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Figure 1 Algorithm for evaluating for simultaneous liver-kidney transplantation in a liver transplant candidate with renal dysfunction. Modified from Saxena et al^[78]. eGFR: Estimation of glomerular filtration rate; T2DM: Type 2 diabetes mellitus; HTN: Hypertension.
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Conflict-of-interest statement: The authors do not have any disclosures to report.

Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

Manuscript source: Invited manuscript

Peer-review started: April 28, 2016

First decision: June 16, 2016

Article in press: July 18, 2016

P- Reviewer: Boin IFSF, Coban M S- Editor: Ji FF L- Editor: A E- Editor: Li D

Table 1 The role of terlipressin and albumin in hepatorenal syndrome-1

Ref.	Terlipressin dose	Albumin	Length	Terlipressin group: Cr (mg/dL) or Cr Cl (mL/min)	Control group: Cr (mg/dL) or Cr Cl (mL/min)	30 d survival (terlipressin vs control)	Transplant free outcome
Hadengue et al^[113]	1 mg twice daily	No	2 d	Cr Cl: 27 ± 4	Cr Cl: 15 ± 2	N/A	N/A
Halimi et al^[49]	4 mg/d	Yes	7 d (mean)	Decline in Cr from 31%-75% from day 0 to day 5	N/A	13/18 (72%) patient response	N/A
Danalioglu et al^[42]	2-4 mg/d	Yes	6 d	N/A	N/A	20% vs 0%	N/A
Testro et al^[54]	1 mg every 6 h (max of 8 mg/d)	Yes	12 d	N/A	N/A	17/49 HRS type 1, 4/20 HRS type 2	All transplant free outcomes responded to terlipressin
Sanyal et al^[46]	1 mg every 6 h (doubled on 4 d if Cr did not < 30%)	No (control group received albumin)	14 d	Cr < 1.5 mg/dL (19/59, 33.9%)	Cr < 1.5 mg/dL (7/56, 12.5%)	N/A	42.9% (24/56) vs 37.5% (21/56) in terlipressin vs control group at 180 d
von Kalckreuth et al^[47]	3.9 mg ± 1.3 mg (responders) vs 3.4 mg ± 1.4 mg (nonresponders)	Yes	6 ± 4.9 d (responder) vs 8 ± 6.3 d (non-responders)	N/A	N/A	Complete response by day 7 was 52%, while at day 17 it was 84%	25/38 (66%) of treatment complete response was achieved
Boyer et al^[44]	1 mg every 6 h	Yes	6.3 d (mean)	Cr: 2.8 mg/dL	Cr: 3.8 mg/dL	N/A	34% non-transplanted survival 100% transplant survival at 180 d
Hinz et al^[51]	2-6 mg/d	Yes	N/A	N/A	N/A	57% of patients (12/21) responded to terlipressin. Age was a negative predictor for treatment response	No difference seen in mortality between responders and non-responders at 60 d
Heidemann et al^[50]	26.43 ± 30.86 (total dose for responders) vs 32.11 ± 31.57 (total dose for non-responders)	Yes	9 d (responders) vs 10.5 d (non-responders)	N/A	N/A	One month survival was longer in responders vs non-responders (P = 0.048)	N/A
Sagi et al^[45] (meta-analysis)	N/A	Yes	Minimum of 3 d of terlipressin	Cr must have been < 1.5 mg/dL at treatment end	N/A	Four trials (n = 223) with RR for reversal in type 1 HRS with terlipressin was 3.66 (95%CI: 2.15-6.23)	N/A
Fabrizi et al^[48] (meta-analysis)	N/A	N/A	N/A	N/A	N/A	Five trials (n = 243 patients) with pooled OR of HRS reversal was 8.09 (95%CI: 3.52; 18.59)	Recovery of renal function occurs in less than 50% of patients with HRS even with terlipressin

Cr: Creatinine; Cr Cl: Creatinine clearance; HRS: Hepatorenal syndrome; N/A: Not available.




Table 2 Comparing outcomes measures between liver transplantation alone vs simultaneous liver kidney transplantation including graft and patient survival as well as need for renal replacement therapy

Ref.	No. of LTA	No. of SLKT	Graft survival (LTA vs SLKT)	Patient survival (LTA vs SLKT)	Renal dysfunction post 1, 5 and 10 yr (LTA vs SLKT)	RRT post-transplantation (LTA vs SLKT)	Additional comments
Jeyarajah et al^[81]	2442 (Cr > 2.0, nationawide)	29 (single center) + 414 (nationwide)	N/A	5 yr survival nationwide (50.4% vs 62.2%)	N/A	N/A	Interestingly, single center study had increased better survival in LTA than SLKT group
Campbell et al^[80]	53	13	N/A	N/A	1 yr (1.4 mg/dL vs 1.5 mg/dL)	2% vs 0% (at 12 mo)	Adjusting for baseline characteristics, SLKT patients had lower Cr than LTA at 12 mo (P = 0.01)
Ruiz et al^[83]	80 (all with HRS)	98 (22 with HRS and 76 with primary renal disease)	1 yr SLKT survival (liver: 76% and kidney: 76%)	1 yr survival (66% LTA vs 72% SLKT)	N/A	Post-op dialysis: (89% LTA pts for median of 9 d vs 55% SLKT pts for median 2.5 d)	1 yr acute kidney rejection in CLKT was 14% vs 23% in 5 yr LT cohort
Locke et al^[84]	19137	1032	N/A	1 yr survival for pts with ≥ 3 mo RRT: (70.8% LTA vs 84.5% SLKT)	N/A	N/A	Even after matched-control analysis, there was no benefit in SLKT cohort vs LTA cohort outside of aforementioned RRT
Mehrabi et al^[85] (literature review)	N/A	3536	Cumulative 5 yr SLKT survival of both organs (60.9%)	Cumulative 5 yr survival 42.6%	N/A	N/A	It is concluded that there is no definitive evidence of better graft/patient survival in SKLT vs LTA
Chava et al^[114]	N/A	39	5 yr SLKT survival (liver: 73.7% and kidney: 70%)	73.7% SLKT patient survival at 5 yr	N/A	N/A	15 surviving patients (53.6%) had mild/moderate kidney dysfunction
Fong et al^[82]	2774	1501	5 yr survival (58.9% LTA vs 65.3%, SLKT, P < 0.001)	5 yr survival (62.9% LTA vs 67.4% SLKT, P < 0.001)	0% with severe renal dysfunction	N/A	Liver graft survival and patient survival was better in SLKT vs LTA group
Martin et al^[88] 2012	66026	2327	15% decreased risk of graft loss with SLKT vs LTA (P = 0.02)	N/A	N/A	N/A	SLKT had higher graft survival rates than both KALT and LAKT
Sharma et al^[86]	2112 (received RRT within 90 d before LT)	N/A	N/A	78% LTA survival at 6 mo (not associated with RRT duration)	N/A	8.90%	Risk for non-recovery increased by 3.6%/day of pre-LT RRT
Catalano et al^[89]	74	37	10 yr survival (77% LTA vs 80% SLKT, P = 0.85)	10 yr survival (79% LTA vs 86% SLKT, P = 0.56)	N/A	N/A	Acute rejection episodes involving the liver were less in SLKT vs LTA

LTA: Liver transplantation alone; SLKT: Simultaneous liver kidney transplantationl; RRT: Renal replacement therapy; HRS: Hepatorenal syndrome; KALT: Kidney after liver transplantation; LAKT: Liver after kidney transplantation; N/A: Not available.