective study of eculizumab treatment in a larger cohort of DEAP-HUS patients is required to validate the applicability of our positive experience.
    Article · Nov 2013 · Pediatric Nephrology
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    [Show abstract] [Hide abstract] ABSTRACT: Nephrotic syndrome (NS) represents a common disease in pediatric nephrology typified by a relapsing and remitting course and characterized by the presence of edema that can significantly affect the health-related quality of life in children and adolescents. The PROMIS pediatric measures were constructed to be publically available, efficient, precise, and valid across a variety of diseases to assess patient reports of symptoms and quality of life. This study was designed to evaluate the ability of children and adolescents with NS to complete the PROMIS assessment via computer and to initiate validity assessments of the short forms and full item banks in pediatric NS. Successful measurement of patient reported outcomes will contribute to our understanding of the impact of NS on children and adolescents. This cross-sectional study included 151 children and adolescents 8-17 years old with NS from 16 participating institutions in North America. The children completed the PROMIS pediatric depression, anxiety, social-peer relationships, pain interference, fatigue, mobility and upper extremity functioning measures using a web-based interface. Responses were compared between patients experiencing active NS (n = 53) defined by the presence of edema and patients with inactive NS (n = 96) defined by the absence of edema. All 151 children and adolescents were successfully able to complete the PROMIS assessment via computer. As hypothesized, the children and adolescents with active NS were significantly different on 4 self-reported measures (anxiety, pain interference, fatigue, and mobility). Depression, peer relationships, and upper extremity functioning were not different between children with active vs. inactive NS. Multivariate analysis showed that the PROMIS instruments remained sensitive to NS disease activity after adjusting for demographic characteristics. Children and adolescents with NS were able to successfully complete the PROMIS instrument using a web-based interface. The computer based pediatric PROMIS measurement effectively discriminated between children and adolescents with active and inactive NS. The domain scores found in this study are consistent with previous reports investigating the health-related quality of life in children and adolescents with NS. This study establishes known-group validity and feasibility for PROMIS pediatric measures in children and adolescents with NS.
    Full-text Article · Mar 2013 · Health and Quality of Life Outcomes
  • Stephen B Freedman · Denis F Geary
    [Show abstract] [Hide abstract] ABSTRACT: Aim: The study aims to assess the risk of developing hyponatraemia when large-volume bolus fluid rehydration therapy is administered. Methods: We conducted a prospective randomised study in a tertiary-care centre emergency department. Participants included children with gastroenteritis and dehydration requiring intravenous rehydration. They were randomised to receive 60 mL/kg (large) or 20 mL/kg (standard) 0.9% saline bolus followed by maintenance 0.9% saline for 3 h. Biochemical tests were performed at baseline and 4 h. The primary outcome measure was the development of hyponatraemia at 4 h. Secondary outcome measures were (i) change in sodium relative to baseline value; (ii) magnitude of decrease among those who experienced a decrease; (iii) risk of hypernatraemia; (iv) correlations between urine parameters and hyponatraemia; and (v) fluid overload. Results: Eighty-four of 224 (38%) participants were hyponatraemic at baseline. At 4 h, 22% (48/217) had a dysnatraemia, and similar numbers of children were hyponatraemic in both groups: large (23% (26/112)) versus standard (21% (22/105)) (P = 0.69). Among initially hyponatraemic children, 63% (30/48) who received large-volume rehydration and 44% (15/34) of those administered standard rehydration were isonatraemic at 4 h (P = 0.10). Overall, children who received 60 mL/kg experienced a larger mean increase (1.6 ± 2.4 mEq/L vs. 0.9 ± 2.2 mEq/L; P = 0.04) and were less likely to experience a sodium decrease of ≥2 mEq/L (8/112 vs. 17/105; P = 0.04) than those administered 20 mL/kg. Conclusions: Large-volume bolus rehydration therapy with 0.9% saline is safe. It does not promote the development of hyponatraemia over the short term, but hastens the resolution of baseline hyponatraemia.
    Article · Feb 2013 · Journal of Paediatrics and Child Health
  • Gareth Morgan · Lee Benson · Denis Geary
    [Show abstract] [Hide abstract] ABSTRACT: Long segment narrowing of the thoracoabdominal aorta or so-called middle aortic syndrome (MAS), is an uncommon lesion presenting variably with physical signs of coarctation of the aorta, hypertension, renal insufficiency and or mesenteric ischemia. The etiologies are multiple, but Takayasu's arteritis is a leading cause. Variable involvement of diverse systemic arterial systems requires individualized management strategies. We report a case of a successful treatment algorithm for severe MAS using a strategy of percutaneous aortic endovascular stent implantation to rebuild the distal aorta and renal auto-implantation to address systemic hypertension.
    Article · Aug 2012 · Catheterization and Cardiovascular Interventions
  • [Show abstract] [Hide abstract] ABSTRACT: Patients undergoing conventional maintenance hemodialysis typically receive three sessions per week, each lasting 2.5-5.5 hours. Recently, the use of more intensive hemodialysis (>5.5 hours, three to seven times per week) has increased, but the effects of these regimens on survival are uncertain. We conducted a retrospective cohort study to examine whether intensive hemodialysis associates with better survival than conventional hemodialysis. We identified 420 patients in the International Quotidian Dialysis Registry who received intensive home hemodialysis in France, the United States, and Canada between January 2000 and August 2010. We matched 338 of these patients to 1388 patients in the Dialysis Outcomes and Practice Patterns Study who received in-center conventional hemodialysis during the same time period by country, ESRD duration, and propensity score. The intensive hemodialysis group received a mean (SD) 4.8 (1.1) sessions per week with a mean treatment time of 7.4 (0.87) hours per session; the conventional group received three sessions per week with a mean treatment time of 3.9 (0.32) hours per session. During 3008 patient-years of follow-up, 45 (13%) of 338 patients receiving intensive hemodialysis died compared with 293 (21%) of 1388 patients receiving conventional hemodialysis (6.1 versus 10.5 deaths per 100 person-years; hazard ratio, 0.55 [95% confidence interval, 0.34-0.87]). The strength and direction of the observed association between intensive hemodialysis and improved survival were consistent across all prespecified subgroups and sensitivity analyses. In conclusion, there is a strong association between intensive home hemodialysis and improved survival, but whether this relationship is causal remains unknown.
    Article · Feb 2012 · Journal of the American Society of Nephrology
  • Rene G. VanDe Voorde · Denis Geary
    [Show abstract] [Hide abstract] ABSTRACT: Decisions concerning the initiation of dialysis during infancy are complex and serve as a prime example of why a pediatric dialysis healthcare team must be comprised of a multidisciplinary group of experts.
    Chapter · Jan 2012
  • Dominik Müller · Denis Geary
    Chapter · Jan 2012
  • N. Al Kalbani · M Frieling · J C Teh · [...] · D F Geary
    [Show abstract] [Hide abstract] ABSTRACT: We have observed infants with renal dysplasia who developed sustained hypercalcemia, without vitamin D or calcium supplementation (idiopathic). This has not been previously described. 1) Define incidence, severity and duration of idiopathic hypercalcemia in infants with renal dysplasia below 12 months of age. 2) Evaluate phosphate, parathyroid hormone (PTH) and vitamin D levels in these infants. Methods: A retrospective study was conducted from June 2005 to June 2008. Patients receiving calcium-containing phosphate binders or daily supplemental vitamin D in excess of 400 IU were excluded. Hypercalcemia was defined as at least three corrected calcium values above normal lab values for age, in a one-week interval. 15 of 99 (15%) infants with renal dysplasia had hypercalcemia. All were males; 10/15 (67%) were below one month of age at presentation; 9/15 (60%) had posterior urethral valves (PUV). Mean hypercalcemia duration was 5.2 ± 6.0 months. Mean corrected calcium was 3.07 mmol/l (12.3 mg/dl). Only 3/10 infants had elevated PTH levels. None had elevated phosphate levels and only 1/8 patients who had 25-hydroxyvitamin D measured had an elevated level. Idiopathic hypercalcemia in infants with renal dysplasia is common. Neonates and those with PUVs are at greatest risk. Most have normal levels of 25-hydroxyvitamin D, phosphate and PTH.
    Article · May 2011 · Clinical nephrology
  • S.D. Soroka · K.M. Beard · D.C. Mendelssohn · [...] · D.F. Geary
    [Show abstract] [Hide abstract] ABSTRACT: Abnormal mineral metabolism is associated with increased morbidity and mortality in dialysis patients. Therefore, the goal of this study was to compare a) mineral metabolism control among a cohort of Canadian peritoneal dialysis (PD) patients to K/DOQI-defined targets and b) the effect of different treatment strategies on mineral metabolism parameters. We looked at a cohort of 317 Canadian PD patients from 9 clinics that used the PhotoGraph™ software program which tracks mineral metabolism management. Serum phosphorus (P), calcium (Ca) and intact parathyroid hormone (iPTH) values were collected for the patients. Data were categorized and analyzed by the type of phosphate binder prescribed, vitamin D use, and dosing and reimbursement criteria for the phosphate binder, sevelamer. The majority of patients achieved K/DOQI-set targets for serum P. Patients who resided in Quebec (QC), which had greater access to sevelamer, had lower mean concentrations of P and Ca, were less likely to take Ca-based phosphate binders (CBBs) exclusively and were exposed to less exogenous Ca than in Ontario (ON). Availability of the phosphate binder sevelamer and reduced doses of elemental Ca were associated with more mineral metabolism parameters within suggested target ranges. Further studies that focus on patient outcomes are warranted.
    Article · May 2011 · Clinical nephrology
  • [Show abstract] [Hide abstract] ABSTRACT: To characterize the attitudes of pediatric nephrologists caring for infants with end-stage renal disease (ESRD) compared with attitudes from a survey published in 1998. Nephrology nurses and social workers were included. An e-mail survey was distributed to pediatric nephrology teams in Canada, Germany, Japan, the United Kingdom, and the United States. Survey responders totaled 270. Renal replacement therapy (RRT) is offered by all nephrologists to some children 1-12 months, and by 98% to some less than 1 month of age (93% in 1998). Of responding nephrologists, 30% offer RRT to all children less than 1 month of age (41% in 1998), and 50%, to all children 1-12 months. Among respondents, 50% indicated that parents can never refuse RRT for children aged 1-12 months, compared with 27% for younger infants. The most influential factor in rejecting RRT for infants was the presence of a co-existing abnormality. Nurses were more likely to believe that parents have the right to refuse RRT for infants. Attitudes of pediatric nephrologists have changed since 1998. Also, nurses have opinions that are different from those of the nephrologists on some issues, and a consensus should be reached before speaking to families.
    Article · Mar 2011
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    [Show abstract] [Hide abstract] ABSTRACT: Antiphospholipid syndrome is a multisystem auto-immune disorder characterized by thrombotic events and the presence of circulating antiphospholipid antibodies. Large vessel involvement in the form of thrombosis/stenosis and thrombotic microangiopathy is a commonly described renal finding. However, non-thrombotic glomerulopathies are increasingly being recognized in patients with antiphospholipid syndrome. We report a rare occurrence of both renal vein thrombosis and membranous nephropathy in a previously healthy adolescent male. Investigations revealed persistently positive antiphospholipid antibodies in the absence of an underlying systemic autoimmune disorder or malignancy. Our patient responded favourably to anti-proteinuric therapy and anticoagulation with complete resolution of proteinuria and a nearly occlusive thrombus.
    Full-text Article · Mar 2011 · Pediatric Nephrology
  • [Show abstract] [Hide abstract] ABSTRACT: Abnormalities in mineral metabolism in chronic kidney disease are associated with increased morbidity and mortality. The Kidney Disease Outcomes Quality Initiative (K/DOQI) clinical practice guidelines were established in 2003 to address issues in the management of mineral and bone metabolism. The goal of this study was to compare (i) mineral metabolism control among Canadian haemodialysis (HD) patients with K/DOQI-defined targets and Dialysis Outcomes and Practice Patterns Study II (DOPPS II) data and (ii) the effect of different treatment strategies. A cross-sectional study of 2215 HD patients was conducted. Phosphorus (P), calcium (Ca), intact parathyroid hormone (iPTH) and calcium-phosphate product (CaXP) were analysed. In addition, management was compared between provinces with more or less restricted access to the phosphate binder sevelamer. K/DOQI targets for P, Ca, iPTH and CaXP K/DOQI targets were met by 59.7%, 58.6%, 29.7% and 83.3%, respectively. A greater proportion of patients were within target compared with those in DOPPS II (2002-2004). Targets were more likely to be reached by patients residing in provinces with formularies allowing less restricted access to sevelamer: P: 61.8% vs 55.7% (P = 0.01); CaXP: 85.5% vs 79.1% (P = 0.0006). As expected, patients in provinces with more restrictive formularies were more often receiving doses of elemental calcium > 1.5 g/day than those with more open listings (62.1% vs 14.0%, P < 0.0001) and were less likely to receive sevelamer (14.1% vs 42.4%, P = 0.0001). Mineral metabolism parameters were more frequently within the target range amongst (i) patients in the current study compared with those in the DOPPS II era and (ii) patients in provinces with less restricted access to sevelamer.
    Article · Jan 2011 · Nephrology Dialysis Transplantation
  • Julianna L Sienna · Rola Saqan · Jun Chuan Teh · [...] · Denis F Geary
    [Show abstract] [Hide abstract] ABSTRACT: Outcome body size of gastrostomy tube (g-tube)-fed children with chronic kidney disease (CKD) was investigated. CKD patients, stages 2-5, who had a g-tube inserted and removed between 1985 and 2007 were retrospectively reviewed (n=20) for anthropometrics, lab values, and steroid use from insertion to latest date. CKD patients never having had a g-tube placed (n=82) acted as the comparison population with similar data collection at start and end of the latest 5-year period. Body mass index (BMI)-for-age, weight (Wt)-for-age, and height (Ht)-for-age z scores were calculated and compared between groups. Median age at insertion and duration of g-tube treatment was 1.7 years (range 0.9-15.6), and 2.9 years (range 0.9-11.8), respectively. There was a significant increase in Wt- (p<0.01), and BMI-for-age (p<0.03) z score, but not for Ht-for-age between insertion and removal for subjects. There were no significant differences in Ht-, Wt-, or BMI-for-age z scores, from removal to 5 years post-removal. In the comparison population, there were no significant differences in Ht-, Wt-, or BMI-for-age z scores over the 5-year period. Approximately 36% of the non-tube-fed comparison population and 50% of the tube-fed subjects were overweight or obese at the most recent evaluation. In both subjects and the comparison group, overweight and obesity is associated with transplant status and steroid use. G-tube feeding is an effective method for achieving catch-up weight and moderate height gain in pediatric CKD patients, and does not apparently predispose patients to obesity after removal; however, overweight and obesity may pose problems to children with CKD whether or not they are tube fed.
    Article · Oct 2010 · Pediatric Nephrology
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    [Show abstract] [Hide abstract] ABSTRACT: The aim of this study was to establish the efficacy and safety of rituximab in refractory nephrotic syndrome (NS). Members of the International Paediatric Nephrology Association were asked to retrospectively fill in a questionnaire with details on the use of rituximab in their centres. We divided the data into three groups: group 1, patients with steroid-dependent and frequently relapsing NS; group 2, with steroid-resistant NS; group 3, with post-transplant recurrence of NS. Seventy questionnaires from 25 centres described the outcome of 28, 27 and 15 patients in groups 1, 2 and 3, respectively. Of these, 82% of patients in group 1, 44% of patients in group 2 and 60% of patients in group 3 had a good initial response. Side effects were observed in 27% of the patients, and these were mostly acute reactions. We present a large multicentre series of children with refractory NS. Children in group 1 showed the best response. The good initial response in group 3 can be biased by the accompanying treatments that were administered at the same time as rituximab. Controlled prospective trials are required to establish the value of rituximab in idiopathic NS.
    Full-text Article · Mar 2010 · Pediatric Nephrology
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    Denis F Geary · Elisabeth M Hodson · Jonathan C Craig
    [Show abstract] [Hide abstract] ABSTRACT: Chronic kidney disease (CKD) resulting in reduced kidney function and the need for dialysis and kidney transplant is associated with abnormalities in blood calcium and phosphorus levels leading to high levels of the parathyroid hormone (PTH) and to bone disease. This may result in bone deformities, bone pain, fractures and reduced growth rates. Commonly used treatments (Vitamin D compounds and phosphate binders) aim to prevent or correct these outcomes. However these treatments may raise levels of blood calcium, allow calcium and phosphorus deposition in blood vessels and lead to early cardiovascular disease, which is known to be a problem in adults with CKD. This review identified only 15 small RCTs involving 369 children comparing different vitamin D compounds, different routes and frequencies of administration of vitamin D compounds and different phosphate binders. Only five RCTs reported on growth rates and no differences were detected between treatments. Renal bone disease, as assessed by changes in PTH levels, was improved by all vitamin D preparations regardless of preparation used or the route or frequency of administration. Fewer episodes of high blood calcium levels and lower overall serum calcium levels occurred with the non calcium-containing binder, sevelamer, compared with calcium-containing binders. As newer treatments for renal bone disease are developed, comparisons with the current standard therapies will be required in well designed RCTs in children using outcome measures including those of direct clinical relevance to children and their families such as rates of growth, reduction in bone fractures and bone pain and reduction in calcification in blood vessels.
    Full-text Article · Jan 2010 · Cochrane database of systematic reviews (Online)
  • [Show abstract] [Hide abstract] ABSTRACT: The occurrence of acute hyponatremia associated with cerebral edema in hospitalized children has been increasingly recognized, with over 50 cases of neurological morbidity and mortality reported in the past decade. This condition most commonly occurs in previously healthy children where maintenance intravenous (IV) fluids have been prescribed in the form of hypotonic saline (e.g., 0.2 or 0.3 NaCl). In response to similar problems at The Hospital for Sick Children (six identified through hospital morbidity and mortality reviews and safety reports prior to fall 2007), an interdisciplinary clinician group from our institution developed a clinical practice guideline (CPG) to guide fluid and electrolyte administration for pediatric patients. This article reviews the evaluation of one patient safety improvement to change the prescribing practice for IV fluids in an acute care pediatric hospital, including the removal of the ability to prescribe hypotonic IV solutions with a sodium concentration of < 75 mmol/L. The evaluation of key components of the CPG included measuring practice and process changes pre- and post-implementation. The evaluation showed that the use of restricted IV fluids was significantly reduced across the organization. Success factors of this safety initiative included the CPG development, forcing functions, reminders, team engagement and support from the hospital leadership. A key learning was that a project leader with considerable dedicated time is required during the implementation to develop change concepts, organize and liaise with stakeholders and measure changes in practice. This project highlights the importance of active implementation for policy and guideline documents.
    Article · Aug 2009 · Healthcare quarterly (Toronto, Ont.)
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    [Show abstract] [Hide abstract] ABSTRACT: Atypical hemolytic uremic syndrome (aHUS) is associated with complement system dysregulation, and more than 25% of pediatric aHUS cases are linked to mutations in complement factor H (CFH) or CFH autoantibodies. The observation of thrombocytopenia and platelet-rich thrombi in the glomerular microvasculature indicates that platelets are intimately involved in aHUS pathogenesis. It has been reported that a releasable pool of platelet CFH originates from alpha-granules. We observed that platelet CFH can arise from endogenous synthesis in megakaryocytes and that platelets constitutively lacking alpha-granules contain CFH. Electron and high-resolution laser fluorescence confocal microscopy revealed that CFH was present throughout the cytoplasm and on the surface of normal resting platelets with no evident concentration in alpha-granules, lysosomes, or dense granules. Therapeutic plasma transfusion in a CFH-null aHUS patient revealed that circulating platelets take up CFH with similar persistence of CFH in platelets and plasma in vivo. Washed normal platelets were also observed to take up labeled CFH in vitro. Exposure of washed normal platelets to plasma of an aHUS patient with CFH autoantibodies produced partial platelet aggregation or agglutination, which was prevented by preincubation of platelets with purified CFH. This CFH-dependent response did not involve P-selectin mobilization, indicating a complement-induced platelet response distinct from alpha-granule secretion.
    Full-text Article · Aug 2009 · Blood

Publication Stats

2k Citations


  • 1988-2014
    • SickKids
      • • Department of Paediatrics
      • • Division of Nephrology
      Toronto, Ontario, Canada
  • 2006-2012
    • University of Toronto
      • Department of Paediatrics
      Toronto, Ontario, Canada
    • UHN: Toronto General Hospital
      Toronto, Ontario, Canada