Burden and impact of acute kidney injury in acute liver failure: A systematic review

Table 1 Study quality assessment

Ref.	Study design and setting are clearly defined	Eligibility and recruitment criteria of patients are clearly described	Operational definitions of ALF and AKI as per standard guidelines	Outcome variables described	Limitations of the study are clearly described	Score
Leithead et al[12]	Yes	No	Yes	No	Yes	3
O’Riordan et al[13]	Yes	Yes	No	Yes	Yes	4
Tujios et al[14]	Yes	Yes	Yes	Yes	Yes	4
Urrunaga et al[15]	Yes	No	No	Yes	Yes	3
Coelho et al[16]	Yes	Yes	Yes	Yes	Yes	5
Hadem et al[17]	No	Yes	No	Yes	Yes	3
Cardoso et al[18]	Yes	Yes	Yes	Yes	Yes	5
Imoto et al[19]	Yes	No	Yes	Yes	No	3
Fidalgo et al[20]	Yes	Yes	Yes	Yes	Yes	5

AKI: Acute kidney injury.

Table 2 Study characteristics

Ref.	Home country	Study design	Length of data collection (years)	Number of centers	AKI criteria	Time frame of AKI assessment	Inclusion criteria	Exclusion criteria	Study location
Leithead et al[12]	United Kingdom	R	14	1	RIFLE	Hospital stay	ALF	MV, already on RRT	LTU
O’Riordan et al[13]	United Kingdom	R	8	1	AKIN	Hospital stay	Patients admitted to LITU with paracetamol poisoning	Liver transplant patients	LTU
Tujios et al[14]	United States	R	12	23	AKIN	Hospital stay	INR > 1.5, HE < 26 weeks of illness without liver disease	NA	NA
Urrunaga et al[15]	United States	R	10	Registry	Others	During the waitlisting period (median duration 3 days)	> 18 years ALF with status 1 or 1A for ALF transplant	NA	NA
Coelho et al[16]	Portugal	R	20	1	KDIGO	NA	18 years with ALF	CLD, CKD on RRT, RRT need before ICU	Gastroenterology, liver ICU
Hadem et al[17]	Germany	R	18	1	AKIN	Hospital stay	Hepatic encephalopathy with available renal function data	Overt sepsis	ICU
Cardoso et al[18]	United States	R	18	Registry	KDIGO	On day 1 of enrolment	> 18 years and ALF	< 3 days, follow up without renal function test on day 3, cirrhosis	NA
Imoto et al[19]	Japan	R	12	1	KDIGO	NA	ALF admitted to hospital	Malignancy, HIV	NA
Fidalgo et al[20]	Portugal	P	7	1	KDIGO	7 days of ICU stay	ALF/ALI > 16 years	NA	ICU

RIFLE: Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease; AKIN: Acute Kidney Injury Network; KDIGO: Kidney Disease Improving Global Outcomes; ALF: Acute liver failure; ALI: Acute liver injury; AKI: Acute kidney injury; CLD: Chronic liver disease; CKD: Chronic kidney disease; RRT: Renal replacement therapy; NA: Not available; LTU: Liver transplant unit; ICU: Intensive care unit; R: Retrospective; P: Prospective; INR: International normalized ratio; HE: Hepatic encephalopathy; MV: Mechanical ventilation.

Table 3 Characteristics of study participants in studies describing acute kidney injury in acute liver failure patients, n (%)

Ref.	Total number of patients	Female gender	Age in years (mean)	Co-morbidities	Severity score	Number of patients developing AKI	AKI with ALF patients requiring RRT	Mortality (%)
Leithead et al[12]	308	175 (56.8)	39.7	NA	NA	208 (67.5)	145 (70)	112 (26.9)
O’Riordan et al[13]	302	178 (59)	37	NA	SOFA, MELD, APACHE II, KCH	239 (79.1)	182 (76)	74 (25)
Tujios et al[14]	1604	1106 (68.9)	NA	DM (n = 84; 5.2%), HTN (n = 93; 5.7%)	NA	1122 (69.9)	491 (43.7)	478 (29.8)
Urrunaga et al[15]	2280	1596 (70)	NA	NA	MELD	1271 (55.7)	NA	NA
Coelho et al[16]	51	28 (54.9)	NA	DM (n = 1; 5.9%), HTN (n = 8; 15.6%), CAD (n = 6; 9.8%), others (n = 5; 9.8%)	SOFA	34 (66.7)	5 (14.7)	22 (43.1)
Hadem et al[17]	134	102 (76.1)	42.5	NA	SOFA, SAPS III, KCH, BiLE	54 (40.3)	52 (96.2)	45 (33.6)
Cardoso et al[18]	1071	731 (68.3)	39	NA	MELD	744 (69.4)	221 (29.7)	324 (33.5)
Imoto et al[19]	174	79 (45.4)	49	NA	MELD	66 (37.9)	NA	20 (11.5)
Fidalgo et al[20]	104	44 (57.7)	44	NA	SOFA	57 (54.80)	32 (56.1)	32 (30.8)

DM: Diabetes mellitus; HT: Hypertension; CAD: Coronary artery disease; SOFA: Sequential Organ Failure Assessment; MELD: Model for End-Stage Liver Disease; APACHE: Acute Physiology and Chronic Health Evaluation; KCH: King's College Hospital criteria; HTN: Hypertension; SAPS: Simplified Acute Physiology Score; BiLE: Bilirubin Lactate and Etiology score; NA: Not available.

Table 4 Etiologies of acute liver failure in different studies on acute kidney injury in acute liver failure, n (%)

Ref.	Drugs	Viral hepatitis	AIH	Budd-Chiari syndrome	Pregnancy	Wilson’s disease	Shock/ischemia	Other/undetermined
Leithead et al[12]	242 (78.5). PCM (89.6), non PCM (10.3)	46 (14.9)	5 (1.6)	5 (1.6)	3 (0.9)	2 (0.6)	0 (0)	5 (1.6)
O’Riordan et al[13]	302 (100). PCM (100)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)
Tujios et al[14]	738 (46). PCM (100)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	84 (5.2)	783 (48.8)
Urrunaga et al[15]	777 (34). PCM (86.7), non PCM (13.2)	216 (9.4)	118 (5.1)	3 (0.1)	19 (0.8)	13 (0.6)	0 (0)	1134 (49.7)
Coelho et al[16]	12 (23.5)	15 (29.4)	3 (5.8)	0 (0)	2 (3.9)	0 (0)	8 (15.6)	11 (21.6)
Hadem et al[17]	45 (33.8). PCM (28.9), non PCM (71.1)	31 (23.3)	2 (1.5)	9 (6.7)	0 (0)	3 (2.2)	1 (0.7)	43 (32.3)
Cardoso et al[18]	497 (46.4)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	573 (53.5)
Imoto et al[19]	5 (2.8). PCM (0), non PCM (100)	71 (40.8)	17 (9.8)	0 (0)	0 (0)	0 (0)	0 (0)	81 (46.5)
Fidalgo et al[20]	36 (34.6). PCM (50), non PCM (50)	11 (10.5)	0 (0)	0 (0)	0 (0)	0 (0)	8 (7.6)	49 (47.1)

PCM: Paracetamol; AIH: Autoimmune hepatitis.