the ins and outs of kidneys from physiomics to transplantation … · 2017. 7. 21. · lecturer:...

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Master and PhD students with a background in biomedical sciences and interest in renal (patho)physiology are eligible.

RadboudUniversitySummerSchoolAugust2017

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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


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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


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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


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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


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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


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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


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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



idtsTutorialBiom

arkers

09.30-10.00OpeningCerem

onyGlom



idtsTutorialBiom

arkersStartExcursion

10.00-10.30(Aula)

Glom


Tubulardisorders-BindelsPreparechallenge

TutorialBiomarkers

10.30-11.00Glom


Tubulardisorders-BindelsPreparechallenge

TutorialBiomarkers

11.00-11.30InsandO

uts-Hoenderop

Glom


Tubulardisorders-BindelsReplacm

ents-Hilbrands

TutorialBiomarkers

11.30-12.00InsandO

uts-Hoenderop

Glom


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


PreparechallengeReplacm

ents-Hilbrands


14.00-14.30InsandO

uts-Hoenderop

Glom


Ciliopathies-Schmidts

Replacments-H

ilbrandsChallengePresentations

14.30-15.00Challengeoutline

PreparechallengeCiliopathies-Schm

idtsReplacm

ents-Hilbrands


15.00-15.30Preparechallenge

PreparechallengeCiliopathies-Schm

idtsReplacm

ents-Hilbrands




idtsReplacm

ents-Hilbrands



idtsReplacm

ents-Hilbrands



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)

the ins and outs of kidneys from physiomics to transplantation … · 2017. 7. 21. · lecturer:...

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