AIRG-E, EKPF, ALCER, FRIAT, REDINREN, RICORS2040, SENEFRO , SET, ONT CKD: The burden of disease invisible to research funders Special article

nefrologia2022;42(1):65–84

w w w . r e v i s t a n e f r o l o g i a . c o m RevistadelaSociedadEspañoladeNefrología

Special article

CKD: The burden of disease invisible to research funders

AIRG-E, EKPF, ALCER, FRIAT, REDINREN, RICORS2040, SENEFRO

, SET, ONT

a r t i c l e i n f o

Articlehistory:

Received15September2021 Accepted19September2021 Availableonline17November2021

Keywords:

Chronickidneydisease Decadeofthekidney Researchfunding Burdenofdisease COVID-19

Kidneytransplantation Kidneyfailure Acceleratedaging

a bs t r a c t

Theuptakeofthecurrentconceptofchronickidneydisease(CKD)bythepublic,physicians andhealthauthoritiesislow.PhysiciansstillmixupCKDwithchronickidneyinsufficiency or failure.Ina recentmanuscript, only23%ofparticipantsinacohortofpersonswith CKDhadbeendiagnosedbytheirphysiciansashavingCKDwhile29%hasadiagnosisof cancerand82%hadadiagnosisofhypertension.Forthewiderpublicandhealthauthorities, CKDevokeskidneyreplacementtherapy(KRT).InSpain,theprevalenceofKRTis0.13%.A prevalentviewisthatforthoseinwhomkidneysfail,theproblemis“solved”bydialysis orkidneytransplantation.However,themainburdenofCKDisacceleratedagingandall- causeandcardiovascularprematuredeath.CKDisthemostprevalentriskfactorforlethal COVID-19andthefactorthatmostincreasestheriskofdeathinCOVID-19,afteroldage.

Moreover,menandwomenundergoingKRTstillhaveanannualmortalitywhichis10–100- foldhigherthansimilaragepeers,andlifeexpectancyisshortenedbyaround40yearsfor youngpersonsondialysisandby15yearsforyoungpersonswithafunctioningkidneygraft.

CKDisexpectedtobecomethefifthglobalcauseofdeathby2040andthesecondcauseof deathinSpainbeforetheendofthecentury,atimewhen1in4SpaniardswillhaveCKD.

However,by2022,CKDwillbecometheonlytop-15globalpredictedcauseofdeaththat isnotsupportedbyadedicatedwell-fundedCIBERnetworkresearchstructureinSpain.

LeadingSpanishkidneyresearchersgroupedinthekidneycollaborativeresearchnetwork REDINRENhavenowappliedfortheRICORScallofcollaborativeresearchinSpainwiththe supportoftheSpanishSocietyofNephrology,ALCERandONT:RICORS2040aimstoprevent thedirepredictionsfortheglobal2040burdenofCKDfrombecomingtrue.However,only thehighestlevelofresearchfundingthroughtheCIBERwillallowtoadequatelyaddressthe issuebeforeitistoolate.

©2021SociedadEspa ˜noladeNefrolog´ıa.PublishedbyElsevierEspa ˜na,S.L.U.Thisisan openaccessarticleundertheCCBYlicense(http://creativecommons.org/licenses/by/4.0/).

∗ Correspondingauthor.

E-mailaddress:[email protected]

1 PleaseseealistoftheauthorsfromtheseorganizationsthatapproveandsupportthemanuscriptinAppendixA.

2 AIRG-E:AsociaciónInformaciónEnfermedadesRenalesGenéticas;EKPF:EuropeanKidneyPatients’Federation;ALCER:Federación NacionaldeAsociacionesparalaLuchaContralasEnfermedadesdelRi ˜nón;FRIAT:FundaciónRenalÍ ˜nigoÁlvarezdeToledo;REDINREN:

ReddeInvestigaciónRenal;RICORS2040:ResultadosenSalud2040;SENEFRO:SociedadEspa ˜noladeNefrología;SET:SociedadEspa ˜nola deTrasplante;ONT:OrganizaciónNacionaldeTrasplantes.

https://doi.org/10.1016/j.nefro.2021.09.004

0211-6995/©2021SociedadEspa ˜noladeNefrolog´ıa.PublishedbyElsevierEspa ˜na,S.L.U.ThisisanopenaccessarticleundertheCCBY license(http://creativecommons.org/licenses/by/4.0/).

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Enfermedadrenalcrónica:lacargasanitariainvisibleparalos organismosque

Palabrasclave:

Enfermedadrenalcrónica LadecadadelRi ˜nón

Financiacióndelainvestigación Cargasanitariadelaenfermedad COVID-19

Trasplanterenal Fallorenal

Envejecimientoacelerado

r e s u m en

Elimpactodelconceptoactualdeenfermedadrenalcrónica(ERC)enlapoblación,médicos yautoridadessanitariashasidobajo.LosmédicosaúnconfundenlaERCconlainsuficiencia renalcrónica.Enunmanuscritoreciente,enunacohortedepersonasconERC,soloel23%

delosparticipantesfuerondiagnosticadosdeERCporsusmédicosmientrasqueel29%

estabandiagnosticadosdecánceryel82%dehipertensión.Paraelpúblicoengeneraly lasautoridadessanitarias,laERCevocalaterapiadereemplazorenal(TRR).EnEspa ˜na,la prevalenciadeTRResdel0,13%.Laopiniónpredominanteesqueparaaquellosenlosque fallanlosri ˜nones,elproblemase“resuelve”mediantediálisisotrasplantederi ˜nón.Sin embargo,laprincipalcargasanitariadelaERCeselenvejecimientoaceleradoylamuerte prematuradecausacardiovascularodecualquiercausa.LaERCeselfactormasprevalente deriesgodemortalidadporCOVID-19despuésdelaedadavanzada.

Además,loshombresymujeresquesesometenaTRRtodavíatienenunamortalidadanual queesde10a100vecessuperiorasusparesdeedadessimilares,ylaesperanzadevidase reduceenalrededorde40a ˜nosparajóvenesendiálisisyen15a ˜nosparajóvenesconun injertorenalfuncionante.

SeesperaquelaERCseconviertaenlaquintacausamundialdemuertepara2040yla segundacausademuerteenEspa ˜naantesdefindesiglo,épocaenlaque1decada4 espa ˜nolestendráERC.

Sinembargo,para2022,laERCseconvertiráenlaúnicacausademuerteentrelas15prin- cipalesanivelmundialquenocuentaconelrespaldodeunaestructuradeinvestigación CIBERenEspa ˜na.

LosPrincipalesgruposdeinvestigaciónrenalenEspa ˜naagrupadosenlareddeinvesti- gacióncolaborativarenalREDINRENhansolicitadolaconvocatoriaRICORSdeinvestigación colaborativaenEspa ˜naconelapoyodelaSociedadEspa ˜noladeNefrología,ALCERyONT:

RICORS040tienecomoobjetivoevitarquesehaganrealidadlasterriblesprediccionessobre lacargamundialdeERCpara2040.Sinembargo,soloelmásaltoniveldefinanciaciónde lainvestigaciónatravésdelCIBERpermitiráabordaradecuadamenteelproblemaantesde queseademasiadotarde.

©2021SociedadEspa ˜noladeNefrolog´ıa.PublicadoporElsevierEspa ˜na,S.L.U.Esteesun art´ıculoOpenAccessbajolalicenciaCCBY(http://creativecommons.org/licenses/by/4.0/).

Thepresent manuscriptsummarizes keyfeaturesofthe conceptofchronickidneydisease(CKD),aswellasinforma- tiononthecurrentandfutureburdenofCKD,andevidence that CKD as a health issue is underestimates by Spanish HealthResearchfundingagencies.Amoreextensivereport hasbeenpreviouslypublished.¹Thesignatoriesbelievethat thecurrentandfutureburdenofCKD,whichisprojectedtohit hardlycountrieswithlonglifeexpectancyandanageingpop- ulationsuchasSpainconstitutesanationalemergencythat requirethehighestlevelavailableofresearchfundingthrough theCIBERorganization.

Chronic kidney disease: an evolving concept not well known outside nephrology

CKDisdefinedasabnormalitiesofkidneystructureorfunc- tion,present for>3 months,with implicationsfor health.² CriteriathatbythemselvesdiagnoseCKDincludeglomerular filtrationrate(GFR)<60ml/min/1.73m²orevidenceofkidney damagesuchaspathological albuminuria(urinaryalbumin creatinineratio,UACR≥30mg/g),abnormalurinesediment,

histologyorimaging,abnormalitiesduetotubulardisorders, or kidneytransplantation.³DiagnosingCKDimpliesassign- ingcauseandG(GFR:G1throughG5)andA(albuminuria:A1 throughA3)categories.G1(GFR≥90ml/min/1.73m²)andA1 (UACR<30mg/g)categoriesarenotdiagnosticofCKDbythem- selves.PersonsincategoryG1A1requiretofulfillanadditional criteriontobediagnosedofCKD,suchasimagingdiagnostic ofpolycystickidneydisease(PKD).^2,3

PersonswithCKDareatanincreasedriskofprogressing torequirekidneyreplacementtherapy(KRT),ofall-causeand cardiovascular death, and ofacute kidney injury (AKI).^2,4–6 There isabidirectionalrelationshipbetweenCKDandAKI.

CKDisthemainriskfactorforAKIandAKImayaccelerate CKD.⁷AKIhasahighmortalityandincreasestheriskofdeath forover a yearafter theepisode.⁷ AKI isalsocommon,as around5%ofhospitalizedpatientsdevelopin-hospitalAKI.⁸ Morerecently,CKDhasbeenidentifiedasthemostprevalent riskfactorforlethalcoronavirusdisease2019(COVID-19),and asthefactorthatmostincreasedtheriskofdeathinCOVID- 19afterolderage^9–11(Fig.1).AKIisalsocommoninCOVID-19 andakeyriskfactorfordeath.⁹

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Fig.1–Chronickidneydisease(CKD)isthemostprevalentriskfactorforsevereCOVID-19andalsotheriskfactorforsevere COVID-19thatisassociatedwiththehighestriskofdeath,afteroldage.(A)CKDasapercentageofpersonsatriskofsevere COVID-19inaglobalscale.Datafrom11.(B)Riskofdeathassociatedwithpre-existentconditionsinpatientswith

COVID-19inanadjustedanalysis.Datafrom10.Reproducedfrom1and9.

IncreasingCKDcategoriesareassociatedwithincreasing riskofall-causeandcardiovasculardeath,evenintheelderly, thusquestioningtheconceptofa“physiological”decreasein eGFRwithage(Fig.2A,B).Albuminuriaaslowas>2.5mg/gis alreadyassociatedwithanincreasedriskofprematuredeath (Fig.2B).Thus,thecurrentalbuminuriathresholdusedtodiag- noseCKDisalateevent.Additionally,bythetimeGFRfallsto 60ml/min/1.73m²,CKDhasprogressedunnoticed(potentially overyears and evendecades) todestroy>50%ofthe func- tioningkidneymass.Thisisthe so-calledblindspotinthe diagnosisofCKD(Fig.2C).Inthisregard,thereisclearmar- ginforearlierdiagnosisandtherapyofCKD.Theautosomal dominantPKDparadigmillustratesthewaytogo:adiagnostic

test(sonography)allowsthediagnosisofCKDdecadesbefore patients fulfillanyother criteriontodiagnose CKD. Similar diagnostic tools are needed for other forms ofCKD. Addi- tionalfuturecriteriatodiagnoseCKDmaybeincludegenetic testsdisclosingclearlypathogenic genevariantsor urinary biomarkersbeyondUACR,suchasurinarypeptidomicsoruri- naryKlotho.^12–14

Kidney failure (end-stage kidney disease, G5, GFR<15ml/min/1.73m²) is the only form of kidney dis- ease well known to the wider public, non-nephrologists and healthcareauthorities.Non-experts usuallyequate the burdenofCKDwiththeburdenofKRTforkidneyfailureas the64,000personsonKRTinSpainconsume2.5–5.0%ofthe

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Fig.2–Chronickidneydisease(CKD)isassociatedwithanincreasedriskofdeathevenintheveryelderly.All-cause mortalityrate(absoluterisk)fordifferenteGFR(A)andUACR(B)valuesbyagecategoriesbasedonweightedaverageacross cohorts,adjustedforcovariates.Asteeperslopeatolderageindicatesahigherabsoluteriskdifferenceassociatedwithlow eGFRascomparedwithyoungeragecategories:thediscontinuousgreenlinerepresentstheoverlayoftheriskforthevery elderlyontopoftherisklinefortheyoungeragerange.Similartrendswereobservedforalbuminuria.Conceptual representationofdatapresentedin5.InpanelA,anincreaseintheriskofdeathobservedinpatientsolderthan55years withhighereGFRvaluesisnotshownasthisisthoughttobeanartifactdependingonlowermusclemassofpatientswho weresickeratbaseline.(C)TheblindspotinCKD,asillustratedbyautosomaldominantpolycystickidneydisease.In ADPKD,CKDispresentfrombirth,butusingconventionalcriteriatodiagnoseCKDasloweGFRorpathological

albuminuria,itcanonlybediagnosed30–40yearslater.However,thereisadiagnostictest,sonography,thatallowsamuch earlierdiagnosisbydemonstratingthepresenceofkidneycysts.Diagnostictestsshouldbedevelopedthatallowto diagnoseCKDfromother,non-ADPKD,causesdecadesearlierthancurrentGFRoralbuminuriacriteriaallow(figurefrom ref.13).Reproducedfrom1.

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Fig.3–ComorbiditiesdiagnosedinaSwedishcohortofpatientswithchronickidneydisease(CKD),representingclinical conditionsthetreatingphysicianswasawareof.InclusioninthecohortrequiredaresearcherdiagnosisofCKDbasedon thepresenceoftwoeGFRvaluesbelow60ml/min/1.73m²separatedbyatleast90daysasperKDIGOdefinition.Patientson kidneyreplacementtherapywereexcluded.Notethatamongpersonsincludedinthecohortbecauseresearchers

retrospectivelydiagnosedCKD,thephysicianinchargediagnosedcancerordiabetesmorecommonlythanCKD.Datafrom 16,figurefrom17.

healthcarebudget.However,thebulkofthehealthburdenof CKDisnotrepresentedbyKRTbutbyacceleratedagingand prematuredeath,as clearlyquantified byGlobalBurden of Disease(GBD)datadiscussedbelow.¹⁵Illustratingthelackof awarenessoftheCKDconcept,inarecentreportofacohort ofpersonsselectedbecause theyhad CKD,as evidencefor loweGFRforatleast3months,CKDwasonlythesixthmore commondiagnosesafterhypertension(82%),cardiovascular disease(39%),cancer(29%),diabetes(29%),heartfailure(28%) (Fig.3).^16,17Thus,only23%ofparticipantsintheCKDcohort hadbeendiagnosedbytheirphysiciansashavingCKDwhile thenumbershouldbe100%.

Kidney replacement therapy:

A success story or a story on failure?

KRTisoneofthesuccessstoriesofhealthcareinthe20th centuryandallowssurvivalfollowingfailureofavitalorgan.

However,KRTisafailureofCKDmanagementthat,if suc- cessful,should havepreventedCKDprogressionthisstage.

Indeed,inpersonsonKRTexpectedremaininglifetimesare severelyreduced–byaround70%(40yearsless)andby25%

(15yearsless)fora20-year-oldondialysisorwithafunction- ingkidneygraft,respectively.^18,19 Theabsolutereductionin expectedremaininglifetimesismilderatolderages,butthe relativereductioninlifeexpectancyremainsconstantupto age89years(Fig.4A).AnnualmortalityofpersonsonKRTis upto100-foldhigherthanforsimilaragedcontrols.⁶Indeed,

the5-yearsurvivalofpatientsondialysisislowerthanforall formsofcancercombined²⁰(Fig.4B).

The most common cause of CKD is unknown:

The need to redefine the CKD etiology landscape

Themost commoncause ofKRTin Spainisdiabetes (25%

of persons initiating KRT), followed by unknown (15%),

“vascular”, glomerulonephritis (14%) and inherited kidney disease.^18,19,21WhilePKDistheonlyinheritedkidneydisease usuallyreportedbylargeregistries,recentMadridandCat- alonianKRTregistrydatafoundallinheritedkidneydiseases combined as frequent as glomerulonephritis.²² Inherited kidney diseases are frequently overlooked by physicians.

Indeed,whole exome sequencingfound monogenickidney diseasesin9%ofadultCKD,andin17–34%ofthosewithCKD ofunknowncause.^23,24

“Vascular”islabeledashypertensionintheEuropeanRenal Association–EuropeanDialysisand TransplantAssociation (ERA-EDTA)Registry.^18,19,21 Inclinicalpractice,hypertension isusuallylistedasacausewhenthereisnoother obvious etiology, following expertrecommendation.²⁵ This practice mayreplaceaninadequateetiologicworkup,downplayingthe incidenceofothercausesofCKDwhilefalselyboostinghyper- tension ascause (rather than asconsequence) ofCKD.^26,27 Thus,thereisnorelationshipbetweenprevalenceofhyper- tension and of hypertensive CKD in different countries.²⁶ In African Americans, hypertensive nephropathyis known

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Fig.4–Severelylimitedsurvivalinpersonsonkidneyreplacementtherapy(KRT).(A)Expectedremaininglifetimesofthe generalpopulationandofdialysisandkidneytransplantpatientsintheEuropeanRenalAssociation(ERA-EDTA)Registry.

ArrowsandnumbersdepictrelativeandabsolutereductionsinlifeexpectancyforyoungadultsonKRT,eitherondialysis (burgundy)orwithafunctioningkidneygraft(orange).^18,19.(B)Percent5-yearsurvivalofKRTmodalities(redbars) (hemodialysis,peritonealdialysis,transplantationafterdeceaseddonationandtransplantationafterlivingdonation)or afterthediagnosisofcancer(bluebars).Onlymalignancieswithanincidenceover3%ofallcancersareillustrated.Orange bar:allcancersaggregated.Basedon2016data.Source:20.Reproducedfrom1.

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Fig.5–Globalburdenofchronickidneydisease(CKD),accordingtotheGlobalBurdenofDisease(GDB)study.(A)2017global disabilityadjustedlifeyears(DALYs),yearslivedwithdisability(YLD)andyearsoflifelost(YLLs)duetoCKD.³⁰(B)Major globalcausesofdeathin2016andpredictedfor2040accordingtotheGBDstudy,rankedbyYLLs.¹⁵CKDismarkedby emptyrectangles.LogostotherightcorrespondtoISCIII-fundedcollaborativeresearchnetworksinSpainthatwilladdress eachcausefrom2022.Atthetimeofthiswriting,thestatusofkidneyresearchin2022isstillunclear.Aninfectiousdisease CIBERwillbecreatedin2022,butathispointweareunawareofthelogo.Thus,theCIBERlogowasusedandtheword

“INFEC”wasadded.Reproducedfrom1.

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Fig.6–CKDburdenandepidemiologyinSpain.(A)ProjectednumbersofannualdeathsinSpainbycause.Alzheimernot shownbutitisprojectedtobecomethefirstcauseofdeathbeforetheendofthecentury,wellabovetheothers.Pastgrowth accordingtoGBD2016Spainwasprojectedintothefuture.³²Theprojectiondidnotconsidertheprogressiveagingofthe Spanishpopulation.Thus,itrepresentsanunderestimationofCKD-relateddeaths.(B)NumberofadultswithCKDinSpain, bygenderandoverall,accordingtotheERICAstudyfrom2010andprojectionintothefutureassumingthesameprevalence ofCKDbyagecategoryandconsideringchangesintheSpanishpopulationagepyramidaccordingtotheWorldHealth Organization(WHO)predictions.^33–35Sincetheincreasingmeanagewithineachagecategorywasnotconsidered,this projectionrepresentsanunderestimation.^33,34Foreachselectedyear,dataformen,womenandallareshown.(C)

PercentageofSpanishadultswithCKDintheERICAstudy(2010)andprojectionintothefuture.^33–35(D)Numberofprevalent personsonKRTinSpainin2019andprojectionintothefuturebasedonthe22%(12,000persons)growthfrom2013to 2019.²¹Inblue,estimatesaccordingtohypothesizedexponentialgrowth;inorange,estimatesaccordingtolineargrowth.

Theprogressiveagingofthepopulationwasnotaccountedfor,potentiallyunderestimatingtheresults.(E)Increasein incidenceandprevalenceofKRTfrom2013to2019inSpain.Reproducedfrom1.

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to represent a familial predisposition to CKD triggered by differentcauses, including humanimmunodeficiency virus (HIV) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)infection.²⁸

IntheERA-EDTARegistrydataforallcountries,themost commoncauseofincidentKRTwasunknown(27%,increas- ing to 39% if we add hypertension) followed by diabetes (20%),glomerulonephritis(11%)andPKD(5%).Forprevalent KRT, the ranking is unknown (27%, increasing to 35% by addinghypertension)followedbyglomerulonephritis(19%), diabetes(15%),andPKD(8%).^18,19Thus,asignificantpercent- ageofpersonslackanetiologicaldiagnosis,whichprecludes etiology-targeted therapy and early prevention campaigns.

AmongthefastestgrowingsegmentofCKDpatients(those aged≥65 years), unknownand hypertensionaccounted for 43%ofincidentKRTpatients,highlightingtheneedtodefine causeintheelderly.Weproposethatacceleratedkidneyaging maybeakeycontributortoCKD,includingintheelderly,and arecurrentlydevisingaworkingdefinitionforacceleratedkid- neyagingthatspursresearchinthisfield.

The growing burden of CKD

Globally,around850millionpersonshaveCKD.²⁹In2017,1.2 millionpeoplediedfrom CKDgloballyandCKDresultedin 35.8milliondisabilityadjustedlifeyears(DALYs),mostofthem (>70%)notduetodiabetickidneydisease,aswellasin7.3mil- lionyearslivedwithdisability(YLD)and28.5millionyearsof lifelost(YLLs)(30)(Fig.5A).However,therearelargegeograph- icaldifferencesinCKDburden.Age-standardizedCKDDALY ratesvariedmorethan15-foldbetweencountries,avariability alsoevidentwithinSpainandevenwithinSpainautonomous communities.^18,30Thisillustratestheneedforidentification andcorrection ofthe driversofahigher burdenincertain regions.

GBDprojectedthatCKDwillbecomethe5thglobalcause ofdeathby2040¹⁵ (Fig.5B).YLLsdue toCKDareexpected todoubleby2040,thefastestincreaseamongmajorcauses ofdeath,afterAlzheimer.By contrast,the burdenofother majorcausesofdeath(e.g.ischemicheartdisease−3.6%or stroke−10.7%)isalreadydecreasing.CKDgrowthasacauseof deathoutpacesdiabetesandresearchisneededindiabetes- independentcausesofCKD.SpainGBDdataidentifiedCKD asthe8thcauseofdeath.However,officialInstitutoNacional deEstadistica(INE)dataunderestimatedtheburdenofCKD, likelyduetolowawarenessofthecondition.^31,32 SpainGBD identifiedCKDasthe2ndfastestgrowingcauseofdeath,the 6thfastestgrowingcauseofYLDandthe7thfastestgrowing causeofDALYsamongthetop25causesforeachcategory.^31,32 ProjectingintothefuturetherecentrateofincreaseofCKD inSpainGBD,CKDwillbecomethe2ndcauseofdeath,after Alzheimer,beforetheendofthecentury³² (Fig.6A).Thisis likelyanunderestimation,astheprogressivechange inthe agepyramidoverthenextfewdecadeswasnotconsidered.

Spanishprojectionsmay alsoapplytoother countrieswith longlifeexpectancy.

ThepopulationofSpainwillbecomeprogressivelyolder anddecrease toaround 23–33millionby2100.^33,34 In2010, 14%ofSpanishadults(6.7million)hadCKD.³⁵CKDwasmore

Fig.7–TheeconomicburdenofCKD.Comparisonof aggregatedannualhealthcarecostsforEuropeofcancer (yellow),diabetesmellitus(red)andCKD(differentshades ofblue).CostsofCKDareacompositeofearlyCKD (stages/categoriesG1–G2innativeortransplantkidneys– lightblue),moreadvancedstagesofCKD(stages/categories G3–G5notondialysisinnativeortransplantkidneys), transplantationanddialysis(darkblue).Source:20.

Reproducedfrom1.

common inmenthan inwomenand inthoseaged45–64- years.Projectingthesenumbersintothefutureintheabsence ofchangestothecurrentstandardofcare,assumingacon- stantprevalenceofCKDwithineachage rangeandgender groupandusingWHOpopulationpredictionestimates,results inatleast8.12millionpersonswithCKDby2040and7.96mil- lionby2100,whichwillrepresent18%and24%oftheSpanish population,respectively(Fig.6B,C).Thisisanunderestima- tion,asprogressiveagingofthepopulation(personsaged65 years or moreare estimated toincrease from 17% in2010 to32%by2040and35%by2100)willalsooccurwithinthe sameagerangecategory,andthiswouldbeassociatedwith anincreasedprevalenceofCKDwithinagecategories,thatwe didnotconsider.Additionally,by2040,mostpersonswithCKD willbe65-year-oldorolder.

The prevalence of KRT in Spain is also increasing. It increased38%from2007to2019(985–1367pmp)andtherate appearstobeaccelerating(itincreased14%from2007to2013 and22%from2013to2019).Atthisrateofgrowth,thenumber ofpersonsonKRTwillhit0.23–1.00millionbytheendofthe century,i.e.around1–4%oftheprojectedpopulationofSpain atthattime(Fig.6D).TheincidenceofKRTalsoincreasedby 22% from2013to2019(125–152pmp)²¹(Fig.6E).Amajority ofpersonsonKRTinSpain(55%)haveafunctioningkidney graft.Thus,improvingkidneyandpersonoutcomesinkidney graftrecipientsisamajoraiminkidneyresearch.AsforCKD, KRTisalsomorecommoninmenthaninwomen.Thus,stud- iesonCKDorKRTthatdonotsplitbygendermayreflectthe

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Fig.8–CKDasalocalandsystemicinflammatorydiseaseleadingtoacceleratedbiologicalaging.(A)Albuminuriaitself maytriggerkidneyinflammationasillustratedbythealbuminoverloadmodelinmice:pathologicalalbuminuriatriggered interstitialmacrophage(F4/80+cells)infiltration(shown)whilekidneyfunctionwaspreserved(notshown).⁴⁰Thus, albuminuriainducesthelossofakeykidneyfunction(productionoftheanti-inflammatory,anti-fibrosisandanti-aging proteinKlotho)wellbeforethekidneyfunctionassessedinroutineclinicalcare(glomerularfiltrationrate)islost.(B) DecreasedurinaryKlothoinpersonswithCKDG1/G2(i.e.highereGFRlevelsthat,perse,arenotdiagnosticofCKD)with pathologicalalbuminuria(consistentwithcellcultureandinvivopreclinicalmodelsinwhichinflammatorycytokinesor albumin/albuminuriadecreasedtubularcellKlothoproductionbyhealthytubularcells)andalsoinpersonswithCKDG3-5 (i.e.reducedeGFR,diagnostic,byitself,ofCKD.InCKDG3-5thedecreaseinKlothoislikelytheconsequence,inpart,of decreasedtubularcellmass.(C)DecreasedurinaryKlothoinpersonswithpathologicalalbuminuriaandpreservedeGFR andalsoinpersonswithdecreasedeGFRirrespectiveofalbuminuria.VerticalaxisreflectsurinaryKlotho,horizontalaxis reflectseGFRanddiameterofcirclereflectsmagnitudeofalbuminuria.⁴⁰Reproducedfrom1.

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Fig.9–RICORS2040conceptandoverallstructureandresearchaims.RICORS2040aimsatimprovingkidneyandperson outcomesinbothmenandwomenwithCKD.Therearetwosetofaims.Thefirstsetaimsatimprovingthediagnosisand managementofthemostcommoncausesofCKDtopreventordelayCKDprogression.Forthis,themaincausesofnative kidneyCKD(diabetes,glomerular,inherited/genetic)willbeaddressed,andtheacceleratedkidneyagingconceptwillbe exploredasafinalcommonpathwayofCKDprogressionandasapotentialcauseofCKDinpersonsinwhomnoother causeisidentified.Sincethelifeexpectancyofkidneyallograftsismarkedlyshorterthanfornativekidneys,chronic allograftdysfunctionwillalsobeexplored.Thesecondsetaimstoimprovepersonoutcomesbyoptimizingthediagnosis andmanagementoftheconsequencesofCKD(orofkidneytransplantationtherapy)onotherorgansandsystems,whatwe havecollectivelynamedastheacceleratedbiologicalagingofCKD.Pleasenotethataim4isfocusedonacceleratedkidney agingasacauseofCKDandonkidneyevents,whileaim6isfocusedontheimpactofCKDonotherorgansandsystems, thatis,onacceleratedbiologicalagingofdiverseorgansandsystemsoccurringasaconsequenceofCKD.Carewillbetaken toidentifyandoptimizethemanagementofgender-relatedissuesandprovideclinicalguidancewithspecificinformation formenandforwomen.Reproducedfrom1.

diseaseinmenandstudiesaddressingriskstratification,diag- nosisandtherapeuticapproachesindependentlyformenand forwomenarerequired.Furthermore,therearelargeregional differences(rangeofincidentKRT85–197pmpandofpreva- lentKRT740–1567pmpfordifferentSpanishregions),which arealsoobservedwithinregions(e.g.inMadrid,rangeofinci- dentKRT50–200pmpandofprevalentKRT980–1700pmpfor differenthealthcarecatchment areas).The causesofthese differencesarenotfullyunderstood,butitiscriticallyimpor- tant todefine them in order toidentify and target factors thatgenerateCKDhotspotsorbenchmarkpotentialhealth- carecontributors.³⁶

TheburdenofCKDisalsoeconomical.Theextrapolated annualcostofallCKDisatleastashighasthatforcanceror diabetesandestimatedatover140billioneurosannuallyin Europeand over130billiondollarsintheUnitedStates^20,37 (Fig.7).

The rationale for RICORS2040

From 2022, the Instituto de Salud Carlos III (ISCIII, Spain Government Agency that funds health research) will fund theRedesde InvestigaciónCooperativaOrientadas aResul- tados en Salud (RICORS, Cooperative Research Networks FocusedonResultsinHealth)programofnetworkresearch.

ThiswillreplacethepriorISCIII-fundedprogramofnetwork researchtermedRETICS.TheSpanishkidneyresearchcom- munity,representedbytheresearchgroupsintegratedintothe

KidneyResearchNetworkRETIC(RETICREDdeINvestigación RENal, REDINREN) and by several working groups of the SpanishSocietyofNephrology(SociedadEspa ˜noladeNefrol- ogía, SEN), such as GLOSEN (glomerular disease working group)andGEENDIAB(diabetesworkinggroup),hassubmit- tedtheRICORS2040proposaltotheRICORScall.RICORS2040 issupportedbySENEFRO,theERA-EDTA,ALCER(Federación Nacional de Asociaciones para la Lucha Contra las Enfer- medadesdelRi ˜nón,SpanishKidneyPatientsAssociation)and ONT.RICORS2040isfocusedonkidneydiseaseswithinoneof thefourthematicareasoftheRICORScall:“Inflammationand immunopathologyoforgansand systems”.³⁸Thisthematic area includes kidney diseases and also non-transmissible immunesystemdiseases,allergicdiseases,multiplesclerosis andeyediseases.

CKD as a chronic inflammatory disease. CKD is a local inflammatorydiseasethatbecomesasystemicinflammatory disease asit progresses.Activation ofthemaster regulator of inflammation (NF␬B), local expression of inflammatory cytokines and immunecell infiltratesare already observed inearlystagesofCKDandcanbetriggeredbyalbuminuria, hyperglycemiaandgeneticdefects,amongothers^39,40(Fig.8A).

KidneyshavemultiplefunctionsandGFRisjustoneofthem.

Thereisincreasingevidencethatproductionoftheantiaging and anti-inflammatory factor Klotho is a key function of kidney tubulesthat islost veryearly inthecourseofCKD (GFRcategoryG1,thatis,normal“kidneyfunction”)partlyin response to local inflammation and/or albuminuria^41–43 (Fig. 8B). Loss of anti-inflammatory molecules and

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Table1–AimsofRICORS2040.

Specificaims:

1.Improvekidneyoutcomesinmenandwomenwithdiabetesordiabetickidneydisease(DKD) ImproveriskstratificationinDKDtofosterprecisionNephrology

Evaluatenovelstrategiesforkidneyprotectionthroughtherapeuticdrugrepositioning

Develop,evaluateandupdateSpanishClinicalPracticeGuidelinefordetectionandmanagementofDKD.

2.Improvekidneyoutcomesinmenandwomenwithprimaryglomerulardisease ImproveriskstratificationinglomerulardiseasetofosterprecisionNephrology Evaluatenovelkidneyprotectiveapproachesinprimaryglomerulardisease Develop,evaluateandupdateclinicalguidancedocuments

3.Improvekidneyoutcomesinmenandwomenwithinheritedkidneydisease

Increaseawarenessofinheritedkidneydiseasewithspecialfocusonglomerularandtubularkidneydisease ImproveriskstratificationininheritedglomerulardiseasetofosterprecisionNephrology

IdentifygeneticpredictorsofCKDprogression

Develop,evaluateandupdateclinicalguidancedocuments

4.DefineacceleratedkidneyagingasacauseofCKDandslowthelossofGFRinmenandwomen Developaworkingdefinitionofacceleratedkidneyaging

DeveloptoolstopredictandassessrapidCKDprogression Testnoveltherapeuticapproachestokidneyprotection Develop,evaluateandupdateclinicalguidancedocuments

5.Improvekidneyallograftoutcomesandimprovetheoutcomesinmenandwomenwithafunctioningkidneygraft Improvetheoutcomeofchronicallograftnephropathy,decreasinggraftloss

Limitthenegativeimpactofimmunesuppressivetherapiesoncomorbiditiesandlife-threateningcomplications.

Develop,evaluate,andupdateclinicalguidancedocumentsforprecisionimmunosuppression

6.ImprovetheoutcomesofmenandwomenwithCKDbytargetingtheacceleratedbiologicalagingwhichisaconsequenceofCKD DevelopnovelriskstratificationtoolsforcardiovasculardiseaseandCKD-MBDtofosterprecisionNephrology Improvetherecognitionandoutcomeoffrailty

Evaluatethelong-termsafetyandefficacyofSARS-CoV-2vaccinesinpersonswithadvancedCKD

Develop,evaluate,andupdateclinicalguidancedocumentsonkeyconsequencesofCKD,suchascardiovasculardisease, CKD-MBD,frailtyandsusceptibilitytosevereSARS-CoV-2infection

ThegeneralaimofRICORS2040istoimprovekidneyandpersonoutcomesinmenandwomenwithCKDorathighriskofCKD.Thename derivesfromtheaimtoprovewrongthedirepredictionsregardingtheglobalburdenofCKDby2040,thatcloselyreflectthoseforSpain:The GBDcollaborationpredictsthatCKDwillbecomethe5thglobalcauseofdeathby2040.

accumulation of uremic toxins leads to systemic inflam- mation,whichisakeypredictorofcardiovasculareventsand deathinCKD,likelycontributingtotheacceleratedbiological agingthatcharacterizesCKD.^44,45

Currentversusfutureburden:The decadeofthekidney.Cur- rentresearchshouldbeguidedbyfutureprojectionsofdisease burdenratherthanbypaststatistics.RICORS2040derivesits namefromitsaimtoprovewrongprojectionsthatCKDwill becomethe5thglobalcauseofdeathby2040.

Emphasisonprevention. RICORS2040isfocusedonpreser- vationofnativeandgraftkidneyfunctionandinimproving outcomes in persons with CKD by preventing systemic consequencesofCKD, collectivelygroupedintotheconcept of accelerated biological aging, including consequences of kidneytransplantationanditstherapy(Fig.9),asamajorityof personsonKRTinSpaincarryakidneygraft.Thus,preventing theneedforKRTinmenandwomenwithnativekidneysor kidneygraftsandimprovingkidneyandpersonoutcomesin kidney graftrecipients aremajoraimsofRICORS2040.Risk stratificationandoptimizationoftherapeuticapproachesto improve quality of life and life expectancy in the dialysis populationarealsoaddressed.

Men and women. There is mounting evidence that CKD courseandcomplicationsarenotthesameinmenandwomen andeventhatthecut-offpointstodefineCKDmaydiffer.⁴⁶ However, westill use the same metric and the same cut- offpointstodiagnoseCKDandforriskstratificationinmen andwomen,evenknowingthatcreatinine excretiondiffers

andthus,thedenominatorforUACRdiffersformenandfor women.RICORS2040willaddressthefactorsbehindthegen- dergapinCKDburdenandaimstoprovideclinicalguidance forbothmenand womenandtoidentifyinformationgaps thatprecludeagender-consciousapproachtothediagnosis, riskstratificationandtreatmentofCKD.

Addressingregionalinequality.RICORS2040willalsoaddress the factors behind geographical differences in CKD bur- denasitincorporatesmultiplecentersfromalloverSpain.

Specifically, kidney research and care centers from 12 of the 17Spanishregions(Autonomouscommunities)encom- passing90%oftheSpanishpopulations,areintegratedinto RICORS2040.

Clinicalguidanceshould be implemented.Akey issueham- pering the achievement of health outcome targets in the poorimplementationofclinicalguidancedocuments.Inthis regard,clinical guidance documentsare rarelyvalidated in real-worldclinicalpracticetoassesspotentialshortcomingsor barrierstoimplementation.RICORS2040willusecontinuous improvementapproachestogenerate,validateandimprove clinical guidancedocumentsfordifferentcauses ofCKDas wellasforassessingandslowingtheprogressionofCKDand oftheassociatedacceleratedbiologicalagingoforgans and systemsinmenandwomenwithnativekidneysorwithkid- ney grafts.Testingtheimplementationofclinical guidance documentsinahighnumberofcentersfromdifferentregional health systems under real world conditions will allow to identifyandcorrectmostshortcomingsandfeasibilityissues.

nefrologia2022;42(1):65–84

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Insummary,RICORS2040isfocusedondecreasingtheneed forKRTbyimprovingprevention,diagnosis,andtherapyfor majorcauses ofCKD(diabetic,glomerular, inherited,accel- erated kidney aging, the latter a concept that RICORS2040 is developing) in native kidneys and of chronic allograft nephropathyaswellasonimprovingoutcomesofmenand women with CKD by preventing, identifying and treating majorconsequences ofCKD or its therapy that contribute to the burden of accelerated aging and premature death (Table 1).This willbeachieved throughsystematization of priorknowledgegeneratedbyitsantecessorREDINRENand theinternationalcommunityinto gender-consciousclinical guidancedocuments,novelresearchtoaddressgapsofknowl- edgeandmonitoringofclinicalguidanceimplementationto generateupdatedclinicalguidancedocumentsasoutputof RICORS2040.

Major shortcomings in Spain health research funding structure

DespiteCKD beingthe 5thpredicted global cause ofdeath by2040,thereisnoconfirmedSpanishresearchnetworkon CKDfrom2022on.Thisisincontrasttoawiderglobalmove- ment to increase awareness ofthe healthburden of CKD, summarizedintheDecadeoftheKidney(2020–2030)strategy inEurope and the USpromoted bythe American Associa- tionofKidneyPatients(AAKP)andadoptedbytheAdvancing AmericanKidneyHealth(AAKH)initiativeoftheUnitedStates Government, the European Kidney Health Alliance (EKHA) andbypatientassociationsacrossEurope.20,37,47–49Moreover, evenifRICORS2040isfunded,CKDlacksdedicatedresearch centers(e.g.SpanishNationalCancerResearchCenter,CNIO andSpanishNationalCardiovascularResearchCenter,CNIC) or well-funded ISCIII CIBER research networks that fund researchonallother majorpredicted 2040globalcauses of death,exceptCKD¹⁴:ischemicheartdisease(CIBERCV),stroke (CIBERCVandfrom2022,strokeRICORS),infection(CIBERfrom 2022)andchronicobstructivepulmonarydisease(CiberRes).

ISCIIIresearchnetworksalsofundprojected2040causesof deathrankedbelowCKD(e.g.CIBERONCforcancerandCIBER- DEMfordiabetes)(Fig.5B).Thisrepresentsamajor,correctable gapinSpain’shealthresearchfundingstructure.

Sources of support

REDINRENRD16/0009.

Note added in press

OnOctober132021,itwasmadepublicthatRICORS2040would befundedbyISCIIIstarting2022.

Conflict of interest

Authors are members of scientificand patient association withaninterestinimprovingtheoutcomesandqualityoflife ofpersonswithkidneydisease.AlbertoOrtizisEditorinChief

forClinicalKidneyJournal,MariaJoseSolerisAssociateEditor andEditorinChiefelectforClinicalKidneyJournalandRoser TorraandJoseMariaCruzadoareAssociateEditorsforClinical KidneyJournal.

Appendix A. Annex listing all authors from these organizations that approve and support the manuscript

Asociaciónparalainformaciónylainvestigacióndelasenfer- medadesrenalesgenéticas(AIRG-E)

MartaRoger,Presidenta

VíctorMartínezJiménez,HospitalVirgendelaArrixacade Murcia

JoséCarlosRodríguezPerez,HospitalUniversitariodeGran CanariaDr.Negrin

MónicaFurlano,FundacióPuigvert LaiaSansAtxer,ParcDeSalutMar

FederaciónEuropeadePacientesRenales(EKPF) DanielGallegoZurro

AsociaciónparalaluchaContralasEnfermedadesRenales (ALCER):

CarlosMaríaRomeoCasabona DanielGallegoZurro

ClementeGómezGómez PilarPérezBermúdez ManuelArellanoArmisen SantiagoAlbaladejoLópez InmaculadaGutiérrezPorras JosefaGómezRuiz

JoséManuelMartinOrgaz MartaMorenoBarón

SociedadEspa ˜noladeNefrología(SENEFRO)council:

Patricia de Sequera Ortiz, Hospital Universitario Infanta Leonor

GabrieldeArribadelaFuente,HospitalUniversitario de Guadalajara

BorjaQuirogaGili,HospitalUniversitariodelaPrincesa GemaFernándezFresnedo,HospitalUniversitarioMarqués deValdecilla

Sagrario Soriano Cabrera, Hospital Universitario Reina SofíadeCórdoba

Javier PérezContreras,Hospital GeneralUniversitario de Alicante

MiquelBlascoPelicano,HospitalClinicdeBarcelona AuxiliadoraMazuecosBlanca,HospitalPuertadelMar Mariano Rodríguez Portillo, Hospital Universitario Reina SofíadeCórdoba

J. Emilio Sánchez Álvarez, Hospital Universitario de Cabue ˜nes

MaríaJoséSolerRomeo,HospitalUniversitarioGeneralVall d’Hebrón

ManuelGorostidiPérez,HospitalUniversitarioCentralde Asturias

MarianGoicoecheaDiezhandino,HospitalGeneralUniver- sitarioGregorioMara ˜nón

SociedadEspa ˜noladeTrasplante(SET)council

DomingoHernández Marrero,Trasplante Renal.Hospital RegionalUniversitariodeMálaga

78

ConstantinoFondevilaCampo,TrasplanteHepático.Hos- pitalClinicdeBarcelona

Eduardo Mi ˜nambres García, Coordinación Trasplantes.

HospitalUniversitarioMarquésdeValdecilla

DoloresGarcía-CosíoCarmona,TrasplanteCardiaco.Hos- pital12deOctubre

ArmandoTorresRamírez,TrasplanteRenal.HospitalUni- versitariodeCanarias

LuisMu ˜nozBellvis,CirugíaHBP.ComplejoAsistencialUni- versitariodeSalamanca

Marina Berenguer Haym, Trasplante Hepático. Hospital UniversitarioyPolitécnicodelaFe

ManuelBarreraGómez,TrasplanteHepático.HospitalUni- versitarioNuestraSe ˜noradelaCandelaria

José Manuel Cifrián Martínez, Grupo de Trasplante Pul- monar.HospitalUniversitarioMarquésdeValdecilla

JosepMaríaCruzadoGarrit,TrasplanteRenal.HospitalUni- versitariodeBellvitge

Rafael San Juan Garrido, Especialidad en Enfermedades Infecciosas.Hospital12deOctubre

Javier Brice ˜no Delgado, Asociación Espa ˜nola de Cirugía.

HospitalUniversitarioReinaSofíadeCórdoba

MartaBodroMarimont,GrupodeEstudiodelaInfecciónen elTrasplante(GESITRA)/SociedadEspa ˜noladeEnfermedades InfecciosasyMicrobiologíaClínica(SEIMC),HospitalClinicde Barcelona

María O. Valentín Mu ˜noz, Organización Nacional de Trasplantes(ONT)

JoséMiguelPérezVillares,SociedadEspa ˜noladeMedicina IntensivaCriticayUnidadesCoronarias(SEMICYUC).Hospital UniversitarioVirgendelasNieves

ÁngelSalvatierraVelázquez,GrupodeTrasplantedePul- móndelaSociedadEspa ˜noladeNeumologíayCirugíaTorácica (SEPAR).HospitalUniversitarioReinaSofíadeCórdoba

Luis Almenar Bonet, Sección Trasplante Cardíaco de la Sociedad Espa ˜nola de Cardiología. Hospital Universitario y PolitécnicodelaFedeValencia

Miguel Ángel Gómez Bravo, Sociedad Andaluza de Trasplantes.HospitalVirgendelRocío

Francesc J. Moreso Mateos, Sociedad Catalana de Trasplantes.HospitalUniversitarioValld‘Hebrón

ManuelMuroAmador,SociedadEspa ˜noladeInmunología, Murcia.HospitalVirgendelaArrixaca

Auxiliadora Mazuecos Blanca, Sociedad Espa ˜nola de Nefrología.HospitaldelMar

JoséA.PonsMi ˜nano,SociedadEspa ˜noladeTrasplanteHep- ático.HospitalVirgendelaArrixaca

Amado Andrés Belmonte, Sociedad Madrile ˜na de Trasplantes.Hospital12deOctubre

Amparo Solé Jover, Sociedad Valenciana de Trasplante.

HospitalUniversitarioyPolitécnicodeLaFe

Daniel Casanova Rituerto, European Union of Medical Specialists (UEMS) Committe Board. Hospital Universitario MarquésdeValdecilla

Fernando PardoSánchezUEMS CommitteBoard. Clínica UniversidaddeNavarra

FundaciónRenalÍ ˜nigoÁlvarezdeToledo:

MaríaDoloresArenasMDPhD RobertoMartinHernándezMD

BlancaMirandaSerranoMDPhD RICORS2040/REDINREN:

Alberto Ortiz,FundaciónInstitutodeInvestigaciónSani- tariaFundaciónJiménezDíaz

AnaBSanz,FundaciónInstitutodeInvestigaciónSanitaria FundaciónJiménezDíaz

AdrianMRamos,FundaciónInstitutodeInvestigaciónSan- itariaFundaciónJiménezDíaz

GinaCórdoba-David,FundaciónInstitutodeInvestigación SanitariaFundaciónJiménezDíaz

JorgeGarcía-Jiménez,FundaciónInstitutodeInvestigación SanitariaFundaciónJiménezDíaz

MiguelFontecha-BarriusoFundaciónInstitutodeInvesti- gaciónSanitariaFundaciónJiménezDíaz

Juan Guerrero-Mauvecin,FundaciónInstituto de Investi- gaciónSanitariaFundaciónJiménezDíaz

AnaM.Lopez-Díaz,FundaciónInstitutodeInvestigación SanitariaFundaciónJiménezDíaz

MaríaDoloresSánchez-Ni ˜no,FundaciónInstitutodeInves- tigaciónSanitariaFundaciónJiménezDíaz

Lara Vali ˜no-Rivas, Fundación Instituto de Investigación SanitariaFundaciónJiménezDíaz

Leticia Cuarental, Fundación Instituto de Investigación SanitariaFundaciónJiménezDíaz

MartaRibagorda,FundaciónInstitutodeInvestigaciónSan- itariaFundaciónJiménezDíaz

AranzazuPintor-Chocano,FundaciónInstitutodeInvesti- gaciónSanitariaFundaciónJiménezDíaz

ChiaraFavero,FundaciónInstitutodeInvestigaciónSani- tariaFundaciónJiménezDíaz

Gloria Alvarez-Llamas, Fundación Instituto de Investi- gaciónSanitariaFundaciónJiménezDíaz

MartínClearyCatalina,FundaciónJiménezDíaz BeatrizFernández-Fernández,FundaciónJiménezDíaz MaríaVanessaPérez-Gómez,FundaciónJiménezDíaz EmmaRaquelAlegredeMontaner,FundaciónJiménezDíaz RaúlFernándezPrado,FundaciónJiménezDíaz

JorgeRojasRivera,FundaciónJiménezDíaz AnaMaríaRamosVerde,FundaciónJiménezDíaz

SolCarriazo,FundaciónInstitutodeInvestigaciónSanitaria FundaciónJiménezDíaz

Sergio Luis-Lima, Fundación Instituto de Investigación SanitariaFundaciónJiménezDíaz

JinnySánchez-Rodríguez,FundaciónInstituto deInvesti- gaciónSanitariaFundaciónJiménezDíaz,

SoledadPizarroSánchez,HospitalUniversitarioReyJuan Carlos

MartaRuizOrtega,UniversidadAutónomadeMadrid Emilio González Parra, Fundación Instituto de Investi- gaciónSanitariaFundaciónJiménezDíaz

SandraRayegoMateos,UniversidadAutónomadeMadrid PabloJavierCannataOrtiz,FundaciónInstitutodeInvesti- gaciónSanitariaFundaciónJiménezDíaz

LauraMárquezExpósito,UniversidadAutónomadeMadrid Antonio Tejera-Mu ˜noz, Fundación Instituto de Investi- gaciónSanitariaFundaciónJiménezDíaz

VanessaMarchant,UniversidadAutónomadeMadrid LuciaTejedor-Santamaria,FundaciónInstitutodeInvesti- gaciónSanitariaFundaciónJiménezDíaz

MatildeAliqueAgilar,UniversidaddeAlcaládeHenares

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FritzDiekmann,FundaciónPrivadaClínic.HospitalClínic deBarcelona.InstitutD’investigacionsBiomèdiquesAugustPi ISunyer(IDIBAPS)

BeatrizBayesGenis,HospitalClínicdeBarcelona

Federico Oppenheimer Salinas, Hospital Clínic de Barcelona. Institut D’investigacions Biomèdiques August PiISunyer(IDIBAPS)

MaríaJoséRamírezBajo,FundacióPrivadaClínic

ElisendaBa ˜nonManeus,FundacióPrivadaClínic.Institut D’investigacionsBiomèdiquesAugustPiISunyer(IDIBAPS)

MartaAriasGuillen,HospitalClínicdeBarcelona

JordiRoviraJuárez,InstitutD’investigacionsBiomèdiques AugustPiISunyer(IDIBAPS)

MartaLazoRodríguez,FundacióPrivadaClínic

Ignacio Revuelta Vicente, Hospital Clínic de Barcelona.

Institut D’investigacions Biomèdiques August Pi I Sunyer (IDIBAPS)

JosepMiquelBlascoPelicano,HospitalClínicdeBarcelona Luis Fernando Quintana Porras, Hospital Clínic de Barcelona.InstitutD’investigacionsBiomèdiquesAugustPiI Sunyer(IDIBAPS)

PedroVenturaAbreuAguiar,HospitalClínicdeBarcelona.

Institut D’investigacions Biomèdiques August Pi I Sunyer (IDIBAPS)

Marc Xipell Font, Institut D’investigacions Biomèdiques AugustPiISunyer(IDIBAPS)

AliciaMolinaAndujar,HospitalClínicdeBarcelona David Cucchiari, Hospital Clínic de Barcelona. Insti- tut D’investigacions Biomèdiques August Pi I Sunyer (IDIBAPS)

EnriqueMontagudMarrah,HospitalClínicdeBarcelona JosepM, Campistol Plana,Hospital Clínic de Barcelona.

Institut D’investigacions Biomèdiques August Pi I Sunyer (IDIBAPS)

GastónJulioPi ˜neiro,HospitalClínicdeBarcelona

CarlosMartínezSalgado,FundaciónInstitutodeEstudios deCienciasdelaSaluddeCastillayLeón(IECSCYL).Institute ofBiomedicalResearchofSalamanca(IBSAL)

AnaI.MoralesMartín,InstituteofBiomedicalResearchof Salamanca(IBSAL)

Francisco J.López Hernández, Institute of Biomedical ResearchofSalamanca(IBSAL)

NélidaEleno Balboa,Institute ofBiomedical Researchof Salamanca(IBSAL)

MartaPrietoVicente,InstituteofBiomedicalResearchof Salamanca(IBSAL)

IsabelFuentesCalvo,InstituteofBiomedicalResearchof Salamanca(IBSAL)

LauraRamudoGonzález,InstituteofBiomedicalResearch ofSalamanca(IBSAL)

LauraVicenteVicente,InstituteofBiomedicalResearchof Salamanca(IBSAL)

Sandra M. Sancho Martínez, Institute of Biomedical ResearchofSalamanca(IBSAL)

AlfredoG.CasanovaPaso,InstituteofBiomedicalResearch ofSalamanca(IBSAL)

MoisésPescadorGarriel,InstituteofBiomedicalResearch ofSalamanca(IBSAL)

JuanJoséVaqueroLópez,UniversidaddeAlcalá

AnaMaríaCuadroPalacios,UniversidaddeAlcalá DavidSucunzaSaénz,UniversidaddeAlcalá PatriciaGarcíaGarcía,UniversidaddeAlcalá JoséLuisAce ˜naBonilla,UniversidaddeAlcalá

ManuelA.FernándezRodríguez,UniversidaddeAlcalá AlbertoDomingoGalán,UniversidaddeAlcalá EstíbalizMerinoMarcos,UniversidaddeAlcalá JavierCarrerasPérez-Aradros,UniversidaddeAlcalá RubénManzanoSanJosé,UniversidaddeAlcalá FranciscoMaquedaZelaya,UniversidaddeAlcalá EsterSansPanadés,UniversidaddeAlcalá ÁlvaroGonzálezMolina,UniversidaddeAlcalá JuliaAtarejosSalido,UniversidaddeAlcalá RoserTorraBalcells,FundacióPuigvert ElisabetArsCriach,FundacióPuigvert

MontserratDíazEncarnación,FundacióPuigvert LluisGuiradoPerich,FundacióPuigvert

MonicaFurlano,FundacióPuigvert CristinaCanalGirol,FundacióPuigvert YolandaArceTerroba,FundacióPuigvert MarcPybusOliveras,FundacióPuigvert LaiaEjarqueVila,FundacióPuigvert NuriaSerraCaba ˜nas,FundacióPuigvert CarmeFacundoMolas,FundacióPuigvert IreneSilvaTorres,FundacióPuigvert

SantiagoLamasPelaez,CentrodeBiologíaMolecularSevero Ochoa

Carlos Rey Serra, Centro de Biología Molecular Severo Ochoa

CarolinaCastilloTorres,HospitalPríncipedeAsturias JessicaPaolaTitua ˜naFajardo,CentrodeBiologíaMolecular SeveroOchoa

JoséIgnacioHerreroLahuerta,CentrodeBiologíaMolecular SeveroOchoa

Verónica Miguel Herranz, Centro de Biología Molecular SeveroOchoa

MarianoRodriguezPortillo,HospitalReinaSofía AlejandroMartinMalo,HospitalReinaSofía SagrarioSorianoCabrera,HospitalReinaSofía

Juan Rafael Mu ˜noz Casta ˜neda, Instituto Maimonides de InvestigaciónBiomédicadeCórdoba(IMIBIC)

MaríaEncarnaciónRodríguezOrtiz,InstitutoMaimonides deInvestigaciónBiomédicadeCórdoba(IMIBIC)

Julio ManuelMartínez Moreno, Instituto Maimonidesde InvestigaciónBiomédicadeCórdoba(IMIBIC)

AnaIsabelRayaBermúdez,InstitutoMaimonidesdeInves- tigaciónBiomédicadeCórdoba(IMIBIC)

RafaelSantamaríaOlmo,HospitalReinaSofía

FátimaGuerreroPavón,InstitutoMaimonidesdeInvesti- gaciónBiomédicadeCórdoba(IMIBIC)

CayetanaMoyanoPeregrin,HospitalReinaSofía

EscolásticoAguileraTejero,InstitutoMaimonidesdeInves- tigaciónBiomédicadeCórdoba(IMIBIC)

Ignacio Lopez Villalba, Instituto Maimonides de Investi- gaciónBiomédicadeCórdoba(IMIBIC)

AndrésCarmonaMu ˜noz,InstitutoMaimonidesdeInvesti- gaciónBiomédicadeCórdoba(IMIBIC)

MaríaVictoriaPendonRuizDeMier,HospitalReinaSofía

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Carmen María Pineda Martos, Instituto Maimonides de InvestigaciónBiomédicadeCórdoba(IMIBIC)

RodrigoLópezBaltanas,InstitutoMaimonidesdeInvesti- gaciónBiomédicadeCórdoba(IMIBIC)

CristianRodeloHaad,HospitalReinaSofía

MarcellaFranquesaBartolomé,FundaciónInstitutoInves- tigaciónGermansTriasIPujol

RicardoLauzurica Valdemoros,HospitalGermans TriasI Pujol

FranciscoEnriqueBorrasSerres,FundaciónInstitutoInves- tigaciónGermansTriasIPujol

MarujaNavarroDíaz,HospitalGermansTriasIPujol Francisco Javier Juega Mari ˜no, Hospital Germans TriasI Pujol

LauraCa ˜nasSole,HospitalGermansTriasIPujol

MariaIsabelTroyaSaborido,HospitalGermansTriasIPujol JordiSolerMajoral,HospitalGermansTriasIPujol MarinaLópezMartínez,HospitalGermansTriasIPujol Emilio Rodrigo Calabia, University Hospital Marqués de Valdecilla/IDIVAL,UniversityofCantabria

JuanCarlosRuizSanMillán,UniversityHospitalMarqués deValdecilla/IDIVAL,UniversityofCantabria

Marcos López-Hoyos, University Hospital Marqués de Valdecilla/IDIVAL,UniversityofCantabria

AdalbertoBenito-Hernández,UniversityHospitalMarqués deValdecilla/IDIVAL,UniversityofCantabria

GemaFernándezFresnedo,UniversityHospitalMarquésde Valdecilla/IDIVAL,UniversityofCantabria

David San Segundo, University Hospital Marqués de Valdecilla/IDIVAL,UniversityofCantabria

Rosalía Valero, University Hospital Marqués de Valdecilla/IDIVAL,UniversityofCantabria

Eliécer Coto García, Hospital Universitario Central de Asturias

Juan Gómez De Ona, Hospital Universitario Central de Asturias

Elias Cuesta Llavona, Hospital Universitario Central de Asturias

FernandoSantosRodríguez,HospitalUniversitarioCentral deAsturias

RebecaLorcaGutiérrez,HospitalUniversitarioCentralde Asturias

HelenaGilPe ˜na,HospitalUniversitarioCentraldeAsturias ManuelGorostidiPérez,HospitalUniversitarioCentralde Asturias

DomingoHernández Marrero, Instituto de Investigación BiomédicadeMálaga(IBIMA)

Verónica López, Hospital Regional Universitario de Malaga/IBIMA

Eugenia Sola, Hospital Regional Universitario de Malaga/IBIMA

Mercedes Cabello, Hospital Regional Universitario de Malaga/IBIMA

Abelardo Caballero, Hospital Regional Universitario de Malaga/IBIMA

Myriam León, Hospital Regional Universitario de Malaga/IBIMA

Pedro Ruiz, Hospital Regional Universitario de Malaga/IBIMA

Juana Alonso, Hospital Regional Universitario de Malaga/IBIMA

JuanNavarro-González,HospitalNuestraSra.Candelaria, Tenerife

MaríaDelCarmenMora-Fernández,HospitalUniversitario NuestraSe ˜noradeCandelaria

Javier Donate-Correa, Hospital Universitario Nuestra Se ˜noradeCandelaria

Ernesto Martín-Nu ˜nez, Hospital Universitario Nuestra Se ˜noradeCandelaria

Nayra Pérez Delgado, Hospital Universitario Nuestra Se ˜noradeCandelaria

SecundinoGigarrán-Guldris,HospitalDaCosta,Burela José Carlos Rodríguez Pérez, Hospital Universitario Dr.

Negrín

José LuisGórriz Teruel,HospitalClínicoUniversitario de Valencia

AlbertoMartínezCastelao,HospitalUniversitarioBellvitge, Hospitalec,Barcelona

JoséManuelValdivielsoRevilla,InstitutodeInvestigación BiomédicadeLleida.FundaciónDr.Pifarre(IRBLLEIDA)

Cristina Martínez Martínez, Instituto de Investigación BiomédicadeLleida.FundaciónDr.Pifarre(IRBLLEIDA)

Milica Bozic Stanojevic, Instituto de Investigación BiomédicadeLleida.FundaciónDr.Pifarre(IRBLLEIDA)

EvaCastroBoque,InstitutodeInvestigaciónBiomédicade Lleida.FundaciónDr.Pifarre(IRBLLEIDA)

María Nuria Sans Rosell, Instituto de Investigación BiomédicadeLleida.FundaciónDr.Pifarre(IRBLLEIDA)

Virtudes Maria De Lamo, Instituto de Investigación BiomédicadeLleida.FundaciónDr.Pifarre(IRBLLEIDA)

Juan Miguel Díaz Tocados, Instituto de Investigación BiomédicadeLleida.FundaciónDr.Pifarre(IRBLLEIDA)

AliciaGarciaCarrasco,InstitutodeInvestigaciónBiomédica deLleida.FundaciónDr.Pifarre(IRBLLEIDA)

Marcelino Bermúdez López, Instituto de Investigación BiomédicadeLleida.FundaciónDr.Pifarre(IRBLLEIDA)

MaiteCausEnriquez,InstitutodeInvestigaciónBiomédica deLleida.FundaciónDr.Pifarre(IRBLLEIDA)

Ana Martinez Bardaji, Instituto de Investigación Biomédica de Lleida. Fundación Dr. Pifarre (IRBLLEIDA)

NuriaDoladeMasot,InstitutodeInvestigaciónBiomédica deLleida.FundaciónDr.Pifarre(IRBLLEIDA)

AuroraPérezGómez,InstitutodeInvestigaciónBiomédica deLleida.FundaciónDr.Pifarre(IRBLLEIDA)

AuriaEritjaSanjuan,InstitutodeInvestigaciónBiomédica deLleida.FundaciónDr.Pifarre(IRBLLEIDA)

AntonioOsunaOrtega,HospitalUniversitarioVirgendelas NievesdeGranada

RosemaryWangensteenFuentes,UniversidaddeJaén MariadelCarmenDeGraciaGuindo,HospitalUniversitario VirgendelasNievesdeGranada

MariadelCarmenRuizFuentes,HospitalUniversitarioVir- gendelasNievesdeGranada

FranciscoO’ValleRavassa,UniversidaddeGranada MercedesCabaMolina,HospitalUniversitarioSanCecilio César Luis Ramírez Tortosa, Hospital Universitario San Cecilio

nefrologia2022;42(1):65–84

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Raimundo García Del Moral Garrido, Universidad de Granada

MaríaJosé SolerRomeo, FundaciónInstituto de Investi- gaciónValledeHebrón

Conxita Jacobs-Cachá, Vall D’Hebron Research Institute (VHIR)

OriolBestardMatamoros,VallD’HebronResearchInstitute (VHIR)

FrancescMoresoMateos,VallD’HebronResearchInstitute (VHIR)

MaríaAntoniaEmiliaMeneghini,VallD’HebronResearch Institute(VHIR)

JoanaSellaresRoig,HospitalUniversitariVallD’Hebron IrinaTorresBetsabé,HospitalUniversitariVallD’Hebron Carlos López Larrea, Hospital Universitario Central de Asturias.Instituto deInvestigaciónSanitariadelPrincipado deAsturias

BeatrizSuarezÁlvarez,InstitutodeInvestigaciónSanitaria delPrincipadodeAsturias

MaríadelCarmenDíazCorte,HospitalUniversitarioCen- tral de Asturias. Instituto de Investigación Sanitaria del PrincipadodeAsturias

RaúlRRodrigues-Diez,InstitutodeInvestigaciónSanitaria delPrincipadodeAsturias

AntonioLópezVázquez,HospitalUniversitarioCentralde Asturias.InstitutodeInvestigaciónSanitariadelPrincipadode Asturias

SegundoGonzálezRodríguez,UniversidaddeOviedo JoséRamónVidalCasti ˜neira,HospitalUniversitarioCentral deAsturias.InstitutodeInvestigaciónSanitariadelPrincipado deAsturias

CristinaMartínMartín,InstitutodeInvestigaciónSanitaria delPrincipadodeAsturias

MaríaLauraSaizÁlvarez,InstitutodeInvestigaciónSani- tariadelPrincipadodeAsturias

VivianaCorteIglesias,InstitutodeInvestigaciónSanitaria delPrincipadodeAsturias

Jesús Martínez Borra, Hospital Universitario Central de Asturias.Instituto deInvestigaciónSanitariadelPrincipado deAsturias

MaríaAuxiliadoraBajoRubio,HospitalUniversitarioLaPaz GloriaDelPesoGilsanz,HospitalUniversitarioLaPaz ManuelLópezCabrera,CentrodeBiologíaMolecularSevero Ochoa

JoséAntonioJiménezHeffernan,HospitalUniversitarioLa Princesa

MartaOssorioGonzález,HospitalUniversitarioLaPaz OlgaCosteroGonzález,HospitalUniversitarioLaPaz María Elena González García, Hospital Universitario La Paz

CarlosJiménezMartín,HospitalUniversitarioLaPaz PilarSandovalCorrea,CentrodeBiologíaMolecularSevero Ochoa

SaraAfonsoRamos,HospitalUniversitarioLaPaz MaríaLópezOliva,HospitalUniversitarioLaPaz Bego ˜naRivasBecerra,HospitalUniversitarioLaPaz CristinaVegaCabrera,HospitalUniversitarioLaPaz Guadalupe Tirma González Mateo, Centro de Biología MolecularSeveroOchoa

RafaelSánchezVillanueva,HospitalUniversitarioLaPaz LauraÁlvarezGarcía,HospitalUniversitarioLaPaz JorgeBCannata Andía,HospitalUniversitarioCentralde Asturias. InstitutodeInvestigaciónSanitariadelPrincipado deAsturias

Manuel Naves Díaz, Hospital Universitario Central de Asturias. InstitutodeInvestigaciónSanitariadelPrincipado deAsturias

JoséLuisFernándezMartín,HospitalUniversitarioCentral deAsturias.InstitutodeInvestigaciónSanitariadelPrincipado deAsturias

NataliaCarrilloLópez,InstitutodeInvestigaciónSanitaria delPrincipadodeAsturias

SaraPanizoGarcía,InstitutodeInvestigaciónSanitariadel PrincipadodeAsturias

Cristina AlonsoMontes, Instituto de InvestigaciónSani- tariadelPrincipadodeAsturias

MinervaRodríguezGarcía,HospitalUniversitarioCentral deAsturias.InstitutodeInvestigaciónSanitariadelPrincipado deAsturias

I ˜nigoLozanoMartínezLuengas,HospitaldeCabue ˜nes EmilioSánchezÁlvarez,HospitaldeCabue ˜nes

LauraMartínezArias,InstitutodeInvestigaciónSanitaria delPrincipadodeAsturias

BeatrizMartínCarro, InstitutodeInvestigaciónSanitaria delPrincipadodeAsturias

JuliaMartínVirgala,InstitutodeInvestigaciónSanitariadel PrincipadodeAsturias

MiguelGarcíaGonzález,ComplejoHospitalariodeSanti- agodeCompostela(CHUS).InstitutodeInvestigaciónSanitaria (IDIS)

JoséMaríaLamasBarreiro,ComplejoHospitalarioUniver- sitariodeVigo

MiguelPérezFontan,ComplejoHospitalarioUniversitario ACoru ˜na

AlfonsoOtero González,ComplejoHospitalarioUniversi- tariodeOurense

Luz María Cui ˜na Barja, Complejo Hospitalario de Pontevedra

Alejandro Sánchez Barreiro, Universidadde Santiago de Compostela

BeatrizPazosArias,PoliclínicoVigoS.A.

ÁngelAlonsoHernández,ComplejoHospitalarioUniversi- tarioACoru ˜na

MaríaPardoPérez,InstitutodeInvestigaciónSanitariade SantiagodeCompostela(IDIS)

JesúsCalvi ˜noVarela,HospitalLucusAugusti

JorgeAmigoLechuga,FundaciónPúblicaGallegadeMedic- inaGenómica

CándidoDíazRodríguez,HospitalClínicoUniversitariode Santiago

MaríaGarcíaMurias,InstitutodeInvestigaciónSanitariade SantiagodeCompostela(IDIS)

AnaMaríaBarciadelaIglesia,InstitutodeInvestigación SanitariadeSantiagodeCompostela(IDIS)

Pablo Bouza Pi ˜neiro, Complejo Hospitalario A. Marcide- NovoaSantos

Álvaro Gil González, Universidad de Santiago de Com- postela

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AdrianCordidoEijo,InstitutodeInvestigaciónSanitariade SantiagodeCompostela(IDIS)

NoaCarreraCachaza,InstitutodeInvestigaciónSanitaria deSantiagodeCompostela(IDIS)

MartaVizosoGonzález,InstitutodeInvestigaciónSanitaria deSantiagodeCompostela(IDIS)

JosepMariaCruzadoGarrit,HospitaldeBellvitge NúriaLloberasBlanch,FundaciónIdibell AnaMariaSolaMartínez,FundaciónIdibell MiguelHuesoVal,HospitaldeBellvitge JulianaBordignonDraibe,HospitaldeBellvitge EdoardoMelilli,HospitaldeBellvitge

AnnaManonellesMontero,HospitaldeBellvitge NúriaMonteroPérez,HospitaldeBellvitge XavierFulladosaOliveras,HospitaldeBellvitge

MartaCrespoBarrio,InstitutoHospitaldelMardeInvesti- gacionesMédicas(FIMIM)

JulioPascualSantos,InstitutoHospitaldelMardeInvesti- gacionesMédicas(FIMIM)

ClaraBarriosBarrera,InstitutoHospitaldelMardeInvesti- gacionesMédicas(FIMIM)

MaríaJoséPérezSáez,InstitutoHospitaldelMardeInves- tigacionesMédicas(FIMIM)

MaríaDoloresRedondoPachón,InstitutoHospitaldelMar deInvestigacionesMédicas(FIMIM)

CarlosAriasCabrales,InstitutoHospitaldelMardeInves- tigacionesMédicas(FIMIM)

AnnaBuxedaPorras,InstitutoHospitaldelMardeInvesti- gacionesMédicas(FIMIM)

EvaRodríguezGarcía,InstitutoHospitaldelMardeInves- tigacionesMédicas(FIMIM)

LaiaSansAtxer,Instituto HospitaldelMarde Investiga- cionesMédicas(FIMIM)

VanesaPalauGonzález,InstitutoHospitaldelMardeInves- tigacionesMédicas(FIMIM)

LauraLlinàsMallol,InstitutoHospitaldelMardeInvesti- gacionesMédicas(FIMIM)

MartaRieraOliva,InstitutoHospitaldelMardeInvestiga- cionesMédicas(FIMIM)

Diego Rodríguez Puyol, Fundación Investigación Biomédica.HospitalPríncipedeAsturias

MaríaPiedadRuizTorres,UniversidaddeAlcalá

SusanaLópezOngil,FundaciónInvestigaciónBiomédica.

HospitalPríncipedeAsturias

LauraCallerosBasilio,UniversidaddeAlcalá GemmaOlmosCentenera,UniversidaddeAlcalá

PatriciaMartínezdeMiguel,HospitalUniversitarioPríncipe deAsturias

Loreto Fernández Rodríguez, Hospital Universitario PríncipedeAsturias

HananeBouarichNadah,HospitalUniversitarioPríncipede Asturias

MaríaPérezFernández,HospitalUniversitarioPríncipede Asturias

ManuelRafaelRamírezChamond,UniversidaddeAlcalá Patricia Sequera Ortiz, Hospital Universitario Infanta Leonor

NuriaGarcía Fernández,Instituto de InvestigaciónSani- tariadeNavarra(IDISNA),

AlbertoBenitoBoillos,UniversidaddeNavarra NereaVaroCenarruzabeitia,UniversidaddeNavarra María Asunción Fernández Seara, Universidad de Navarra

InésDíazDorronsoro,UniversidaddeNavarra

PalomaMartinMoreno,ClínicaUniversidaddeNavarra FranciscoJavierLavilla,ClínicaUniversidaddeNavarra ArmandoTorres,HospitalUniversitariodeCanarias.Uni- versidaddeLaLaguna

Domingo Marrero Miranda, Hospital Universitario de Canarias

AurelioPastorRodríguezHernández,HospitalUniversitario deCanarias

Eduardo De Bonis Redondo, Hospital Universitario de Canarias

EstebanPorrini,UniversidaddeLaLaguna

MaríadelosÁngelesCoboCaso,HospitalUniversitariode Canarias

María Lourdes PérezTamajón, Hospital Universitario de Canarias

Margarita Rufino Hernández, Hospital Universitario de Canarias

María Sagrario García Rebollo, HospitalUniversitario de Canarias

PatriciaDelgadoMallen,HospitalUniversitariodeCanarias Alejandra Álvarez González, Hospital Universitario de Canarias

Ana María González Rinne, Hospital Universitario de Canarias

RosaMiquelRodríguez,HospitalUniversitariodeCanarias SaraEstupi ˜nanTorres,HospitalUniversitariodeCanarias DiegoÁlvarezSosa,HospitalUniversitariodeCanarias Beatriz Escamilla Cabrera, Hospital Universitario de Canarias

Nayara Zamora Rodríguez, Hospital Universitario de Canarias

Arminda Fari ˜na Hernández, Hospital Universitario de Canarias

María José RodríguezGamboa,Hospital Universitario de Canarias

CoboCaso,MariadeLosAngeles,HospitalUniversitariode Canarias

PerezTamajon, Maria Lourdes, Hospital Universitario de Canarias

Rufino Hernandez, Margarita, Hospital Universitario de Canarias

Garcia Rebollo, MariaSagrario, HospitalUniversitario de Canarias

Delgado Mallen, Patricia, Hospital Universitario de Canarias

AlvarezGonzalez, Alejandra, Hospital Universitario de Canarias

Gonzalez Rinne, Ana Maria, Hospital Universitario de Canarias

MiquelRodriguez,Rosa,HospitalUniversitariodeCanarias Estupi ˜nanTorres,Sara,HospitalUniversitariodeCanarias AlvarezSosa,Diego,HospitalUniversitariodeCanarias Escamilla Cabrera, Beatriz, Hospital Universitario de Canarias

nefrologia2022;42(1):65–84

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Zamora Rodiguez, Nayara, Hospital Universitario de Canarias

Fari ˜na Hernandez, Arminda, Hospital Universitario de Canarias

RodriguezGamboa, MariaJose, Hospital Universitario de Canarias

MaríaLauraGarcíaBermejo, InstitutoRamónyCajal de InvestigaciónSanitaria(IRYCIS)

MilagrosFernándezLucas,HospitalRamónyCajal ElisaConde Moreno,InstitutoRamónyCajal deInvesti- gaciónSanitaria(IRYCIS)

LauraSalinasMu ˜noz,InstitutoRamónyCajaldeInvesti- gaciónSanitaria(IRYCIS)

SilviaSerranoHuertas,InstitutoRamónyCajaldeInvesti- gaciónSanitaria(IRYCIS)

EsperanzaMacarenaRodríguezSerrano,InstitutoRamóny CajaldeInvestigaciónSanitaria(IRYCIS)

MirenEdurneRamosMu ˜noz,Instituto RamónyCajalde InvestigaciónSanitaria(IRYCIS)

LorenaCrespo Toro, Instituto RamónyCajal de Investi- gaciónSanitaria(IRYCIS)

CarolinaPilar Blanco Agudo,Instituto Ramóny Cajalde InvestigaciónSanitaria(IRYCIS)

CristinaGaleanoÁlvarez,InstitutoRamónyCajaldeInves- tigaciónSanitaria(IRYCIS)

JoséPortoles,FundaciónInvestigaciónBiomédicaHospital PuertadeHierro

MaríaMarqués,FundaciónInvestigaciónBiomédicaHospi- talPuertadeHierro

EstherRubio,FundaciónInvestigaciónBiomédicaHospital PuertadeHierro

Beatriz Sánchez-Sobrino, Fundación Investigación BiomédicaHospitalPuertadeHierro

Estefanya García-Menéndez, Fundación Investigación BiomédicaHospitalPuertadeHierro

Alberto Lázaro Fernández, Universidad Complutense de Madrid

MarianGoicoechea Diezhandin, IISGM.Hospital General UniversitarioGregorioMara ˜nón

PatrocinioRodríguezBenítez,IISGM.HospitalGeneralUni- versitarioGregorioMara ˜nón

María Ángeles González-Nicolás González, Universidad ComplutensedeMadrid

Meritxell López Gallardo, Universidad Complutense de Madrid

GemaMaríaFernándezJuárez,HospitalUniversitarioFun- daciónAlcorcón

EduardoGutiérrezMartínez,InstitutodeInvestigaciónHos- pital12deOctubre(i+12)

ManuelPragaTerente,InstitutodeInvestigaciónHospital 12deOctubre(i+12)

AnaTatoRibera,HospitalUniversitarioFundaciónAlcorcón TeresaCaveroEscribano,InstitutodeInvestigaciónHospi- tal12deOctubre(i+12)

FernandoCaravacaFontan,InstitutodeInvestigaciónHos- pital12deOctubre(i+12)

Amir Shabaka Fernández, Hospital Universitario Fun- daciónAlcorcón

NicolásRobertoRoblesPérez-Monteoliva,ComplejoHospi- talarioUniversitariodeBadajoz

EnriqueLunaHuerta,ComplejoHospitalarioUniversitario deBadajoz

Guillermo Gervasini Rodríguez, FacultaddeMedicina de Badajoz

SergioBarrosoHernández,ComplejoHospitalarioUniver- sitariodeBadajoz

SoniaMotaZamorano,FacultaddeMedicinadeBadajoz JuanManuelLópezGómez,ComplejoHospitalarioUniver- sitariodeBadajoz

RománHernándezGallego,ComplejoHospitalarioUniver- sitariodeBadajoz

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