Hepatorenal syndrome

Table 3 Non-invasive therapies

Authorand Year	n (# Type 1,# Type 2)	Study design	Intervention	Outcomemeasures	MeanbaselineSCr	Meanfollow-upSCr	Other results	Comments
Moreau et al[38] 2002	99 (99/0)	Multicenter, retrospective	Terlipressin (75% received albumin)	Reduction of SCr to < 130 μmol/L or a decrease of at least 20% at end of treatment)	272 ± 114 μmol/L	Responders: 138 ± 59 μmol/L Nonresponders: 382 ± 210 μmol/L	Renal function improved in 58% of patients.	Twenty-three patients had adverse events that may have been terlipressin-related. Three patients required RRT 40% survival at 1 mo.
Kiser et al[44] 2005	43 (32/11)	Observational (retrospective cohort)	Vasopressin (AVP) vs octreotide vs combination	Clinical response; SCr 1.5 mg/dL or less	3.9 ± 3.3 mg/dL	Responders: SCr decreased by 62% ± 9% Nonresponders: SCr increased by 46% ± 119%	42% complete response with AVP vs 38% with AVP and octreotide vs 0% with octreotide alone.	No adverse effects related to AVP. RRT rates: 50% in AVP group, 58% in combination group, and 31% in octreotide alone group.
Solanki et al[43] 2003	24 (24/0)	Randomized placebo- controlled single-blind	Terlipressin vs placebo (all patients received albumin) for 4-15 d	Reversal of HRS and survival at 15 d	Terlipressin: 2.9 ± 0.1 mg/dL Placebo: 2.2 ± 0.2 mg/dL	Terlipressin: 1.2 ± 0.2 mg/dL at d 15 Placebo: no survival at d 15 (SCr 3.9 ± 0.2 mg/dL on d 8)	In terlipressin group, 5 of 12 patients survived. None survived by d 15 in placebo group.
Ortega et al[39] 2002	21 (16/5)	Prospective, nonrandomized	Terlipressin with albumin vs without albumin for 4-14 d	SCr 1.5 mg/dL or lower	Terlipressin with albumin: 3.6 ± 1.5 mg/dL Terlipressin without albumin: 3.4 ± 0.3 mg/dL	Terlipressin with albumin: 1.5 ± 0.2 mg/dL Terlipressin without albumin: 3.4 ± 0.7 mg/dL	10 of 13 patients who received terlipressin and albumin responded. Of 8 patients who received terlipressin alone, 2 responded.	One patient had ischemic side effects (finger ischemia). At 1 mo, there was a 5% recurrence of HRS after complete response.
Pomier- Layrargues et al[61] 2003	19 (NS)	Randomized, double-blind, placebo- controlled, crossover	Placebo, then octreotide (Group 1) vs octreotide, then placebo (Group 2) (all patients received albumin)	20% decrease in SCr after 4 d	Group 1: 215 ± 32 μmol/ Group 2: 208 ± 16 μmol/L	Group 1: 222 ± 41 μmol/L after placebo; 270 ± 54 μmol/L after octreotide Group 2: 194 ± 34 μmol/L after octreotide; 204 ± 47 μmol/L after placebo	Treatment with octreotide was not effective.	The study included types 1 and 2 HRS patients (numbers in each group not specified). No side effects reported.
Colle et al[42] 2002	18 (18/0)	Chart review (retrospective analysis)	Terlipressin (some patients received albumin)	Decrease in SCr to < 130 μmol/L or decrease of at least 20% leading to a stable value; evaluation of predictive factors	Patients with improved SCr: 276 ± 47 μmol/L1 Patients without improved SCr: 295 ± 891μmol/L	Patients with improved SCr: 130 ± 13 μmol/L Patients with improved SCr: 411 ± 89 μmol/L	11 patients had improved renal function	Some of these patients were included in the Moreau study. Patients with improved renal function had less severe cirrhosis than patients without. Patients without a precipitating factor for HRS or who responded to terlipressin were more likely to survive.
Halimi et al[41] 2002	18 (16/2)	Multicenter pilot (retrospective)	Terlipressin for 2-16 d	> 30% decrease in baseline SCr	298 ± 124 μmol/L	145 ± 85 μmol/L	13 of 18 had improved renal function; 8 had a normal SCr at d 5	Three patients had ischemic side effects. One had severe bronchospasms after terlipressin administration, and subsequently died.
Guevara et al[49] 1998	16 (Type NS)	Open pilot study	Ornipressin and albumin for 3 vs 15 d	Efficacy	3-d arm: 2.9 ± 0.5 mg/dL 15-d arm: 3.0 ± 0.5 mg/dL	3-d arm: 2.2 ± 0.4 mg/dL 15-d arm: 0.7 ± 0.1 mg/dL	75% of patients had improved renal function.	Treatment was stopped in 4 patients on the 15-d protocol because of ischemic complications.
Angeli et al[62] 1999	13 (13/0)	Nonrandomized	Dopamine and albumin (Group A) vs midodrine, octreotride, and IV albumin (Group B)	Efficacy	Group A: 3.6 ± 0.6 mg/dL Group B: 5.0 ± 0.9 mg/dL	Group A: 5.1 ± 1.5 mg/dL at 15 d (only 1 patient survived to d 20) Group B: 3.3 ± 0.7 mg/dL at 20 d	All Group B patients had improved GFR. 7 of 8 patients in Group A had worsening renal function and died.	No significant side effects.
Holt et al[33] 1999	12 (NS)	Open label	N-acetylcysteine for 5 d	Efficacy	222 ± 27 μmol/L	169 ± 7 μmol/L		67% survival at 1 mo, and 58% at 3 mo (2 patients received liver transplants).
Mulkay et al[40] 2001	12 (12/0)	Pilot	Terlipressin for 1 wk to 2 mo	Safety and efficacy	3.4 mg/dL	1.8 mg/dL		Three patients received liver transplants, and had near-normal renal function. The other 9 died during follow-up. No ischemic complications.
Duvoux et al[48] 2002	12 (12/0)	Pilot	Noradrenalin (NA), albumin, and furosemide for at least 5 d	Safety and efficacy	2.6 ± 1.1 mg/dL pre- furosemide/ albumin; 3.9 ± 1.8 mg/dL after infusion (pre-NA)	1.6 ± 0.8 mg/dL	Reversal of HRS in 10 of 12 patients	Two patients had previously received terlipressin (underwent 48-h washout before starting NA). Transient myocardial ischemia was observed in 1 patient.
Hadengue et al[63] 1998	9 (9/0)	Double-blind, short-term, controlled crossover study	Terlipressin and placebo for 2 d in randomized order	Efficacy	Baseline CrCl: 15 ± 2 mL/min	CrCl after terlipressin (includes both groups): 27 ± 4 mL/min CrCl after placebo (includes both groups): 16 ± 3 mL/min		No side effects reported.
Uriz et al[37] 2000	9 (6/3)	Pilot	Terlipressin with albumin for 5-15 d	Reduction of serum creatinine to < 1.5 mg/dL	3.9 ± 0.7 mg/dL	1.5 ± 0.2 mg/dL	Reversal of HRS in 7 of 9 patients.	One patient did not complete the study due to pancreatitis. No ischemic complications.
Angeli et al[45] 1998	8 (0/8) + 17 cirrhotic patients without HRS	Open label	Midodrine (one dose)	Renal function and renal hemo- dynamics (acute effects)	GFR: 39.0 ± 6.4 mL/min	GFR: 45.1 ± 7.6 mL/min	No significant acute effect on renal hemodynamics or renal function.	This study looked at the acute effect of one dose of midodrine. The results include cirrhotic patients without HRS.
Gulberg et al[64] 1999	7 (7/0)	Nonrandomized	Orinpressin, dopamine, and albumin for 5-27 d	2× increase in Crcl (to > 40 mL/min)	Treatment success group: 4.6 ± 0.9 mg/dL, and improved to 1.3 ± 0.2 mg/dL	Treatment success group: 1.3 ± 0.2 mg/dL	HRS was reversed in 4 of 7 patients	Two responders had a relapse. One of them responded to retreatment, but treatment was stopped in the other because of a ventricular tachyarrhythmia. Treatment was stopped in another patient because of intestinal ischemia.
Kaffy et al[65] 1999	5 (NS)	Pilot	Octreotide for 5 d	Efficacy	194 μmol/L in 4 patients	96 μmol/L in 4 patients	Improvement of SCr in 4 of 5 patients,	but 4 of 5 patients eventually died. HRS rapidly recurred when octreotide was stopped, and did not respond to further octreotide infusion.

SCr: Serum Creatinine; RRT: Renal replacement therapy; NS: Not Specified; CrCl: Creatinine Clearance. Cr conversion from μmol/L to mg/dL: divide by 88.4.