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
Received July 3, 2013; revised August 2, 2013; accepted August 13, 2013
Copyright © 2013 Laura Connor, Geoffrey Teehan. This is an open access article distributed under the Creative Commons Attribu-
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
C
opyright © 2013 SciRes. OJNeph

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.
REFERENCES
[1] C. Alessandria, A. Ottobrelli, W. Debernardi-Venon, L.
Todros, M. T. Cerenzia, S. Martini, et al., “Noradrenalin
vs Terlipressin in Patients with Hepatorenal Syndrome: A
Prospective, Randomized, Unblinded, Pilot Study,” Jour-
nal of Hepatology, Vol. 47, No. 4, 2007, pp. 499-505.
doi:10.1016/j.jhep.2007.04.010
[2] S. J. Munozo, “The Hepatorenal Syndrome,” Medical Cli-
nics of North America, Vol. 92, No. 4, 2008, pp. 813-837.
doi:10.1016/j.mcna.2008.03.007
[3] T. H. Kiser, R. Maclaren and D. N. Fish, “Treatment of
Hepatorenal Syndrome,” Pharmacotherapy, Vol. 29, No.
10, 2009, pp. 1196-1211. doi:10.1592/phco.29.10.1196
[4] P. Angeli, R. Volpin, G. Gerunda, R. Craighero, P. Roner,
R. Merenda, et al., “Reversal of Type 1 Hepatorenal Syn-
drome with the Administration of Midodrine and Octreo-
tide,” Hepatology, Vol. 29, No. 6, 1999, pp. 1690-1697.
doi:10.1002/hep.510290629
[5] E. Esrailian, E. R. Pantangco, N. L Kyulo, K. Q. Hu and
B. A. Runyon, “Octreotide/Midodrine Therapy Signifi-
cantly Improves Renal Function and 30-Day Survival in
Patients with Type 1 Hepatorenal Syndrome,” Digestive
Diseases and Sciences, Vol. 52, No. 3, 2007, pp. 742-748.
doi:10.1007/s10620-006-9312-0
[6] G. Pomier-Layragues, S. C. Paquin, Z. Hassoun, M. La-
fortune and A. Tran, “Octreotide in Hepatorenal Syn-
drome: A Ransomized Double-Blind, Placebo-Controlled,
Corssover Study,” Hepatology, Vol. 38, No. 1, 2003, pp.
238-243. doi:10.1053/jhep.2003.50276
[7] R. Moreau, F. Durand, T. Poy nard, C. Duhamel, J. P. Cer-
voni, P. Ichai, et al., “Terlipressin in Patients with Cir-
rhosis and Type 1 Hepatorenal Syndrome: A Retroepsc-
tive Mulitcenter Study,” Gastroenterology, Vol. 122, No.
4, 2002, pp. 923-930. doi:10.1053/gast.2002.32364
[8] C. Halimi, P. Bonnard, D. Bernard, P. Mathurin, A. Mo-
fredj, V. Martino, et al., “Effect of Terlipressin (Gly-
pressin) on Hepatorenal Syndrome in Cirrhotic Patients:
Results of a Multicentre Pilot Study,” European Journal
of Gastroenterology & Hepatology, Vol. 14, No. 2, 2002,
pp. 153-158. doi:10.1097/00042737-200202000-00009
[9] A. J. Sanyal, T. Boyer, G. Ga rcia-Tsao, F. Regenstein, L.
Rossaro, B. Appenrodt, et al., “A Randomized, Pros-
pective, Double-Blind, Placebo-Controlled, Trial of Terli-
pressin for Type 1 Hepatorenal Syndrome,” Gastroente-
rology, Vol. 143, No. 5, 2008, pp. 1360-1368.
doi:10.1053/j.gastro.2008.02.014
[10] P. Solanki, A. Chawla, R. Garg, R. Gupta, M. Jain and S.
K. Sarin, “Beneficial Effects of Terlipressin in Hepa-
torenal Syndrome: A Prospective, Randomized Placebo-
Controlled Clinical Trial,” Journal of Gastroenterology
Hepatology, Vol. 18, No. 2, 2003, pp. 152-156.
doi:10.1046/j.1440-1746.2003.02934.x
[11] Y. Narahara, H. Kanazawa, C. Sakamoto, H. Maruyama,
O. Yokosuka, S. Mochida, et al., “The Efficacy and Safe -
ty of Terlipressin and Albumin in Patients with Type 1
Hepatorenal Syndrome: A Multicenter, Open-Label, Ex-
plorative Study,” Journal of Gastroenterology, Vol. 47,
No. 3, 2011, pp. 313-320.
doi:10.1007/s00535-011-0485-8
[12] A. G. Testro, S. Wongseelashote, P. W. Angus and P. J.
Gow, “Long-Term Outcome of Patients Treated with Ter-
lipre ssi n fo r Ty pe s 1 a nd 2 He pa tor e na l Sy n dr ome , ” Jour-
nal of Gastroenterology and Hepatology, Vol. 23, No. 10,
2008, pp. 1535-1540.
doi:10.1111/j.1440-1746.2007.05176.x
[13] S. Neri, D. Pulvirenti, M. Malaguarnera, B. M. Cosimo,
G. Bertino, L. Ignaccolo, et al., “Terlipressin and Albu-
min in Patients with Cirrhosis and Type I Hepatorenal
Syndrome,” Digestive Diseases and Sciences, Vol. 53, No.
3, 2008, pp. 830-835. doi:10.1007/s10620-007-9919-9
[14] M. Martin-Llahi, M. N. Pepin, M. Guevara, F. Diaz, A.
Torre, A. Monescillo, et al., “Terlipressin and Albumine
vs. Albumin in Patients with Cirrhosis and Hepatorenal
Syndrome: A Randomized Study,” Gastroenterology, Vol.
134, No. 5, 2008, pp. 1353-1359.
doi:10.1053/j.gastro.2008.02.024
[15] R. Ortega, P. Gines, J. Uriz, A. Cardenas, B. Calahorra, D.
De Las Heras, et al., “Terlipressin Therapy with and
without Albumin for Patients with Hepatorenal Syndrome:
Results of a Prospective, Nonrandomized Study,” Hepa-
tology, Vol. 36, No. 4, 2002, pp. 941-941.
doi:10.1053/jhep.2002.35819
[16] M. Guevera, P. Gines, G. Fernandez-Esparrach, P. Sort, J.
M. Salmero, W. Jimenez, et al., “Reversibility of Hepa-
torenal Syndrome by Prolonged Administration of
Ornipressin and Plasma Volume Expansion,” Hepatology,
Vol. 27, No. 1, 1998, pp. 35-41.
doi:10.1002/hep.510270107
[17] V. Gulberg, M. Blizer and A. L. Gerbes, “Long-Term
Therapy and Retreatment of Hepatorenal Syndrome Type
1 with Ornipressin and Dopamine,” Hepatology, Vol. 30,
No. 4, 1999, pp. 870-875. doi:10.1002/hep.510300430
[18] T. H. Kiser, D. N. Fish, M. D. Obritsch, R. Jung, R.
MacLaren and C. R. Rarikh, “Vasopressin, Not Octreo-
tide, May Be Beneficial in the Treatment of Hepatorenal
Syndrome: A Retrospective Study,” Nephrology Dialysis
Transplantation, Vol. 20, No. 9, 2005, pp.1813-1820.
doi:10.1093/ndt/gfh930