l’insufficienza renale nel cirrotico - gastrolearning®

Acute renal failure in patients with cirrhosis

“Gastrolearning”Padova 8 Aprile 2013

P. AngeliUnit of Hepatic Emergencies and Liver Transplantation

Dept. of MedicineUniversity of Padova, Italy

[email protected]

• Diagnosis of AKI/HRS

• Pharmacological treatment of HRS

Hepatorenal syndrome (HRS)

Topics


Diagnosis of AKI/HRS

Phenotypes of renal dysfunction in patients with cirrhosis

AKI in cirrhosis

G. Garcia-Tsao et al. Hepatology 2008 ; 48 : 2064—2077 (modified).

Definition of ARF/AKI = a rapid reduction in kidney function currently defined as a percentage increase in serum creatinine of more or equal to 50 % (1.5-fold from baseline) to a final value equal or higher than 1.5 mg/dl.

Hospitalized patients with cirrhosis

ARF/AKI (19%)

CKD (1%)

Definition and staging of Acute Kidney Injury (AKI) according to AKIN criteria

R.L. Mehta et al. Crit. Care 2007 ; 11 : R31.

Definition of AKI = an abrupt (within 48 hours) reduction in kidney function currently defined as an absolute increase in serum creatinine of more than or equal to 0.3 mg/dl ( 26.4 μmol/l), or a percentage increase in serum creatinine of more or equal to 50 % (1.5-fold from baseline).

Stage Serum creatinine criteria

1°Increase in serum creatinine equal or less than 200 % ( 2-fold ) from baseline

2°Increase in serum creatinine to more than 200% to 300% (> 2- to 3-fold) from baseline

3°

Increase in serum creatinine to more than 300 % (> 3-fold) from baseline or serum creatinine of more or equal to 4.0 mg/dl ( 354 μmol/l) with an acute increase of at least 0.5 mg/dl (44 μmol/l) or need for renal replacement therapy

AKI in cirrhosis

Definition

AKI in cirrhosis

Further and larger prospective studies are needed to assess the ability of new criteria versus the conventional criteria of renal dysfunction in the prediction of survival in patients with cirrhosis.

P. Angeli et al. Liver Int. 2012 (Epub ahead of print)

Criteria Sensibility95 % CI

Specificity95% CI

PPV95% CI

NPV95% CI

LR+95% CI

LR-95% CI

Conventional criterion 0.5152(0.33 - 0.69)

0.9450(0.90 - 0.97)

0.6071(0.40 - 0.78)

0.9220(0.87 - 0.95)

9.3664(4.8 - 18.17)

0.5131(0.36 - 0.73)

AKIN criteria 0.6667(0.48 - 0.82)

0.8100(0.74 - 0.86)

0.3667(0.24 - 0.50)

0.9364(0.88 - 0.96)

3.5088(2.41 - 5.10)

0.4115( 0.25 - 0.66)

Accuracy of conventional criterion vs AKIN criteria in the precition of in-hospital mortality in a series of 233 patients with cirrhosis and ascites

S. Piano et al. (J. Hepatol. 2013 ; in press)

Renal failure in cirrhosis

Patient survival with the acute kidney injury (AKI) andnon-AKI groups

AKI in cirrhosis

CD. Tsien et al. Gut 2013 ; 62 : 131-137

0

20

40

60

80

100

No AKIN AKI stage 1 AKI stage 2 AKI stage 3

P<0.001

P<0.0001

P<0.0001

P=N.S.P<0.025

P<0.01

Initial acute Kidney Injury Network (AKIN) stage (panel A) and in-hospital mortality


Serum creatinine < 1.5 mg/dl


Initial Stage 1 (72.1%) Initial Stage 2 (14.8%) Initial Stage 3 (13.1%)

Dynamics of AKI stage after initially fullfilling AKIN criteria (1)

Peak Stage 1 (52.5%)

72.7 %65.6 %


11.4 %


15.9 % 44.4 %



Criteria Sensibility95 % CI

Specificity95% CI

PPV95% CI

NPV95% CI

LR+95% CI

LR-95% CI

Conventional criterion 0.5152(0.33 - 0.69)

0.9450(0.90 - 0.97)

0.6071(0.40 - 0.78)

0.9220(0.87 - 0.95)

9.3664(4.8 - 18.17)

0.5131(0.36 - 0.73)

AKIN criteria 0.6667(0.48 - 0.82)

0.8100(0.74 - 0.86)

0.3667(0.24 - 0.50)

0.9364(0.88 - 0.96)

3.5088(2.41 - 5.10)

0.4115( 0.25 - 0.66)

AKIN withProgression

0.5455(0.36 - 0.71)

0.9450(0.90 - 0.97)

0.6207(0.42 - 0.79)

0.9265(0.88 - 0.95)

9.9174(5.15 - 19.06)

0.4810(0.33 - 0.70)

Accuracy of conventional criterion vs AKIN criteria in the precition of in-hospital mortality in a series of 233 patients with cirrhosis and ascites



Non-progressors(n° = 37)

Progressors(n° = 16)

P

Age (years) – mean (SD) 67.4 (10.6) 70.4 (7) 0.3707

Gender M/F – n° (%) 20 (54%) / 17 (46%) 8 (50%) / 8 (50%) 1.00

Child Pugh score – median (min-max) 10 (5-14) 10.5 (5-14) 0.9286

MELD score – median (min-max) 19 (9-38) 21 (11-37) 0.5540

Albumin (g/dl) – median (min-max) 2.7 (1.9-4.3) 2.7 (1.8-4.5) 0.8824

Bilirubin (µmol/L) – median (min-max) 63.3 (7.9-477.8) 85.3(8.9-631) 0.5571

Protrombin time (%) – mean (SD) 45.3 (13.9) 48.4 (16.0) 0.3563

Baseline sCr (mg/dl) – median (min-max) 1.1 (0.48-3.0) 1.2 (0.7-2.9) 0.3090

Baseline sCr ≥ 1.5 mg/dl – n (%) 14 (37.8) 5 (31.3) 0.7363

19 (51.4) 15 (93.7)

Bacterial infections – n (%) 24 (64.9) 11 (68.8) 1.000

Leukocyte counts el/µl – median (min-max) 6,500 (1,240-18,480)6,170 (2,750-

13,570)0.9764

Characteristics of patients with and without progression of initial stage of Acute Kidney Injury (AKI) according to the Acute Kidney Injury Network criteria

(AKIN)


0.0041sCr ≥ 1.5 mg/dl at diagnosis of AKI –n (%)


%

0

20

40

60

80

100

sCr < 1.5 mg/dl sCr > 1.5 mg/dl-

Probability of AKIN stage progression according to the cut off of 1.5 of serum creatinine (sCr)


p < 0.01


Initial Stage 1 (72.1%) Initial Stage 2 (14.8%) Initial Stage 3 (13.1%)

Dynamics of AKI stage after initially fullfilling AKIN criteria (2)


72.7 % 65.6 %


11.4 %


15.9 % 44.4 %


Resolution

62.5 % 36.8 %40 %


%

0

20

40

60

80

100

sCr < 1.5 mg/dl sCr > 1.5 mg/dl-

Probability of AKIN 1 stage regression accordind to the cut off of 1.5 of serum creatinine (sCr)


p < 0.01


Proposal of an algorithm for AKI management

Withdrawal of diuretics (if not yet applied) and volume expansion with albumin

(1g/kg) for 2 days

Initial AKI# stage 1 and sCr ≥ 1.5 mg/dl° or initial AKI# stage > 1

Initial AKI# stage 1 and sCr < 1.5 mg/dl°

° = sCr at the first fulfilling of AKIN crieria

#= AKI at the first fulfilling of AKIN crieria

* Treatment of SBP includes albumin infusion

Close monitoringRemove risk factors (withdrawal of nephrotoxic drugs, vasodilators and NSADs, taper/withdraw

diuretics treat infections*when diagnosed)

Progression ?

NO

Close follow up

YES

Response ?

YES NO

Does AKI Meet criteria of HRS ?

Specific treatment for other AKI phenotypes

NO

Terlipressin and albumin

YES



• The acceptance of the main point that derived from the application of AKIN criteria that is to focus attention on and to manage promptly even small increases in sCr.

• A clear dinstinction between AKI and hepatorenal syndrome (which is only one of the possible phenotypes of AKI)

• A more rationale application of the therapeutic resources (avoiding of potentially dangerous consequences of an overtreatment of AKI as a consequence of an uncritical application of the AKIN criteria)

• The definitive removal of any cut off of serum creatinine from the criteria for diagnosis of HRS

Clinical consequences of our proposal of an algorithm for AKI management



Proposal of an algorithm for AKI management

Withdrawal of diuretics (if not yet applied) and volume expansion with albumin

(1g/kg) for 2 days

Initial AKI# stage 1 and sCr ≥ 1.5 mg/dl° or initial AKI# stage > 1

Initial AKI# stage 1 and sCr < 1.5 mg/dl°

° = sCr at the first fulfilling of AKIN crieria

#= AKI at the first fulfilling of AKIN crieria

* Treatment of SBP includes albumin infusion

Close monitoringRemove risk factors (withdrawal of nephrotoxic drugs, vasodilators and NSADs, taper/withdraw

diuretics treat infections*when diagnosed)

Progression ?

NO

Close follow up

YES

Response ?

YES NO

Does AKI Meet criteria of HRS ?

Specific treatment for other AKI phenotypes

NO

Terlipressin and albumin

YES




Treatment of HRS

Pharmacologic therapy for HRS

• Albumin (20-40 g/day intravenously)

• Terlipressin (0.5-2 mg/4-6hr intravenously)

J. Uriz et al. J. Hepatol. 2000 ; 33 : 43-48.



0

20

40

60

80

100

Noradrenalin Terlipressin

P. Sharma et al. Am. J. Gastroenterol. 2008 ; 103:1689–1697.

Percent of responders after at day 15

P = N.S.

50 % 40 %


Cumulative probability of survival during therapy of patients treated with noradrenaline and terlipressin

V. Singh et al. J. Hepatol. 2012 ; 56 : 1293–1298


0

500

1000

1500

2000

2500

3000

Noradrenalin Terlipressin

P. Sharma et al. Am. J. Gastroenterol. 2008 ; 103:1689–1697.

Cost of treatment in USD excluding that of albumin

P < 0.05

6 mg/day for 15 days

1.5 mg/h for 15 days

Patients with response to treatment


0

20

40

60

80

100

Group A (Terlipressin) Group B (Midodrine + Octreotide)

All responders Full responders

% P < 0.0175.0

25.0

P < 0.01

54.2

8.3

M. Cavallin et. al. (manuscript in preparation)

Pharmacologic therapy for HRS

• Albumin (20-40 g/day intravenously)

• Terlipressin (0.5-2 mg/4-6hr intravenously)

J. Uriz et al. J. Hepatol. 2000 ; 33 : 43-48.


The facts

• Vasoconstrictors and albumin are effective in less of 50 % of patients with type 1 HRS.

• Vasoconstrictor and albumin improve survival slightly.

• Vasoconsctrictors and albumin can not be used in all patients with type 1 HRS.

• In up to 25 % of patients the treatment should be discontinued for adverse effects.

• High cost of treatment.


P. Angeli et al. Liver Int. 2012 (Epub ahead of print)

Limitations of terlipressin plus albumin

• Inherent

• Extrinsic


HRS is a functional renal failure caused by intrarenal vasoconstriction which occurs in patients with end stage liver disease as well as in patients with acute liver failure or alcoholic hepatitis.HRS is characterized by impaired renal function, marked alterations in cardiovascular function, and overactivity in the endogenous vasoactive systems.


Definition of HRS

F. Salerno et al. Gut 2007 ; 56 : 1310-1318.

CKD AKI

Serum creatinine > 1.5 mg/dl for 3 months

/type 2 HRS* /type 1 HRS*

* Proteinuria < 0.5 g/l and no hematuria


JM. Trawale et al. Liver Int. 2010 ; 30 : 725-732.

Serum creatinine levels >1.5 mg/dl

Proteinuria > 0.5 g/day Haematuria

18

20

9

5

4

2

7



Renal vascular injury

Acute tubulointerstitialinjury

Chronic tubulointerstitial

injury

10 (18)

13 (18)12 (18)



0

100

200

300

400

no HRS HRS

NGAL urinary levels in patients with cirrhosis and ascites according to the diagnosis of type 1 HRS

M. Cavallin at al. AASLD 2011

P < 0.025

(ng/ml)


Instrinsic AKI

*

*

*

*

** *

*

*

*

*

*

**

*

*

*****

** *

E. Singer et al. Kidney Int. 2011 ; 80 : 405-414

0

100

200

300

400

500

Full responders Partial or non responders

p < 0.0025

M. Cavallin. et. al. AASLD 2011

NGAL urinary levels in patients with type 1 HRS according to the response to terlipressin and albumin

(ng/ml)


The ratio of urinary excretion of -glutamyltranspeptidase to glomerular filtration rate in patients with type 1 HRS

treated with vasonsctrictors and albumin

0

100

200

300

400

500* = P < 0.05 ; ** = P < 0.025

*

**

*

B D5 D10 B D5 D10

Nonresponders Responders

D20

P. Angeli et al. Hepatology 1999 ; 29 : 1690-1697.

Normal range


Peripheral arterial vasodilation “hypothesis”

Portal hypertension/liver failure

Reduction of effective circulating volume

Severe renal arterial vasoconstriction

Maximal activation of endogenous vasocontrictor systems

RW. Schrier, et al. Hepatology 1988 ; 8 : 1151-1157 (revised)

Increased release of NO, CO and other vasodilators

Splanchnic arterial vasodilationTerlipressin

Albumin



HRS after SBP resolution

No HRS after SBP resolution

P

MAP (mm Hg) 738 838 < 0.025

SVR (dyn sec/cm ) 1268320 968226 N.S.

Plasma NE (pg/ml) 1290.5415.3 317.195.3 <.025

CO (l/min) 4.60.7 6.82.0 < 0.01

RAP (mm Hg) 4.62.7 4.11.7 N.S.

PCWP (mm Hg) 7.4 2.6 7.02.3 N.S.

HR (bpm) 879 7916 N.S.

5

Systemic heamodynamics before and after the onset of HRS after the resolution of SBP

L. Ruiz-del-Arbol et. al. Hepatology 2003 ; 38 : 1210-1218

Baseline At the diagnosis of

HRS P

MAP (mm Hg) 809757

< 0.001

HVPG (mm Hg) 19.53.020.04.0

< 0.005

SVR (dyn sec/cm ) 1158285 1096327 N.S.

CO (l/min) 6.01.2 5.41.3 < 0.001

RAP (mm Hg) 6.92.65.72.2

< 0.05

PCWP (mm Hg) 9.2 2.67.52.6

< 0.001

Systemic heamodynamics before and after the onset of type 1 HRS in patients with cirrhosis and ascites without a precipitating factor

L. Ruiz-del-Arbol et. al. Hepatology 2005 ; 62 : 439-447.

5


Peripheral arterial vasodilation “hypothesis” (revised)

Portal hypertension/liver failure

Reduction of effective circulating volume

Severe renal arterial vasoconstriction

Maximal activation of endogenous vasocontrictor systems

RW. Schrier et al. Hepatology 1988 ; 8 : 1151-1157 (revised)

Increased release of NO, CO and other vasodilators

Splanchnic arterial vasodilation Reduced cardiac output

?



Y. Narahara et al. J. Gastroenterol. Hepatol. 2009 ; 24 : 1791-1797

Parameter BaselineAfter

terlipressinP

Heart rate (bpm) 83 ± 16 72 ± 16 < 0.005

Mean arterial pressure (mm Hg) 89 ± 11 105 ± 14 < 0.005

Systemic vascular resistance (dynes/s · cm5) 1295 ±293 1653 ± 465 < 0.005

Cardiac output (l/min) 5.2 ± 1.0 4.9 ± 1.1 < 0.05

Pulmunary capillary wedged pressure

(mm Hg)9.6 ± 3.1 12.3 ± 2.6 < 0.005

Systemic hemodynamics at baseline and 30 min. after terlipressin in patients with cirrhosis and ascites


ParameterContrl

subjects (n° = 46)

Patients with cirrhosis and

without ascites (n° = 36)


responsive ascites

(n° = 31)


refractory ascites

(n° = 46)

Heart rate (beat/min) 67±10 70±10 68±11 78±13*#

Mean arterial pressure (mm Hg)

97±7 99±10 96±11 87±9*##

Systemic vasciular

resistance (din s/cm5m2) 3371±648 2925±641*** 2860±776*** 2439±573***#

Stroke volume (ml/beat) 64±10 75±12** 77±11** 73±17**

Cardiac output (L/min) 4.27±0.80 5.28±1.11*** 5.29±1.42*** 5.60±1.50***

Systemic hemaodynamics according to the stage of cirrhosis

* = p < 0.01 ; ** = p < 0.001 ; *** = p < 0.001 versus control subjects ; # = p < 0.05 ; ## = < 0.001 versus other groups of patients with cirrhosis

M. Cesari et al. (manuscript submitted)

Cardiac output in cirrhotic patients according to the Child-Pugh-Turcotte class

3000

6000

9000

12000

15000

Class A Class B Class C

Basal After i.v. albumin (40 g)

K. Brinch et al. J. Hepatol. 2003 ; 39 : 24-31

* = P < 0.025

* *

(ml/min)

* ** * = P < 0.01


0

5

10

15

20

P < 0.005

Overall transvascular transport of albumin in cirrhosis

J. H. Henriksen et al. J. Hepatol. 2001 ; 34 : 53-60.

Controls Cirrhotics with ascites

Cirrhotics with refractory ascites

P < 0.01

(% IVM • h )-1


dmcs

Esto ocurre principalmente porque la albúmina es de los kilómetros expansores del plasma. Incluso en etapas más avanzadas de la enfermedad hepática sigue siendo en gran medida y largo en el compartimiento vascular.

Effects of albumin on cardiac contractility in cirrhotic rats

-10.0 -9.5 -9.0 -8.5 -8.0

0

5

10

15

20

25

L

VD

P (

mm

Hg)

Control

Cirrhotic

Log . Isoproterenol

Cirrhotic + albumin

* = P < 0.01

**

Cirrhotic + starch


A. Bortoluzzi et al. Hepatology 2013 ; 57 : 266-276

dmcs

Una demostración de este hecho es que si se mide ex vivo la contractilidad miocárdica en respuesta a un agonista alfa, que aparece reducido en condiciones básicas, pero es casi completamente normalizzta si, la cirrosis animales antes del sacrificio se tratò con albúmina a las mismas dosis usadas clínicamente en patientes con peritonitis bacteriana espontáneaPorque ocurre esto?

?


dmcs

Esta diapositiva muestra la ruta del sistema adrenérgico en los cardiomiocitos. La actividad de la adenilato ciclasa es controlado por el receptor beta1 a través de proteínas estimuladoras. El aumento de cAMP activa PKA que determina a través de sus acciones sobre los canales de membrana per il calcio e sobre el sistema retículo-endoplásmico, un aumento del calcio libre en el citosol. Esto desencadena el mecanismo contráctil.Hemos dicho que el estrés oxidativo reduce vivo contractilidad? Con qué mecanismo?

NAD(P)H•

p67

p47

gp91

rac

•O2-

O2 H+

NAD(P)+

p22phox

NADH/NADPH Oxidase

The NADPH/NADH oxidase


dmcs

Si se analiza el sistema de nicotinamida adenina dinucleótido fosfato oxidasa, que es una de las fuentes de ROS en la célula, se ha de destacar como la sistenma es mucho más activo como algunos de sus componentes están unidos a la membrana plasmática. Así que la mayor es la relación entre la parte unida a la membrana y la parte libre en el citosol de estos componentes es stanto mayor es la producción de ROS.

0

0,5

1

1,5

2

control rats treated with V control rats treated with A

rats with cirrhosis treated with V rats with cirrhosis treated with A

Mem

bra

ne

/ cyt

osol

rat

io

(fol

d o

f in

crea

se)

*p <0.05 vs controls ; # = p <0.05 vs rats with cirrhosis treated with V

*

#

p47-phox Rac-1

*

#

Effects of albumin on the NADH/NADPH oxidase in the cardiac tissue according to treatment with saline (V) or albumin (A)



dmcs

Como se puede ver esta relación es mayor en el tejido cardíaco de las ratas con cirrosis con ascitis en comparación con las ratas control. Sin embargo, esta relación se normaliza mediante la administración de albúmina.

?TNF-


dmcs

Así albúmina es contrarrestar los efectos negativos directos de ROS en la vía adrenérgica.Pero el efecto principal de ROS en la adrenérgico manera es probablemente indirecta que pasa a través de la translocación de NFKB y por lo tanto el incremento en la expresión de genes que condificano la iNOS y TNF-alfa. El consequente aumento de la liberación de NO tiene, a través del aumento de GMP cíclico, varios efectos importantes negativos sobre la vía adrenérgica.Cuál es el efecto de la albúmina sobre la translocación de NFkB?

0

0,2

0,4

0,6

0,8

1

1,2

1,4

1,6

1,8

Control rats treatedwith V

Control rats treatedwith A

Rats with cirrhosistreated with V

Rats with cirrhosistreated with A

Fol

d of

incr

ease

*

#

* p<0.05 vs control rats # p<0.05 vs rats with cirrhosis treated with V

Levels of NF-kB traslocation in the cardiac tissue according to treatment with saline (V) or with albumin (A)



dmcs

La translocación NFkB se incrementa en condiciones basales en tejido cardíaco de ratas cirróticas con ascitis. La albúmina reduce la translocación de NF-kB a valores similares a los observados en las ratas de control. A través de este efecto .....

Pro

tein

exp

ress

ion

(fol

d of

incr

ease

) *

#

* p<0.05 vs controls

Effects of albumin on TNF- protein expression in the cardiac tissue according to treatment with saline (S) or albumin (A)

# p<0.05 vs rats with cirrhosis treated with A

0

0,5

1

1,5

2

2,5

Control rats treatedwith S


Rats with cirrhosistreated with S




dmcs

A través de este efecto, la'lbumina reduce TNF alfa expresión de la proteína en el tejido del corazón de ratas con ascitis cirrótica

Pro

tein

exp

ress

ion

(fol

d of

incr

ease

) *

#

* p<0.05 vs controls

Effects of albumin on iNos protein expression in the cardiac tissue according to treatment with saline (S) or albumin (A)

# p<0.05 vs rats with cirrhosis treated with A

0

0,5

1

1,5

2

2,5

Control rats treatedwith S


Rats with cirrhosistreated with S




dmcs

y, a continuación, a través de este efecto, la albúmina 'reduce la expresión de la proteína iNOS en el tejido del corazón de ratas con ascitis cirrótic

TNF-


dmcs

Todo esto explica cómo la albúmina va a contrarrestar los efectos negativos del NO sobre el mecanismo contrácti

?


dmcs

como la proteína Gi-alfa cuya expresión está controlada por los receptores beta2 adrenérgicos y por receptores tipo 1 de cannabinoidesQué efecto tiene la administración de albúmina en la expresión de esta proteína?

* = p < 0.01 vs controll

Effects of albumin on β-adgrenergic signaling in cardiac tissue according to treatement with saline (V) or albumin (A)

0

0,5

1

1,5

2

2,5

β1 β2 Adcy3 Gαi2

control rats treated with V control rats treated with A

rats with cirrhosis treated with V rats with cirrhosis treated with A

**

*

*

# #

* p<0.05 vs controls ; # p<0.05 vs ascites with saline

Gen

e ex

pres

sion

(F

old

of

incr

ease

)

**



dmcs

La administración de albúmina reduce la expresión de esta proteína, g-alfai, sin modificar la expresión de los receptores adrenérgicos beta2 que sigue siendo mayor en el tejido cardíaco de las ratas con cirrosis y ascitis


dmcs

Esto autoriza a pensar que este efecto de la albúmina, lo que ayuda a normalizar la contractilidad miocárdica en el curso de la infección bacteriana, puede pasar a través de los receptores de cannabinoides.

Limitations of terlipressin plus albumin

• Inherent

• Extrinsic


Response to tretament (%) according to the baseline serum creatinine value

0

10

20

30

40

50

60

3.0 mg/dl < 3 - 5 mg/dl > 5.0 mg/dl

TD. Boyer et al. J. Hepatol. 2011 ; 55 ; 315-321.

%

MANAGEMENT OF RENAL DYSFUNCTION IN PATIENTS WITH CIRRHOSIS

Summary • The application of conventional criterion is more accurate than a formal

application of AKIN criteria in the prediction of in-hospital mortality in patients with cirrhosis and ascites.

• Nevertheless, the addition of either the progression of AKIN stage or the cut-off of serum creatinine ≥1.5 mg/dl, to the AKIN improves their prognostic accuracy in these patients .

• The potential effects of implementation of the conventional criterion with the most innnovative aspects of AKIN criteria, should be tested by interventional clinical trials in the next future.

• Terlipressin and albumin are effective in patients with type 1 HRS.• Noradrenalin and albumin but not midodrine, octreotide and albumin can

represent an alternative in the treatment of type 1 HRS. • Some of the limits of the treatment with terlipressin and albumin may be

related to the fact that HRS may not be completely functional in nature and/or to the fact that the global effect of the treatment on cardiac output may be negative in some patients.


P. Angeli et al. Liver Int. 2013 ; 33 : 16-23

l’insufficienza renale nel cirrotico - gastrolearning®

Education

serum creatinine equal

serum creatinine levels

baselineor serum creatinine

definition of aki

akin aki stage

sbpresolutionno hrs

hepatorenal syndrome

hospitalized patients