Postoperative acute kidney injury in living donor liver transplantation recipients

Abstract

Purpose:

There are many risk factors for postoperative acute kidney injury in liver transplantation. The aim of this study is to investigate the risk factors for postoperative acute kidney injury in living donor liver transplantation recipients.

Methods:

220 living donor liver transplantation recipients were retrospectively evaluated in the study. According to the Kidney Disease Improving Global Outcomes Guidelines, acute kidney injury in postoperative day 7 was investigated for all patients. The patient’s demographic data, preoperative and intraoperative parameters, and outcomes were recorded.

Results:

Acute kidney injury was found in 27 (12.3%) recipients. In recipients with acute kidney injury, female population, model for end-stage liver disease score, norepinephrine requirement, duration of mean arterial pressure less than 60 mmHg, the usage of gelatin and erythrocyte suspension and blood loss were significantly higher than recipients with nonacute kidney injury (for all p<0.05). In multivariate analyses, the likelihood of acute kidney injury on postoperative day 7 were increased 2.8-fold (1.1-7.0), 2.7-fold (1.02-7.3), 3.4-fold (1.2-9.9) and 5.1-fold (1.7-15.0) by postoperative day 7, serum tacrolimus level ≥10.2 ng dL⁻¹, intraoperative blood loss ≥14.5 mL kg⁻¹, the usage of gelatin >5 mL kg⁻¹ and duration of MAP less than 60 mmHg ≥5.5 minutes respectively (for all p<0.05).

Conclusions:

In living donor liver transplantation recipients, serum tacrolimus levels, intraoperative blood loss, hypotension period and the usage of gelatin may be risk factors for acute kidney injury in the early postoperative period.

Keywords

Acute kidney injury Liver transplantation Outcomes

Introduction

Postoperative acute kidney injury (AKI) is frequently seen in liver transplantation recipients and it is associated with increased mortality, prolonged length of intensive care unit (ICU) stay, and increased infection risk and costs (1, 2). In liver transplantation recipients, ischemia and immunosuppressive drug toxicity are the principal causes of early postoperative AKI, while infection is the most common etiology for the late postoperative AKI (3, 4). Baseline creatinine ≥1.5 mg dl⁻¹, model for end-stage liver disease (MELD) score ≥21, ICU admission prior to liver transplantation, duration of surgery, total clamping time, hemodynamic instability, intraoperative blood product requirement, intravenous contrast agent use, infection, immunosuppression and reoperation have been defined as risk factors for AKI (5 -10). Recently, important studies have also demonstrated the correlation between the amount of intravenous (IV) fluid administered and AKI in critically ill patients (11 -14). Even though there are some studies indicating that gelatin has fewer renal side effects than hydroxyethyl starch (HES), it was demonstrated that chloride-rich fluids, HES, gelatin and low-molecular-weight artificial colloid solutions can lead to postoperative AKI in liver transplantation recipients (15, 16). In the literature, postoperative AKI was usually investigated in deceased donor liver transplantation (DDLT) recipients. Yet, it is known that incidence of AKI was lower in living donor liver transplantation (LDLT) recipients than DDLT recipients (17). Hence, in this study, we investigated risk factors for postoperative AKI in LDLT recipients.

Methods

Ethics committee approval was received from Acıbadem University Medical Faculty Medical Research Council for the present study. This was a retrospective study of LDLT recipients carried out at a tertiary care, private hospital over a 31-month period between September 2011 and March 2014. A total of 246 consecutive adult LDLT recipients within the specified study period were evaluated. Among these, 220 patients who were over 18 years old, living donor liver transplantation recipients, received standard general anesthesia and surgery protocol, under immunosuppressive drug (tacrolimus) and prophylactic antibiotherapy were included in this study. The recipients who were under 18 years old, transplanted from cadaveric donors and needed preoperative renal replacement therapy were excluded (Fig. 1). Graft weight:recipient weight (GW:RW) ratios were ≥0.8% for all recipients.

Fig. 1

Study flowchart. AKI = acute kidney injury; RRT = renal replacement therapy.

Postoperative day 7 AKI was defined by using 2012 Kidney Diseases Improving Global Outcomes (KDIGO) Clinical Practice Guideline (18). They were categorized as patients with AKI or not (Tab. I).

Table I

Staging of AKI

Stage	Serum creatinine	Urine output
I	Increase in SCr 1.5-1.9 times baseline within prior 7 day or ≥0.3 mg dL⁻¹ within 48 hours	<0.5 mL kg⁻¹ h⁻¹ for 6-12 h
II	Increase in SCr 2.0-2.9 times baseline	<0.5 mL kg⁻¹ h⁻¹ for ≥12 h
III	Increase in SCr 3.0 times baseline or Increase in SCr ≥4.0 mg dL⁻¹ or Initiation of renal replacement therapy or In patients <18 years, decrease in eGFR to <35 mL min⁻¹ per 1.73 m²	<0.3 mL kg⁻¹ h⁻¹ for ≥24 h or anuria for ≥12 h

From 2012 Kidney Diseases Improving Global Outcomes (KDIGO) Clinical Practice Guideline (18).

The recipients’s age, gender, actual body weight (ABW), etiology, Charlson Comorbidity Index (CCI), MELD score (the patients diagnosed with cirrhosis and hepatocellular carcinoma who were accepted as suitable for liver transplantation in accordance with Milan Criteria had a MELD score of 24 points) (19), duration of operation (hours), clamping time (minutes), intraoperative norepinephrine requirement (µg kg⁻¹ min⁻¹), duration of mean arterial pressure (MAP) less than 60 mmHg (minutes), the usage of crystalloid (mL kg⁻¹ h⁻¹) (Isolyte-S; Na: 141 mmol L⁻¹, Cl: 98 mmol L⁻¹ and 5% dextrose manufactured by Baxter Healthcare), the usage of gelatin (mL kg⁻¹) (4% gelatin; NaCl; Na:154mmol L⁻¹, Cl:120 mmol L⁻¹), the usage of 20% albumin (mL kg⁻¹) (behring low salt albumin Na:125 mmol L⁻¹, Cl:100 mmol L⁻¹), intraoperative fluid balance, intraoperative and total clamping diuresis, blood loss (mL kg⁻¹), amount of ascites (mL), increase in creatinine on days 1, 2, 4 and 7, serum tacrolimus level at postoperative day 7 (ng dL⁻¹), renal replacement therapy (RRT) requirement, length of ICU and hospital stay, hospital and first year mortality rate were recorded.

Increase in creatinine (Cr) on days 1, 2, 4 and 7 were calculated as Cr_{1st day}/Cr_preop ; Cr_{2nd day}/Cr_preop ; Cr_{4th day}/Cr_preop ; Cr_{day 7}/Cr_preop.

Serum creatinine was measured using the COBAS Integra Creatinine plus version 2 assay (Roche Diagnostics Corp). This is an enzymatic method based on the determination of hydrogen peroxide after conversion of creatinine with the aid of creatininase, creatinase, and sarcosine oxidase.

Recipient data required for the study was extracted by the research team from the patient’s anesthesia chart, electronic medical records and laboratory-computerized results.

Statistical analysis methodology

The characteristics of patients were summarized with median (interquartile); whereas categorical variables were summarized with count and percentage. Pearson Correlation tests were used for correlations. Effects of parameters to estimate day 7 total AKI were evaluated with multivariate logistic regression models. Multivariate analyses included gender (female), MELD score (≥22), blood loss (≥14.5 mL kg⁻¹), noradrenalin requirement (≥0.08 mcg kg⁻¹ min⁻¹), the usage of gelatin (>5 mL kg⁻¹), duration of MAP less than 60 mmHg (≥5.5 minutes), postoperative day 7 serum tacrolimus level (≥10.2 ng dL⁻¹). Analyses were performed on Wizard Pro Version 1.7.18.

Results

Two hundred and twenty LDLT recipients were included in the study. Hepatocellular carcinoma (HCC) was the most common etiologic factor (Tab. II). Recipients with postoperative AKI were 12.3% (n = 27) (Fig. 1). The first-year recipient and graft survival were 89.5% and 98.6% respectively. There were 3 graft losses due to hepatic artery thrombosis in 1 recipient and acute rejection in 2 recipients. AKI was observed in all 3 and they were lost due to multi-organ failure and acute hepatic failure. The causes of first-year mortality were sepsis and multiple organ failure (4 patients with AKI and 12 patients with non-AKI), acute hepatic failure (1 patient with AKI and 2 patients with non-AKI), metastasis of HCC (1 patient with AKI and 1 patient with non-AKI), cardiac failure (1 patient with non-AKI) and disseminated intravascular coagulopathy (1 patient with non-AKI).

Table II

Etiologic factors

	n
Hepatitis B virus	89
Hepatitis C virus	49
Hepatocellular carcinoma	92
Cryptogenic	47
Alcoholic cirrhosis	7
Autoimmune	5
Wilson disease	2
Toxic hepatitis	4
Caroli disease	1
Primary sclerosing cholangitis	1

In recipients with postoperative AKI, female population, MELD score, norepinephrine requirement, duration of MAP less than 60 mmHg, the usage of gelatin, the usage of erythrocyte suspension, blood loss, first-year mortality and RRT requirement were significantly higher than recipients with postoperative non-AKI (p = 0.019, p = 0.002, p = 0.021, p<0.001, p = 0.009, p = 0.014, p = 0.002, p = 0.033 and p<0.001 for others, respectively) (Tabs. III and IV). There were poor positive correlations between increase in creatinine on postoperative day 7 and duration of MAP less than 60 mmHg, MELD score and the usage of gelatin (r² = 0.12, p<0.001; r² = 0.04, p = 0.005, r² = 0.02, p = 0.045, respectively).

Table III

Demographic data and preoperative parameters

		AKI (n = 27)	non-AKI (n = 193)	p
Age		54 (45-61)	53 (46-59)	0.420
Female		16 (59.3)	69 (35.8)	0.019
MELD score		24 (19-27)	20 (17-24)	0.002
ABW		69 (64-73)	70 (65-75.5)	0.145
CCI		8.5 (5-10)	8 (4-9)	0.358
GW:RW ratio	(%)	1.02 (0.97-1.07)	1.01 (0.96-1.07)	0.651
Etiologic factors
Viral	n (%)	18 (66.7)	120 (62.3)	0.651
Hepatocellular cancer	n (%)	7 (25.9)	85 (44.0)	0.074
Preoperative laboratory values
Hemoglobin	g dL⁻¹	10 (8.1-11.4)	9.7 (8.4-11.4)	0.535
Albumin	g dL⁻¹	3.1 (2.8-3.3)	3.3 (2.9-3.6)	0.062
Lactate	mmol L⁻¹	1.3 (1.1-1.5)	1.3 (1.1-1.6)	0.841
Creatinine	mg dL⁻¹	0.6 (0.4-0.7)	0.7 (0.6-0.9)	0.345
Platelet counts	x103 mm⁻³	61 (36-73)	61 (44-81)	0.256
Total bilirubin	mg dL⁻¹	2.4 (1.9-4.0)	3 (1.9-4.6)	0.188
Na⁺	mEq L⁻¹	138 (135-140)	139 (136-141)	0.267
Cl⁻	mEq L⁻¹	108 (105-110)	109 (106-111)	0.300
INR		1.7 (1.4-1.9)	1.4 (1.2-1.6)	0.068

ABW = actual body weight; AKI = acute kidney injury; GW:RW = graft weight:recipient weight; MELD = model for end-stage liver disease. Results are given as median (interquartile).

Table IV

Intraoperative parameters and outcomes

		AKI (n = 27)	non-AKI (n = 193)	p
Duration of operation	h	11.5 (10.5-13)	11 (10.3-11.7)	0.067
Clamping time	min	70 (70-75)	70 (68-75)	0.667
Diuresis
Total	mL kg⁻¹ h⁻¹	2.8 (1.7-3.6)	2.7 (2.1-3.5)	0.743
Clamping	mL kg⁻¹ h⁻¹	1.1 (0.8-1.4)	1.1 (0.8-1.3)	0.906
Fluid balance	mL	500 (200-600)	400 (100-600)	0.398
Noradrenalin requirement	μg kg⁻¹ min⁻¹	0.1 (0.07-0.19)	0.08 (0.04-0.11)	0.021
Duration of MAP less than 60 mmHg	min	6.7 (5.6-7.3)	5.3 (4.3-6.2)	<0.001
The usage of crystalloid	mL kg⁻¹ h⁻¹	1.7 (1.3-1.9)	1.5 (1.2-1.9)	0.234
The usage of gelatin	mL kg⁻¹	7.7 (0-14.5)	0 (0-12.8)	0.009
The usage of 20% albumin	mL kg⁻¹	4.3 (3.7-6)	4.1 (3-5.3)	0.240
The usage of erythrocyte suspension	U	2 (1-4)	1 (0-2)	0.014
Ascites	mL	0 (0-2500)	0 (0-1000)	0.473
Blood loss	mL kg⁻¹	22.4 (13.7-34.2)	13.7 (10.0-21.4)	<0.001
Serum tacrolimus level at day 7	ng dL⁻¹	10.3 (7.6-12.5)	8.9 (7.2-11.7)	0.268
Length of ICU stay	day	1.0 (0.8-1.0)	0.9 (0.8-1.0)	0.570
Length of hospital stay	day	21 (17-25)	20 (18-22)	0.360
RRT requirement	n (%)	8 (29.6)	10 (5.2)	<0.001
Hospital mortality	n (%)	3 (11.1)	8 (4.1)	0.120
first year mortality	n (%)	6 (22.2)	17 (8.8)	0.033

AKI = acute kidney injury; MAP = mean arterial pressure; RRT = renal replacement therapy. Results are given as percentage and median (interquartile).

In multivariate analyses, the likelihood of postoperative day 7 AKI were increased 2.8-fold (1.1-7.0), 2.7-fold (1.02-7.3), 3.4-fold (1.2-9.9) and 5.1-fold (1.7-15.0) by postoperative day 7 serum tacrolimus level ≥10.2 ng dL⁻¹, intraoperative blood loss ≥14.5 mL kg⁻¹, the usage of gelatin >5 mL kg⁻¹ and duration of MAP less than 60 mmHg ≥5.5 minutes respectively (p = 0.031, p = 0.033, p = 0.024, p = 0.003, respectively) (Tab. V).

Table V

Multivariate logistic regression model for postoperative day 7 AKI

		OR (95% CI)	p
Female		1.9 (0.7-4.8)	0.186
Norepinephrine requirement ≥0.08	μg kg⁻¹ min⁻¹	3.0 (0.9-8.8)	0.052
MELD Score ≥22		2.5 (0.8-7.1)	0.100
Postoperative day 7tacrolimus level ≥10.2	ng dL⁻¹	2.8 (1.1-7.0)	0.031
The usage of gelatin >5	mL kg⁻¹	3.4 (1.2-9.9)	0.024
Blood loss ≥14.5	mL kg⁻¹	2.7 (1.02-7.3)	0.033
Duration of MAP below60 mmHg ≥5.5	min	5.1 (1.7-15.0)	0.003
GW/RW ratio <0.96	%	0.5 (0.2-1.6)	0.231

CI = confidence interval; GW:RW = graft weight:recipient weight; MAP = mean arterial pressure; MELD = model for end-stage liver disease; OR = odds ratio.

Conclusions

The present study showed that postoperative serum tacrolimus level, intraoperative amount of blood loss, prolonged hypotension period and the usage of gelatin were associated with postoperative day 7 AKI in our LDLT recipients.

In this study, postoperative AKI was discussed via preoperative, intraoperative and postoperative reasons. Hilmi et al claimed that incidence of postoperative AKI was lower in LDLT recipients than DDLT recipients because of LDLT recipients who were young and had a decreased MELD score, preoperative creatinine level, cold ischemia time and postreperfusion syndrome (17). In many studies, in which their data were about DDLT recipients, the most important preoperative risk factors for postoperative AKI were etiology of liver disease, preoperative albumin and creatinine levels and increased MELD score (7, 20 -23). Nadeem et al, whose 65.8% of evaluated patients were LDLT recipients, demonstrated that increased MELD score was a decisive factor for postoperative AKI (16). However, they did not evaluate the relationship between preoperative MELD score and postoperative AKI only in LDLT recipients. Lee et al also claimed that small-for-size (SFS) syndrome, MELD score and pretransplant renal function were risk factors for postoperative AKI in LDLT recipients (24). Yet, according to some studies, MELD score was not a risk factor for postoperative AKI in LDLT recipients (17, 25). In our study, there was no SFS syndrome because GW:RW ratios were over 0.8%. Even though 41.8% of etiology of all recipients was HCC, the median MELD score was 20. We found that the MELD score was higher in recipients with postoperative AKI but, on the other hand, there was a poor positive correlation between the MELD score and an increase in serum creatinine level on postoperative day 7 (r² = 0.04, p = 0.005). Additionally, we did not find any relationship between the MELD score and postoperative day 7 AKI in multivariate analysis (Tab. V). Furthermore, the etiology of liver disease, preoperative albumin and creatinine levels were similar in both groups and there was no correlation between all of them and postoperative AKI. In our opinion, the reason our LDLT recipients had a better clinical status before liver transplantation is that they did not have end-stage liver disease or hepatorenal syndrome. Therefore, we can argue that preoperative features may not relate to postoperative AKI in our LDLT recipients.

In recent studies, duration of operation and clamping, amount of blood loss, increased norepinephrine requirement, prolonged hypotension period and the usage of chloride-rich fluid were defined as intraoperative risk factors for postoperative AKI (5, 9, 10, 16, 26 -31). Sun et al demonstrated that exposure to MAP less than 60 mmHg for 11 to 20 minutes was associated with postoperative AKI (10). Lankadeva et al also claimed that renal medullar hypoxia was increased by resuscitation of blood pressure with norepinephrine (26). Schortgen et al also showed that 20% albumin might be associated with acute renal injury (32). They have explained this result with increased intracapillary oncotic pressure and decreased glomerular filtration pressure.

It is also known that HES is related to proximal tubular injury (15, 28 -32). Lira et al emphasized that there was no sufficient evidence supporting that the usage of gelatin on shock was a good option and they did not recommend the usage of gelatin (30). Besides, it was also stated that 4% gelatin was an independent risk factor in terms of AKI development (15, 31).

Recently, intraoperative hypotension was found to be a decisive factor for postoperative AKI in LDLT recipients too (17, 33). We also found that the amount of blood loss, duration of hypotension, norepinephrine requirement and the usage of gelatin were higher in recipients with AKI (Tab. IV). Moreover, all of them except norepinephrine requirement were an independent risk factor for postoperative AKI in accordance with multivariate analysis (Tab. V). In this study, blood loss could have resulted in a prolonged hypotension period, increased norepinephrine requirement and the usage of gelatin. Gelatin should also be closely monitored because it may lead to proximal tubular injury alike to HES effects on kidney.

Serum tacrolimus level and sepsis are postoperative risk factors for postoperative AKI (7, 34) Cosner et al demonstrated that proximal tubular injury may occur due to acute tacrolimus nephrotoxicity (34). In their experimental study, the mean serum tacrolimus level was found to be 10.85 ng dL⁻¹ in patients with renal medullary injury. We did not observe sepsis in any patients in the early postoperative period. However, postoperative day 7, serum tacrolimus level ≥10.2 ng dL⁻¹ was related with postoperative AKI (Tab. V). For this reason, we think that the balance between infection and immunosuppression therapy should be carefully adjusted in LDLT recipients.

As a result, the incidence of postoperative AKI is lower in LDLT recipients. However, the serum tacrolimus level and intraoperative amount of blood loss, the usage of gelatin and prolonged hypotension period can be considered perioperative risk factors for postoperative AKI. These variables, which could possibly be the reason for postoperative AKI, are important because they can be managed during intraoperative and postoperative periods. Therefore, more studies are needed for a better understanding of the pathophysiology of postoperative AKI development in LDLT recipients.

Footnotes

Acknowledgements

The authors thank Dr. Mehmet Berktas from Yeditepe University for his support in statistical analysis.

Disclosures

Financial support: No grants or funding have been received for this study.

Conflict of interest: None of the authors has financial interest related to this study to disclose.

References

Karapanagiotou

Kydona

Dimitriadis

et al . Acute kidney injury after orthotopic liver transplantation. Transplant Proc. 2012;44(9):2727-2729.

Barri

Sanchez

Jennings

et al . Acute kidney injury following liver transplantation: definition and outcome. Liver Transpl. 2009;15(5):475-483.

Eckardt

. Renal failure in liver disease. Intensive Care Med. 1999;25(1):5-14.

Lewandowska

Matuszkiewicz-Rowinska

. Acute kidney injury after procedures of orthotopic liver transplantation. Ann Transplant. 2011;16(2):103-108.

Lima

Zanetta

Castro

et al . Risk factors for development of acute renal failure after liver transplantation. Ren Fail. 2003;25(4):553-560.

Wei

Zhang

Lin

et al . Factors related to post-liver transplantation acute renal failure. Transplant Proc. 2006;38(9):2982-2984.

Cabezuelo

Ramírez

Ríos

et al . Risk factors of acute renal failure after liver transplantation. Kidney Int. 2006;69(6):1073-1080.

Pham

Wilkinson

. Management of renal dysfunction in the liver transplant recipient. Curr Opin Organ Transplant. 2009;14(3):231-239.

Walsh

Devereaux

Garg

et al . Relationship between intraoperative mean arterial pressure and clinical outcomes after noncardiac surgery: toward an empirical definition of hypotension. Anesthesiology. 2013;119(3):507-515.

10.

Sun

Wijeysundera

Tait

Beattie

. Association of intraoperative hypotension with acute kidney injury after elective noncardiac surgery. Anesthesiology. 2015;123(3):515-523.

11.

Zarychanski

Abou-Setta

Turgeon

et al . Association of hydroxyethyl starch administration with mortality and acute kidney injury in critically ill patients requiring volume resuscitation: a systematic review and meta-analysis. JAMA. 2013;309(7):678-688.

12.

Rochwerg

Alhazzani

Sindi

et al . Fluids in Sepsis and Septic Shock Group. Fluid resuscitation in sepsis: a systematic review and network meta-analysis. Ann Intern Med. 2014;161(5):347-355.

13.

Perel

Roberts

Ker

. Colloids versus crystalloids for fluid resuscitation in critically ill patients. Cochrane Database Syst Rev. 2013;2(2):CD000567.

14.

Roche

James

. Colloids and crystalloids: does it matter to the kidney? Curr Opin Crit Care. 2009;15(6):520-524.

15.

Bayer

Reinhart

Sakr

et al . Renal effects of synthetic colloids and crystalloids in patients with severe sepsis: a prospective sequential comparison. Crit Care Med. 2011;39(6):1335-1342.

16.

Nadeem

Salahuddin

El Hazmi

et al . Chloride-liberal fluids are associated with acute kidney injury after liver transplantation. Crit Care. 2014;18(6):625.

17.

Hilmi

Damian

Al-Khafaji

et al . Acute kidney injury after orthotopic liver transplantation using living donor versus deceased donor grafts: A propensity score-matched analysis. Liver Transpl. 2015;21(9):1179-1185.

18.

James

Bouchard

et al . Canadian Society of Nephrology commentary on the 2012 KDIGO clinical practice guideline for acute kidney injury. Am J Kidney Dis. 2013;61(5):673-685.

19.

Heimbach

Hirose

Stock

et al . Delayed hepatocellular carcinoma model for end-stage liver disease exception score improves disparity in access to liver transplant in the United States. Hepatology. 2015;61(5):1643-1650.

20.

Klaus

Keitel

Silva

Meinerz

et al . Acute kidney injury after liver transplantation: incidence and mortality. Transplant Proc. 2014;46(6):1819-1821.

21.

McGuire

Julian

Bynon

Jr et al . Brief communication: Glomerulonephritis in patients with hepatitis C cirrhosis undergoing liver transplantation. Ann Intern Med. 2006;144(10):735-741.

22.

Barreto

Daher

Silva Junior

et al . Risk factors for acute kidney injury and 30-day mortality after liver transplantation. Ann Hepatol. 2015;14(5):688-694.

23.

Nicolau-Raducu

Gitman

Ganier

et al . Adverse cardiac events after orthotopic liver transplantation: a cross-sectional study in 389 consecutive patients. Liver Transpl. 2015;21(1):13-21.

24.

Lee

Park

Kim

et al . Early postoperative renal dysfunction in the adult living donor liver transplantation. Transplant Proc. 2007;39(5):1517-1519.

25.

Selzner

Kashfi

Cattral

et al . Live donor liver transplantation in high MELD score recipients. Ann Surg. 2010;251(1):153-157.

26.

Lankadeva

Kosaka

Evans

Bailey

Bellomo

May

. Intrarenal and urinary oxygenation during norepinephrine resuscitation in ovine septic acute kidney injury. Kidney Int. 2016;90(1):100-108.

27.

The SAFE Study Investigators. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med. 2004;350(22):2247-2256.

28.

Dart

Mutter

Ruth

Taback

. Hydroxyethyl starch (HES) versus other fluid therapies: effects on kidney function. Cochrane Database Syst Rev. 2010;(1):CD007594.

29.

Schabinski

Oishi

Tuche

et al . Effects of a predominantly hydroxyethyl starch (HES)-based and a predominantly non HES-based fluid therapy on renal function in surgical ICU patients. Intensive Care Med. 2009;35(9):1539-1547.

30.

Lira

Pinsky

. Choices in fluid type and volume during resuscitation: impact on patient outcomes. Ann Intensive Care. 2014;4:38.

31.

Schick

Isbary

Schlegel

et al . The impact of crystalloid and colloid infusion on the kidney in rodent sepsis. Intensive Care Med. 2010;36(3):541-548.

32.

Schortgen

Girou

Deye

Brochard

, for the CRYCO Study Group. The risk associated with hyperoncotic colloids in patients with shock. Intensive Care Med. 2008;34(12):2157-2168.

33.

Mizota

Hamada

Matsukawa

Seo

Tanaka

Segawa

. Relationship Between Intraoperative Hypotension and Acute Kidney Injury After Living Donor Liver Transplantation: A Retrospective Analysis. J Cardiothorac Vasc Anesth. 2017;31(2):582-589.

34.

Cosner

Zeng

Zhang

. Proximal Tubular Injury in Medullary Rays Is an Early Sign of Acute Tacrolimus Nephrotoxicity. J Transplant. 2015;2015:142521.