change perspective
Master and PhD students with a background in biomedical sciences and interest in renal (patho)physiology are eligible.
RadboudUniversitySummerSchoolAugust2017
1
InsandOutsofKidneyfromPhysiomicstowardsTransplantationLecturer:JoostHoenderop,PhDDuration:2hrsLearningobjectivesAftercompletingthispart,participants:1. willbeabletodiscussingeneraltermsthemainissuesrelatedtorenaldisorders;2. willbeabletointroducethetopics:glomerulardiseases,tubulardisorders,ciliopathiesandrenal
replacementtherapies;3. willbeabletopresentacaserelatedtooneoftherenaltopics.DescriptionAskick-offofthisrenalweek,ageneralintroductionaboutthetopicRenalDisorderswillbepresentedincludingthefollowingtopics:
- Glomerulardiseases- Tubulardisorders- Ciliopathies- Renalreplacementtherapies
Inaddition,thechallengewillbeintroducedbywhichtheparticipantsingroupsof2-4willaddressaquestionrelatedtooneoftheaforementionedtopicsbystudyingthepresentedcase,searchliterature,discusswithfellowparticipants.Inrelationtothechallenge,apresentationwillbegivenbyeachgrouponthelastdayofthecoursewithrespecttotheirtopic.Finally,aninsightintothetutorialontheusageofbiomarkerswillbegiven.Program• Lecture:Somepracticalinformation• Interactivelecture:Introductiontothetopicofrenaldisorders• Workshop:Thechallenge Prerequisites• Basicbiological/physiologicalknowledgeofthehumanbodyandpreferentiallybasicknowledgeof
thekidneyRecommendedreading• HumanPhysiology,Boron&Boulpaep,3rdedition,2016• TheKidney,Seldin&Giebisch,5thedition,2012• TheKidney,Brenner&Rector,10thedition,2016
RadboudUniversitySummerSchoolAugust2017
2
TheChallengeLecturer:AllDuration:Monday-FridayLearningobjectivesAftercompletingthispart,participants:1. willbeabletodiscussandpresentindetailaclinicalcaserelatedto:glomerulardiseases,tubular
disorders,ciliopathiesorrenalreplacementtherapies;2. willhavebasicknowledgeofcasesrelatedtotheserenaltopics.DescriptionA case will be presented related to: Glomerular diseases, Tubular disorders, Ciliopathies or Renalreplacementtherapies.Workasateamingroupsof2-4participantstostudyonechallengingmedicalcaseandgiveadetailedpresentationonthelastdayofthecourse.- Glomerulardiseases:Presentastep-by-stepapproachtoidentifythesolublefactorcausingpost-
transplantrecurrenceinpatientswithidiopathicnephroticsyndrome.- Tubulardisorders:MutationsintheSLC12A3genearethecauseofGitelmansyndrome.Oneofthe
maincharacteristicsishypomagnesemia.Describekeyobjectivesandstudydesigntoexaminethecauseofthehypomagnesemia.
- Ciliopathies:Aboyof12-yearswithfemurfractureafterminortrauma,routinebloodvaluesrevealrenal insufficiency as incidental finding.Describe yourworkupof the case including differentialdiagnosisandfurtherclinicalmanagement.
- Renalreplacementtherapies:Theshortageofhumandonorkidneyshaspromptedthesearchforalternativesourcesofdonororgans.Amongstothers,theuseofporcinekidneysfortransplantationinhumanshasbeenexplored.Currentlytherearetwoapproaches:Useofwholeporcinekidneysforxenotransplantationordecellularizationofporcinekidneystoobtainascaffoldwhichcanberepopulatedwithhumancells.Forbothapproachesseveralhurdleshavetobetakenbeforeclinicalimplementationcanberealized.Yourchallengeistoidentifythemajorhurdlesandtoprovideanideawhichwouldtakeoneofthetwostrategiesasignificantstepfurther.
Program• Participantswillworkonthischallengeduringtheweek• OnFriday,thecaseswillbepresentedbytheindividualgroupsPrerequisites• Basicbiological/physiologicalknowledgeofthehumanbodyandpreferentiallybasicknowledgeof
thekidneyRecommendedreading• Onlineliteraturerelatedtoyourcase
RadboudUniversitySummerSchoolAugust2017
3
GlomerularDiseasesLecturer:BartSmeets,PhDDuration:5hrsLearningobjectivesAftercompletingthispart,participantswillbeableto:1. understand the pathological and clinical presentation of the most
commonglomerulardiseases2. visualizeandinterpretrenaltissuemorphology,markerexpressionand
ultrastructureusingdifferentmicroscopicapproachesforthediagnosisofpatientswithglomerulardiseases.
3. understand the relevance and limitations of the diagnostic andtherapeuticneedssuchasdeterminationofrenalfunctionandbiomarkersofglomerulardiseases.
4. understandtheneedforresearchtogainabetterunderstandingofglomerulardiseases.DescriptionEach kidney ismade up of approximately onemillion nephrons that all contain a glomerulus. Theglomerulusplaysanessentialroleinthefiltrationofbloodandtheformationofurine.Damagetotheglomeruliresultsintheescapeofsubstanceslikeprotein,andevenredorwhitebloodcellsintotheurinary fluid. As the damage progresses, glomerular function is lost. This impairs the excretion ofharmfultoxicwastes,leadingtotheirbuildupinthebody.Whentheglomerulibecomedamagedandlosetheirfunction,itiscalledaglomerulardisease.Program• Interactivelecture:Introductiontotheclinicalpresentationofglomerulardiseases• Interactivelecture:Introductiontothepathologyofglomerulardiseases• Demonstrativelecture:"Fromdiseasedkidneytodiagnosis"discussingsamplepreparation,tissue
sectioningandmicroscopictechniques.• Group assignment: Interpretation and evaluation electronmicroscopic images of patientswith
differentglomerulardiseases.• Interactive lecture:Methods of determination of renal function, biomarkers and personalized
treatment• Interactivelecture:State-ofthe-artresearchapproachestostudyglomerulardisease Prerequisites• BasicbiologicalknowledgeofthehumanbodyandpreferentiallybasicknowledgeofthekidneyRecommendedreading• The emergence of the glomerular parietal epithelial cell. Shankland SJ, Smeets B, Pippin JW,
MoellerMJ.NatRevNephrol.10:158-73,2014• Parietal epithelial cells and podocytes in glomerular diseases. Smeets B, Moeller MJ. Semin
Nephrol.32:357-67,2012
RadboudUniversitySummerSchoolAugust2017
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TubularDisordersLecturer:RenéBindels,PhD,JoostHoenderop,PhD,EstherPeters,PhDDuration:5hrsLearningobjectivesAftercompletingthispart,participantswillbeableto:1. understandtheclinicalpresentationandthemolecular
disturbanceofthemostcommontubulopathies2. describe the various model systems to study renal
transportfunctions
DescriptionThetubularsegmentsofthekidneyarelinedbyspecializedepithelialcellswhichplayanessentialroleinhomeostasisbyreabsorbing,secretingandexcretingsolutesandthusfixingthefinalcompositionofurine.Multiple raredisordershavebeendescribedaffecting thesespecialized functions, leading toinappropriaterenallossesofNaCl,calcium,magnesium,waterandphosphate,hypertensionandacid-base disturbances. These disorders are often affecting children and causing multi-systemic, life-threateningcomplicationsandprogressiontorenalfailure.Knowledgeoftheprimarycauseoftheserenaldiseases isessential tounderstand itsmolecularmechanismsand foradequateclassification,prognosis, and treatment. Here we will present genotype-phenotype correlations of varioustubulopathies includingthecharacterizationofnovel identifiedrenalelectrolytetransportersatthemolecular, cellular and functional level, and finally at a systemic level that intertwines amultidisciplinaryapproachtoestablishcomprehensivemodelsforrenalsalttransport.Thefunctiomicsof themutatedrenalproteinswillbediscussed inorder toelucidate themolecularmechanismsofrenaldiseases. Program• Interactivelecture:Aguidedtouralongthenephron• Interactivelecture:Anoverviewofthetubulopathies• Demonstration:modelstostudykidneyfunctionincludingzebrafishandrenalcelllines• Hands-on:Measuretubulartransportfunction Prerequisites• BasicbiologicalknowledgeofthehumanbodyandpreferentiallybasicknowledgeofthekidneyRecommendedreading• Gitelman's syndrome: towards genotype-phenotype correlations? Riveira-Munoz E, Chang Q,
BindelsRJ,DevuystO.PediatrNephrol.22:326-32,2007• Inheritedrenaldiseases.LeungJC.CurrPediatrRev.10:95-100,2014• Magnesium inman: implications forhealthanddisease.deBaaij JH,HoenderopJG,BindelsRJ.
PhysiolRev.95:1-46,2015
RadboudUniversitySummerSchoolAugust2017
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CiliopathiesLecturer:MiriamSchmidts,MD,PhDDuration:5hrs LearningobjectivesAftercompletingthispart,participantswillbeableto:1. understandthepathologicalandclinicalpresentationofthemost
commonciliopathieswithrenalinvolvement2. understand the relevance and limitations of the diagnostic and
therapeutic approaches such as disease classification byphenotypeassessment,renalimagingapproaches,humangeneticsapproachesandciliaryvisualization
3. understandtheneedforresearchtogainabetterunderstandingofciliopathieswithrenalinvolvement
DescriptionCiliaarehair-likestructuresextendingfrommosthumancells includingtherenal tubules.Overthepast2decades,anessentialroleoftheseevolutionarilyextremelywellconservedorganellesindiversecell signalling pathways as emerged and ciliary dysfunction and/or malfunction of ciliary proteinsresults in diverse humanphenotypes including renalmalformations, cyst development and loss orrenal function. During this tutorial, youwill get hands-on experience on how to diagnose a renalciliopathyand identifytheunderlyinggeneticcause inahumanpatient.YouwillgetanoutlookonCiliopathyresearch,includingpotentialtherapeuticapproaches.Ifyouhaveanunsolvedcaseyouareinvitedtobringyourowndataset. Program• Interactivelecture:Introductiontotheclinicalspectrumofciliopathies(withrenalinvolvement)• Demonstrative lecture: Introduction to ciliopathy genetics and Next generation sequencing
techniques• Groupassignment:InterpretationandevaluationofclinicalandNGSsequencingdataofpatients
with different renal ciliopathies (Case review, whole exome sequencing data filtering, shortinternetsearchandconcisepresentationofresultstotheothergroups)
• Interactivelecture:State-ofthe-artresearchapproachestostudyciliopathies Prerequisites• Basicbiologicalknowledgeofthehumanbodyandpreferentiallybasicknowledgeofthekidney• BasicknowledgeofhumangeneticsRecommendedreading• Arerenalciliopathies (replication)stressedout?SlaatsGG,GilesRH.TrendsCellBiol.25:317-9,
2015• Ciliopathies:GeneticsinPediatricMedicine.OudMM,LamersIJ,ArtsHH.JPediatrGenet.6:18-29,
2017
RadboudUniversitySummerSchoolAugust2017
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Renal Replacement Therapies Lecturer:LuukHilbrands,MD,PhDandMartijnWilmer,PhDDuration:5hrsLearningobjectivesAftercompletingthispart,participantswillbeableto:1. discuss the various replacement therapies given to patients
withakidneydisease2. describetherecentdevelopmentsinthisfield
DescriptionPatientswithend-stagerenaldisease (ERSD)areunabletoremovewasteproductsandfluids fromtheirbody.Tostayalive,theyhavetobetreatedwithrenalreplacementtherapy.Currently,therearetwo available renal replacement treatment options for individuals with ESRD: dialysis and kidneytransplantation.Bothmodesoftreatmentshavetheirownmeritsandshortcomings.Inaplenarylecture,wewilldiscussthe current state-of-the-art of dialysis and transplantation and address the limitations of thesetreatmentoptions.Thelecturewillbeillustratedbyaguidedtouronthedialysiswardofouruniversityhospitalwheretheworkingmechanismofdialysismachinesisdemonstratedduringthetreatmentofpatients.Moreover,youwillhaveaninterviewwithapatientwhounderwentrenaltransplantation.Theshortageofdonorkidneysfromdeceaseddonors,hasstimulatedtheuseofkidneysfromlivingdonors.Currently,morethan60%ofthekidneytransplantations intheNetherlandsareperformedwithlivingkidneydonors.Withinnovativesolutions,wearenowabletocrosstraditionalbarriers,e.g.enablingthetransplantationbetweenbloodgroupincompatibledonorsandrecipients.Program• Interactivelecture:Introductiontorenalreplacementtherapies• Interviewwithapatientwhounderwentrenaltransplantation• Hands-oninthelaboratoryoftheBiokid• AtouratthedialysiscenteroftheRadbouduniversitymedicalcenter Prerequisites• Basicbiological/physiologicalknowledgeofthehumanbodyandpreferentiallybasicknowledgeof
thekidneyRecommendedreading• UrinarymicroRNAasbiomarkerinrenaltransplantation.vandeVrieM,DeegensJK,EikmansM,
vanderVlagJ,HilbrandsLB.AmJTransplant.2016Oct15.doi:10.1111• Astrategyforgeneratingkidneyorganoids:Recapitulatingthedevelopmentinhumanpluripotent
stemcells.TakasatoM,LittleMH.DevBiol.420:210-20,2016
RadboudUniversitySummerSchoolAugust2017
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KidneyBiomarkersfromBenchtoBedside:atutorialLecturer:JanvandenBrand,PhDDuration:3hrsLearningobjectivesAftercompletingthetutorial,participants:1. willbeable toprovideaworkingdefinitionof the
conceptbiomarker2. willhaveabasicunderstandingofepidemiological
researchdesignstoevaluatepredictiveperformanceofbiomarkers3. can calculate and interpret predictive performance measures in diagnostic and prognostic
biomarkerstudies4. willbeablecreateabasicmultivariatepredictionmodelusinglogisticregression(orCoxregression
–advanced)5. canexplaintheneedforexternalvalidation,clinicalimpactassessmentandmodelupdatingprior
toapplyinganewbiomarkertoyourspecificsetting
DescriptionDuringthistutorial,youwillgethands-onexperienceonhowtodesign,analyzeandinterpretaclinicalepidemiologicalstudytoevaluatethepredictiveperformanceofapossiblediagnosticorprognosticbiomarkerinkidneydisease.Thetutorialwillconsistofinteractivelecturesandassignmentstogetyoustartedonyourownclinicalstudy.Ifyouareworkingonaclinicalpredictionmodelfordiagnosisorprognosisyouareinvitedtobringyourowndataset. Prerequisites• Basic skills ina statistical softwareprogramcapableof runningmultivariate regressionanalysis
(e.g.SPSS,SAS,Stata,R).AccesstoSPSS,SASandRisavailableoncampus.Ifyouprefertouseanotherprogram,bringyourownlaptop!
Recommendedreading• BiasinClinicalResearch.G,JagerKJ,DekkerFW,WannerC,ZoccaliC.KidneyInt.73:148-53,2008• DiagnosticmethodsI:sensitivity,specificity,andothermeasuresofaccuracy.vanStralenKJ,Stel
VS,ReitsmaJB,DekkerFW,ZoccaliC,JagerKJ.KidneyInt.75:1257-63,2009• Prognosis and prognostic research: what, why and how?Moons KG, Royston P, Vergouwe Y,
GrobbeeDE,AltmanDG.BMJ.338:b375,2009
SundayMonday
TuesdayWednesday
ThursdayFriday
Saturday
week1:
06/08/201707/08/2017
08/08/201709/08/2017
10/08/201711/08/2017
12/08/2017
08.30-09.00Welcom
eGlom
erulardiseases-Smeets
Tubulardisorders-BindelsCiliopathies-Schm
idtsTutorialBiom
arkers
09.00-09.30(Aula)
Glom
erulardiseases-Smeets
Tubulardisorders-BindelsCiliopathies-Schm
idtsTutorialBiom
arkers
09.30-10.00OpeningCerem
onyGlom
erulardiseases-Smeets
Tubulardisorders-BindelsCiliopathies-Schm
idtsTutorialBiom
arkersStartExcursion
10.00-10.30(Aula)
Glom
erulardiseases-Smeets
Tubulardisorders-BindelsPreparechallenge
TutorialBiomarkers
10.30-11.00Glom
erulardiseases-Smeets
Tubulardisorders-BindelsPreparechallenge
TutorialBiomarkers
11.00-11.30InsandO
uts-Hoenderop
Glom
erulardiseases-Smeets
Tubulardisorders-BindelsReplacm
ents-Hilbrands
TutorialBiomarkers
11.30-12.00InsandO
uts-Hoenderop
Glom
erulardiseases-Smeets
PreparechallengeReplacm
ents-Hilbrands
ChallengePresentations
12.00-12.30Lunch/
12.30-13.00Lunch
LunchLunch
LunchHandinbikes
13.00-13.30
13.30-14.00InsandO
uts-Hoenderop
Glom
erulardiseases-Smeets
PreparechallengeReplacm
ents-Hilbrands
ChallengePresentations
14.00-14.30InsandO
uts-Hoenderop
Glom
erulardiseases-Smeets
Ciliopathies-Schmidts
Replacments-H
ilbrandsChallengePresentations
14.30-15.00Challengeoutline
PreparechallengeCiliopathies-Schm
idtsReplacm
ents-Hilbrands
ChallengePresentations
15.00-15.30Preparechallenge
PreparechallengeCiliopathies-Schm
idtsReplacm
ents-Hilbrands
ChallengePresentations
15.30-16.00Preparechallenge
Tubulardisorders-BindelsCiliopathies-Schm
idtsReplacm
ents-Hilbrands
16.00-16.30Preparechallenge
Tubulardisorders-BindelsCiliopathies-Schm
idtsReplacm
ents-Hilbrands
16.30-17.00Preparechallenge
Tubulardisorders-BindelsCiliopathies-Schm
idtsReplacm
ents-Hilbrands
17.00-17.30
17.30-18.00
18.00-18.30Handinbikes
18.30-19.00(CarParkSpinoza)
19.00-19.30
19.30-20.00
20.00-20.30
20.30-21.00EndExcursion
21.00-21.30
21.30-22.00
ScheduleRadboudSummerSchool2017
Guestlecture
(Aula)
followedby
aBBQBikedistribution
(CarParkSpinoza)
Welcom
ereception
(Aula)
Sportsprogramme
(SportsCentre)
Pubquiz
(citycenter)
Citytour
or
Boattrip
Pancakedinner
CertificateCeremony
FarewellReception
(Aula)
Registration
&
handingoutkeyto
accommodation
(Aula)