Mannitol for Prevention of AKI After Liver Transplantation

Abstract and Introduction

Abstract

Background: Acute kidney injury (AKI) is a common complication after liver transplantation, which is associated with increased morbidity and mortality. Therefore, this study investigated mannitol as an oxygen-free radical scavenger and its role in the prevention of early AKI after living donor liver transplantation (LDLT).

Methods: A total of 84 adult patients who underwent LDLT were randomly assigned to two equal groups: the M group, where patients received 1 g/kg mannitol 20%, or the S group, where patients received an equal volume of saline. The primary outcome was the incidence of early AKI, defined as a 0.3 mg/dl increase in the serum creatinine 48 h postoperatively. Laboratory assessments of the graft and creatinine were recorded until 3 months after transplantation besides the post-reperfusion syndrome and the intraoperative hemodynamic measurements.

Results: The AKI incidence was comparable between groups (relative risk ratio of 1.285, 95% CI 0.598–2.759, P = 0.518). Moreover, AKI stages and serum creatinine 3 months after transplantation, P = 0.23 and P = 0.25, respectively. The incidence of the post-reperfusion syndrome was comparable in both groups, 29/39 (74.4%) and 31/41 (75.6%) in M and S groups, respectively, P = 0.897. The intraoperative hemodynamic parameters showed no significant difference between groups using the area under the curve.

Conclusion: The current LDLT recipient sample was insufficient to demonstrate that pre-reperfusion 1 g/kg mannitol infusion would reduce the risk of early AKI or post-reperfusion syndrome.

Clinical Trial Registration Number: Pan African Clinical Trials Registry (PACTR202203622900599); https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=21511.

Introduction

Liver transplantation became the standard treatment for end-stage liver disease and selected cases of liver neoplasms.^[1] The incidence of acute kidney injury (AKI) can reach up to 95% after the liver transplantation (LT) setting due to ischemia-reperfusion injury (IRI).^[2]

Degradation of adenosine triphosphate (ATP) molecules results in an accumulation of hypoxanthine during liver graft ischemia. Hypoxanthine produces toxic reactive oxygen species (ROSs) by xanthine oxidase after reperfusion and reoxygenation of the graft.^[2,3] Those ROS produce cellular injury by lipid peroxidation of the cell membranes, leukocyte activation, chemotaxis, and leukocytes-endothelial adhesion.^[2,3]

Mannitol, vitamin C, vitamin E, superoxide dismutase, N-acetyl cysteine, and allopurinol are common examples of antioxidants.^[4] Mannitol and ascorbic acid were effective in scavenging and inhibiting ROS after liver IRI on the histopathological and biochemical levels.^[5] Additionally, mannitol creates a hyperosmolar environment, which may blunt the IRI.^[6]

Mannitol drip within 15 min of cross-clamping enhances renal preservation during living donor kidney transplantation.^[7] While in LT, mannitol infusion during the anhepatic phase could ameliorate post-reperfusion syndrome (PRS),^[8] Whitta and colleagues found no protective effect of mannitol on kidney function during LT.^[9]

We hypothesized that using mannitol during the anhepatic phase in living donor liver transplantation (LDLT) would decrease the early AKI incidence. The aim of the study was to investigate the role of mannitol for prevention of AKI and PRS in LDLT.

Table 1. Liver transplantation recipients' baseline characteristics and preoperative laboratory results
	Group (M) N = 39	Group S N = 41	P-Value
Age (years)	53 (43–57)	54 (45–57)	0.858
Sex (Male/Female No., %)	27/12 (69.2/30.8%)	29/12 (70.7/39.3%)	0.884
Weight (Kg)	77.62 (10.7)	78.59 (10.9)	0.69
Height (m)	1.68 (0.08)	1.68 (0.07)	0.893
Body Surface Area (m²)	1.87 (0.15)	1.88 (0.02)	0.645
MELD score	15 (12–17)	15 (11–17)	0.703
CPC	8 (7–10)	8 (6–10)	0.873
Etiology (No., %)
Viral hepatitis	19/39 (48.7%)	15/41 (36.6%)	0.445
Hepatocellular carcinoma	12/39 (30.8%)	19/41 (46.3%)
Autoimmune disease	7/39 (17.9%)	5/41 (12.2%
Cryptogenic	1/39 (2.6%)	2/41 (4.9%)
Comorbidities (No., %)
HTN	0/39	1/41 (2.5%)	0.119
DM	10/39 (25.6%)	11/41 (27.5%)
DM and HTN	0/39	5/41 (12.5%)
Cardiac (mild mitral regurgitation)	0/39	1/41 (2.5%)
Hypothyroidism	1/39 (2.6%)	0/41
S.Cr. (mg/dL)	0.7 (0.6–0.8)	0.7 (0.6–0.9)	0.221
S. AST (u/mL)	40 (30–60)	48 (39–76)	0.068
S. ALT (u/mL)	21 (21–34)	27 (21–54)	0.35
S. total bilirubin (mg/dL)	2.3 (1.6–3.3)	1.9 (1.55–3.4)	0.765
S. direct bilirubin (mg/dL)	1 (0.6–1.5)	1.1 (0.55–1.8)	0.821
S. albumin (g/dL)	2.9 (0.68)	2.8 (0.53)	0.41
INR	1.5 (0.29)	1.46 (0.29)	0.577
CRP (mg/dL)	0 (0–8)	0 (0–9)	0.808

Data are presented as mean (SD) or median (IQR), and No. (%), SD standard deviation, IQR interquartile range, M group mannitol group, S group saline group, MELD model for end-stage liver disease, CPC Child-Pugh classification, HCC hepatocellular carcinoma, HTN hypertension, DM diabetes mellitus, INR international normalized ratio, AST Aspartate Transaminase, ALT Alanine Transaminase, S serum, Cr Creatinine, CRP C-reactive protein

Table 2. Intraoperative ischemia and anhepatic phase times, operative duration, intraoperative blood product transfusion, UO, and total doses of furosemide, norepinephrine, and epinephrine
	Group (M) N = 39	Group (S) N = 41	P-Value
Cold ischemia (minutes)	28.7 (10.5)	29.8 (9.9)	0.655
Warm ischemia (minutes)	35.8 (8.6)	38.4 (9.2)	0.2
Anhepatic phase duration (minutes)	70 (15.6)	73.6 (17.3)	0.348
Operative duration (minutes)	567.6 (70.4)	576 (78.2)	0.636
RBCs (No. of patients)	24/38 (63.2%)^#	28/41 (68.3%)	0.644
Fresh frozen plasma (No. of patients)	3/38 (7.9%)^#	5/41 (12.2%)	0.713
Platelets (No. of patients)	0/38	0/41	-
RBCs (No. of units)	1 (0–3.25)	2 (0–3.5)	0.695
Plasma (No. of units)	0 (0–7)	0 (0–5)	0.549
Anhepatic phase UO (mL)	350 (200–500)	150 (50–325)	0.003*
Total UO (mL)	2100 (1340–3350)	1400 (1025–2425)	0.027*
Total intraoperative furosemide (mg)	5 (0–10)	5 (0–10)	0.528
Total intraoperative norepinephrine (mcg)	200 (77.5–275)	190 (120–270)	0.97
Total intraoperative epinephrine (mcg)	0 (0–25)	0 (0–20)	0.35

Data are presented as mean (SD), median, (IQR) or No. (%). * Indicates statistical significance (P-value <0.05), M group mannitol group, S group saline group, UO urine output, RBCs Red blood cells
#missed data of one patient

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Mannitol for Prevention of Acute Kidney Injury After Liver Transplantation

A Randomized Controlled Trial

Abstract and Introduction

Abstract

Introduction

Mannitol for Prevention of Acute Kidney Injury After Liver Transplantation

A Randomized Controlled Trial

Abstract and Introduction

Abstract

Introduction

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Tables

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Authors and Disclosures

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