ReportoftheESPNCKD-MBDWorkingGroup2018,ESPNCouncilMeetingLeuvenCoordinator:D.Haffner;boardmembers:J.Groothoff,R.Shroff,R.Bacchetta,S.Bakkaloglu

Educationalprojects1)PhosphateEducationProgram(PEP)(coordinator:S.Bakkaloglu):• Newstrategiesinhyperphosphatemiamanagement; ESPNresearchgrant2014.01• Itisplannedto preparedetailed educational materialwhich willbe distributed to ESPN

units.Thiswillinclude acell phone application.2)CKD-MBDmasterclassatESPNinAntalya2018(togetherwithdialysisWG)

Finishedguidelinesandrecommendationsin2017ClinicalpracticerecommendationsforvitaminDtreatmentinchildrenwithCKDandondialysis(coordinator:R.Shroff).Jointproject:ESPNCKD-MBD&dialysisWGs

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Special Report

Clinical practice recommendations for native vitamin Dtherapy in children with chronic kidney diseaseStages 2–5 and on dialysis

Rukshana Shroff1, Mandy Wan1, Evi V. Nagler2, Sevcan Bakkalo!glu3, Dagmar-C. Fischer4, Nicholas Bishop5,

Mario Cozzolino6, Justine Bacchetta7, Alberto Edefonti8, Constantinos J. Stefanidis9, Johan Vande Walle10,

Dieter Haffner11, Gunter Klaus12 and Claus Peter Schmitt13 on behalf of the European Society for Paediatric

Nephrology Chronic Kidney Disease Mineral and Bone Disorders and Dialysis Working Groups1Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK, 2Ghent University Hospital, Ghent, Belgium, 3Gazi University

Hospital, Ankara, Turkey, 4Rostock University Medical Centre, Rostock, Germany, 5University of Sheffield, Sheffield, UK, 6Department of Health

Sciences, Ospedale San Paolo, University of Milan, Milan, Italy, 7Hopital Femme Mere Enfant, Lyon University, Bron, France, 8Fondazione

IRCCS C"a Granda Ospedale Maggiore Policlinico, Milan, Italy, 9“A & P Kyriakou”, Children’s Hospital, Athens, Greece, 10Ghent University,

Utopaed, Belgium, 11Children’s Hospital, Hannover, Germany, 12KfH Pediatric Kidney Center, Marburg, Germany and 13Center for Pediatric &

Adolescent Medicine, Heidelberg, Germany

Correspondence and offprint requests to: Rukshana Shroff; E-mail: Rukshana.Shroff@gosh.nhs.uk

A B S T R A C T

Vitamin D deficiency is widely prevalent and often severe inchildren and adults with chronic kidney disease (CKD).Although native vitamin D {25-hydroxyvitamin D [25(OH)D]}is thought to have pleiotropic effects on many organ systems, itsskeletal effects have been most widely studied. The 25(OH)Ddeficiency is causally linked with rickets and fractures in healthychildren and those with CKD, contributing to the CKD–mineral and bone disorder (MBD) complex. There are few stud-ies to provide evidence for vitamin D therapy or guidelines forits use in CKD. A core working group (WG) of the EuropeanSociety for Paediatric Nephrology (ESPN) CKD–MBD andDialysis WGs have developed recommendations for the evalua-tion, treatment and prevention of vitamin D deficiency in chil-dren with CKD. We present clinical practice recommendationsfor the use of ergocalciferol (vitamin D2) and cholecalciferol(vitamin D3) in children with CKD Stages 2–5 and on dialysis.A parallel document addresses treatment recommendations foractive vitamin D analogue therapy. The WG has performed anextensive literature review to include meta-analyses andrandomized controlled trials in healthy children as well as

children and adults with CKD, and prospective observationalstudies in children with CKD. The Grading ofRecommendation, Assessment, Development and Evaluation(GRADE) system has been used to develop and grade the rec-ommendations. In the absence of applicable study data, theopinion of experts from the ESPN CKD–MBD and DialysisWGs is provided, but clearly GRADE-ed as such and must becarefully considered by the treating physician, and adapted toindividual patient needs as appropriate.

Keywords: children, cholecalciferol, chronic kidney disease(CKD), dialysis, vitamin D

I N T R O D U C T I O N

Vitamin D deficiency is widely prevalent and often severe inchildren and adults with chronic kidney disease (CKD), andcontributes to abnormalities in calcium, phosphate and para-thyroid hormone (PTH) homeostasis. The mineral dysregula-tion in CKD directly affects bone strength, mineralization [1, 2]and architecture [1], and is called CKD–mineral and bone dis-order (CKD–MBD) [3]. CKD–MBD in childhood presents||

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VC The Author 2017. Published by Oxford University Presson behalf of ERA-EDTA. All rights reserved.

1

Nephrol Dial Transplant (2017) 1–16doi: 10.1093/ndt/gfx065

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Special Report

Clinical practice recommendations for treatment with activevitamin D analogues in children with chronic kidney diseasestages 2–5 and on dialysis

Rukshana Shroff1, Mandy Wan1, Evi V. Nagler2, Sevcan Bakkalo!glu3, Mario Cozzolino4, Justine Bacchetta5,

Alberto Edefonti6, Constantinos J. Stefanidis7, Johan Vande Walle8, Gema Ariceta9, Gunter Klaus10,

Dieter Haffner11 and Claus Peter Schmitt12 on behalf of the European Society for Paediatric Nephrology

Chronic Kidney Disease Mineral and Bone Disorders and Dialysis Working Groups.1Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK, 2Ghent University Hospital, Ghent, Belgium, 3Gazi

University Hospital, Ankara, Turkey, 4Ospedale San Paolo, Department of Health Sciences, University of Milan, Milan, Italy, 5Hopital Femme

Mere Enfant, Lyon University, Bron, France, 6Fondazione IRCCS C"a Granda Ospedale Maggiore Policlinico, Milan, Italy, 7"A. and P. Kyriakou"

Children’s Hospital, Athens, Greece, 8Ghent University, Utopaed, Belgium, 9Servicio de Nefrolog#ıa Pedi#atrica, Hospital Universitari Vall

d’Hebron, Barcelona, Espa~na, 10KfH Pediatric Kidney Center, Marburg, Germany, 11Children’s Hospital, Hannover, Germany and 12Center for

Pediatric and Adolescent Medicine, Heidelberg, Germany

Correspondence and offprint requests to: Claus Peter Schmitt; E-mail: ClausPeter.Schmitt@med.uni-heidelberg.de

A B S T R A C T

In patients with chronic kidney disease (CKD), renal synthesisof active vitamin D [1,25-dihydroxyvitamin D (1,25(OH)2D)]declines and is associated with hypocalcaemia, secondary hyper-parathyroidism and the spectrum of CKD–mineral and bonedisorder (MBD). In advanced CKD, active vitamin D analogues,including alfacalcidol, calcitriol and paricalcitol, are routinelyadministered. There are few studies on the use of vitamin Danalogues in children with CKD and on dialysis. It is difficult todefine bone-specific outcomes that can guide treatment withactive vitamin D analogues in children with CKD-MBD. A coreworking group (WG) of the European Society for PaediatricNephrology (ESPN) CKD-MBD and Dialysis WGs has devel-oped recommendations for the use of active vitamin D therapyin children with CKD and on dialysis. A second document inparallel with this one covers treatment recommendations fornative vitamin D therapy. The WGs have performed an exten-sive literature review to include systematic reviews and random-ized controlled trials in adults and children with CKD and pro-spective observational studies in children with CKD. TheGrading of Recommendation, Assessment, Development and

Evaluation (GRADE) system was used to develop and grade therecommendations. In the absence of applicable study data, theopinion of experts from the ESPN CKD-MBD and DialysisWGs is provided, but clearly GRADE-ed as such and must becarefully considered by the treating physician and adapted toindividual patient needs as appropriate.

Keywords: chronic kidney disease (CKD), CKD-MBD, dialy-sis, pediatrics, vitamin D

I N T R O D U C T I O N

In patients with chronic kidney disease (CKD), renal synthesisof active vitamin D [1,25-dihydroxyvitamin D (1,25(OH)2D)]declines with kidney function loss. Low serum 1,25(OH)2Dconcentrations contribute to hypocalcaemia, secondary hyper-parathyroidism and the spectrum of CKD–mineral and bonedisorder (MBD) [1]. In more advanced stages of CKD,active vitamin D analogues, including calcitriol [the naturallyoccurring form of 1,25(OH)2D3], alfacalcidol (1a hydroxyvita-min D3, a synthetic prohormone that requires activation by||

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VC The Author 2017. Published by Oxford University Presson behalf of ERA-EDTA. All rights reserved.

1

Nephrol Dial Transplant (2017) 1–14doi: 10.1093/ndt/gfx080

Guidelinesandbestpracticerecommendations

1. ClinicalpracticerecommendationsforuseofGHinchildrenwithCKD(coordinator:D.Haffner)

• Jointproject:ESPNCKD-MBD,Dialysis&TransplantWGs;2meetingwereheld(n=9)

• Plan:submissionofthemanuscripttoNephrolDialTransplant inOctober2018

2.Positionpaperontheuseofcinacalcet inchildrenondialysis(coordinator:J.Bacchetta)• Jointproject:ESPNCKD-MBD&DialysisWGs• 1st meetingwasheldon7-8.6.2018inLeuven;firstdraftwaswritten

3.ClinicalpracticerecommendationsforboneevaluationinpediatricCKD(coordinator:S.Bakkaloglu)• Joinedproject:ESPNCKD-MBDWGandEUROD(PieterEvenepoel)• 1st meetingplannedinearly2019

NewInitiative:RenalNutritionTaskforce (coordinatorR.Shroff)CollaborationofCKDanddialysisWGs,14membersfromEuropeandNorthAmerica;7nephrologistsand7dietitians.Twoguidelinesforcompletingthisyear:

1. Protein-energymanagementofchildrenwithCKD2-5D(1stmeetingwasheldinJune)2. Dieteticmanagementofcalcium-phosphateinCKD2-5D(1stmeetinginNovember)

Clinicalstudies:EffectsofvitaminDsupplementationonbonemetabolisminpediatric CKDpts.(coordinator:D.Haffner)• Jointproject:ESPNCKD-MBDWGand4CStudyconsortium;ESPNresearchgrant2014.01

Assessmentofcalciumbalance inchildrenwith chronic kidney disease tooptimisetreatment strategies (Cal-Bal study),(coordinator:R.Shroff)• Jonitventure:ESPNCKD-MBD&DialysisWGs;7centresin6countries:London,

Heidelberg,Hannover,Lyon,Athens,AdanaandVilnius• Costs willbe partly covered by the ESPNgrant2016.02 (€15,000)• Enrollmentwasstartedontimein2017.Recruitedn=74children(CKD-Dialysisand

healthycontrols)fromLondon,AdanaandAthensDieterHaffner onbehalfofthemembersoftheESPNCKD-MBDworkinggroup,5.9.2018

Financialoverview:

DieterHaffner onbehalfofthemembersoftheESPNCKD-MBDworkinggroup,5.9.2018

ESPNListofexpensesDialysisandCKD-MBDWorkingGroups(WG)2017

06.12.2017SevcanA.Bakkaloglu DialysisonlypublicationinNephronexcesspagecharges 674,93EUR17.10.2017FrancisCalderDialysisonlyTravelExpensesESPNGlasgowGuidelinesMtg 369,16EUR23.06.2017 JustineBacchettaDialysisandCKD-MBDGuidelinesMtgExpensesHeidelberg22.05.2017 355,85EUR23.06.2017Marjolein Bonthuis DialysisandCKD-MBDGuidelinesMtg ExpensesHeidelberg21.05.2017 298,90EUR23.06.2017FernandoSantosDialysisandCKD-MBDGuidelinesMtgExpensesHeidelberg21.05.2017 676,32EUR3.06.2017 RukshanaShroff DialysisandCKD-MBDGuidelinesMtg ExpensesAthens28.04.2017 330,60EUR23.06.2017ChungManWanDialysisandCKD-MBDGuidelinesMtg ExpensesHeidelberg21.05.2017 221,35EUR31.05.2017ElkeWühl DialysisandCKD-MBDGuidelinesMtg ExpensesHeidelberg05.17Catering 36,27EUR22.06.2017Hip-HotelHeidelbergDialysisandCKD-MBDGuidelinesMtg Re.-Nr.2217039049270517 220,00EUR29.05.2017FernandoSantosDialysisandCKD-MBDGuidelinesMtgHeidelberg05/17Travelexp. 676,32EUR

SubtotalcombinedmeetingsDialysisandCKD-MBD €2815,61(dividedby2WG)

=TotalCKD-MBDWorkingGroup €1407,805

=TotalDialysisWorkingGroup €2451,895

Remainingmoneyfor2018:incentivefor2publishedguidelines(4,000€)50%foreachWG