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INTERACTION BETWEEN KİDNEY AND
HEART FAİLURE:
Prof Dr Rasim ENAR
Istanbul University
Cerrahpasa Medical Faculty
Cardiology 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
1
 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.
2
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.
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.
(European Heart Journal (2010) 31, 703–711)
3
4
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)
5
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 kidney
injury;
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.
Characteristics of the cardiorenal syndrome Type 1:
6
• 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)
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 reninangiotensin-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:
8
(J Am Coll Cardiol 2012;60:1031–42)
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 Gramnegative 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-onchronic 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)
11
Claudıo Ranco Slides,
Paris.2011
PRİNCİPLES OF MANAGEMENT CRS TYPE 1,2:
12
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.
13
Claudıo Ranco Slides, Paris 2011 .
14
Earliest marker of
Kidney injury:
NGAL, Cystatin C,
KIM 1.
Assesment of renal functıon:
15
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
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.
16
Iatrogenesis and Type 1 CRS
12
(J Am Coll Cardiol 2012;60:1031–42)
Hypertensıon & Diabetes:
• Accelerated
Los of
Nefrons
and
HTALack of
BP control
14
CAD,
LVH,
Remodelling,
dilatatıon
• GFR
• Glmerular
Dysfunctıon,
damage
and
• Loss of
Functioning
units
Endotelial mesangial,
and podocyte injury
Diabetes-
Albuminuria
Prox tubular cell:
Workload of reabs.
• Renal cell
apoptozis,
Nephron loss.
Excesive quantities
albumin in
Bowman’ space
CKD
Fibrosis,
sclerosıs
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 Creactive 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 level
KIM-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 time
NAG: 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 HF
can 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 enddiastolic 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/or
dysfunction. 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 or
dysfunction. This subtype refers to a more chronic state of kidney
disease complicating chronic heart disease.
Acute reno-cardiac syndrome (type 3)
Acute worsening of kidney function leading to heart injury and/or
dysfunction. This subtype refers to abnormalities in cardiac function
secondary 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 the
heart occurring secondary to CKD. There is a graded and independent
association between the severity of CKD and adverse cardiac
outcomes. In a recent meta-analysis,13
Secondary cardio-renal syndromes (type 5)
Systemic conditions leading to simultaneous injury and/or dysfunction
of heart and kidney.
The pathophysiology of angiotensin II and renal
fibrosis.
Vasoconstrictıon
Natriüresis↓
Afterload↑
SNS
RAAS
Endotelin
↑Water ɐxretion
↑Sodıum excretıon
↑Urea reabsorb.
CRS TYPE -1
COMPANSATORY
MECHANISMS
İN HF
Compensatory
Mechanisms
Natriüresis↑
Afterload↓
Diüretic Peptides
Chinin-Kalickrein System
Prostaglandins
Endotelial Relaxin Factor
↑Water
excretıon
↑Sodıum
excretıon
Vazodilatatıon
↓Urea reabsorb.
)
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
Obese
Secrete
cytokines
IL-6, TNF
alpha
Ekokardiyografi
LVH and dilatatıon,
İmpaired relaxatıon
Release
of
Hs- CRP
Abdominal adipociytes; IL-6,İnto the portal circulatıon,
- transit to the liver.
Obesity-related
Glomerulopathy:
Hyperfiltratıon,
9
Claudıo Ranco Slides,
Paris.2011
The complex bidirectional relationship between heart
failure and renal disease.
CRS Type -I
CRS Type -II
AKI
CKD
Markers of
Functıon:
Markers of
Damage:
NGAL,Cyst
atin C,
KIM -1
BUN,
Creatinin,
GFR/eGFR
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 of
Kidney 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 with
increased 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
ADHFCHF
AKICKD
AKICKD
ADHFCHF
Physiological
derangements
Renal
dysfunctıon
Physiological
derangements
Heart
dysfunctıon
• Type 1 CRS (acute CRS), occurs in approximately %25-33 of
5
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)
8
(Circulation. 2010;121:2592-2600.)
Pathophysiology of Low-Output Cardiac Failure
With 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