A Case of Type I Hepatorenal Syndrome Treated with Vasopressin

doi:10.4236/ojneph.2013.33025

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Open Journal of Nephrology, 2013, 3, 135-138

http://dx.doi.org/10.4236/ojneph.2013.33025 Published Online September 2013 (http://www.scirp.org/journal/ojneph)

A Case of Type I Hepatorenal Syndrome Treated with

Vasopressin

Laura Connor1, Geoffrey Teehan2,3

1Department of Internal Medicine, Lankenau Medical Center, Wynnewood, USA

2Department of Nephrol ogy, Lankenau Medical Center, Wynnewood, USA

3Lankenau Institute of Medical Research, Wynnewood, USA

Email: [email protected]

Received July 3, 2013; revised August 2, 2013; accepted August 13, 2013

tion License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly

cited.

ABSTRACT

Hepatorenal syndrome (HRS) is a grave complication of end-stage liver disease and is associated with a very high mor-

tality. This case report described a 42-year-old female with advanced alcohol-induced cirrhosis who developed HRS

that was initially treated with Midodrine an d Octreotide bu t renal function co ntinu ed to deterior ate. Vasopressin therapy

was added and HRS was successfully reversed. There are few data available on the use of vasopressin for HRS and this

case supports its use in treatment of HRS, particularly in countries where the more widely studied Terlipressin is un-

available. This case also demons trates that a patient failing one medical therapy for HRS may respond to an alternative

or adjunctive therapy. Therefore, this should be attempted to increase the patie nt’s chance of survival.

Keywords: Hepatorenal Syndrome; Vasopressin

1. Introduction

Hepatorenal syndrome (HRS) is a grave complication of

end-stage liver disease and is associated with a very high

mortality. It is characterized by arterial vasodilation of

the splanchnic vessels leading to pronounced renal vaso-

constriction, marked reduction in renal blood flow and

glomerular filtration rate [1]. HRS is classified into two

types based on the rate of progression of the renal dys-

function. Type 1 is characterized by an abrupt onset and

a rapid progression of renal failure over a period of two

weeks or less with a median survival of one to two weeks.

Type 2 causes a more slowly progressive renal failure,

typically over months with a median survival of about six

months [2]. Management of HRS is challenging since the

ideal treatment is liver transplantation, which is usually

difficult to accomplish in a short timeframe. Therefore,

patients with HRS are typically managed medically with

the goal to improve renal function and survival as a

bridge to transplantation. In Europe, the Vasopressin ana-

logue Terlipressin, has been used successfully. Unfortu-

nately, this medication is costly and not available in

many countries, including North America [1]. Here, we

present a case of Type 1 Hepatorenal Syndrome that is

successfu l l y reverse d w i t h v asopress in.

2. Case Report

A 43-year-old female with no significant past medical

history presented to the emergency department complain-

ing of bilateral lower extremity edema, abdominal pain,

nausea, and vomiting that had progressively worsened

over the past month. Review o f systems was positive for

jaundice, increased abdominal girth, fevers, and occasio-

nal hematochezia and hematemesis. She had been taking

three to four grams of Acetaminophen daily for the past

three months for rib pain, and been consuming two to

three alcoholic drinks per day, three to four times a week.

She was admitted to the hospital February 2011 for in-

vestigation of her symptoms.

The workup disclosed probable alcohol-induced cir-

rhosis compounded by concomitant use of acetamino-

phen. On hospital day 9, the patient’s urine output de-

clined to 14 cc/hr an d urine sodium was low (<10 meq/l)

suggesting Hepatorenal Syndrome despite a stable creati-

nine. She was treated with Octreotide and Midodrine for

5 days while the serum creatinine remained stable. On

hospital day 18, the patient developed acute kidney

injury with creatinine increasing from 1.0 mg/dl to 1.3

mg/dl. The etiology was either pre-renal from increasing

diuretics versus hepatorenal syndrome. Urine sodium

L. CONNOR, G. TEEHAN

136

was low (<10 meq/l), however serum creatinine improved

with holding diuretics and giving an intravenous fluid

challenge. Creatinine returned to baseline and diuretics

were resumed on hospital day 21. On hospital day 23,

urine output decreased to 23 cc/hr despite diuretics so

Octreotide and Midodrine were again initiated for

treatment of possible HRS. By hospital day 25, creatinine

rose to 1.2 mg/dl and the patient continued to be diuretic

resistant. Urine sodium was found to be 87 meq/l in the

setting of diuretic use. The following day creatinine was

1.3 mg/dl, diuretics were discontinued and urine sodium

was <10 meq/l consistent with hepatorenal syndrome.

Octreotide, midodrine and albumin were continued. De-

spite being on this therapy for eleven days, creatinine

continued to rise from 1.0 mg/dl to 3.6 mg/d l during this

time period. There were no obvious nephrotoxic expo-

sures, episodes of low blood pressure, nor any evidence

of urinary retention.

Failing Octreotide and Midodrine therapy and being an

unsuitable candidate for liver transplantation due to al-

cohol use, on hospital day 33, she was transferred to the

intensive care unit to begin Vasopressin infusion. Oc-

treotide, Midodrine and albumin were continued as on-

going adjunctive therapy. Vasopressin was initially ad-

ministered at 0.02 units/min. The following morning

creatinine rose from 3.6 mg/dl to 3.8 mg/dl and vaso-

pressin was increased to 0.04 units/min. After appro-

ximately 48 to 72 hours of vasopressin infusion, serum

creatinine began to tren d down. Vasopressin therapy was

continued for 12 days until creatinine was 1.2 mg/dl, n ear

baseline of 0.8 mg/dl. Vasopression dose was decreased

by 50% for one day, then removed completely. Creati-

nine remained stable after being off vasopressin for 48

hours at which point Octreo tide and Midodrine were dis-

continued. Creatinine co ntinued to remain stable and was

1.1 mg/dl at the time of discharge. At two an d ten weeks

post-hospital discharge, creatinine had returned and re-

mained stable at baseline of 0.8 mg/dl.

During treatment with Vasopressin, no improvement

in liver function tests or coagulation factors occurred.

Child-Pugh score was 10 before and after treatment with

vasopressin. MELD score decreased from 33 to 21 from

beginning to end of treatment owing to the decrease in

serum creatinine achieved.

In summary, a 43-year-old female who presented with

bilateral lower extremity edema, abdominal pain and in-

creased girth, nausea and vomiting was found to have

end-stage liver disease secondary to alcohol. During her

hospitalization she developed type 1 hepatorenal syn-

drome. Initially she was treated with Midodrine, Oc-

treotide and albumin but renal function continued to de-

cline. Vasopressin was added and her renal function re-

covered to baseline.

3. Discussion

The only definitive therapy to reverse renal failure in

hepatorenal syndrome is successful liver transplantation.

HRS carries a very poor prognosis with high mortality

rate, which makes liver transplan tation often not possible

before the disease is fatal [3]. There are several pharma-

cologic therapies that have been shown to improve renal

function in patients with HRS. These treatments can be

used to improve survival until a transplant is possible.

Data suggests that the combination of Midodrine, a

selective α-1 adrenergic agonist and systemic vaso-

constrictor, and Octreotide, a somatostatin analog and

inhibitor of endogenous vasodialators, to be effective in

prolonging survival in HRS [4,5]. One study using Oc-

treotide alone did prove to be effective in the treatment

of HRS [6]. Results of these studies are summarized in

Table 1 [4-6]. A benefit to using the combination of oral

Midodrine and subcutaneous Octerotide is the ability to

use this therapy in the outpatient setting [3]. In this

presented case, however, treatment with Midodrine,

Table 1. Summary of studies involving midodrine and octreotide for treatment of HRS.

Author Study Design Participants Treatment Outcomes

Angeli [4] Prospective,

single center 13 patients with

type 1 HRS

Midodrine + octreotide

+ albumin vs

dopamine + albumin

Midodrine and octreotide in combination

with intravenous albumin lowered serum

creatinine, increased GFR, and increased

urine volume in 5 of 5 patients compared

to 1 of 8 patients treated with dopam ine

and albumin.

Esrailian [5] Retrospective,

single center 81 patients with

type 1 HRS Midodrine + octreotid

vs untreated controls

40% of patients treated with midodrine

and octreotide had sustained reduction in

serum creatinine compared to 10% in

untreated controls. 30-day survival was

57% in treated patients compared to 29%

in untreated controls.

Pomier-Layragues

[6]

Prospective,

randomized,

double-blind,

cross-over, single

center

19 patient with

type 1 or type 2

HRS

Octreotide + albumin vs

placebo + albumin Octreotide did not prove to be

effective in the treatment of HRS

L. CONNOR, G. TEEHAN 137

Octreotide, and albumin did not reverse HRS and renal

function continued to deteriorate on therapy. Our patient

was not a candidate for a liver transplant causing us to

search for another treatment alternative.

Many studies have shown promising results using va-

sopressin analogs (Terlipressin and Ornipressin) particu-

larly for prolonging survival in the rapidly fatal type 1

HRS. Vasoconstriction of the splanchnic vascular bed is

believed to be responsible for the reversal of HRS by

ultimately decreasing compensatory renal vasoconstric-

tion and increasing renal perfusion [3]. Terlipressin and

Ornipressin are unavailable in many countries, including

the United States. Although Terlipressin has been more

widely studied, the wide availability of Vasopression in

countries where Terlipressin is unavailable has led to its

use in treatment of HRS. A summary of studies using

Vasopressin and its analogs can be found in Table 2 [7-18].

Little data exists on Vasopressin for HRS and this case

further supports its use in treatment of HRS. Specifically

in this case, Vasopressin, in conjunction with Midodrine,

Table 2. Summary of studies involving vasopressin and vasopressin analogs in treatment of HRS.

Author Study Design Participants Treatment Outcomes

Moreau [7] Retrospective,

multicenter 99 patients with type I

HRS Terlipressin 64% of patients had improved renal

function. Survival rate was 40% at 1 month.

Halimi [8] Retrospective,

multicenter

19 patients with type 1

HRS; 2 patients with

Type 2 HRS Terlipressin 72% of patients had improved renal function. Long term

survival was achieved in two patients.

Sanyal [9]

Prospective, r andomized,

double-blind,

placebo-controlled,

multicenter

56 patients with type 1

HRS Terlipressin v s p l a c e bo

+ albumin

HRS reversal was achieved in 34% treated with

Terlipressin versus 13% treated with placebo plus

albumin. Reversal of HRS significantly

improved surviva l a t 18 0 d ays

Solanki [10] Prospective, r andomized.

single-blind, single center 24 patients with type 1

HRS Terlipressi n vs placebo5 of 12 patien ts treated with Terlipressin survived to day 15

versus 0 of 12 patients in the placebo group

Narahara [11] Prospective,

multicenter, open-label 8 patients with

type 1 HRS Terlipressin + album in75% of patients had a complete response (Cr < 1.5 m g/dl)

to treatment. Median survival was 35 days.

Testro [12] Retrospective, single

center

49 patients with type 1

HRS; 20 patients with

type 2 HRS Terlipressin + album in

37 of 49 (77.5%) pa ti en ts wi th T ype 1 HRS and 4 of 20

(20%) patients with Type 2 HRS responded to tre a t ment. 17

of 49 (35%) patients with Type 1 HRS and 4 of 20 (20%)

patients with Type 2 HRS achieved long -term survival.

Neri [13] Prospective, r andomized,

multicenter 52 patients with type 1

HRS Terlipressin + a lb u min

vs albumin

80% of patients treated with Terlipressin plus albumin

demonstrated a complete response (Cr < 1.5 mg/dl)

compared to 19% of patients treated wit h albumin alone.

Reversal of HRS was strongly associated with

improved survival.

Martin-Llahi

[14] Prospective, randomized,

multicenter

35 patients with type 1

HRS; 11 patients with

type 2 HRS

Terlipressin + a lb u min

vs albumin

Terlipressin pl u s a lb umin improved renal function

compared to alb umin alone (45% vs 8.7%). No significant

different in 3-month survival between terlipressin plus

albumin vs albumin montherapy (27% vs 19%) .

Ortega [15] Prospective,

observational, single

center

16 patients with type 1

HRS; 5 patients with

type 2 HRS

Terlipressin + a lb u min

vs terlipressin

Acomplete response was seen in 77% of patients receiving

terlipressin plus albumin compared t o 2 5 % o f p at i e nt s

treated with terlipressin alone. Occurrence of complete

response was associated with an improved survival.

Guevera [16] Prospective,

nonrandomize d, single

center

16 patient with HRS

(Type not specified)Ornipressin + albuminOrnipression plus albumin was successful at reversing HRS

with 15 days of treatment. Three patients dev elo pe d

ischemic complications.

Gulberg [17] Prospective,

nonrandomize d, single

center

7 patients with type 1

HRS Ornipressin + do pamineHRS reverted in 4 of 7 patients treated wit h ornipressin plus

dopamine. 3 of 7 survived to transplantat i o n.

Kiser [18] Retrospective

observations, si ngle

center

32 patients with type 1

HRS; 11 patients with

type 2 HRS

Vasopressin + octreotide

vs vasopressin

vs octreotide

Complete response occurred in 42% of patients treated

with vasopressin plus octreotid e, 38% of patients treated

with vasopressin alone and 0% of patients treated with

octreotide alone. Survival was improved in patients

treated with vasopressin and they were more likely

to receive a liver transplant

L. CONNOR, G. TEEHAN

138

Octreotide and albumin successfully reversed HRS. This

case also demonstrates that a patient failing one medical

therapy for H RS may respond to an altern ativ e or adjun c-

tive therapy; therefore these methods should be attemp-

ted to increase the patient’s chance of survival.

4. Conclusion

In conclusion, we have reported a case of type 1 HRS

that is successfully treated with vasopressin. There are

studies in Europe using terlipressin that have shown

some success, however, terlipressin is not available in

many countries. Since terlipressin is not available in the

United States, vasopressin is used as an alternative and is

successful in this reported case. We would advocate the

use of vasopressin where terlipressin is unavailable, par-

ticularly when other available treatments are failing to

reverse r e n a l failure.

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