Publications by authors named "Damien Noone"

53 Publications

Social vulnerability and COVID-19: A call to action for paediatric clinicians.

Paediatr Child Health 2021 Feb 24;26(1):1-3. Epub 2020 Nov 24.

Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario.

The COVID-19 pandemic has had dramatic effects on the lives of children globally. However, socially vulnerable children have been particularly impacted. Certain populations have increased vulnerabilities, including children and youth experiencing homelessness. Increased infection risk due to congregant living and challenges with physical distancing are contributing factors. An urgent need exists for a wholistic approach to care with unique cross-sectoral partnerships across disciplines. A recognition of the unintended consequence of the COVID-19 pandemic on this population is urgently required by all those supporting children. Families should receive direct support in clinical settings to identify their social needs. Partnership with community agencies and advocacy for appropriate isolation facilities for patients experiencing homelessness are critical.
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http://dx.doi.org/10.1093/pch/pxaa121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717406PMC
February 2021

Inherited Kidney Complement Diseases.

Clin J Am Soc Nephrol 2021 Feb 3. Epub 2021 Feb 3.

Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Laboratory of Immunology, Paris, France.

In the past 20 years, we have witnessed tremendous advances in our ability to diagnose and treat genetic diseases of the kidney caused by complement dysregulation. Staggering progress was realized toward a better understanding of the genetic underpinnings and pathophysiology of many forms of atypical hemolytic uremic syndrome (aHUS) and C3-dominant glomerulopathies that are driven by complement system abnormalities. Many of these seminal discoveries paved the way for the design and characterization of several innovative therapies, some of which have already radically improved patients' outcomes. This review offers a broad overview of the exciting developments that have occurred in the recent past, with a particular focus on single-gene (or Mendelian), complement-driven aHUS and C3-dominant glomerulopathies that should be of interest to both nephrologists and kidney researchers. The discussion is restricted to genes with robust associations with both aHUS and C3-dominant glomerulopathies (complement factor H, complement component 3, complement factor H-related proteins) or only aHUS (complement factor B, complement factor I, and membrane cofactor protein). Key questions and challenges are highlighted, along with potential avenues for future directions.
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http://dx.doi.org/10.2215/CJN.11830720DOI Listing
February 2021

Multicentric carpotarsal osteolysis syndrome (MCTO) with generalized high bone turnover and high serum RANKL: Response to denosumab.

Bone Rep 2021 Jun 8;14:100747. Epub 2021 Jan 8.

Department of Paediatrics, The Hospital for Sick Children, Toronto, ON, Canada.

MCTO is a rare disorder, caused by mutations in the gene, a negative regulator of receptor activator of nuclear factor-кB ligand (RANKL). Manifestations include carpal and tarsal osteolysis and renal failure. Pathophysiology is poorly understood, and no effective treatment is available. In this case report we describe a patient with MCTO (, mutation c.206C>T, p.Ser69Leu), diagnosed at the age of 5 years. At 7 years, skeletal survey showed diffuse osteopenia. BMD was mildly reduced, and bone turnover markers increased. He was treated with denosumab, a human monoclonal RANKL inhibitor for two years. Each injection was followed by a marked reduction in C-telopeptide (CTX). Following denosumab his BMD and bone symptoms improved and the osteolysis stabilized. At the age of 13 years, osteoporosis was diagnosed using high resolution peripheral quantitative computed tomography (HRpQCT) and serum RANKL was found to be markedly increased. This initial experience suggests that the associated osteoporosis may be ameliorated by denosumab, although further study will be needed to understand the appropriate dose, frequency, and the extent of efficacy. Monitoring of CTX and bone specific alkaline phosphatase will be especially useful in this regard. Further study in other MCTO patients is also needed to determine whether high bone turnover is specific to this mutation or more common than previously appreciated. We propose a model in which osteolysis in this condition is strongly associated with the systemic osteoporosis.
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http://dx.doi.org/10.1016/j.bonr.2021.100747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815641PMC
June 2021

Management of Canadian Pediatric Patients With Glomerular Diseases During the COVID-19 Pandemic: Recommendations From the Canadian Association of Pediatric Nephrologists COVID-19 Rapid Response Team.

Can J Kidney Health Dis 2020 13;7:2054358120970713. Epub 2020 Nov 13.

Department of Paediatrics, Division of Nephrology, McMaster University, Hamilton, ON, Canada.

Purpose: The goal of these recommendations is to provide guidance on the optimal care of children with glomerular diseases during the COVID-19 pandemic. Patients with glomerular diseases are known to be more susceptible to infection. Risk factors include decreased vaccine uptake, urinary loss of immunoglobulins, and treatment with immunosuppressive medications. The Canadian Society of Nephrology (CSN) recently published guidelines on the care of adult glomerulonephritis patients. This guideline aims to expand and adapt those recommendations for programs caring for children with glomerular diseases.

Sources Of Information: We used the CSN COVID-19 Rapid Response Team adult glomerulonephritis recommendations, published in the , as the foundation for our guidelines. We reviewed documents published by nephrology and non-nephrology societies and health care agencies focused on kidney disease and immunocompromised populations. Finally, we conducted a formal literature review of publications relevant to pediatric and adult glomerular disease, chronic kidney disease, hypertension, and immunosuppression in the context of the COVID-19 pandemic.

Methods: The leadership of the Canadian Association of Pediatric Nephrologists (CAPN), which is affiliated with the CSN, identified a team of clinicians and researchers with expertise in pediatric glomerular diseases. The aim was to adapt Canadian adult glomerulonephritis guidelines to make them applicable to children and discuss pediatric-specific considerations. The updated guidelines were peer-reviewed by senior clinicians with expertise in the care of childhood glomerular diseases.

Key Findings: We identified a number of key areas of glomerular disease care likely to be affected by the COVID-19 pandemic, including (1) clinic visit scheduling, (2) visit types, (3) provision of multidisciplinary care, (4) blood work and imaging, (5) home monitoring, (6) immunosuppression, (7) other medications, (8) immunizations, (9) management of children with suspected COVID-19, (10) renal biopsy, (11) patient education and support, and (12) school and child care.

Limitations: There are minimal data regarding the characteristics and outcomes of COVID-19 in adult or pediatric glomerular disease patients, as well as the efficacy of strategies to prevent infection transmission within these populations. Therefore, the majority of these recommendations are based on expert opinion and consensus guidance. To expedite the publication of these guidelines, an internal peer-review process was conducted, which may not have been as rigorous as formal journal peer-review.

Implications: These guidelines are intended to promote optimal care delivery for children with existing or newly diagnosed glomerular diseases during the COVID-19 pandemic. The implications of modified care delivery, altered immunosuppression strategies, and limited access to existing resources remain uncertain.
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http://dx.doi.org/10.1177/2054358120970713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672717PMC
November 2020

CanVasc Consensus Recommendations for the Management of Antineutrophil Cytoplasm Antibody-associated Vasculitis: 2020 Update.

J Rheumatol 2020 Sep 15. Epub 2020 Sep 15.

A. Mendel, MD, MSc, C.A. Pineau, MD, Division of Rheumatology, Lupus and Vasculitis Clinic, McGill University, Montréal, Québec; D. Ennis, MD, C. Baldwin, MD, N. Dehghan, MD, N. Dhindsa, MD, Division of Rheumatology, University of British Columbia, Vancouver, British Columbia; E. Go, MD, R.S. Yeung, MD, PhD, Division of Rheumatology, Hospital for Sick Children, University of Toronto, Toronto, Ontario; V. Bakowsky, MD, Division of Rheumatology, QEII Health Sciences Centre, Dalhousie University, Halifax, Nova Scotia; S.M. Benseler, MD, PhD, M. Twilt, MD, PhD, Division of Rheumatology, Department of Pediatrics, Alberta Children's Hospital, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta; D.A. Cabral, MBBS, Division of Pediatric Rheumatology, BC Children's Hospital, University of British Columbia, Vancouver, British Columbia; S. Carette, MD, MPhil, C. Pagnoux, MD, MSc, MPH, Division of Rheumatology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario; M. Clements-Baker, MD, T.E. Towheed, MD, MS, Division of Rheumatology, Queen's University, Kingston, Ontario; A.H. Clifford, MD, J.W. Cohen Tervaert, MD, PhD, E. Yacyshyn, MD, Division of Rheumatology, University of Alberta, Edmonton, Alberta; G. Cox, MB, Firestone Institute for Respiratory Health, McMaster University, Hamilton, Ontario; C. Dipchand, MD, MSc, Division of Nephrology, QEII Health Sciences Centre, Dalhousie University, Halifax, Nova Scotia; L. Famorca, MD, S. Garner, MD, MSc, N. Khalidi, MD, Division of Rheumatology, McMaster University, Hamilton, Ontario; A. Fifi-Mah, MD, Division of Rheumatology, University of Calgary, Calgary, Alberta; L.P. Girard, MD, MSc, Division of Nephrology, University of Calgary, Calgary, Alberta; C. Lessard, MD, Centre de Recherche Musculo-Squelettique, Trois-Rivières, Québec; P. Liang, MD, Division of Rheumatology, Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke, Sherbrooke, Québec; D. Noone, MB, BCh, BAO, MSc, Division of Nephrology, Hospital for Sick Children, University of Toronto, Toronto, Ontario; J.P. Makhzoum, MD, M. Rhéaume, MD, Division of Internal Medicine, Hôpital du Sacré-Coeur de Montréal, Université de Montréal, Montréal, Québec; N. Milman, MD, MSc, Division of Rheumatology, The Ottawa Hospital, University of Ottawa and Ottawa Hospital Research Institute, Ottawa, Ontario; H.N. Reich, MD, PhD, Division of Nephrology, University Health Network, University of Toronto, Toronto, Ontario; D.B. Robinson, MD, MSc, Section of Rheumatology, University of Manitoba, Winnipeg, Manitoba; D.G. Rumsey, MD, MSc, Division of Pediatric Rheumatology, University of Alberta, Edmonton, Alberta; J. Trudeau, MD, Division of Rheumatology, CISSS Chaudière- Appalaches, Université Laval, Québec City, Québec; L.B. Barra, MD, Division of Rheumatology, Department of Medicine, Western University, London, Ontario, Canada. VB reports advisory board attendance from AbbVie, Eli Lilly, and Janssen, outside the submitted work. AHC reports other fees from AbbVie and personal fees from Roche, outside the submitted work. JWCT reports Chair of the Independent Data Monitoring Committee for InflaRx, outside the submitted work. ND reports personal fees from Novartis, Sandoz, and Amgen, outside the submitted work. SG reports grants from the Vasculitis Foundation and Roche, during the conduct of the submitted work. PL reports grants from Roche, Amgen, Janssen, AbbVie, BMS, and Novartis, outside the submitted work. JT reports personal fees from Roche, personal fees from Medexus, and other fees from Medpace, outside the submitted work. LB reports honoraria from Roche, Bristol Myers Squibb, Boehringer Ingelheim, and Pfizer, outside the submitted work. NK reports personal fees and nonfinancial support from Roche, and nonfinancial support from Bristol Myers Squibb, outside the submitted work. CP reports grants and personal fees from Roche; grants and personal fees from GSK; and personal fees from ChemoCentryx, Sanofi, and InflaRx GmbH, outside the submitted work. The remaining authors have nothing to disclose. Address correspondence to Dr. A. Mendel, Montreal General Hospital, 1650 Cedar Avenue, Montreal, QC H3G 1A4, Canada. Email: Accepted for publication September 5, 2020.

Objective: In 2015, the Canadian Vasculitis Research Network (CanVasc) created recommendations for the management of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV) in Canada. The current update aims to revise existing recommendations and create additional recommendations, as needed, based on a review of new available evidence.

Methods: A needs assessment survey of CanVasc members informed questions for an updated systematic literature review (publications spanning May 2014 to September 2019) using Medline, Embase, and Cochrane. New and revised recommendations were developed and categorized according to the level of evidence and strength of each recommendation. The CanVasc working group used a 2-step modified Delphi procedure to reach > 80% consensus on the inclusion, wording, and grading of each new and revised recommendation.

Results: Eleven new and 16 revised recommendations were created and 12 original (2015) recommendations were retained. New and revised recommendations are discussed in detail within this document. Five original recommendations were removed, of which 4 were incorporated into the explanatory text. The supplementary material for practical use was revised to reflect the updated recommendations.

Conclusion: The 2020 updated recommendations provide rheumatologists, nephrologists, and other specialists caring for patients with AAV in Canada with new management guidance, based on current evidence and consensus from Canadian experts.
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http://dx.doi.org/10.3899/jrheum.200721DOI Listing
September 2020

Impact of steroids and steroid-sparing agents on quality of life in children with nephrotic syndrome.

Pediatr Nephrol 2021 01 15;36(1):93-102. Epub 2020 Jul 15.

Child Health Evaluative Sciences, Research Institute, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.

Background: Steroids and/or steroid-sparing medications are commonly used for nephrotic syndrome treatment; however, the impact of these medications on health-related quality of life over time is not well described.

Methods: Longitudinal cohort is up to 5 years where children were assessed with baseline and annual Pediatric Quality of Life Inventory questionnaire. A mixed-effects linear regression determined differences in scores among children receiving steroids and/or steroid-sparing agents for at least 30 days compared with those not on medication at 1, 3, 6, and 12 months prior to assessment.

Results: Among 295 children, 64% were male, with a median age of 3.7 (interquartile range [IQR], 2.7, 5.9) years at diagnosis, and comprised 25% Europeans, 40% South Asians, and 8% East/Southeast Asians. Adjusted HRQOL scores were reduced among children taking steroids and steroid-sparing agents among 705 HRQOL measures (median 2 [IQR, 1, 3] per child). Compared to children without medication, steroid and steroid-sparing agent use up to 12 months prior to assessment were associated with an overall HRQOL drop of 3.17 (95% confidence interval [CI], - 5.25, - 1.08) and 3.18 (95% CI, - 5.24, - 1.12), respectively, after adjustment. Functioning domain scores were reduced by 4.41 points (95% CI, - 6.57, - 2.25) in children on steroids, whereas fatigue domain scores were reduced by 5.47 points (95% CI, - 9.28, - 1.67) in children on steroid-sparing agents after adjustment.

Conclusions: HRQOL is consistently decreased in children receiving steroids and steroid-sparing agents, with differential effects on functioning and fatigue. Counseling families on possible effects of prolonged treatment periods is important in the management of childhood nephrotic syndrome.
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http://dx.doi.org/10.1007/s00467-020-04684-3DOI Listing
January 2021

Hemodialysis Catheters in Infants: A Retrospective Single-Center Cohort Study.

J Vasc Interv Radiol 2020 05 15;31(5):778-786. Epub 2020 Apr 15.

Image Guided Therapy, Department of Medical Imaging, The Hospital for Sick Children, University of Toronto, 555 University Ave, Toronto, ON M5G 1X8, Canada.

Purpose: Evaluate technical aspects and outcomes of insertion/maintenance of hemodialysis (HD) central venous catheter (CVC) during infancy.

Materials And Methods: Single-center retrospective study of 29 infants who underwent 49 HD-CVC insertions between 2002 and 2016. Demographics, procedural, and post-procedural details, interventional radiology (IR) maintenance procedures, technical modifications, complications, and outcomes were evaluated. Technical adjustments during HD-CVC placement to adapt catheter length to patient size were labeled "modifications." CVCs requiring return visit to IR were called IR-maintenance procedures. Mean age and weight at HD-CVC insertion were 117 days and 4.9 kg.

Results: Of the 29 patients, 13 (45%) required renal-replacement-therapy (RRT) as neonates, 10 (34%) commenced RRT with peritoneal dialysis (PD), and 19 (66%) with HD. Fifteen nontunneled and 34 tunneled HD-CVCs were inserted while patients were ≤1 year. Technical modifications were required placing 25/49 (51%) HD-CVCs: 5/15 (33%) nontunneled and 20/34 (59%) tunneled catheters (P = .08). Patients underwent ≤6 dialysis-cycles/patient during infancy (mean 2.3), and a mean of 4.1 and 49 HD-sessions/catheter for nontunneled and tunneled HD-CVCs, respectively. Mean primary and secondary device service, and total access site intervals for tunneled HD-CVCs were 75, 115, and 201 days, respectively. A total of 26 of 49 (53%) patients required IR-maintenance procedures. Nontunneled lines had greater catheter-related bloodstream infections per 1,000 catheter-days than tunneled HD-CVCs (9.25 vs. 0.85/1,000 catheter days; P = .02). Nineteen patients (65%) survived over 1 year. At final evaluation (December 2017): 8/19 survived transplantation, 5/19 remained on RRT, 2/19 completely recovered, 1/19 lost to follow-up, and 3 died at 1.3, 2, and 10 years.

Conclusions: Placement/maintenance of HD-CVCs in infants pose specific challenges, requiring insertion modifications, and IR-maintenance procedures to maintain function.
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http://dx.doi.org/10.1016/j.jvir.2020.01.020DOI Listing
May 2020

Prediction of Short- and Long-Term Outcomes in Childhood Nephrotic Syndrome.

Kidney Int Rep 2020 Apr 27;5(4):426-434. Epub 2019 Dec 27.

Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada.

Introduction: It is unknown whether steroid sensitivity and other putative risk factors collected at baseline can predict the disease course of idiopathic nephrotic syndrome in childhood. We determined whether demographic, clinical, and family reported factors at presentation can predict outcomes in idiopathic nephrotic syndrome.

Methods: An observational cohort of 631 children aged 1 to 18 years diagnosed with idiopathic nephrotic syndrome between 1993 and 2016 were followed up until clinic discharge, 18 years of age, end-stage kidney disease (ESKD), or the last clinic visit. Baseline characteristics were age, sex, ethnicity, and initial steroid sensitivity. Of these, 287 (38%) children also reported any family history of kidney disease, preceding infection, microscopic hematuria, and history of asthma/allergies. The outcomes were complete remission after initial steroid course, need for a second-line agent, frequently relapsing disease, and long-term remission. The discriminatory power of the models was described using the c-statistic.

Results: Overall, 25.7% of children had no further disease after their initial steroid course. In addition, 31.2% developed frequently relapsing disease; however, 77.7% were disease-free at 18 years of age. Furthermore, 1% of children progressed to ESKD. Logistic regression modeling using the different baseline exposures did not significantly improve the prediction of outcomes relative to the observed frequencies (maximum c-statistic, 0.63; 95% confidence interval [CI], 0.59-0.67). The addition of steroid sensitivity did not improve outcome prediction of long-term outcomes (c-statistic, 0.63; 95% CI, 0.54-0.70).

Conclusions: Demographic, clinical, and family reported characteristics, specifically steroid sensitivity, are not useful in predicting relapse rates or long-term remission in idiopathic nephrotic syndrome. Further studies are needed to address factors that contribute to long-term health.
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http://dx.doi.org/10.1016/j.ekir.2019.12.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136435PMC
April 2020

Vascular endothelial cells evade complement-mediated membrane injury via Weibel-Palade body mobilization.

J Thromb Haemost 2020 06;18(6):1484-1494

Cell Biology Program, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada.

Background: Defective complement inhibition can lead to the formation of membrane attack complexes (MAC; C5b-9) on the plasma membranes of vascular endothelial cells, resulting in injury that drives the progression of thrombotic microangiopathy (TMA), a key pathology in kidney disease.

Objective/methods: We examined the response of human endothelial cells to complement-mediated damage using blood outgrowth endothelial cells (BOECs) derived from healthy donors. BOECs were sensitized to complement factors present in normal human serum to induce the formation of C5b-9 on their plasma membranes.

Results: This triggered an expected abrupt rise in intracellular Ca reflecting membrane leakage. Remarkably, while intracellular Ca remained elevated, membrane leakage ceased within 30 minutes, and cells did not show significant death. Extensive mobilization of Weibel-Palade bodies (WPBs) was observed along with secretion of von Willebrand factor (VWF). The potential role of WPBs and VWF in mitigating complement-mediated damage was examined by comparing the effects of C5b-9 on BOECs derived from von Willebrand disease (VWD) patients expressing reduced amounts of VWF, lacking expression of functional VWF, or lacking both VWF and WPBs. BOECs lacking WPBs were not resistant to complement-mediated damage, but became resistant when transfected to express VWF (and thus WPBs).

Conclusion: We conclude that BOECs exposed to C5b-9 attack respond by mobilizing WPBs, which mitigate and repair damage by fusing with the plasma membrane. We propose that a similar cell-specific response may protect the vascular endothelium from complement-mediated damage in vivo.
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http://dx.doi.org/10.1111/jth.14767DOI Listing
June 2020

Hyperuricemia and Hypertension: Links and Risks.

Integr Blood Press Control 2019 24;12:43-62. Epub 2019 Dec 24.

Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.

Hyperuricemia has long been recognized to be associated with increased cardiovascular risk, including risk of developing hypertension. Epidemiological findings suggest that the link with hypertension is stronger in children and adolescents. Uric acid acts as a strong antioxidant compound in the extracellular environment but has pro-inflammatory effects within the intracellular setting. A chronic phase of microvascular injury is known to occur after prolonged periods of hyperuricemia. This is proposed to contribute to afferent arteriolopathy and elevation of blood pressure that may become unresponsive to uric acid-lowering therapies over time. Studies have struggled to infer direct causality of hyperuricemia due to a vast number of confounders including body mass index. The aim of this review is to present the available data and highlight the need for large scale prospective randomized controlled trials in this area. At present, there is limited evidence to support a role for uric acid-lowering therapies in helping mitigate the risk of hypertension.
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http://dx.doi.org/10.2147/IBPC.S184685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935283PMC
December 2019

The long and the short of it - the impact of acute kidney injury in critically ill children.

J Pediatr (Rio J) 2020 Sep - Oct;96(5):533-536. Epub 2020 Jan 6.

University of Toronto, The Hospital for Sick Children, Department of Pediatrics, Division of Nephrology, Toronto, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.jped.2019.12.002DOI Listing
November 2020

Helping nephrologists find answers: hyperinsulinism and tubular dysfunction: Answers.

Pediatr Nephrol 2020 02 16;35(2):257-260. Epub 2019 Sep 16.

Division of Nephrology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1007/s00467-019-04348-xDOI Listing
February 2020

Helping nephrologists find answers: hyperinsulinism and tubular dysfunction: Questions.

Pediatr Nephrol 2020 02 16;35(2):253-255. Epub 2019 Sep 16.

Division of Nephrology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.

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http://dx.doi.org/10.1007/s00467-019-04345-0DOI Listing
February 2020

Association of low birth weight and prematurity with clinical outcomes of childhood nephrotic syndrome: a prospective cohort study.

Pediatr Nephrol 2019 09 11;34(9):1599-1605. Epub 2019 Apr 11.

Child Health Evaluative Sciences, Research Institute, Hospital for Sick Children, 686 Bay St, Toronto, ON, M5G 0A4, Canada.

Background: Low birth weight (LBW)/prematurity have been proposed as risk factors for the development of kidney disease in adulthood. Whether there is an association between LBW/prematurity and poor renal outcomes in childhood onset nephrotic syndrome remains unknown.

Methods: Children with nephrotic syndrome diagnosed between 1 and 18 years of age were followed prospectively from 1996 to 2016 at The Hospital for Sick Children (N = 377). LBW/prematurity was defined as birth weight < 2500 g or gestational age < 36 weeks. Normal birth weight (NBW) was defined as birth weight ≥ 2500 g. Measures evaluating clinical course of nephrotic syndrome include initial steroid-resistant nephrotic syndrome (SRNS), time to first relapse, and frequently relapsing nephrotic syndrome. Kaplan-Meier survival analysis, logistic regression, and Cox proportional hazards regression were used to determine the association of LBW/prematurity with clinical outcomes.

Results: Median birth weights in LBW/premature (n = 46) and NBW (n = 331) children were 2098 g (interquartile range [IQR] 1700-2325 g) and 3317 g (IQR 2977-3685 g), respectively. Odds of having SRNS were 3.78 (95% confidence interval [CI] 1.28-11.21) times higher among LBW/premature children than NBW children. An 8% decrease in odds of developing SRNS was observed for every 100 g increase in birth weight (adjusted odds ratio [OR] 0.92; 95% CI 0.86-0.98). Median time to first relapse did not differ (hazard ratio [HR] 0.89; 95% CI 0.53-1.16).

Conclusions: LBW/premature children were more likely to develop SRNS but did not have a difference in time to first relapse with NBW children. Understanding the impact and mechanism of birth weight and steroid-resistant disease needs further study.
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http://dx.doi.org/10.1007/s00467-019-04255-1DOI Listing
September 2019

Kidney disease and organ transplantation in methylmalonic acidaemia.

Pediatr Transplant 2019 06 11;23(4):e13407. Epub 2019 Apr 11.

Department of Paediatrics, Western University, London, Ontario, Canada.

Objectives: MMA is associated with chronic tubulointerstitial nephritis and a progressive decline in GFR. Optimal management of these children is uncertain. Our objectives were to document the pre-, peri-, and post-transplant course of all children with MMA who underwent liver or combined liver-kidney transplant in our centers.

Design And Methods: Retrospective chart review of all cases of MMA who underwent organ transplantation over the last 10 years.

Results: Five children with MMA underwent liver transplant (4/5) and combined liver-kidney transplant (1/5). Three were Mut and two had a cobalamin B disorder. Four of five were transplanted between ages 3 and 5 years. Renal dysfunction prior to transplant was seen in 2/5 patients. Post-transplant (one liver transplant and one combined transplant) renal function improved slightly when using creatinine-based GFR formula. We noticed in 2 patients a big discrepancy between creatinine- and cystatin C-based GFR calculations. One patient with no renal disease developed renal failure post-liver transplantation. Serum MMA levels have decreased in all to <300 μmol/L. Four patients remain on low protein diet, carnitine, coenzyme Q, and vitamin E post-transplant.

Conclusions: MMA is a complex metabolic disorder. Renal disease can continue to progress post-liver transplant and close follow-up is warranted. More research is needed to clarify best screening GFR method in patients with MMA. Whether liver transplant alone, continued protein restriction, or the addition of antioxidants post-transplant can halt the progression of renal disease remains unclear.
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http://dx.doi.org/10.1111/petr.13407DOI Listing
June 2019

Prevalence of Asthma and Allergies and Risk of Relapse in Childhood Nephrotic Syndrome: Insight into Nephrotic Syndrome Cohort.

J Pediatr 2019 05 4;208:251-257.e1. Epub 2019 Feb 4.

Child Health and Evaluative Sciences, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada; University of Toronto, Toronto, Ontario, Canada; Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada; University Health Network, Toronto, Ontario, Canada. Electronic address:

Objective: To determine the lifetime prevalence of allergies in childhood nephrotic syndrome, the seasonality of presentation and relapses, and the impact of allergies on subsequent relapses.

Study Design: In a longitudinal cohort of children with nephrotic syndrome (ages 1-18 years), assessment for allergic diseases was conducted using the validated and modified version of the International Study of Asthma and Allergies in Childhood questionnaire at enrollment. Outcomes included frequently relapsing nephrotic syndrome, relapse rates, and the relapse-free duration after initial steroid therapy.

Results: Among 277 participants, the majority were male (65%) with a median age of 3.7 years (IQR 2.8-5.8) at presentation. A total of 64% reported lifetime allergies with 20% having asthma, 33% wheezing, 27% eczema, and 24% rhinitis. Over 3.3 years of follow-up, presence of asthma and allergies was not associated with frequently relapsing nephrotic syndrome (OR 1.20; 95% CI 0.60, 2.40), higher relapse rates (relative risk 0.95; 95% CI 0.71, 1.27), or risk of first relapse (hazard ratio 1.10; 95% CI 0.83, 1.47) compared with those with no history of allergic diseases. There was also no seasonal variation evident at initial presentation or frequency of relapses.

Conclusions: Two-thirds of children with nephrotic syndrome at presentation have allergic symptoms and asthma; however, neither are associated with an increased frequency of relapses.
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http://dx.doi.org/10.1016/j.jpeds.2018.12.048DOI Listing
May 2019

Quality improvement in pediatric nephrology-a practical guide.

Pediatr Nephrol 2020 02 5;35(2):199-211. Epub 2019 Jan 5.

Division of Nephrology, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.

Improving quality of care delivery is an important focus for all practicing physicians. Frontline clinicians are in a great position to identify clinical problems and find innovative solutions. The current review describes the method used for quality improvement based on the Model for Improvement, a structural framework to guide improvement work. At its basis are three fundamental questions: What are we trying to accomplish? How will I know that a change will lead to improvement? And what changes could we make that will result in improvement? This preparation phase aims to identify and understand the problem, choose an intervention, and determine reliable measures to gauge improvement. The intervention is then tested using PLAN-DO-STUDY-ACT (PDSA) cycles, an iterative approach to systematically improve processes and outcomes. PLAN focuses on defining the goal of the cycle and describing in details what will be done. DO concentrates on the concrete application of the plan. STUDY focuses on data analyses as ACT identifies lessons learned from the cycle and orientate the goals of the following PDSA cycle. Learning from each cycle, developing an interdisciplinary team and repeated interventions are core principles involved in implementing a sustainable quality improvement program. The Model for Improvement will be illustrated by a common quality problem in pediatric nephrology.
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http://dx.doi.org/10.1007/s00467-018-4175-0DOI Listing
February 2020

Clinical Characteristics and Treatment Patterns of Children and Adults With IgA Nephropathy or IgA Vasculitis: Findings From the CureGN Study.

Kidney Int Rep 2018 Nov 3;3(6):1373-1384. Epub 2018 Aug 3.

Department of Medicine, Division of Nephrology, Columbia University College of Physicians and Surgeons, New York, New York, USA.

Introduction: The Cure Glomerulonephropathy Network (CureGN) is a 66-center longitudinal observational study of patients with biopsy-confirmed minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy (IgAN), including IgA vasculitis (IgAV). This study describes the clinical characteristics and treatment patterns in the IgA cohort, including comparisons between IgAN versus IgAV and adult versus pediatric patients.

Methods: Patients with a diagnostic kidney biopsy within 5 years of screening were eligible to join CureGN. This is a descriptive analysis of clinical and treatment data collected at the time of enrollment.

Results: A total of 667 patients (506 IgAN, 161 IgAV) constitute the IgAN/IgAV cohort (382 adults, 285 children). At biopsy, those with IgAV were younger (13.0 years vs. 29.6 years,  < 0.001), more frequently white (89.7% vs. 78.9%,  = 0.003), had a higher estimated glomerular filtration rate (103.5 vs. 70.6 ml/min per 1.73 m,  < 0.001), and lower serum albumin (3.4 vs. 3.8 g/dl,  < 0.001) than those with IgAN. Adult and pediatric individuals with IgAV were more likely than those with IgAN to have been treated with immunosuppressive therapy at or prior to enrollment (79.5% vs. 54.0%,  < 0.001).

Conclusion: This report highlights clinical differences between IgAV and IgAN and between children and adults with these diagnoses. We identified differences in treatment with immunosuppressive therapies by disease type. This description of baseline characteristics will serve as a foundation for future CureGN studies.
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http://dx.doi.org/10.1016/j.ekir.2018.07.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6224619PMC
November 2018

Presentation and Disease Course of Childhood-Onset Versus Adult-Onset Takayasu Arteritis.

Arthritis Rheumatol 2019 02 29;71(2):315-323. Epub 2018 Dec 29.

The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada.

Objective: To compare the clinical features, efficacy and safety of treatment regimens, and outcomes of childhood- and adult-onset Takayasu arteritis (TAK).

Methods: The study was designed as a retrospective cohort study comparing patients with childhood-onset TAK (from 1986 onward) to patients with adult-onset TAK (from 1988 onward) who were followed up until 2014 or 2015 at 4 centers in Ontario, Canada. Demographic, clinical, laboratory, and angiographic features, treatment regimens, and outcomes were recorded throughout the course of the disease. Disease activity and damage scores were completed retrospectively.

Results: Twenty-nine children and 48 adults (median age at diagnosis 12.1 years and 31.2 years, respectively) were included. A lower predominance of females was observed among the childhood-onset TAK cohort (76% versus 100% of patients with adult-onset TAK; P < 0.01), and children had a shorter delay to diagnosis (median 6.0 months versus 12.2 months for adults; P = 0.03). The distribution of vascular involvement was also different, with children having significantly more aortic and renal artery involvement and a higher frequency of arterial hypertension. Relapses in the first year after diagnosis were common both in children (39%) and in adults (28%). Two children, but no adults, died.

Conclusion: Childhood-onset TAK has a lower female predominance and a higher frequency of aortic and renal involvement compared to adult-onset TAK. Relapses and disease burden were high in both groups, corroborating the need for careful monitoring of disease activity and aggressive therapeutic management.
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http://dx.doi.org/10.1002/art.40690DOI Listing
February 2019

Idiopathic nephrotic syndrome in children.

Lancet 2018 07 14;392(10141):61-74. Epub 2018 Jun 14.

Department of Paediatrics, University of Toronto, Toronto, ON, Canada; Division of Nephrology, The Hospital for Sick Children, Toronto, ON, Canada; Child Health Evaluative Sciences, Research Institute, Hospital for Sick Children, Toronto, ON, Canada; University Health Network, Toronto, ON, Canada; Dalla Lana School of Public Health, and Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada. Electronic address:

The incidence of idiopathic nephrotic syndrome (NS) is 1·15-16·9 per 100 000 children, varying by ethnicity and region. The cause remains unknown but the pathogenesis of idiopathic NS is thought to involve immune dysregulation, systemic circulating factors, or inherited structural abnormalities of the podocyte. Genetic risk is more commonly described among children with steroid-resistant disease. The mainstay of therapy is prednisone for the vast majority of patients who are steroid responsive; however, the disease can run a frequently relapsing course, necessitating the need for alternative immunosuppressive agents. Infection and venous thromboembolism are the main complications of NS with also increased risk of acute kidney injury. Prognosis in terms of long-term kidney outcome overall is excellent for steroid-responsive disease, and steroid resistance is an important determinant of future risk of chronic or end-stage kidney disease.
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http://dx.doi.org/10.1016/S0140-6736(18)30536-1DOI Listing
July 2018

An Update on Hypertension in Children With Type 1 Diabetes.

Can J Diabetes 2018 Apr 6;42(2):199-204. Epub 2018 Mar 6.

Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada; Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada. Electronic address:

The prevalence of hypertension in children with type 1 diabetes is reported to be between 6% and 16%. This potentially modifiable cardiovascular risk factor may go undiagnosed and undertreated, particularly in children with type 1 diabetes. Recent updated Canadian clinical practice guidelines recommend blood pressure screening every 2 years in children with type 1 diabetes as well as routine use of ambulatory blood pressure monitoring. Risk factors for hypertension in type 1 diabetes include poor glycemic control, overweight and obesity and genetic predisposition for hypertension. In terms of pathophysiology, sustained hyperglycemia, angiotensin I and II and inflammatory cytokines have been implicated. Endothelial and vascular dysfunction, with impaired endothelial-dependent vasodilation and increased carotid artery intima-media thickness, are evident in preclinical and clinical studies of children and not just in adults with type 1 diabetes. Early targeted therapy is critical to the control of hypertension and the development of related morbidity. As with hypertension in adults with type 1 diabetes, lifestyle modifications remain first-line therapy, including diet and glycemic control. Initial antihypertensive therapy should be an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker because of their associated effects of reducing microalbuminuria and improving renovascular outcomes. Pediatric hypertension in type 1 diabetes is an area of evolving study and opinion; identification and appropriate treatment is critical for the prevention of micro- and macrovascular complications in adulthood.
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http://dx.doi.org/10.1016/j.jcjd.2018.02.008DOI Listing
April 2018

Childhood Takayasu arteritis: disease course and response to therapy.

Arthritis Res Ther 2017 Nov 22;19(1):255. Epub 2017 Nov 22.

Division of Rheumatology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.

Background: Takayasu arteritis (TAK) is a large vessel vasculitis that rarely affects children. Data on childhood TAK are scarce. The aim of this study was to analyze the presenting features, course and outcome of children with TAK, compare efficacy of treatment regimens and identify high-risk factors for adverse outcome.

Methods: A single-center cohort study of consecutive children fulfilling the EULAR/PRINTO/PReS criteria for childhood TAK between 1986 and 2015 was performed. Clinical phenotypes, laboratory markers, imaging features, disease course and treatment were documented. Disease activity was assessed using the Pediatric Vasculitis Disease Activity Score at each visit.

Outcome: disease flare defined as new symptoms and/or increased inflammatory markers necessitating therapy escalation and/or new angiographic lesions, or death.

Analysis: logistic regression tested relevant variables for flare. Kaplan-Meier analyses compared treatment regimens.

Results: Twenty-seven children were included; 74% were female, median age at diagnosis was 12.4 years. Twenty-two (81%) children presented with active disease at diagnosis. Treatment regimens included corticosteroids alone (15%), corticosteroids plus methotrexate (37%), cyclophosphamide (19%), or a biologic agent (11%). Adverse outcomes were documented in 14/27 (52%) children: two (7%) died within 6 months of diagnosis, and 13 (48%) experienced disease flares. The 2-year flare-free survival was 80% with biologic treatments compared to 43% in non-biologic therapies (p = 0.03); at last follow-up, biologic therapies resulted in significantly higher rates of inactive disease (p = 0.02). No additional outcome predictor was identified.

Conclusions: Childhood TAK carries a high disease burden; half of the children experienced flares and 7% died. Biologic therapies were associated with better control of disease activity.
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http://dx.doi.org/10.1186/s13075-017-1452-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5700506PMC
November 2017

Impact of Adjuvant Urinary Diversion versus Valve Ablation Alone on Progression from Chronic to End Stage Renal Disease in Posterior Urethral Valves: A Single Institution 15-Year Time-to-Event Analysis.

J Urol 2018 03 20;199(3):824-830. Epub 2017 Oct 20.

Division of Urology, The Hospital for Sick Children and Department of Surgery, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Purpose: Long-term progression to end stage renal disease of valve ablation alone vs ablation followed by additional urinary diversion were compared among children with stage 3 chronic kidney disease due to posterior urethral valves.

Materials And Methods: We performed a retrospective study of children with posterior urethral valves and stage 3 chronic kidney disease treated at a single institution between 1986 and 2011. The 3 treatment groups were classified as group 1-valve ablation alone, group 2-ablation plus subsequent vesicostomy and group 3-ablation followed by ureterostomies and/or pyelostomies. Baseline demographic characteristics were analyzed. Statistical analyses compared the incidence of time to end stage renal disease among the intervention groups using the Fisher-Freeman-Halton exact test and Kaplan-Meier analysis with the log rank test. Cox regression was used to determine predictors of end stage renal disease progression.

Results: A total of 40 eligible patients were included in the study (group 1-14 patients, group 2-13 patients, group 3-13 patients). Baseline characteristics and post-intervention estimated glomerular filtration rate revealed no significant between-group differences. A statistically significant difference in progression to end stage renal disease was noted within 1 year after diagnosis of stage 3 chronic kidney disease among the treatment groups (log rank test p=0.02). However, cumulative end stage renal disease incidence at 15-year followup showed no statistical difference (log rank test p=0.628). Cox regression analysis determined that bilateral renal dysplasia (HR 2.76, 95% CI 1.21-6.30) and estimated glomerular filtration rate 60 ml/minute/1.73 m or greater after intervention (HR 0.23, 95% CI 0.09-0.61) were predictive of the likelihood of progression to end stage renal disease.

Conclusions: Urinary diversion following valve ablation in children with stage 3 chronic kidney disease associated with posterior urethral valves may temporarily delay progression to end stage renal disease. However, no long-term benefit was noted from diversion in the ultimate incidence of end stage renal disease, suggesting that these interventions should be seen as a temporizing measure. Bilateral renal dysplasia and post-intervention estimated glomerular filtration rate are independent variables predicting overall chronic kidney disease progression.
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http://dx.doi.org/10.1016/j.juro.2017.10.024DOI Listing
March 2018

Nephrotic syndrome in infants and children: pathophysiology and management.

Paediatr Int Child Health 2017 Nov 15;37(4):248-258. Epub 2017 Sep 15.

a Department of Paediatrics , Univeristy of Toronto , Toronto , Canada.

Nephrotic syndrome is defined by nephrotic-range proteinuria (≥40 mg/m/hour or urine protein/creatinine ratio ≥200 mg/mL or 3+ protein on urine dipstick), hypoalbuminaemia (<25 g/L) and oedema. This review focuses on the classification, epidemiology, pathophysiology, management strategies and prognosis of idiopathic nephrotic syndrome of childhood, and includes a brief overview of the congenital forms.
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http://dx.doi.org/10.1080/20469047.2017.1374003DOI Listing
November 2017

A Toddler Presenting with Pulmonary Renal Syndrome.

Case Rep Nephrol Dial 2017 May-Aug;7(2):73-80. Epub 2017 Jun 23.

Division of Nephrology, The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada.

Pulmonary renal syndrome refers to an association of pulmonary and glomerular disease and includes disorders, such as the ANCA-associated vasculitides, anti-glomerular basement membrane antibody disease, systemic lupus erythematosus, and IgA vasculitis (Henoch-Schönlein purpura). We present the medical history of a 26-month-old boy with an extensive purpuric rash, involving the limbs, trunk, and face, who developed clinically significant pulmonary hemorrhage and renal involvement. Rapid recognition of this rare but potentially life-threatening condition is crucial. In this report, we discuss the differential diagnosis, diagnostic studies, and treatment options to consider when facing a young child presenting with a pulmonary renal syndrome.
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http://dx.doi.org/10.1159/000477662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5567106PMC
June 2017

Hypertension in pediatric patients with chronic kidney disease: management challenges.

Int J Nephrol Renovasc Dis 2017 26;10:205-213. Epub 2017 Jul 26.

Division of Nephrology, The Hospital for Sick Children, Toronto, ON, Canada.

In contrast to adults where hypertension is a leading cause of chronic kidney disease, in pediatrics, hypertension is predominantly a sequela, however, an important one that, like in adults, is likely associated with a more rapid decline in kidney function or progression of chronic kidney disease to end stage. There is a significant issue with unrecognized, or masked, hypertension in childhood chronic kidney disease. Recent evidence and, therefore, guidelines now suggest targeting a blood pressure of <50th percentile for age, sex, and height in children with proteinuria and chronic kidney disease. This often cannot be achieved by monotherapy and additional agents need to be added. Blockade of the renin angiotensin aldosterone system represents the mainstay of therapy, although often limited by the side effect of hyperkalemia. The addition of a diuretic, at least in the earlier stages of chronic kidney disease, might help mitigate this problem.
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http://dx.doi.org/10.2147/IJNRD.S100891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538700PMC
July 2017

A curious case of growth failure and hypercalcemia: Answers.

Pediatr Nephrol 2018 06 7;33(6):995-999. Epub 2017 Aug 7.

Division of Nephrology, University of Toronto, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.

Background: Sarcoidosis is a multisystem granulomatous disease of unknown etiology that rarely presents in childhood. Here, we report a case of pediatric sarcoidosis, presenting with renal failure and hypercalcemia.

Case Diagnosis/treatment: A previously well 14-year-old Caucasian boy was admitted to the Hospital for Sick Children, Canada, for hypertension and renal failure following work-up by his family physician for initial concerns of growth failure. On admission, his weight was 35 kg (<3rd percentile), his height was 148 cm (<3rd percentile), and his blood pressure was 154/116 mmHg (>99th percentile for height). Laboratory findings showed elevated creatinine (218 umol/L), hypercalcemia (3.21 mmol/L), and normocytic anemia (hemoglobin 105 g/L). His further assessment showed a urinary concentrating defect with hypercalciuria (calcium/creatinine 1.76 mmol/mmol) and nephrocalcinosis on ultrasound. His eye examination showed uveitis with conjunctival biopsy remarkable for granulomas, which led to pursuit of a diagnosis of possible sarcoidosis. Angiotensin Angiotensin-converting enzyme was found to be high at 96 U/L, and he had a renal biopsy that was consistent with interstitial nephritis with granulomas. Treatment was started with prednisone leading to resolution of his hypercalcemia but persistence of his mild chronic kidney disease.

Conclusions: This case represents an atypical presentation of a rare pediatric disease and highlights the spectrum of renal manifestations and treatment options in sarcoidosis.
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http://dx.doi.org/10.1007/s00467-017-3769-2DOI Listing
June 2018

A curious case of growth failure and hypercalcemia: Questions.

Pediatr Nephrol 2018 06 7;33(6):991-993. Epub 2017 Aug 7.

Division of Nephrology, University of Toronto, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.

Background: Sarcoidosis is a multisystem granulomatous disease of unknown etiology that rarely presents in childhood. Here, we report a case of pediatric sarcoidosis presenting with renal failure and hypercalcemia.

Case Diagnosis/treatment: A previously well 14-year-old Caucasian boy was admitted to the Hospital for Sick Children, Canada, for hypertension and renal failure following work-up by his family physician for initial concerns of growth failure. On admission, his weight was 35 kg (<3rd percentile), his height was 148 cm (≪3rd percentile), and his blood pressure was 154/116 mmHg (>99th percentile for height). Laboratory findings showed elevated creatinine (218 μmol/L), hypercalcemia (3.21 mmol/L), and normocytic anemia (hemoglobin 105 g/L). His further assessment showed a urinary concentrating defect with hypercalciuria (calcium/creatinine 1.76 mmol/mmol) and nephrocalcinosis on ultrasound. His eye examination showed uveitis with conjunctival biopsy remarkable for granulomas, which led to pursuit of a diagnosis of possible sarcoidosis. Angiotensin-converting enzyme was found to be high at 96 U/L, and he had a renal biopsy that was consistent with interstitial nephritis with granulomas. Treatment was started with prednisone leading to resolution of his hypercalcemia but persistence of his mild chronic kidney disease.

Conclusions: This case represents an atypical presentation of a rare pediatric disease and highlights the spectrum of renal manifestations and treatment options in sarcoidosis.
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http://dx.doi.org/10.1007/s00467-017-3768-3DOI Listing
June 2018

Outcome of kidney transplantation in pediatric patients with ANCA-associated glomerulonephritis: a single-center experience.

Pediatr Nephrol 2017 Dec 1;32(12):2343-2350. Epub 2017 Aug 1.

Division of Nephrology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.

Objectives: Data on kidney transplant outcomes for pediatric patients with end-stage renal disease (ESRD) secondary to anti-neutrophil cytoplasmic antibody glomerulonephritis (ANCA GN), particularly granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), is limited. We describe our experience of kidney transplantation in pediatric ANCA GN patients.

Methods: We performed a retrospective review of patients with ANCA GN who developed ESRD and were transplanted at a single center between the years 2000 and 2014.

Results: Since 2000, there were seven pediatric patients with ANCA GN (four MPA) transplanted. Mean age at ANCA GN diagnosis was 11.8 ± 2.8 (range, 7.2-15.4) years. All seven were ANCA (three anti-PR3/four anti-MPO) positive. Estimated glomerular filtration rate (eGFR) at diagnosis was 11.7 ± 6.3 ml/min/1.73 m. All received steroids and cyclophosphamide and three (23.3%) received plasma exchange. Six were dialysis dependent by 6 months post diagnosis. Time from diagnosis to transplant was 30 ± 12 (range, 17-48) months. Six of the seven received a deceased donor transplant. All patients received induction therapy and standard maintenance immunosuppression post transplant. Median duration of follow-up post transplantation was 27 months (range, 13-88 months). Median eGFR at last follow-up was 77 ml/min/1.73 m (range, 7.9-83.5). One patient lost her transplant to acute cellular rejection following non-adherence to immunosuppression after 21 months of stable transplant function. No patient had recurrence of vasculitis, either renal or extra-renal.

Conclusions: Short-term patient and allograft survival in pediatric patients with ESRD secondary to ANCA GN seems excellent, with no recurrence of vasculitis post transplant in this small cohort.
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http://dx.doi.org/10.1007/s00467-017-3749-6DOI Listing
December 2017