Journal of The Association of Physicians of India Vol.

64 December 2016

41

Original Article

Cardiorenal Syndrome: Clinical Outcome Study

HR Shah1, NP Singh2, NP Aggarwal 3, D Singhania4, LK Jha3, A Kumar5

Abstract

Editorial Viewpoint

Background: Over recent years, the field of medicine has been

challenged by the twin epidemic of heart failure and renal insufficiency.
The coexistence of the two problems in the same patient, referred to
as cardiorenal syndrome (CRS), is defined as disorders of the heart and
kidneys whereby acute or chronic dysfunction in one organ may induce
acute or chronic dysfunction of the other. The mechanisms underlying
this interaction are complex and multifactorial in nature.

Coexistence of heart failure

and renal insuffficiency is
referred to as cardiorenal
syndrome.

Objective of Study: Identify and classify patients admitted with

cardiorenal syndrome into various subtypes and assess clinical outcome
at discharge and at three months.
Methods: Ours was a longitudinal study of 50 patients admitted in ICU
with CRS. They were classified as per RONCO classification (2008) into
various subtypes. Outcomes was addressed as favourable for patients
stable at discharge and at 3 months follow up, whereas outcome
was termed non-favourable for patients who expired or initiated on
hemodialysis.
Results: Of 50 patients, two-third patients were males (66%), with mean
age of males and females being 64.18 years and 64.64 years respectively.
Majority of the patients had Type-1 CRS (46%) followed by twenty two
percent Type-2, twenty six percent type-4 and six percent Type-5. There
were no patients with type-3 CRS. At the end of the study, 24 (48%)
patients were stable, 12 (24%) required dialysis and 14 (28%) patients
had expired. The total non-favourable outcomes (dialysis / death) were
higher with subtypes CRS-4 (n-11, 22%) and CRS-1 (n-8, 16%). Anemia,
raised serum creatinine, low eGFR values, low ejection fraction were
significant predictors of non-favourable outcome in our study
Conclusion: CRS occurs in all age groups, more commonly in elderlies
with a male preponderance. Prevalence of CRS-1 was higher followed
by CRS-4. Prognosis was unfavourable in CRS-1, CRS-4 and CRS-5. Sepsis
was predominant cause of death in patients with CRS-5 with hundred
percent mortality during hospital stay. Risk factors like pre-existing
renal impairment, anemia, reduced e GFR and low ejection fraction were
significantly associated with worse outcomes. There is need for large
scale population / community based studies to chart the prevalence of
cardiorenal subtypes and prognosticate each individually

Introduction

ver recent years, the field of

medicine has been challenged
by t h e t w i n e pidemic of heart
failure and renal insufficiency.

This study finds elderly

male preponderance.
Sepsis with CRS-5 was
predominant cause of
death.
Co-existence of the two problems
in the same patient, referred to
as cardiorenal syndrome (CRS),
is defined as disorders of the
heart and kidneys whereby acute
or chronic dysfunction in one
organ may induce acute or chronic
dysfunction of the other. The
mechanisms underlying this
interaction are complex and
multifactorial in nature. Changes in
the renin-angiotensin-aldosterone
system (RAAS), the imbalance
between nitric oxide (NO) and
reactive oxygen species (ROS), the
sympathetic nervous system and
inflammation are the cardiorenal
connectors to develop cardiorenal
syndrome. It has been classified in
five types by Ronco et al (2008). 1
Acute Cardiorenal Syndrome
(Type 1 CRS) is characterised
by a rapid worsening of cardiac
function leading to acute kidney
injury (AKI). Acute heart failure is
manifested in form of hypertensive
pulmonary edema, acutely
decompensated heart failure
(ADHF), cardiogenic shock and
acute coronary syndrome (ACS). 2

DNB Resident, Dept. of Medicine, 2Director, Meedicine Allied Specialities, 3Senior Consultant, Dept. of
Nephrology, 4Senior Consultant, Dept. of Cardiology, 5Research Associate, Dept. of Medicine, Max Super
Specialitiy Hospital, Ghaziabad, Uttar Pradesh
Received: 11.03.2016; Revised: 28.06.2016; Accepted: 06.07.2016

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Journal of The Association of Physicians of India Vol. 64 December 2016

35

Table 1: Clinical parameters of study

subjects

29

30
25

21-40 years

20

41-60 years

15
10
5

10
6

61-80 years
> 80 years

0
Age in years

the management of cardiorenal

syndrome.

Fig. 1: Distribution of study population in different age groups

Chronic Cardiorenal syndrome

(Type 2 CRS) is characterised by
chronic heart failure that leads
t o p r o g r e s s i ve d e c l i n e i n G F R
and ultimately chronic kidney
disease (CKD). Acute Renocardiac
Syndrome (type 3 CRS) manifests
as acute kidney injury, which can
occur as a primary event (e.g. acute
glomerulonephritis) or a secondary
event (e.g. radiocontrast, exogenous
or endogenous nephrotoxins,
postsurgical, etc.), followed by
cardiac dysfunction as its sequel.
Chronic Renocardiac Syndrome
(Type 4 CRS) is a condition
characterised by increased
cardiovascular risk in patients
with CKD. Secondary Cardiorenal
Syndrome (Type 5) is associated
with multiple systemic conditions,
either acute or chronic which
target both organs simultaneously.
Examples include sepsis, systemic
lupus erythematosus, amyloidosis
and diabetes mellitus. The
coexistence of cardiac and renal
d i se a se si g n i f i c a n t ly inc reases
mortality, morbidity, complexity
and cost of care. The aim of this
study was to identify different
types of cardiorenal syndrome
at our tertiary care hospital, risk
factors associated and clinical
outcome during hospital stay and
at 3 months.

Materials and Methods

Ours was a longitudinal study.
A total of 50 patients, of above 18

Parameters
Number of patients
Dyspnea
50
NYHA grade 1
1
NYHA grade 2
5
NYHA grade 3
24
NYHA grade 4
20
Pedal edema
35
Chest pain
24
Decrease urine output
22
Nocturia
20
Syncope
5

years of age admitted with both

cardiac and renal dysfunction were
evaluated in detail and investigated.
Heart failure was classified as per
NYHA classification. CKD was
staged as per KDOQI guidelines.
Special attention was paid to patient
with risk factors like hypertension,
diabetes, dyslipidemia, coronary
artery disease, hypothyroidism,
COPD, nephrotoxic drugs ingestion
and contrast exposure. Patients
we r e e va l u a t e d a t t h e t i m e o f
discharge and at three months
follow up. Outcome was addressed
as favourable for patients stable
at discharge and 3 months follow
up whereas, non-favourable for
p a t i e n t s w h o e x p i r e d o r we r e
initiated on hemodialysis.
Investigations included complete
hemogram, kidney function tests,
cardiac enzymes, pro-BNP, lipid
profile, thyroid function test,
urine routine and microscopy
with culture. Electrocardiograms
we r e d o n e f o r a r r h y t h m i a s o r
ST-T changes. Ultrasound
whole abdomen was carried out
to evaluate renal parenchymal
disease or any other abnormal
changes in urinary tract. eGFR
was calculated using MDRD study
equation. Patients were subjected
to 2 dimensional echocardiography
to assess the ejection fraction at
admission and at 3 months follow
up. All patients were classified as
per RONCO guidelines (2008) into
various CRS subtypes and standard
treatment was administered per

Statistical Analysis

A descriptive statistical analysis

based on frequency tables of
categorical values was performed,
using a Pearson`s Chi-square test,
to test the significance of the
association between qualitative
variables. A Student`s t test for
independent samples was used to
compare means between groups.
Statistical data processing was
performed using SPSS 20.0 for
windows. Differences with a
probability of type 1 error less than
5% were considered statistically
significant.

Results
Demographic profile

Out of 50 patients, about

t wo-t hird pat ient s wer e ma l es
(66%). Mean age of males was
6 4 . 1 8 1 2 . 9 5 ye a r s a n d f e m a l e s
were 64.64 19.36 years. Majority
of patients belonged to elderly age
group of 61-80 years as shown in
Figure 1.
Clinical Parameters of Study Subjects
Symptomatology

All patients presented with

dyspnea (n-50), mainly of NYHA
grade 3. Pedal edema was also a
common symptom manifesting in
35 subjects. All the other symptoms
were given in Table 1.
Laboratory Parameters

Out of 50 study subjects, 25

patients were known cases of CKD
with mean baseline creatinine of
2.63 mg/dl and eGFR of 29.07 ml/

Journal of The Association of Physicians of India Vol. 64 December 2016

Table 2: Laboratory parameters of

study subjects
Laboratory
parameters

No. of
patients
(n=50)

MeanSD

25
25
29

2.631.36
29.0711.67
45.3413.55

50

9.882.33

Baseline
Creatinine(mg / dl)
eGFR (ml/min)
EF (%)
Admission
Hemoglobin (gm/
dl)
Hb < 10 g/ dl
Hb > 10 g/dl
Creatinine (mg/dl)
e GFR (ml/min)
Uric acid (mg/dl)
Sodium (mEq / l)
Potassium (mEq/ l)
Albumin (gm / dl)
EF (%)
Discharge
Creatinine (mg/dl)
e GFR (ml/min)
Uric acid (mg / dl)
3 months
Creatinine mg/dl)
e GFR (ml/min)
EF (%)
Uric acid (mg/dl)

29

30
25

21-40 years

20

41-60 years

15

10

10

3.382.18
27.1017.59
7.971.90
134.564.50
4.581.00
3.250.48
31.7012.8

42
42
42

3.281.68
24.416712.48
6.50861.79

36
36
36
36

3.19311.71
26.902915.18
38.47229.89
6.47141.87

CRS-1 (n-23)

Fig. 2: Prevalence of co-morbidities amongst study population

Table 3: Prevalence of CRS subtypes at discharge and on follow-up at 3 months
CRS
subtype
CRS-1
CRS-2
CRS-4
CRS-5

Outcome at discharge (n)

Stable Dialysis Death
Total
15
6
2
23
7
2
2
11
4
8
1
13
0
0
3
3

Outcome at discharge (n-50)

16%

Stable (n-26)

52%

Dialysis (n-16)
Death (n-8)

Outcome at 3 months (n)

Stable Dialysis Death
Total
15
3
5
23
7
2
2
11
2
7
4
13
0
0
3
3

Outcome at 3 months (n-50)

28%
24%

Stable (n-24)

48%

Dialysis (n-12)
Death (n-14)

CRS-2 (n-11)
CRS-4 (n-13)

22%

> 80 years

Age in years

32%
46%

61-80 years

27
23
50
50
50
50
50
50
50

6%
26%

35

43

CRS-5 (n-3)

Fig. 3: Distribution of CRS

subtypes at baseline visit

min/1.73m 2. Twenty nine subjects

had heart failure with reduced
ejection fraction (HFrEF) with
mean baseline ejection fraction
(EF) of 45.34%. Renal, cardiac and
hematological parameters recorded
at admission, discharge and at
three months are demonstrated in
Table 2.

Fig. 4: Outcome population at discharge and at 3 month

dyslipidemia (Figure 2).

Prevalence of Cardiorenal Syndromes (CRS)
Subtypes

Out of 50 patients enrolled in

study, 23 (46%) subjects presented
with type 1 CRS, 11 (22%) subjects
with type 2 CRS, 13 (26%) subjects
with type 4 CRS and 3 (6%) subjects
with type 5 CRS. No individual
came under the category of type 3
CRS (Figure 3).
Outcome and Factors Affecting
Outcome

Prevalence of co-morbidities

Prevalence of CRS Subtypes at Discharge

and on Follow-up at 3 months

Among the study population, 39

(78%) patients were hypertensive
and 32 (64%) were diabetic.
Whereas, 25 (50%) had underlying
chronic kidney disease, 24 (48%)
patients had CAD and 22 (44%) had

At discharge, mortality rate

was 16 % (n-8). Of 42 patients that
survived, 21 (50%) belonged to CRS
type 1 group, 9 (21%) to CRS type
2 and 12 (28.57%) to group CRS 4
group. Eight patients had expired

during the study period. Out of

which, 3 patients were in CRS-5
group, two patients each in CRS
1 and 2 and one in CRS -4 group.
On follow up at 3 months, total
mortality increased to 28% (n-14),
as 6 more patients had expired.
Three patients, each from CRS-1
and CRS-4 group had expired.
Thus, 36 pat ient s survi ved, of
which patients belonging to CRS
1 group were 18 (50%) and 9 (25%)
patients each belonged to CRS 2
and CRS 4 group. Summary of
outcome were shown in Table 3
and Figure 4.
Association of CRS Subtypes with Outcome

Study subjects were classified

into two groups on the basis of
their outcomes as: favourable
outcome group including patients

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Journal of The Association of Physicians of India Vol. 64 December 2016

Table 4: Association of CRS subtypes with outcome at discharge and at 3 months

CRS
Outcome at discharge (n)
Outcome at 3 months (n)
subtype Favourable
NonpFavourable
Nonpfavourable value
favourable value
CRS-1
15
8
0.05
15
8
0.003
CRS-2
7
4
7
4
2
11
CRS-4
4
9
CRS-5
0
3
0
3
Table 5: Association of laboratory parameters with outcome (*Statistical significant
value)
Variables
Baseline
creatinine (mg/dl)
e GFR (ml/min / 1.73m2)
Admission
Hemoglobin (g/dl)
Creatinine (mg/dl)
eGFR (ml/min / 1.73m2)
Uric acid (mg/dl)
Sodium (mEq / l)
Potassium (mEq/l)
Albumin (g/dl)
EF (%)
Outcome at discharge
Creatinine (mg/dl)
e GFR (ml/min/1.73m2)
Uric acid (mg/dl)
Outcome at 3 months
Creatinine (mg/dl)
e GFR (ml/min/1.73m2)
Uric acid (mg/dl)
EF

Favourable

Non-favourable

p-value

1.830 .33
36.097.97

3.361.55
22.5910.93

0.003*
0.002*

10.752.34
2.310..97
35.0018.75
7.491.57
135.264.36
4.520.83
3.320.47
33.0713.57

8.951.97
4.552.53
18.5411.42
8.492.11
133.794.60
4.651.16
3.160.48
30.2012.02

0.005*
<0.001*
0.001*
0.062
0.250
0.649
0.238
0.43

2.280.70
31.211.88
6.6710.87

4.911.54
13.361.66
6.234.33

0.001*
0.001*
0.452

2.2 0.63
33.2513.71
6.3 2.01
42.08 9.7

5.24 1.4
13.03 6.6
6.81.5
31.25 5.69

0.001*
0.001*
0.446
0.001*

Table 6: Association of co-morbidities with outcome

Co-morbidities

Outcome at discharge (n)

Favourable
Nonpfavourable
value
Hypertension
20 (40%)
19(38%)
0.848
Diabetes
14 (28%)
18(36%)
0.119
Dyslipidemia
12 (24%)
10(20%)
0.490
Hypothyroidism
6 (12%)
2(4%)
0.155
COPD
7 (14%)
2(4%)
0.087
CAD
14 (28%)
10(20%)
0.563

stable at discharge and follow

up; non-favourable outcome
group including patients who were
initiated on dialysis or expired
before discharge or within 3
months. The difference between
associations of CRS subtypes with
outcome is statistically significant
for outcome at discharge and for
outcome at 3 months (Table 4).
Association between Gender and outcome

There was no statistically

significant association between

Outcome at 3 months (n)

Favourable
Nonpfavourable value
18(36%)
14 (28%)
0.831
13(26%)
12(24%)
0.414
10(20%)
6(12%)
0.582
5(10%)
1(2%)
0.161
5(10%)
2(4%)
0.403
11(22%)
9(18%)
0.990

gender and outcome at discharge (p

value-0.616). Mean age of patients
with favourable outcome (n-26) was
68.811.97, and for patients with
non-favourable outcome (n-24)
was 59.4117.02). This difference of
means was statistically significant
(p-value 0.027).
Association of Laboratory Parameters with
Outcome

The difference between means

of baseline creatinine and eGFR;
haemoglobin; creatinine and eGFR

at admission, creatinine and eGFR

at discharge with outcome was
statistically significant (Table 5).
Association of Co-morbidities with
Outcome

The association of co-morbidities

with outcome were found to be
statistically insignificant and the
results were shown in Table 6.

Discussion
Over the past decade with
the increase in lifespan and high
prevalence of lifestyle disorders
like hypertension, diabetes and
cardiorenal syndrome has emerged
as a significant problem amongst
patients. Studies in the West have
been conducted to understand the
complex relationship between heart
and kidneys. However in Indian
scenario, cardiorenal syndrome
(CRS) remains an uncharted
territory. There is a paucity of
population or hospital based
studies which can reflect upon
the magnitude of cardiorenal
syndrome in Indian setting, hence
this baseline longitudinal study
wa s c o n d u c t e d a t o u r t e r t i a r y
care hospital. Our study aimed at
identifying and classifying patients
with cardiorenal syndromes and
assessing their clinical outcome at
discharge and at follow up after
three months. The purpose of the
study also included association of
various co-morbid conditions on
outcome of patients under different
CRS subtypes. In the following,
we discuss the demography,
distribution of CRS sub-types,
outcomes associated with each type
and major risk factors (previous
renal insufficiency, anemia,
reduced eGFR and low ejection
fraction) significantly affecting the
clinical outcome.
In our study, there was male
preponderance (M:F-2:1) which
could be due to increase in the
number of acute coronary events and
other risk factors like hypertension,
diabetes and dyslipidemia in men,
now diagnosed even at younger age
groups, whereas women usually

Journal of The Association of Physicians of India Vol. 64 December 2016

develop such illnesses to a lesser

extent mostly at later stages in life
after menopause. More than half
of our study population was in
elderly age group i.e. above sixty
years. Structural abnormalities
with fibrosis and calcification
of the heart and central arteries,
along with autonomic dysfunction,
underlie reduced cardiac
performance leading to cardiac
decompensation and heart failure
(HF). HF is characterized by the
hearts inability to maintain an
adequate cardiac output and may
be the result of systolic or diastolic
dysfunction or reduced compliance.
The effects of decrease eGFR per se
interact with the effects of aging in
cardiovascular end-organ damage
and in the genesis of heart failure
(HF) and cardiorenal syndrome
(CRS).
Almost half of the patients had
non-favourable outcome. One
fourth of the patient subset expired
during the study. Prevalence of
n o n - f a v o u r a b l e o u t c o m e s wa s
significantly higher in CRS-4 and
CRS-1 with maximum deaths
and dialysis requiring population
occurring within these two groups.
This could be due to devastating
presentations of patients in CRS-1
with acute coronary syndromes,
acute decompensated heart failure
or cardiogenic shock leading to
AKI associated with increased
cardiovascular mortality, prolonged
hospitalisation, increased readmissions and accelerated
progression to CKD stages 4-5.
This was previously purported in a
single centred based study on acute
cardiorenal syndrome wherein AKI
during hospitalization occurred
four times more frequently in Acute
Decompensated Heart Failure
(ADHF) patients than in ACS
patients, and patients with ACS had
increased in-hospital mortality. 5
Co-existing renal insufficiency is
one of the strongest independent
risk factors and predictors of
mortality. 6
Our study reported half of the
population with haemoglobin less

than 10 g/dl. The term Cardiorenal

Anemia Syndrome (CRAS), coined
by Silverberg et al defined as a
condition induced by dysfunction
of either organ exacerbating
dysfunction of either organ. Anemia
causes increase in oxidative stress
and lack of oxygen supply to heart
leading to compensatory increase
in heart rate and stroke volume
which activates RAAS and SNS
causing renal vasoconstriction
and fluid retention. 9 In a previous
s t u d y , i t wa s e s t a b l i s h e d t h a t
t h e p r e va l e n c e o f a n e m i a wa s
high amongst patients with
cardio-renal syndrome, present in
almost one-third of CRS patients.
However, it was not associated
with increased mortality, as raised
serum creatinine and low ejection
fraction were other variables also
contributing to adverse outcome. 3
Similar trend was observed in our
study.
Three-fourth population
in our study had significant
LV d y s f u n c t i o n w i t h e j e c t i o n
fraction less than forty percent at
admission. All these patients had
non-favourable outcome at follow
up. This association was notable,
adding to the evidence that patients
with heart failure (HF) have
poor outcomes in terms of rapid
deterioration of renal function with
increase in morbidity and mortality.
This is due to a complex interplay
of various factors such as imbalance
of failing heart (low cardiac output
and hypotension), neuro-hormonal
system activation, sympathetic
over activity, nitric oxide (NO)
reactive oxygen species (ROS) and
inflammatory cascade. These form
a vicious cycle and cause further
worsening of heart and kidneys.
Risk factors contributing towards
worsening renal function during
heart failure include old age,
comorbidities, drugs like diuretics
causing renal hypoperfusion, ACE
(angiotensin converting enzyme)
inhibitors and ARBs (angiotensin
receptor blockers) for RAAS
(renin-angiotensin-aldosterone
system) blockade leading to renal

45

impairment, prior myocardial

infarction and previous renal
insufficiency.
On similar grounds in a past
e x p e r i e n c e i t wa s d e t e r m i n e d
thatpatients with CHF, renal
dysfunction is common,
d e t e r i o r a t e s o ve r a r e l a t i ve l y
short period of time, is unlikely to
recover substantially and augurs
a poor prognosis. 10 A noteworthy
contribution by CHARM STUDY
investigators also concluded that
decreased renal function had been
found as an independent risk factor
for poor cardiovascular outcomes
in patients with chronic heart
failure with markedly reduced left
ventricular ejection fraction. 11
Many studies have reproduced
in detail the complex connections
and associations involving heart
renal dysfunction and its impact
on the patient outcome. Our study
wa s a p r e l i m i n a r y a t t e m p t t o
prognosticate the umbrella term
cardiorenal syndrome and its
subtypes individually in Indian
scenario.
Limitations in Study

Sample size was small which

resulted in certain known
statistically significant
relationships to come out to
be insignificant. Cystatin C
could not be evaluated due
t o u n a va i l a b i l i t y o f t e s t a t
our centre. CKD staging
was applied as per older
classification based on e
GFR as albuminuria was not
quantified in our study Only
ejection fraction (EF%) from
va r i o u s e c h o c a r d i o g r a p h i c
parameters was evaluated at
admission and follow up to
judge the outcome, thereby
patients with HFpEF (diastolic
heart failure) could be underdiagnosed. Treatment details
in form of drugs administered/
therapeutic interventions/
devices were not taken into
account that can alter the
outcome
F o l l o w u p a t 6 m o n t h s o r

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Journal of The Association of Physicians of India Vol. 64 December 2016

1 ye a r c o u l d d e r i ve b e t t e r
understanding and more
confident analysis of the natural
history and dynamic course of
various CRS sub-types
Conclusions

Cardiorenal syndrome is
nowadays being recognised as a
common entity in patients having
both cardiac and renal dysfunction,
thereby being classified in either
of CRS sub-types on the basis of
etiology. Our study concluded that
CRS can occur in all age groups,
more commonly in elderlies with
a male preponderance. Prevalence
o f C R S - 1 wa s h i g h e r f o l l o we d
by CRS-4. CRS -2 had a slightly
better outcome may be by chance
as patients were steady after 3
months; whereas non-favourable
outcome were significantly higher
in CRS-1 , CRS-4 and CRS-5. Sepsis
was predominant cause of death in
patients with CRS-5 with hundred
percent mortality during hospital
stay. Risk factors like pre-existing
renal impairment, anemia, reduced
e GFR and low ejection fraction
were significantly associated with
worse outcomes across all CRS
sub-types. There is scope for large
scale population /community based
studies to chart the prevalence

of cardiorenal subtypes and

prognosticate each individually.
Follow-up studies should be
undertaken to understand the
natural history of cardiorenal
syndrome with time and perceive
the dynamicity of each subtypes
during the course. Suitable disease
models for mechanistic oriented
investigations are needed to provide
further impact on management of
cardiorenal syndrome and lay
down better standard of care for
patients.

Centre Study of Acute Cardiorenal

Syndrome: Incidence, Risk Factors and
Consequences.Cardiorenal Medicine 2012;
2:168-176.
6.

Dries DL, Exner DV, Domansk i MJ,

Greenberg B,Stevenson LW. The prognostic
implications of renal insufficiency in
asymptomatic and symptomatic patients
with left ventricular systolic dysfunction. J
Am Coll Cardio 2000; 20:462-65.

7.

Go AS, Chertow GM, Fan D, McCulloch

CE, Hsu CY. Chronic kidney disease and
the risks of death, cardiovascular events,
and hospitalization. N Engl J Med 2004;
351:12961305.

8.

Smith GL, Lichtman JH, Bracken MB, Shlipak

MG, Phillips CO, DiCapua P et al. Renal
impairment and outcomes in heart failure:
systematic review and meta-analysis. J Am
Coll Cardiol 2006; 47:1987.

9.

Silverberg DS, Wexler D, Blum M. The

correction of anemia in severe resistant
heart failure with erythropoietin and
intravenous iron prevents the progression
of both the heart and the renal failure and
markedly reduces hospitalization. Clinical
Nephrology 2002; 58:3745.

References
1.

2.

Ronco C, Haapio M, House AA, Anavekar

N, Bellomo R. Cardiorenal syndrome.
Journal of the American College of Cardiology
2008; 19:152739.
Forman DE, Butler J, Wang Y, Abraham WT,
OConnor CM, Gottlieb SS et al. Incidence,
predictors at admission, and impact of
worsening renal function among patients
hospitalized with heart failure. J Am Coll
Cardiol 2004; 43:617.

3.

Silva RP, Barbosa PH, Kimura OS, Sobrinho

CR,Sousa Neto JD,Silva FA et al. Prevalance
of anemia and its association with cardiorenal syndrome. International Journal of
Cardiology 2007; 120:2326.

4.

Santoro A. Heart failure and cardiorenal

syndrome in elderly. J Nephrol 2012;
25:67-72.

5.

Eren Z, Ozveren O, Buvukoner E, Kaspar

E, Degertekin M, Kantarci G. A Single-

10. De Silva R, Nikitin NP, Witte KK, Rigby

AS, Goode K, Bhandari S et al. Incidence
of renal dysfunction over 6 months in
patients with chronic heart failure due
to left ventricular systolic dysfunction:
Contributing factors and relationship to
prognosis.Eur Heart J2006; 27:56981.
11. Hillege HL, Nitsch D, Pfeffer MA,Swedberg
K,McMurray JJ,Yusuf S et al. Renal function
as a predictor of outcome in a broad
spectrum of patients with heart failure.
Circulation 2006; 113:671.