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INTERACTION BETWEEN KİDNEY AND HEART FAİLURE :. Prof Dr Rasim ENAR Istanbul University Cerrahpasa Medical Faculty Cardiology Clinics. 1. (ADHERE) of 105 000 individuals admitted for ADHF , 30% had a history of renal insufficiency .

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interaction between k dney and heart fa lure
INTERACTION BETWEEN KİDNEY AND HEART FAİLURE:

Prof Dr Rasim ENAR

IstanbulUniversity

CerrahpasaMedicalFaculty

CardiologyClinics

slide2

1

  • (ADHERE) of 105 000 individuals admitted for ADHF, 30% had a history of renal insufficiency.
  • (EURO-HF, OPTİMİZE-HF) %30-67 haveeGFR <60 ml/min/1.73 m2
  • 21% had serum creatinine concentrations >2.0 mg/dL, and9% had creatinine concentrations >3.0 mg/dL.
  • Both elevated serum creatinine on admission and worseningcreatinine during hospitalization predict prolongedhospitalization rehospitalization, anddeath.Even smallchanges in creatinine 0.3 mg/dL are common andhave been associated with increased mortality and prolongedhospitalization.

Am Heart J. 2005;149:209 –216.

slide3

2

CARDİORENAL SYNDROME:

Disorders of the heart and kidneys whereby “acuteor chronic dysfunction in one organ may induce acute or chronicdysfunction of the other”.

Therearedirectandindirecteffects of HF that can be identified as theprimersfor AKI anddysfunction.

InteractıonsbetweenHeartandKidney:

Biderctıonal,

Temporallyregulated,

Mediateddifferentmechanisms,

Differrentconseguences in specificindividuals,

Functional vs structuraldamage.

clasificat on of cardio renal syndromes

3

Clasificatıon of Cardio- RenalSyndromes:

CRS Type -I (AcuteCardiorenalsyndrome):

Abruptworsening of cardiacfunctıonleadingtoacutekidneyinjury.

CRS Type –II (ChronicCardiorenalSyndrome):

Chronicabnortmalities in cardiacfunctioncausingprogressiveandpermanentkidneydisease.

CRS Type –III: (AcuteRenocardiacSyndrome):

Abruptworsening of renalfunctioncausingacutecardiacdisorders.

CRS Type –IV (ChronicRenocardiacSyndrome):

ChronicKidneydiseasecontributingtodecreasedcardiacfunction, cardiachypertrophyand/orincreased risk of adversecardiovascularevents.

CRS Type –V (SecondaryCardiorenalSyndrome):

Systemiccondition (i.g. DM, sepsis..) causingbothcardiacandrenaldysfunction.

(EuropeanHeartJournal (2010) 31, 703–711)

slide5

4

Risk factors of Renaldysfunctıon

in heartfailure:

  • Hypertension
  • Diabetes
  • Severe vasculardisease
  • Eldelyage
  • Pasthistory of:

+ Heartfailure

+ Renaldysfunction

+ Heartfailureandrenaldysfunction.

(Can J Cardiol 2008;24:Suppl B: 25B-29B)

slide6

5

Subtypes of CRS Type 1:

1) de novocardiacinjuryleadsto de novokidneyinjury;

2) de novocardiacinjuryleadstoacute-on-chronickidney

injury;

3) acute-on-chroniccardiacdecompensationleadsto de novokidneyinjury;

4) acute-on-chroniccardiacdecompensationleadstoacute-on-chronickidneyinjury.

slide7

6

Characteristics of the cardiorenal syndromeType 1:

  • Decreasedcardiacoutput
  • Increasedvenouscongestion
  • Increasedrenovascularresistance
  • ReducedRBF and GFR
  • Albuminuria
  • Tubulardamage
  • Worseningrenalfunction
  • Diureticresistance
  • Activation of thetubulo-glomerularfeedback,
  • Anemia
  • Increasedmortality

(Circulation. 2010;121:2592-2600.)

(J Am CollCardiol 2012;60:1031–42)

Progress in Cardiovascular Diseases 54 (2011) 144–153)

slide8

7

Pathways of AcutePathophysıology of CRS Type 1:

  • Fundamental mechanisms designed to maintain constantblood volume and organ perfusion under continuously changingconditions are responsible for CRS.
  • When primary cardiac or renal dysfunction develops; therenin-angiotensin-aldosteronesystem (RAAS), pressuresensingbaroreceptors, cellular signaling, and SNS mechanisms turn from friend to foe(Gottlieb SS. 2010).
  • HemodynamicsderangementsandincreasedCentralvenouspressureandsystemicvenouscongestıon.
  • Neurohormonalactivatıon,
  • Hypothalamic- pituituiarystressreactıon.
  • İnflamatıonandımmuncellsignaling,
  • The role of gut andendotoxemia,
  • Superimposedinfectıon.
  • İatrogenesis.
pathogenesis of type 1 crs
Pathogenesis of Type 1 CRS:

8

(J AmCollCardiol 2012;60:1031–42)

slide10

CRS CONNECTORS HumorallyandlmmunemediatedMechanisms:

Inflammationandimmunecellsignaling:imbalancebetweentheimmunesystemcellsignalingpathwayspromotingandinhibitinginflamatıon

  • İn HF, an immunedysregulation;- “cytokinescouldproducedistant organ damage ( AKI) alongfurthermyocytesdamaging”.
  • Inflammatoryactivationmayhave a role in HF bycontributingtobothvasculardysfunctionandfluidoverload .

The role of the gut andendotoxemia: Underperfusionandhypoxia of theintestineandthehematogenousrelease of endotoxin.

  • İn HF as a result o localproduction of lipopolysaccharideandsystemicendotoxemia; Disruption of intestinaltranslocation of Gram-negativebacteriaorlipopolysaccharides as well as cytokines.

Superimposedinfection: Superimposedinfection, oftenpneumonia, is a commonprecipitatingorcomplicatingfactor in ADHF.

9

slide11

10

PREDİSPOSITION OF CARDİORENAL SYNDROME:

Thereare a host of predisposingfactorsthatcreatebaseline risk for CRS type 1, whichcommonlyoccurs as an acute-on-chronicdisorder.

  • Obesityandcardiometabolicchanges,
  • Cachexia,
  • Hypertensıonanddiabetes,
  • Uremicsoluteretentıon,
  • Anemia,
  • Proteinuria,
  • Repeated of subclinical AKI.

(J AmCollCardiol 2012;60:1031–42)

slide12

11

ClaudıoRancoSlides,

Paris.2011

slide13

12

PRİNCİPLES OF MANAGEMENT CRS TYPE 1,2:

  • Interruptıon of SNS and RAAS themostimportantgoal in management of Type 2.
  • Principle of managementstrategy of Type 1; restoration of impairedhemodynamicsbysupportivemeasures.

Recomendatıons:

  • Recognizepatientsubsetand risk factors.
  • Biomarkersforearlyidentificatıon of injury,
  • Understandprecipitatingfactors;

+Medicatıons,

+Procedures.

  • Toıntroduceapropriatestrategy as soon as possible.
slide14

13

ClaudıoRancoSlides, Paris 2011 .

slide15

14

Earliest marker of

Kidneyinjury:

NGAL, Cystatin C,

KIM 1.

assesment of renal funct on

15

Assesment of renalfunctıon:

Abbreviations: BSA, body surfacearea; CKD-EPI; ChronicKidneyDiseaseEpidemiologyCollaboration;

MDRD; Modification of Diet in Renal Diseases; Alb, serum albumin; sCr, serum creatinine; sU,

serum uricacid.

MedClin N Am 96 (2012) 955–974

slide17

CONCLUSION:

“Tıme is Nephron”.

  • Primaryprincples: Earlydiagnosıs of AKI in “Golden hours” topreventingcellularchangesandstoppingevolutıon of functıonalderangement.

2. Biomarkersmaygiveimportantcluesforpathophysiologicpathways; newearlytubulardamagemarkersthatmaypredict WRF andoutcome, evenwhen GFR is andsCrstillunaffected.

3. From a HF perspective, themaincontributingmechanismsarehemodynamicallydrivenimpairedrenalperfusionandincreased CVP. Thesepathwaysshould be themaintargetsfortreatment:

“ Should be ensuredandmaintainingadeguatesystemicperfusıon”.

  • Othercardiorenalconnectorsmaymodulatethisrelationshipand can thereforeserve as alternativeassociatedtreatmenttargets.

16

iatrogenesis and type 1 crs
Iatrogenesis and Type 1 CRS

12

(J Am CollCardiol 2012;60:1031–42)

slide20

Hypertensıon & Diabetes:

14

  • Accelerated
  • Los of
  • Nefrons
  • and
  • GFR

CAD,

LVH,

Remodelling,

dilatatıon

HTA-

Lack of

BP control

  • GlmerularDysfunctıon,damage
  • and
  • Loss of
  • Functioningunits

Endotelialmesangial,

andpodocyteinjury

Diabetes-

CKD

Fibrosis,

sclerosıs

Albuminuria

  • Proxtubularcell:
  • Workload of reabs.
  • Renalcellapoptozis,
  • Nephronloss.

Excesivequantitiesalbumin in

Bowman’ space

slide21

CRS TYPE 1:

  • In CRS Type 1 patients, pre-morbidchronickidneydisease is commonandpredisposesto AKI in approximately 60% of cases.
  • AKI is an independent risk factorfor 1-yearmortality in ADHF patients.
  • Decreasedcardiacoutputalongincreasedcentralvenouspressure has a pivotal role in pathophysıology.
  • AKI ınducedbyprimarycardiacdysfunctıonsuggestsinadequaterenalperfusıonuntilprovenotherwise.
  • Toconsidered LOS and/ormarkedincreased in venouspressure:“Decreasedcardiacoutputthatresult in decreased organ hyoperfusıon” leadingtokidneyinjury.
slide22

PATHOPHYSIOLOGY OF CRS TYPE 1:

  • Highlightedsome of thekeyconcept of pathophysıology of thecardıorenalsyndrome in HF:

1. PrimaryHemodynamicderangement :

  • decreasedardiacoutput, increasedcentralvenouspressure.

2. Cardiorenalconnectors:

  • Venouscongestion, SNS dysfunction, anemia, activation of the RAAS, disruption of thehypothalamic-pituitaryaxis,
  • a markedalteration of immuneandsomaticcellsignaling.
slide23

Neurohormonalactivation:

  • TheRAAShas an important role in theinitiationandmaintenance of vascular, myocardial, andrenaldysfunctionleadingtoedema in HF.
  • Increasedreninsecretionoccursearly in biventricularfailure, whichleadstostimulation of angiotensin II. has manyphysiologicaleffects,
  • whichincludestimulation of centralneuralcentersassociatedwithincreasedthirstandsystemicvasoconstrictortocompensatefortheinitialdecrease in strokevolumeassociatedwithventricularfailurewhile at thesame time increasingcontractility.
  • Angiotensin II is alsoknownto be a potentstimulator of theSNS, whichincreasessystemicvascularresistance, venoustone, andcongestion.
  • Angiotensin II has directtrophiceffects on cardiomyocytesandrenaltubularcellsthatpromotescellularhypertrophy, apoptosis,
  • Patientswithbiventricularfailuremayalsohavepoorhepaticperfusionanddecreasedclearance of aldosterone, therebycontributingto an elevation in theplasmaaldosteroneconcentration .
slide24

Inflammationandimmunecellsignaling:

Theterminflammationin CRS has beentermed “low-grade” orimbalancebetweentheimmunesystemcellsignalingpathwayspromotingandinhibitinginflamatıon .

  • inflammatorycytokinesmayalso be producedbycardiomyocytes, followingischemicormechanicalstimuli, alsobytheparticularlyimmuneresponse,( representedbyToll-likereceptors, pentraxin-like C-reactive protein, andpentraxin 3).
  • Thesefindingssuggestthat in HF, an immunedysregulationmayexist; cytokines not onlycouldproducedistant organ damagesuch as AKI, but theyalsomayplay a role in furtherdamagingmyocytes.
  • Inflammatoryactivationmayhave a role in HF bycontributingtobothvasculardysfunctionandfluidoverload in theextravascularspace (interstitiumandalveoli).
  • Recentstudieshaveshownthatinflammationinterfereswiththisprocessleadstopulmonaryfluidoverloaddespite no increase in total body fluid.
  • Thismechanismcould be a causeforinadequaterenalperfusionpressures, peritubularedema, pathologicalreduction of glomerularfiltration, andfinally, mixedinflammatoryandischemictubulardamage.

(Eur J Heart Fail 2008;10:165- 9)

slide25

Superimposedinfection:

  • Superimposedinfection, oftenpneumonia, is a commonprecipitatingorcomplicatingfactor in ADHF.
  • An inflammatorypathogenesis can be a commonkeyfeatureforboththekidneysandcardiovascularsystemduringsepsis, leadingtocellultrastructuralalterationsand organ dysfunction.
  • Proinflammatorycytokines ( TNF-alpha, IL-1, and IL-6), inducemyocardialdysfunction, causemicrocirculatorydamage, and
  • contributetoalteredtissueperfusionandoxygendelivery/consumption;- contributingtobothheartandkidney

failure.

  • Enhancedendothelialexpression of leukocyteadhesionmoleculesandalteration of endothelialcellcontacts can increasemicrovascularpermeability;- leadingtoextravascularfluidshift, fluidoverload, hypovolemia;- reducedvenousreturn, andlowercardiacoutput.
slide26

The role of the gut andendotoxemia.

Underperfusionoftheintestineandthehematogenousrelease of endotoxininpatientswith HFresult of progression of HF and CRS type 1, particularly in patientswithcachexia (proposed as a mechanism).

1) In HF, bloodflow is presumablyshuntedawayfromthesplanchnicregion, andischemia is particularlypronounced at thetips of theintestinalvilli; instates of intestinalunderperfusion, theparacellularpermeabilityof theintestinalwall is increased as a result ofhypoxia, andlocalproduction of lipopolysaccharideandsystemicendotoxemiaoccurs.

  • 2) Disruption of intestinalfunctionandtranslocation of Gram-negativebacteriaorlipopolysaccharides as well ascytokines( TNF--alpha,IL-1, and IL-6) can exacerbatemyocytedysfunction.
  • 3) Theyexerttheircardiosuppressiveeffectsprimarilybyalteringmyocardialintracellularcalcium, reducingmitochondrialactivity, causingimbalance of autonomicnerveactivity, thusaffectingmanyotherorgans, includingthekidneys .
slide27

BİOMARKERS OF AKI BUN: Correlateswellwithprognosis, inexpensive, andeasytomeasureGreatlyaffectedby protein intake, catabolism, andtubularreabsorption/poormeasure of truerenalfunctionCystatin: excellent marker of GFR (betterthansCr); not affectedbyintake, catabolism, andsoforth; good marker of prognosis in CHF morecostlythansCr; cliniciansunfamiliarwithuseandnormals/abnormalsNGAL: excellentsensitivityandspecificitytodetect AKI; levelsincrease >24 h beforesCrincreases in responsetoinjury.Plasma NGAL levelsincrease in settings of inflammation, makingthemlessspecificthanurinary NGAL levelKIM-1: Levelsareelevatedevenwith minimal GFR reductions; associatedwithdeathor HF hospitalizationindependent of GFR; increases 24 h beforesCr in responsetorenalinjuryVeryfewstudies in HF at this timeNAG: Excellentpredictor of AKI; levelsareelevatedeven in thesetting of minimallyreduced GFR; associatedwith risk of deathor HF hospitalizationVeryfewstudies in HF at this timeFABP: Presence in theurine is sensitiveandspecificfor AKI andpredictstheneedforrenalreplacementtherapyanddeath No data on abilitytopredict WRF in CHFAlbuminuria: Inexpensive, easytomeasure; correlateswithworseprognosis in HFcan be found in otherdiseasestates (DM, HTN), thereforelowspecificityAbbreviations: AKI, acutekidneyinjury; BUN, bloodureanitrogen; DM, diabetesmellitus; FABP, fattyacid–binding protein; HTN, hypertension; KIM-1, kidneyinjurymolecule 1; NAG, N-acetyl-b- D-glucosaminidase; NGAL, neutrophilgelatinase-associatedlipocalin.

slide28

Acute HF:

  • Decreased RBF, ±cCr, eGFR.
  • RBF wasstronglydecreased in thesetting of acute HF.
  • Creatininandestimated GFR did not showanycorrelatıonwithcardiacoutput (ESCAPE).
  • However, Renalimpairment in acute HF is highlyprevalentandassociatedwithimpairedprognosıs.
slide29

Chronic HF:

  • Decreased CO, RBF, GFR.
  • Changes in cardiacoutputaround %25 result in a reductıon of renalbloodflow (RBF) of morethan %50. Therefore, renalperfusıon is stronglydependenttochanges in hemodynamics.
  • Givendirectphysiologicrelatıonshipbetween RBF and GFR: GFR todecreasewhen RBF decreasesbecause of decreasedcardiacoutput.
  • However, thekidney is abletopreserve GFR byautoregulatıonof efferentandafferentvasotone of theglomerulus. Decline in cardiacoutputwassucceeded (followed) bydecline in RBF, GFR remainedconstantbecause of an increasedfiltratıonfractıon (FF = GFR/ RBF) upto a certaindegree of RBF.
  • Thisautoregulatorymechanismallowsthekidneytopreservefiltratıonfunctıonwithdecreasing RBF andcardiacoutput.
slide30

ACEİ therapyprobablypositivelyeffectstheratıo of declineobservedwithdeclining RBF.

  • İt willhowever, alsohamperpreservatıon of GFR in patientswithextremelylow RBF whereefferentvasoconstrictıon is essentialtopreserveintraglomerularpressureandtherebyfiltratıon. Inthissetting, thekidney is unabletomaintainfiltratıonpressure, as apparentfrom a sharpdecrease in FF, whereasrenalvascularresistanceincreasessubstantially, indicatingrenalefferentvasoconstrictıon.
  • This is because of adenosine A1- mediatedvasoconstrictıon, (as thiseffectseems at leastpartiallyblockedby A1 receptorantagonists).
slide31

İn thechronic HF setting, thestrongest determinant of reductıon of GFR is decreased RBF. However, on top of thisincreasedcentralvenouspressure (CVP) orvenouscongestıonmaycontrıbutetorenaldysfunctıon.

  • InPatientswithelevated CVP andcardiacdysfunctıon, decreased RBF, increased CVP wasassociatedwithfurtherdecreased in GFR.
  • İmportantly, in thosepatientswithrelativelypreserved RBF, increased CVP was not associatedwithdecrease in GFR.
  • İn aditıon, haveshownthatsymptomsandsıgn of congestıonwererelatedtorenaldysfunctıon, andbothhigh CVP andsignandsymptoms of congestıonareassociatedwithpooroutcome.
  • Theeffect of CVP in thesetting of HF is mostpronounced. İmportantly, high normal levels of CVP mayactuallyimprove RBF and GFR bythe “Frank- Starlingmechanism” via an increase in end- diastolicvolumeand, subsequently, cardiacoutput (strokevolume).
  • Onlywhen CVP increasesabove normal valuesdoes GFR decline.
slide32

Pathophysiologic interactions between heart and kidney in type 2 or“chronic CRS” (long-term abnormalities in cardiac function; eg, chronic heart failure) causing progressive chronic kidneydisease

slide33

Consensus definition and classification of cardio-renalsyndromes: E E uropean Heart Journal (2010) 31, 703–711

slide35

↑Waterɐxretion

↑Sodıumexcretıon

↑Ureareabsorb.

Vasoconstrictıon

Natriüresis↓

Afterload↑

SNS

RAAS

Endotelin

CRS TYPE -1

COMPANSATORY

MECHANISMS

İN HF

Compensatory

Mechanisms

DiüreticPeptides

Chinin-KalickreinSystem

Prostaglandins

EndotelialRelaxinFactor

↑Waterexcretıon

↑Sodıumexcretıon

↓Ureareabsorb.

Natriüresis↑

Afterload↓

Vazodilatatıon

slide37

)

Pathophysiologic interactions between heart and kidney in type 1 or“acute CRS” (abrupt worsening of cardiac function; eg, acute cardiogenic shock or acute decompensation of chronic heartfailure) leading to kidney injury.

AmCollCardiol 2008;52:1527–39

obes ty
OBESİTY
  • ADİPOCYTES İn thehuman body can increase 10-foldboth in numberand in size

Ekokardiyografi

LVH anddilatatıon,

İmpairedrelaxatıon

Obese

Release of

Hs- CRP

Secretecytokines

IL-6, TNF alpha

Obesity-related

Glomerulopathy:

Hyperfiltratıon,

Abdominaladipociytes; IL-6,-

İntotheportalcirculatıon,

- transit totheliver.

slide39

9

ClaudıoRancoSlides,

Paris.2011

slide42

CRS Type -I

CRS Type -II

AKI

CKD

Markers of Functıon:

BUN, Creatinin,

GFR/eGFR

Markers of Damage:

NGAL,Cystatin C,

KIM -1

slide43

Hemodynamicsandcongestıon:

  • Registry data haveshownthat it is thepulmonarycongestionthatbringsthepatientstothehospital. Inthe ADHERE registry, 50% of patientswhowereadmittedtothehospital had a systolicbloodpressure of 140 mm Hgorhigher, andonly 2% had a systolicbloodpressure of _90 mm Hg.
  • Theincrease in bloodpressure is likely a reflection of sodiumretentionandsympatheticactivation.
  • A dysfunctioning LV is particularlysensitivetoafterloadvariations, andtherefore, increase in BP can abruptlyworsen LV fillingpressures, leadingtopulmonarycongestionirrespective of total intravascularvolume.
  • Subsequently, viciouscyclearises in whichcardiacremodelingleadstofunctional MR, furtherincrease in LA pressure, and PHTA.
  • Temporaryisolatedelevation of CVP can impairment of renalfunction.
  • Chronicpassivecongestion of thekidneysresults in attenuatedvascularreflexesover time.
  • As withtheheart, venouscongestion is one of themostimportanthemodynamicdeterminants of CRS and has beenassociatedwiththedevelopment of renaldysfunction in thesetting of ADHF
slide44

Earliest marker of

Kidneyinjury:

NGAL, Cystatin C,

KIM 1,NAG.

slide45

Albuminuria:

  • Albuminuriaandgrossproteinuria has beenconsistentlyassociatedwiththe risk of AKI in a variety of settings.
  • Albuminuria in the general population is predictive of thedevelopment of HF, and in thosewithestablished HF, it is present in 30% andassociatedwithhospitalizationandmortality .
  • Microalbuminuria, is a risk marker forcardiovasculardiseaseand CKD, and is probably a pathogenicfactor in theprogression of CKD.
slide47

Cachexia:

  • Oppositetoobesityandmetabolicsyndromes, combineddisorders of theheartandkidneyarealsolikelytodevelop in the presence of somedegree of cachexiaandsarcopeniaandareassociatedwith organ cross talk via TNF-alphaandotherpro-inflammatorycytokines.
  • Inthesecircumstances, a viciouscirclecouldarise, in whichcachexiaandnutritionaldeficienciesassociatedwitheither HF or CKD maycontributetofurtherdamageandfibrosis of theother organ .
  • Thus, wespeculatethattheoccurrence of chronic CRS andcachexiacould be a harbinger (habercisi) of seriouscomplicationssuch as infectionordeath.
slide49

Uremicsoluteretention.

  • Studieshavedemonstratedthaturemiacausesmyocytedysfunctionmanifestedbyimpairedmovement of calcium in thecytosolleadingtoimpairedcontraction of myocyteelements .
  • Inaddition, uremiadirectlycontributestoacceleratedfibrosisandadversecardiacremodelingaftermyocardialinfarction.
  • Hyperuricemia is associatedwithuremiaand has beenassociatedwithatherosclerosisandcardiovasculardeath in multiplestudies .
slide50

Uremicsoluteretention:

  • Relief of chronicuremiawithrenaltransplantation has beenassociatedwithmanychanges, includingimprovement in LV systolicfunction; reduction in LV mass, andreduction in LV size.

Observationalstudies of patientswithgoutand HF haveshownthatallopurinol is associatedwithimprovedoutcomes.

Smallrandomizedtrialssuggestthatloweringuricacidmayinfluencethenaturalhistoryandsymptoms Of both CKD andcardiovasculardisease.

  • Therefore, as a predisposingfactorrelatedtouremia, hyperuricemiawarrantsadditionalattention as a potentialtreatmenttargetintervention.
slide51

Iatrogenesis (I):

  • Metformin is an antidiabeticdrugthat can result in lacticacidaccumulationandworseningheartfunctiondueto a negativeinotropiceffect.
  • Chemotherapeuticagentsused in solidtumortreatmentsmayinduce a tumorlysissyndrome, with a suddenincrease in circulatinguricacidlevels. Such an effect, althoughlessdramatic, mayalso be inducedbydiuretictherapy. Uricacid, is potentiallytoxictothemyocardium as well as forthetubulointerstitialcomponent of thekidney .
  • Antibioticsmaycauseinterstitialnephritisandtubulardysfunction, andcontributiontoprogressiverenalinsufficiency, especiallywhenglomerularfiltration is stressedby a lowcardiacoutputandactivation of the RAAS.
  • Iodinatedcontrastcauses a muchdifferent form of AKI characterizedbytransientvasoconstrictionanddecreasedperfusionfollowedbydirecttubulartoxicity as thecontrast is takenupbyproximaltubularcellsandtransportedintotheinterstitium in thekidney . Contrast-inducednephropathy can be an importantcause of negativefeedback on theheartwithprogressiveworsening of cardiacdiseaseduetouremiccomplications.
slide52

Iatrogenesis (II).

Progressive salt andwaterretentionalterintraglomerularhemodynamicsandtherebyinfluencephysiologicaltubularglomerularfeedback .

  • RAAS inhibitors : Patientsmayalready be undergoingtreatmentwithACEİs, ARBs, directrenininhibitor, and/or AA, all of whichmaynegativelyimpacttubuloglomerularfeedback .
  • Combinations of ACEİs, ARBs, directrenininhibitor, andespecially AA when GFR is reducedbelow 45 ml/min, mayleadtosecondaryhyperkalemia.
  • NSAİ agents, reversiblyinhibitcyclooxygenases 1 and 2, impairprostaglandinsynthesis, andresult in sodiumandfluidretention, as well as tissueedema,whichconsistentlyworsen HF outcomes.
  • Inthekidney, edemamayresult in impairedoxygenationandmetabolitediffusion, distortedtissuearchitecture, obstruction of
  • capillarybloodflowandlymphaticdrainage, anddisturbedcell– cellinteractionsthatmaythencontributetoprogressive organ dysfunction.
  • Oral andintravenousloopdiuretics, as theymayresolvecongestion but worsenrenalperfusionbyarterialunderfillingandheightenedactivation of thesympatheticand RAAS leadingtoType 1 CRS.
integrated pathways of the cardiorenal syndrome in hf
Integrated pathways of the cardiorenal syndrome in HF.

Progress in Cardiovascular Diseases 54 (2011) 144–153

slide54

Heart- KidneyInteractıons:

  • Biderctıonal,
  • Temporallyregulated,
  • Mediateddifferentmechanisms,
  • Differrentconseguences in specificindividuals,
  • Functional vs structuraldamage,
slide56

Anemia:

  • Anemia is common in HF and is associatedwith

increasedmortality, morbidity, andworseningrenalfunction.

  • Thepathogenesis of anemia in HF is multifactorial, encompassinghemodilutionduetowaterretention, blockade of normal iron transport, inflammation/cytokineinducederythropoietindeficiency, andtissueresistance, malnutrition, cachexia, vitamin deficiency, allamplifiedinthe presence of pre-existing CKD.
slide57

Pathophysiologic interactions between heart and kidney in type 1 or“acute CRS” (abrupt worsening of cardiac function; eg, acute CS or acute decompensation of CHF) leadingtokidneyinjury.

cardio renal interact on basically a vicious circle
Cardio - RenalInteractıon: Basically a Viciouscircle

PrimaryInsult

PrimaryInsult

ADHF-

CHF

AKI-

CKD

ADHF-

CHF

AKI-CKD

Physiological

derangements

Physiologicalderangements

Heart

dysfunctıon

Renal

dysfunctıon

slide59

5

  • Type 1 CRS (acute CRS), occurs in approximately %25-33 of patientsadmitedwith ADHF
  • An acuteincrease in serum creatininelevelaccompanies 21%-45% of hospitalizationsfor ADHF.
  • Decreasedkidneyfunctionalso is present as a significantcomorbidcondition in approximately 50% of patientswithchronicheartfailure.
  • Renal dysfunction is one of the most important independentriskfactors for poor outcomes and all-cause mortality inpatients with HF.
  • Baseline glomerular filtration rate (GFR)appears to be a stronger predictor of mortality in patients withHF than LVEF or NYHA functionalclass.

(Circulation. 2010;121:2592-2600.)

(J Am CollCardiol 2012;60:1031–42)

slide60

8

(Circulation. 2010;121:2592-2600.)

slide61

Pathophysiology of Low-Output Cardiac FailureWith arterial underfilling secondary to a decrease in cardiac output the neurohumoral axis is activated to maintain arterial circulatory integrity. The kidney becomesvasoconstricted as part of this process.

JACC Vol. 59, No. 19, 2012