C d R l dCardio-Renal Syndrome
首 都 医 科 大 学 急 诊 医 学 系
首都医科大学附属北京朝阳医院急诊科都 科 科
何新华
2011-08-27
Cardio-Renal Syndrome (CRS)
It is a disorder of the heart and kidneys It is a disorder of the heart and kidneys
whereby acute or chronic dysfunction in
i d t h i one organ may induce acute or chronic
dysfunction of the other.
Subtypes
I: acute worsening of heart function (AHF-ACS)
leading to kidney injury and/or dysfunction.
II: chronic abnormalities in heart function (CHF-
CHD) leading to kidney injury or dysfunction.
III t i f kid f ti (AKI) III: acute worsening of kidney function (AKI)
leading to heart injury and/or dysfunction.
IV: chronic kidney disease (CKD) leading to heart IV: chronic kidney disease (CKD) leading to heart
injury, disease and/or dysfunction.
V: systemic conditions leading to simultaneous V: systemic conditions leading to simultaneous
injury and/or dysfunction of heart and kidney.
Pathophysiological Mechanismsp y g
Fig. 1 Diagram illustrating and summarizing the major pathophysiological
interactions between heart and kidney in types 1 and 3 cardio-renal
syndromes (acute interactions)syndromes (acute interactions)
Fig.2 Diagram illustrating and summarizing the major mechanisms involved in
renal hypoperfusion in CRS type I
Fig.3 Diagram illustrating and summarizing the major compensateory
mechanisms involved in CRS type Imechanisms involved in CRS type I
Fig.4 Diagram illustrating and summarizing major pathophysiological
interactions between heart and kidney in type 2 and type 4 CRS (chronic
interactions)interactions)
Fig.5 Diagram illustrating and summarizing the major pathophysiological
interactions between heart and kidney in type 5 CRSinteractions between heart and kidney in type 5 CRS
Fig.6 Heart and kidney interactionsg y
Diagnosis and BiomarkersDiagnosis and Biomarkers
Biomarkers of CRS
To (early) identify and classify CRS?
To risk-stratify patients with regard to To risk stratify patients with regard to
reversibility?
As targets for treatment? As targets for treatment?
To monitor the effects of treatment?
Can imaging of the heart and kidneys be
combined effectively with biomarkers
h f d d
y
across the spectrum of diagnosis and
treatment of CRS?
Natriuretic peptides and HF
Natriuretic peptides (NPs) are elevated
in patients with CRS (type 1) in which in patients with CRS (type 1) in which
AKI occurs as a consequence of ADHF.
They have shown prognostic utility in
patients with various stages of renal p g
insufficiency, demonstrating potential
applications in CRS types 2 and 4.app cat n n typ an .
Biomarkers of renal injuryBiomarkers of renal injury
Neutrophil gelatinase-associated Neutroph l gelat nase assoc ated
lipocalin (NGAL)
In a recent study, a single measurement
of urinary NGAL was able to of urinary NGAL was able to
differentiate those with subsequent AKI,
with a sensitivity and specificity of 90 with a sensitivity and specificity of 90
and 99%.
NGAL could be used as an earlier marker
of impending WRF during the treatment f mp n ng W F ur ng th tr atm nt
of ADHF.
Cystatin C
Cystatin C appears to be a better
predictor of glomerular function than predictor of glomerular function than
serum creatinine in patients with CKD.
In AKI, urinary excretion of cystatin C
has been shown to predict the p
requirement for RRT earlier than
creatinine.cr at n n .
Kidney injury molecule-1K dney njury molecule
(KIM-1)
KIM-1 is a protein detectable in the
urine after ischaemic or nephrotoxic urine after ischaemic or nephrotoxic
insults to proximal tubular cells.
Urinary KIM-1 seems to be highly
specific for ischaemic AKI and not for p
pre-renal azotemia, CKD, or contrast
induced nephropathy.n uc n phr pathy.
N-acetyl-β-(D)glucosaminidase
N-acetyl-β-(D) glucosaminidase has been
shown to function as a marker of kidney shown to function as a marker of kidney
injury, reflecting particularly the degree
of tubular damage of tubular damage.
It is not only found in elevated urinary y y
concentrations in AKI and CKD, but also
in diabetic patients, patients with n a t c pat nt , pat nt w th
essential hypertension, and HF.
Interleukin-18
It displays good sensitivity and
specificity for ischaemic AKI with an specificity for ischaemic AKI with an
AUC >90% with increased levels 48 h
prior to increases in serum creatinineprior to increases in serum creatinine.
Urinary NGAL and IL-18 have been y
studied as joint biomarkers for delayed
graft function following kidney graft funct n f w ng n y
transplantation.
Bioimpedance vector analysis
This may be used in combination with
NGAL and BNP to guide fluid NGAL and BNP to guide fluid
management strategies.
Patients will be kept within the narrow
window of adequate hydration preventing q y p g
worsening of both kidney and heart
function.funct n.
Imaging
Suspected CRS, to avoid the use of iodinated
contrast media if not strictly necessary. y y
The presence of coronary disease should be
excluded by stress echo or stress myocardial excluded by stress echo or stress myocardial
perfusion (SPECT/PET) in types III, IV, and V
CRS and in types I and II CRS when the CRS and in types I and II CRS when the
primary cardiac disease is valvular, congenital,
or myopathic.y p
Prevention
Type 1
Blood pressure control
Block the RAAS Block the RAAS
Beta adrenergic blockers (BB)
Coronary artery disease risk factor
modificationm f
Compliance with dietary and drug
treatmentstreatments.
Type 2
ACE-I
ARB ARB
BB
Aldosterone receptor blockers,
combination of nitrates and hydralazine, m f y ,
and cardiac re-synchronization therapy.
Type 3
Avoidance of hypervolaemia should help
prevent cardiac decompensationprevent cardiac decompensation.
Uremic changes, hyperkalaemia, and
mediators of inflammation can have
adverse cardiac consequences.q
Type 4
The core prevention concept beyond
attention to usual risk factor attention to usual risk factor
modification is that the reduction in the
rate of progression of CKD may lead to rate of progression of CKD may lead to
reduced rates of type 4 CRS.
Type 5
To treatment of the primary illness.
d ll diabetes mellitus
Amyloidosis Amyloidosis
Sepsisp
Rhabdomyolysis
haemorrhagic shock, etc.
Management strategies
Type 1
Vasodilators and loop diuretics are widely
recommended in cases of ADHF and in CRS
type 1.
Vasodilators (e.g. nesiritide) may also affect ( g ) y
renal function and in some cases exacerbate
renal injury.
Vasopressin receptor 2 antagonists can improve
hyponatraemia, but without any clear survival
benefit. If congestion coincides with low blood
pressure, inotropic agents should be considered.
Cardiogenic shock
Dobutamine or dopamine
Phosphodiesterase inhibitors milrinone and Phosphodiesterase inhibitors, milrinone, and
levosimendan.
Extracorporeal ultrafiltration may be useful in
ADHF associated with diuretic resistance.
For systemic hypotension, norepinephrine ,
elective ventilation and/or intra-aortic balloon
pumping, CABG.
Type 2
ACEIs, β-blockers, ARBs, and aldosterone
antagonists significantly reduce mortality and
morbidity in CHF morbidity in CHF.
The optimal approach is to combine ACE-I and β-
blocker titrate dosages to which either an ARB blocker, titrate dosages, to which either an ARB
or aldosterone antagonist is subsequently added
depending on clinical condition and patient
characteristics In patients unable to tolerate characteristics. In patients unable to tolerate
these agents, hydralazine and nitrates may be an
option.
Digoxin and diuretics improve symptoms in CHF
but have no effect on mortality.
Cardiac re-synchronization therapy is now
recommended for symptomatic CHF patients
(NYHA III IV) ith l ft t i l (NYHA III–IV) with poor left ventricular
ejection fraction (LVEF) and QRS prolongation,
as are implantable cardiac defibrillators for as are implantable cardiac defibrillators for
both survivors of cardiac arrest and/or
sustained ventricular arrhythmias and also for y
symptomatic CHF patients with impaired LVEF.
In selected patients who do not respond to p p
treatment, mechanical assist devices and/or
cardiac transplantation may be appropriate.
More intensive diuretic treatment is needed.
Thiazide diuretics may be less effective and Thiazide diuretics may be less effective, and
loop diuretics are preferred. To improve
natriuresis loop diuretic infusions are more natriuresis, loop diuretic infusions are more
potent, and combinations with amiloride,
aldosterone antagonists, or metolazone may be aldosterone antagonists, or metolazone may be
considered, as increasing doses of loop
diuretics are associated with worse outcomes.
In refractory cases, RRT may be required.
ACEI and ARB initiation may cause deterioration in
renal function, which is frequently transient and
reversible Patients with CKD or renal artery reversible. Patients with CKD or renal artery
stenosis are at a higher risk, and careful
monitoring is recommended.g
If renal function declines, then other secondary
causes such as excessive diuresis, persistent p
hypotension, prescription of nephrotoxic agents or
underlying renovascular disease should be excluded.
k l h h d Hyperkalaemia occurs with these agents and
dietary restriction may be required.
Anaemia is often present in patients with
type 2 CRS, and correction of anaemia yp ,
may improve symptoms without
increasing survival. g
Renal dysfunction is associated with
altered drug clearances and some drugs altered drug clearances, and some drugs,
e.g. digoxin and allopurinol, require dose
adjustment and the risk of spontaneous adjustment, and the risk of spontaneous
haemorrhage with warfarin is increased.
Type 3
As previously discussed, type 3 CRS has only
recently been recognized as a clinical entity, y g y
hence there is little known about the
treatment of this complication.
Since a typical clinical scenario would include
AKI following contrast exposure, or following AKI following contrast exposure, or following
cardiovascular surgery (CSA-AKI), prevention
likely affords a better chance to improve y p
outcome than treating established disease.
In terms of prevention of CSA-AKI, in a
recent prospective double-blind study recent prospective, double blind study
of patients with left ventricular
dysfunction undergoing cardiac surgery dysfunction undergoing cardiac surgery,
nesiritide was associated with improved
post operative renal function compared post-operative renal function compared
with patients without nesiritide, thus
ti t ti tsuggesting a renoprotective property.
Type 4
Despite cardioprotective strategies such as ACE-Is and/or β-
blockers only a minority of dialysis patients are prescribed
these drugs. Antihypertensives have been thought to g yp g
increase intradialytic hypotension, but this has not been
proven.
Progressive CKD often leads to sodium retention due to Progressive CKD often leads to sodium retention due to
reduced renal excretion, and similarly during haemodialysis
due to dietary noncompliance, inappropriately high dialysate
sodium and inability to achieve target or ‘dry’ weightsodium and inability to achieve target or dry weight.
Besides preventing hypervolaemia and a positive sodium
balance, the other key management strategies include
d l l fcorrecting anaemia and minimizing vascular calcification.
Conclusions
To facilitate better understanding of
epidemiologyepidemiology
To have opportunities for early diagnosis
thr u h bi m rkers through biomarkers
To develop the preventive strategies
To apply evidence-based management
strategiesstrategies