INTERACTION BETWEEN KİDNEY AND HEART FAİLURE:

Prof Dr Rasim ENARIstanbul UniversityCerrahpasa Medical FacultyCardiology Clinics

(ADHERE) of 105 000 individuals admitted for ADHF, 30% had a history of renal insufficiency.

(EURO-HF, OPTİMİZE-HF) %30-67 have eGFR <60 ml/min/1.73 m2

21% had serum creatinine concentrations >2.0 mg/dL, and 9% had creatinine concentrations >3.0 mg/dL.

Both elevated serum creatinine on admission and worsening creatinine during hospitalization predict prolonged hospitalization rehospitalization, and death. Even small changes in creatinine 0.3 mg/dL are common and have been associated with increased mortality and prolonged hospitalization.

Am Heart J. 2005;149:209 –216.

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CARDİORENAL SYNDROME:

• Disorders of the heart and kidneys whereby “acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other”. • There are direct and indirect effects of HF that can be identified as the primers for AKI and dysfunction.

Interactıons between Heart and Kidney: Biderctıonal, Temporally regulated, Mediated different mechanisms, Differrent conseguences in specific individuals, Functional vs structural damage.

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Clasificatıon of Cardio- Renal Syndromes: CRS Type -I (Acute Cardiorenal syndrome):Abrupt worsening of cardiac functıon leading to acute kidney injury.CRS Type –II (Chronic Cardiorenal Syndrome):Chronic abnortmalities in cardiac function causing progressive and

permanent kidney disease.CRS Type –III: (Acute Renocardiac Syndrome):Abrupt worsening of renal function causing acute cardiac disorders.CRS Type –IV (Chronic Renocardiac Syndrome):Chronic Kidney disease contributing to decreased cardiac function,

cardiac hypertrophy and/or increased risk of adverse cardiovascular events.

CRS Type –V (Secondary Cardiorenal Syndrome):Systemic condition (i.g. DM, sepsis..) causing both cardiac and

renal dysfunction.

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(European Heart Journal (2010) 31, 703–711)

Risk factors of Renal dysfunctıon in heart failure:• Hypertension• Diabetes• Severe vascular disease• Eldely age• Past history of: + Heart failure + Renal dysfunction + Heart failure and renal dysfunction.

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

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Subtypes of CRS Type 1:

1) de novo cardiac injury leads to de novo kidney injury;2) de novo cardiac injury leads to acute-on-chronic kidneyinjury; 3) acute-on-chronic cardiac decompensation leads to de novo

kidney injury; 4) acute-on-chronic cardiac decompensation leads to acute-on-

chronic kidney injury.  

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Characteristics of the cardiorenal syndrome Type 1:

• Decreased cardiac output• Increased venous congestion

• Increased renovascular resistance• Reduced RBF and GFR• Albuminuria• Tubular damage• Worsening renal function

• Diuretic resistance• Activation of the tubulo-glomerular feedback,• Anemia• Increased mortality

(Circulation. 2010;121:2592-2600.) (J Am Coll Cardiol 2012;60:1031–42) Progress in Cardiovascular Diseases 54 (2011) 144–153)

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Pathways of Acute Pathophysıology of CRS Type 1:

• Fundamental mechanisms designed to maintain constant blood volume and organ perfusion under continuously changing conditions are responsible for CRS.

• When primary cardiac or renal dysfunction develops; the renin-angiotensin-aldosterone system (RAAS), pressure sensing baroreceptors, cellular signaling, and SNS mechanisms turn from friend to foe (Gottlieb SS. 2010).

Hemodynamics derangements and increased Central venous pressure and systemic venous congestıon.

Neurohormonal activatıon, Hypothalamic- pituituiary stress reactıon. İnflamatıon and ımmun cell signaling, The role of gut and endotoxemia, Superimposed infectıon. İatrogenesis.

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Pathogenesis of Type 1 CRS:

(J Am Coll Cardiol 2012;60:1031–42)

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CRS CONNECTORS Humorally and lmmune mediated Mechanisms:

Inflammation and immune cell signaling: imbalance between the immune system cell signaling pathways promoting and inhibiting inflamatıon

• İn HF, an immune dysregulation;- “cytokines could produce distant organ damage ( AKI) along further myocytes damaging”.

• Inflammatory activation may have a role in HF by contributing to both vascular dysfunction and fluid overload .

The role of the gut and endotoxemia: Underperfusion and hypoxia of the intestine and the hematogenous release of endotoxin.

• İn HF as a result o local production of lipopolysaccharide and systemic endotoxemia; Disruption of intestinal translocation of Gram-negative bacteria or lipopolysaccharides as well as cytokines.

Superimposed infection: Superimposed infection, often pneumonia, is a common precipitating or complicating factor in ADHF.

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PREDİSPOSITION OF CARDİORENAL SYNDROME:

There are a host of predisposing factors that create baseline risk for CRS type 1, which commonly occurs as an acute-on-chronic disorder.

• Obesity and cardiometabolic changes,• Cachexia,• Hypertensıon and diabetes,• Uremic solute retentıon,• Anemia,• Proteinuria,• Repeated of subclinical AKI. (J Am Coll Cardiol 2012;60:1031–42)

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Claudıo Ranco Slides, Paris.2011

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PRİNCİPLES OF MANAGEMENT CRS TYPE 1,2:

a. Interruptıon of SNS and RAAS the most important goal in management of Type 2.

b. Principle of management strategy of Type 1; restoration of impaired hemodynamics by supportive measures.

Recomendatıons: • Recognize patient subset and risk factors.• Biomarkers for early identificatıon of injury,• Understand precipitating factors; +Medicatıons, +Procedures.• To ıntroduce apropriate strategy as soon as possible.

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Claudıo Ranco Slides, Paris 2011 .

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Earliest marker ofKidney injury:NGAL, Cystatin C, KIM 1.

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Assesment of renal functıon:

Abbreviations: BSA, body surface area; CKD-EPI; Chronic Kidney Disease Epidemiology Collaboration;MDRD; Modification of Diet in Renal Diseases; Alb, serum albumin; sCr, serum creatinine; sU,serum uric acid.

Med Clin N Am 96 (2012) 955–974

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CONCLUSION: “Tıme is Nephron”.

1. Primary princples: Early diagnosıs of AKI in “Golden hours” to preventing cellular changes and stopping evolutıon of functıonal derangement.

2. Biomarkers may give important clues for pathophysiologic pathways; new early tubular damage markers that may predict WRF and outcome, even when GFR is and sCr still unaffected.

3. From a HF perspective, the main contributing mechanisms are hemodynamically driven impaired renal perfusion and increased CVP. These pathways should be the main targets for treatment:

“ Should be ensured and maintaining adeguate systemic perfusıon”.

• Other cardiorenal connectors may modulate this relationship and can therefore serve as alternative associated treatment targets.

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Iatrogenesis and Type 1 CRS

(J Am Coll Cardiol 2012;60:1031–42)

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HTA-Lack of BP control

Diabetes-

CAD,LVH,Remodelling,dilatatıon

CKDFibrosis,sclerosıs

• Accelerated Los of

Nefrons and

• GFR

• Glmerular Dysfunctıon,damage and • Loss ofFunctioning units

Hypertensıon & Diabetes:

Endotelial mesangial, and podocyte injury

Excesive quantities albumin in Bowman’ space

Prox tubular cell:Workload of reabs.• Renal cell apoptozis,Nephron loss.

Albuminuria

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CRS TYPE 1:

• In CRS Type 1 patients, pre-morbid chronic kidney disease is common and predisposes to AKI in approximately 60% of cases.

• AKI is an independent risk factor for 1-year mortality in ADHF patients.

• Decreased cardiac output along increased central venous pressure has a pivotal role in pathophysıology.

• AKI ınduced by primary cardiac dysfunctıon suggests inadequate renal perfusıon until proven otherwise.

• To considered LOS and/or marked increased in venous pressure: “Decreased cardiac output that result in decreased organ hyoperfusıon” leading to kidney injury.

PATHOPHYSIOLOGY OF CRS TYPE 1:

• Highlighted some of the key concept of pathophysıology of the cardıorenal syndrome in HF:

1. Primary Hemodynamic derangement : • decreased ardiac output, increased central

venous pressure. 2. Cardiorenal connectors: • Venous congestion, SNS dysfunction, anemia,

activation of the RAAS, disruption of the hypothalamic-pituitary axis,

• a marked alteration of immune and somatic cell signaling.

• Neurohormonal activation:• The RAAS has an important role in the initiation and maintenance

of vascular, myocardial, and renal dysfunction leading to edema in HF.

• Increased renin secretion occurs early in biventricular failure, which leads to stimulation of angiotensin II. has many physiological effects,

• which include stimulation of central neural centers associated with increased thirst and systemic vasoconstrictor to compensate for the initial decrease in stroke volume associated with ventricular failure while at the same time increasing contractility.

• Angiotensin II is also known to be a potent stimulator of the SNS, which increases systemic vascular resistance, venous tone, and congestion.

• Angiotensin II has direct trophic effects on cardiomyocytes and renal tubular cells that promotes cellular hypertrophy, apoptosis,

• Patients with biventricular failure may also have poor hepatic perfusion and decreased clearance of aldosterone, thereby contributing to an elevation in the plasma aldosterone concentration .

Inflammation and immune cell signaling: The term inflammation in CRS has been termed “low-grade” or imbalance between the immune

system cell signaling pathways promoting and inhibiting inflamatıon . • inflammatory cytokines may also be produced by cardiomyocytes, following ischemic or

mechanical stimuli, also by the particularly immune response,( represented by Toll-like receptors, pentraxin-like C-reactive protein, and pentraxin 3).

• These findings suggest that in HF, an immune dysregulation may exist; cytokines not only could produce distant organ damage such as AKI, but they also may play a role in further damaging myocytes.

• Inflammatory activation may have a role in HF by contributing to both vascular dysfunction and fluid overload in the extravascular space (interstitium and alveoli).

• Recent studies have shown that inflammation interferes with this process leads to pulmonary fluid overload despite no increase in total body fluid.

• This mechanism could be a cause for inadequate renal perfusion pressures, peritubular edema, pathological reduction of glomerular filtration, and finally, mixed inflammatory and ischemic tubular damage.

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

Superimposed infection:• Superimposed infection, often pneumonia, is a common

precipitating or complicating factor in ADHF. • An inflammatory pathogenesis can be a common key feature

for both the kidneys and cardiovascular system during sepsis, leading to cell ultrastructural alterations and organ dysfunction.

• Proinflammatory cytokines ( TNF-alpha, IL-1, and IL-6), induce myocardial dysfunction, cause microcirculatory damage, and

• contribute to altered tissue perfusion and oxygen delivery/consumption;- contributing to both heart and kidney

failure.• Enhanced endothelial expression of leukocyte adhesion

molecules and alteration of endothelial cell contacts can increase microvascular permeability;- leading to extravascular fluid shift, fluid overload, hypovolemia;- reduced venous return, and lower cardiac output.

The role of the gut and endotoxemia. Underperfusion ofthe intestine and the hematogenous release of endotoxin in patients with HF result of progression of HF and CRS type 1, particularly in patients with cachexia (proposed as a mechanism).

1) In HF, blood flow is presumably shunted away from the splanchnic region, and ischemia is particularly pronounced at the tips of the intestinal villi; in states of intestinal underperfusion, the paracellular permeability of the intestinal wall is increased as a result of hypoxia, and local production of lipopolysaccharide and systemic endotoxemia occurs.

• 2) Disruption of intestinal function and translocation of Gram-negative bacteria or lipopolysaccharides as well as cytokines ( TNF--alpha,IL-1, and IL-6) can exacerbate myocyte dysfunction.

• 3) They exert their cardiosuppressive effects primarily by altering myocardial intracellular calcium, reducing mitochondrial activity, causing imbalance of autonomic nerve activity, thus affecting many other organs, including the kidneys .

BİOMARKERS OF AKI BUN: Correlates well with prognosis, inexpensive, and easy to measure Greatly affected by protein intake, catabolism, and tubular reabsorption/poor measure of true renal function

Cystatin: excellent marker of GFR (better than sCr); not affected by intake, catabolism, and so forth; good marker of prognosis in CHF more costly than sCr; clinicians unfamiliar with use and normals/abnormals

NGAL: excellent sensitivity and specificity to detect AKI; levels increase >24 h before sCr increases in response to injury.Plasma NGAL levels increase in settings of inflammation, making them less specific than urinary NGAL levelKIM-1: Levels are elevated even with minimal GFR reductions; associated with death or HF hospitalization independent of GFR; increases 24 h before sCr in response to renal injury Very few studies in HF at this timeNAG: Excellent predictor of AKI; levels are elevated even in the setting of minimally reduced GFR; associated with risk of death or HF hospitalization Very few studies in HF at this time

FABP: Presence in the urine is sensitive and specific for AKI and predicts the need for renal replacement therapy and death No data on ability to predict WRF in CHF

Albuminuria: Inexpensive, easy to measure; correlates with worse prognosis in HFcan be found in other disease states (DM, HTN), therefore low specificity 

Abbreviations: AKI, acute kidney injury; BUN, blood urea nitrogen; DM, diabetes mellitus; FABP, fatty acid–binding protein; HTN, hypertension; KIM-1, kidney injury molecule 1; NAG, N-acetyl-b- D-glucosaminidase; NGAL, neutrophil gelatinase-associated lipocalin.

• Acute HF: • Decreased RBF, ±cCr, eGFR.• RBF was strongly decreased in the setting of acute HF.• Creatinin and estimated GFR did not show any

correlatıon with cardiac output (ESCAPE). • However, Renal impairment in acute HF is highly

prevalent and associated with impaired prognosıs.•

• Chronic HF: • Decreased CO, RBF, GFR.

• Changes in cardiac output around %25 result in a reductıon of renal blood flow (RBF) of more than %50. Therefore, renal perfusıon is strongly dependent to changes in hemodynamics.

• Given direct physiologic relatıonship between RBF and GFR: GFR to decrease when RBF decreases because of decreased cardiac output.

• However, the kidney is able to preserve GFR by autoregulatıon of efferent and afferent vasotone of the glomerulus. Decline in cardiac output was succeeded (followed) by decline in RBF, GFR remained constant because of an increased filtratıon fractıon (FF = GFR/ RBF) up to a certain degree of RBF.

• This autoregulatory mechanism allows the kidney to preserve filtratıon functıon with decreasing RBF and cardiac output.

• ACEİ therapy probably positively effects the ratıo of decline observed with declining RBF.

• İt will however, also hamper preservatıon of GFR in patients with extremely low RBF where efferent vasoconstrictıon is essential to preserve intraglomerular pressure and thereby filtratıon. In this setting, the kidney is unable to maintain filtratıon pressure, as apparent from a sharp decrease in FF, whereas renal vascular resistance increases substantially, indicating renal efferent vasoconstrictıon.

• This is because of adenosine A1- mediated vasoconstrictıon, (as this effect seems at least partially blocked by A1 receptor antagonists).

• İn the chronic HF setting, the strongest determinant of reductıon of GFR is decreased RBF. However, on top of this increased central venous pressure (CVP) or venous congestıon may contrıbute to renal dysfunctıon.

• In Patients with elevated CVP and cardiac dysfunctıon, decreased RBF, increased CVP was associated with further decreased in GFR.

• İmportantly, in those patients with relatively preserved RBF, increased CVP was not associated with decrease in GFR.

• İn aditıon, have shown that symptoms and sıgn of congestıon were related to renal dysfunctıon, and both high CVP and sign and symptoms of congestıon are associated with poor outcome.

• The effect of CVP in the setting of HF is most pronounced. İmportantly, high normal levels of CVP may actually improve RBF and GFR by the “Frank- Starling mechanism” via an increase in end- diastolic volume and, subsequently, cardiac output (stroke volume).

• Only when CVP increases above normal values does GFR decline.

 

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 kidney disease

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

Acute cardio-renal syndrome (type 1)Acute worsening of heart function leading to kidney injury and/ordysfunction. This is a syndrome of worsening renal function (WRF)complicating acute heart failure (AHF) and/or acute coronary syndrome(ACS).

Chronic cardio-renal syndrome (type 2)Chronic abnormalities in heart function leading to kidney injury ordysfunction. This subtype refers to a more chronic state of kidneydisease complicating chronic heart disease.Acute reno-cardiac syndrome (type 3)Acute worsening of kidney function leading to heart injury and/ordysfunction. This subtype refers to abnormalities in cardiac functionsecondary to AKI.Chronic reno-cardiac syndrome (type 4)Chronic kidney disease (CKD) leading to heart injury, disease, and/or dysfunction. This subtype refers to disease or dysfunction of theheart occurring secondary to CKD. There is a graded and independentassociation between the severity of CKD and adverse cardiacoutcomes. In a recent meta-analysis,13Secondary cardio-renal syndromes (type 5)Systemic conditions leading to simultaneous injury and/or dysfunctionof heart and kidney.

The pathophysiology of angiotensin II and renal fibrosis.

↑Water ɐxretion

↑Sodıum excretıon

↑Urea reabsorb.

↑Water excretıon

↑Sodıum excretıon

↓Urea reabsorb.

Diüretic PeptidesChinin-Kalickrein SystemProstaglandinsEndotelial Relaxin Factor

SNSRAASEndotelin

VasoconstrictıonNatriüresis↓Afterload↑

Natriüresis↑Afterload↓

Vazodilatatıon

CompensatoryMechanisms

CRS TYPE -1COMPANSATORYMECHANISMSİN HF

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 heart failure) leading to kidney injury.

)

Am Coll Cardiol 2008;52:1527–39

OBESİTY• ADİPOCYTES İn the human body can increase 10-fold both in

number and in size

Secrete cytokinesIL-6, TNF alpha

Abdominal adipociytes; IL-6,-İnto the portal circulatıon, - transit to the liver.

Release ofHs- CRP

EkokardiyografiLVH and dilatatıon,İmpaired relaxatıon

Obesity-relatedGlomerulopathy:Hyperfiltratıon,

Obese

Claudıo Ranco Slides, Paris.2011

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The complex bidirectional relationship between heart failure and renal disease.

Markers of Functıon:

BUN, Creatinin,GFR/eGFR

Markers of

Damage:

NGAL,Cystatin C,KIM -1

CRS Type -I

CRS Type -II

CKDAKI

Hemodynamics and congestıon:• Registry data have shown that it is the pulmonary congestion that

brings the patients to the hospital. In the ADHERE registry, 50% of patients who were admitted to the hospital had a systolic blood pressure of 140 mm Hg or higher, and only 2% had a systolic blood pressure of _90 mm Hg.

• The increase in blood pressure is likely a reflection of sodium retention and sympathetic activation.

• A dysfunctioning LV is particularly sensitive to afterload variations, and therefore, increase in BP can abruptly worsen LV filling pressures, leading to pulmonary congestion irrespective of total intravascular volume.

• Subsequently, vicious cycle arises in which cardiac remodeling leads to functional MR, further increase in LA pressure, and PHTA.

• Temporary isolated elevation of CVP can impairment of renal function.

• Chronic passive congestion of the kidneys results in attenuated vascular reflexes over time.

• As with the heart, venous congestion is one of the most important hemodynamic determinants of CRS and has been associated with the development of renal dysfunction in the setting of ADHF

Earliest marker ofKidney injury:NGAL, Cystatin C, KIM 1,NAG.

Albuminuria: • Albuminuria and gross proteinuria has been

consistently associated with the risk of AKI in a variety of settings.

• Albuminuria in the general population is predictive of the development of HF, and in those with established HF, it is present in 30% and associated with hospitalization and mortality .

• Microalbuminuria, is a risk marker for cardiovascular disease and CKD, and is probably a pathogenic factor in the progression of CKD.

Cachexia: • Opposite to obesity and metabolic syndromes,

combined disorders of the heart and kidney are also likely to develop in the presence of some degree of cachexia and sarcopenia and are associated with organ cross talk via TNF-alpha and other pro-inflammatory cytokines.

• In these circumstances, a vicious circle could arise, in which cachexia and nutritional deficiencies associated with either HF or CKD may contribute to further damage and fibrosis of the other organ .

• Thus, we speculate that the occurrence of chronic CRS and cachexia could be a harbinger (habercisi) of serious complications such as infection or death.

Uremic solute retention. • Studies have demonstrated that uremia

causes myocyte dysfunction manifested by impaired movement of calcium in the cytosol leading to impaired contraction of myocyte elements .

• In addition, uremia directly contributes to accelerated fibrosis and adverse cardiac remodeling after myocardial infarction.

• Hyperuricemia is associated with uremia and has been associated with atherosclerosis and cardiovascular death in multiple studies .

Uremic solute retention: • Relief of chronic uremia with renal transplantation

has been associated with many changes, including improvement in LV systolic function; reduction in LV mass, and reduction in LV size.

Observational studies of patients with gout and HF have shown that allopurinol is associated with improved outcomes.

Small randomized trials suggest that lowering uric acid may influence the natural history and symptoms Of both CKD and cardiovascular disease.

• Therefore, as a predisposing factor related to uremia, hyperuricemia warrants additional attention as a potential treatment target intervention.

Iatrogenesis (I): • Metformin is an antidiabetic drug that can result in lactic acid

accumulation and worsening heart function due to a negative inotropic effect.

• Chemotherapeutic agents used in solid tumor treatments may induce a tumor lysis syndrome, with a sudden increase in circulating uric acid levels. Such an effect, although less dramatic, may also be induced by diuretic therapy. Uric acid, is potentially toxic to the myocardium as well as for the tubulointerstitial component of the kidney .

• Antibiotics may cause interstitial nephritis and tubular dysfunction, and contribution to progressive renal insufficiency, especially when glomerularfiltration is stressed by a low cardiac output and activation of the RAAS.

• Iodinated contrast causes a much different form of AKI characterized by transient vasoconstriction and decreased perfusion followed by direct tubular toxicity as the contrast is taken up by proximal tubular cells and transported into the interstitium in the kidney . Contrast-induced nephropathy can be an important cause of negative feedback on the heart with progressive worsening of cardiac disease due to uremic complications.

• Iatrogenesis (II). Progressive salt and water retention alter intraglomerular hemodynamics

and thereby influence physiological tubularglomerular feedback .• RAAS inhibitors : Patients may already be undergoing treatment with

ACEİs, ARBs, direct renin inhibitor, and/or AA, all of which may negatively impact tubuloglomerular feedback .

• Combinations of ACEİs, ARBs, direct renin inhibitor, and especially AA when GFR is reduced below 45 ml/min, may lead to secondary hyperkalemia.

• NSAİ agents, reversibly inhibit cyclooxygenases 1 and 2, impair prostaglandin synthesis, and result in sodium and fluid retention, as well as tissue edema,which consistently worsen HF outcomes.

• In the kidney, edema may result in impaired oxygenation and metabolite diffusion, distorted tissue architecture, obstruction of

• capillary blood flow and lymphatic drainage, and disturbed cell– cell interactions that may then contribute to progressive organ dysfunction.

• Oral and intravenous loop diuretics, as they may resolve congestion but worsen renal perfusion by arterial underfilling and heightened activation of the sympathetic and RAAS leading toType 1 CRS.

Integrated pathways of the cardiorenal syndrome in HF.

Progress in Cardiovascular Diseases 54 (2011) 144–153

Heart- Kidney Interactıons:

• Biderctıonal,• Temporally regulated,• Mediated different mechanisms,• Differrent conseguences in specific individuals,• Functional vs structural damage,

Claudıo RancoSlides,Paris.2011

Anemia: • Anemia is common in HF and is associated withincreased mortality, morbidity, and worsening renal

function.

• The pathogenesis of anemia in HF is multifactorial, encompassing hemodilution due to water retention, blockade of normal iron transport, inflammation/cytokine induced erythropoietin deficiency, and tissue resistance, malnutrition, cachexia, vitamin deficiency, all amplified inthe presence of pre-existing CKD.

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) leading to kidney injury.

Cardio - Renal Interactıon: Basically a Vicious circle

Primary Insult

Primary Insult

AKI-CKD

AKI-CKD

Physiologicalderangements

Physiological derangements

Heartdysfunctıon

ADHF-

CHF

Renal dysfunctıon

ADHF- CHF

• Type 1 CRS (acute CRS), occurs in approximately %25-33 of patients admited with ADHF

• An acute increase in serum creatinine level accompanies 21%-45% of hospitalizations for ADHF.

• Decreased kidney function also is present as a significant comorbid condition in approximately 50% of patients with chronic heart failure.

Renal dysfunction is one of the most important independent risk factors for poor outcomes and all-cause mortality in patients with HF.

Baseline glomerular filtration rate (GFR) appears to be a stronger predictor of mortality in patients with HF than LVEF or NYHA functional class.

(Circulation.

2010;121:2592-2600.) (J Am Coll Cardiol 2012;60:1031–42)

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

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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

Med Clin N Am 96 (2012) 955–974