Renal Dysfunction After Orthotopic Liver Transplantation Y. Sirivatanauksorn, T. Parakonthun, N. Premasathian, S. Limsrichamrern, P. Mahawithitwong, P. Kositamongkol, C. Tovikkai, and S. Asavakarn ABSTRACT Background. Identiﬁcation of risk factors of acute renal failure (ARF) after orthotopic liver transplantation (OLT) may avoid the development and attenuate the impact on patient outcome. Therefore, the incidence and risk factors of ARF after OLT at Siriraj Hospital were analyzed. Methods. The study was retrospectively analyzed from the OLT patients at the Siriraj Hospital between January 2002 and December 2009. ARF was deﬁned as an increased in serum creatinine level more than 1.5 times within the ﬁrst week postoperation compared with the preoperative level. Results. A total of 81 liver transplant patients were analyzed. The mean age was 52.45 years (range, 22 to 71) and there were 25 women (30.86%) and 56 men (69.14%). Indications for OLT were end-stage liver cirrhosis (n ¼ 43, 53.09%), hepatocellular carcinoma (n ¼ 36, 44.44%), and fulminant hepatic failure (n ¼ 2, 2.47%). Fifty-eight patients (71.60%) developed ARF, and the perioperative mortality of these was 18.97%. The univariate analysis identiﬁed the presence of preoperative coagulopathy, prolonged intraoperative hypotension, more blood loss, and postoperative hypotension as the risk factors of ARF. By the multivariate analysis, prolonged intraoperative hypotension more than 30 minutes and presence of postoperative hypotension were the independent risk factors of ARF. During the intraoperative and postoperative periods, ARF group required more blood and blood components transfusion, longer intensive care unit stay, and higher in-hospital mortality. Seven patients (12.07%) in the ARF group required postoperative renal replacement therapy. Four patients (9.52%) developed chronic renal failure, and one of them required long-term hemodialysis. Conclusions. ARF was a common complication after OLT, which caused increased morbidity and mortality. Although some patients required dialysis, most of them recovered normal renal function. Prolonged intraoperative hypotension and presence of postoperative hypotension were the independent risk factors of ARF after OLT.
RTHOTOPIC LIVER TRANSPLANTATION (OLT) is one of the standard treatment of end-stage liver diseases including hepatocellular carcinoma (HCC), and the result of OLT has been improved due to the development of preoperative preparation, operative technique, and peri- and postoperative management. Though many techniques and medications were applied in OLT to prevent and decrease the complications, acute renal failure (ARF) is still one of the major medical problems during the postoperative period of OLT. The incidence of this complication varies from 12% to 70%, according to the
0041-1345/14/$esee front matter http://dx.doi.org/10.1016/j.transproceed.2013.11.124 818
From the Hepatopancreatobiliary and Transplant Surgery Unit, Division of General Surgery, Department of Surgery (Y.S., T.P., S.L., P.M., P.K., C.T., S.A.) and Division of Nephrology (N.P.), Department of Medicine, Siriraj Organ Transplantation Center, Siriraj Hospital, Bangkok, Thailand. This work was supported by a Siriraj Grant for Research Development. Address reprint requests to Yongyut Sirivatanauksorn, Division of General Surgery, Department of Surgery, Siriraj Hospital, 2 Prannok Road, Bangkoknoi, Bangkok 10700, Thailand. E-mail: [email protected]
ª 2014 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 46, 818e821 (2014)
RENAL DYSFUNCTION AFTER OLT
variety of criteria for diagnosis such as serum creatinine level [1e6]. The etiologies of renal dysfunction after OLT are multifactorial such as baseline preoperative renal function, hemodynamic status, and nephrotoxic drugs [1,2,4]. Although renal function recovers within 4 weeks in most patients, some of them develop chronic renal failure or endstage renal disease . Moreover, it is associated with an increase in post-transplant morbidity and mortality, especially those who require renal replacement therapy [1e3,8e10]. The objectives of this study were to obtain the incidence and risk factors for renal dysfunction after OLT and to observe the consequence of this complication in patients who underwent OLT in Siriraj Hospital.
819 Table 1. Demographic Data of the ARF and non-ARF Groups After Liver Transplantation Non-ARF
Number of patients 23 (28%) 58 (72%) 81 (100%) Age mean, range (y) 52.13, 26e67 52.76, 22e71 52.45, 22e71 Male:female (%) 17:6 (74:26) 39:19 (67:33) 56:25 (69:31) Indications for liver transplant Cirrhosis 10 (43.48%) 33 (56.90%) 43 (53.09%) Hepatocellular 12 (52.17%) 24 (41.38%) 36 (44.44%) carcinoma Fulminant hepatic 1 (4.35%) 1 (1.72%) 2 (2.47%) failure Abbreviation: ARF, acute renal failure.
PATIENTS AND METHODS The study was retrospectively analyzed of adult patients who underwent OLT at the Department of Surgery, Siriraj Hospital between January 2002 and December 2009. The exclusion criteria were patients who had preoperative serum creatinine more than 2.0 mg/dL or end-stage renal disease or received preoperative hemodialysis or underwent simultaneous liver-kidney transplantation or dead in early postoperative period. ARF was deﬁned as an increased in serum creatinine level more than 1.5 times within the ﬁrst week postoperation compare with preoperative level. Longterm renal dysfunction was characterized by serum creatinine more than 2.0 mg/dL after 1 year of ARF diagnosis. The data were analyzed for demographic data, indication for OLT, liver function test, coagulogram, and serum creatinine level in the preoperative period. During the surgery, the data of anesthetic time, surgical time, duration of hypotension (mean arterial pressure; mean arterial pressure less than 70 mm Hg), amount of blood loss, volume of ﬂuid, and blood transfusion replacement were collected. In the postoperative period, the length of intensive care unit and hospital stay, postoperative bleeding and hypotension, amount of blood transfusion, serum creatinine level, infection, graft dysfunction or rejection, renal replacement therapy, and in-hospital dead were recorded. Serum creatinine level was assessed at the ﬁrst 7 days and 4, 12, 24, and 48 weeks after OLT. The clinical courses of ARF and mortality rate were observed for 1 year postoperatively. The SPSS version 11.5 software package (StataCorp, Texas, USA) was used for statistical analysis. The incidence of ARF after OLT was calculated by one proportion group method. The relationship between categorical data was analyzed using the c2 test. Continuous data from the 2 groups were compared using the unpaired t test and the Mann-Whitney U test. Multivariate analysis by logistic regression analysis was performed to identify the risk factors for ARF after OLT. Statistical signiﬁcance was deﬁned as a P < .05.
There were 98 adult patients who underwent OLT, 17 patients were excluded, 12 patients had high preoperative serum creatinine level, 4 patients received preoperative hemodialysis, 2 patients received simultaneous liver-kidney transplantation, and 1 patient died in early postoperative period. We analyzed the clinical and biochemical data of 81 patients. The mean patient’s age was 52.45 years (range, 22e71 years), there were 25 women (30.86%) and 56 men (69.14%). Indications for OLT were end-stage liver cirrhosis
(n ¼ 43, 53.09%), HCC (n ¼ 36, 44.44%), and fulminant hepatic failure (n ¼ 2, 2.47%; Table 1). Fifty-eight of 81 patients (71.60%) developed ARF during the ﬁrst week after OLT (ARF group). There was no difference between groups regarding age, gender, and the indications for OLT. Furthermore, there was no difference in preoperative biochemical data between groups (Table 2). During the intraoperative period, the ARF group presented longer duration of hypotension (32.5 vs 15 minutes), more blood loss (3350 vs 2100 mL), and more blood transfused (2475 vs 1620 mL) than those in the non-ARF group. No difference between the 2 groups was observed regarding surgical time, anesthetic time, and volume of intravenous ﬂuid and blood components usage (Table 3). Postoperatively, the ARF group developed more episode of hypotension (39.66% vs 8.7%) and required more volume of blood transfusion (2026.5 vs 833 mL) and longer intensive care unit stay (57 vs 24 hours) compared with those in non-ARF group. There was no in-hospital mortality in nonARF group, but 11 of 58 patients (18.97%) in the ARF group died during the postoperative period. The causes of 11 patients death were sepsis (6, 54.55%), graft nonfunction (2, 18.18%), postoperative bleeding (1, 9.09%), massive upper gastrointestinal hemorrhage (1, 9.09%), and Table 2. Preoperative Biochemical Data (Mean, Range) of the non-ARF and ARF Groups After Liver Transplantation Parameters
Total bilirubin (mg/dL) Direct bilirubin (mg/dL) Aspartate aminotransferase (IU/L) Alanine aminotransferase (IU/L) Alkaline phosphatase (IU/L) Gamma glutamyltransferase (IU/L) Albumin (g/dL) Prothrombin time (s) Serum creatinine (mg/dL)
2.50 (0.3e39.6) 1.1 (0e24.5) 66 (16e760) 39 (14e700) 140 (63e604) 71 (24e400)
2.85 (0.5e49.9) 1.4 (0.2e29.2) 70 (30e1729)
.58 .49 .41
140 (52e522) 97.5 (14e872)
3.15 (2.2e4.6) 3.0 (1.6e4.4) .23 13.9 (12.5e53.4) 16.3 (10.6e34.2) .08 0.99 (0.5e1.9) 1.03 (0.4e1.9) .83
Abbreviation: ARF, acute renal failure.
SIRIVATANAUKSORN, PARAKONTHUN, PREMASATHIAN ET AL
Table 3. Intraoperative Data (Mean, Range) of the non-ARF and ARF Groups After Liver Transplantation Quantity
Anesthetic time (min) Surgical time (min) Crystalloid infusion (mL) Colloid infusion (mL) Hypotension (MAP < 70 mm Hg) (min) Blood loss (mL) Blood transfusion (mL) Blood components transfusion (mL)
385 295 4100 950 15
(240e480) (180e405) (2600e8450) (0e2000) (0e125)
345 265 4900 1000 32.5
(225e540) (160e450) (1500e15,000) (0e3000) (0e200)
2100 (500e9000) 3350 (800e28,600) 1620 (0e4596) 2475 (228e17,482) 1317 (0e2527) 1376 (0e14,000)
.58 .53 .46 .32 .03 .02 .01 .36
Table 5. Univariate Analysis of the Risk Factors of Acute Renal Failure After Liver Transplantation Factors
Crude OR (95% CI)
Preoperative prothrombin time > 15 s Intraoperative hypotension > 30 min Blood loss > 2500 mL Intraoperative blood transfusion > 2500 mL Postoperative hypotension Postoperative blood transfusion > 1000 mL
2.74 (1.01e7.41) 1.81 (0.66e4.94)
7.10 (1.52e33.26) 5.42 (1.45e20.26)
Abbreviations: CI, conﬁdence interval; OR, odds ratio.
Abbreviations: ARF, acute renal failure; MAP, mean arterial pressure.
intracerebral hemorrhage (1, 9.09%). The occurrence of ARF does not affect the graft function and length of hospital stay. In the ARF group, 7 (12.07%) patients required renal replacement therapy. Most of patients in ARF group recovered their renal function, but 4 of 42 patients (9.52%) developed chronic renal failure, and 1 of them (2.38%) required long-term hemodialysis. Within the ﬁrst year postoperation, 1 patient in the non-ARF group and 5 patients in the ARF group died from sepsis (4 of 6 patients, 66.67%), bony and pulmonary metastasis (2 of 6 patients, 33.33%; Table 4). The univariate analysis, we identiﬁed preoperative prothrombin time longer than 15 seconds, intraoperative hypotension longer than 30 minutes, intraoperative blood loss more than 2500 mL, presence of postoperative hypotension, and requirement of more than 1000 mL blood Table 4. Postoperative Data of the non-ARF and ARF Groups After Liver Transplantation Factors
Patients with 2/23 (8.70%) 16/58 (27.59%) .12 postoperative bleeding Patients requiring 14/23 (60.87%) 24/58 (41.38%) .18 blood transfusion Amount of blood 833 (100e4472) 2026.5 (285e9234) .049 transfusion (mL) Postoperative 2/23 (8.70%) 23/58 (39.66%) .012 hypotension Graft dysfunction 3/23 (13.04%) 10/58 (17.24%) .75 Intensive care unit 24 (0e151) 57 (0e924) .001 stay (h) Hospital stay (d) 10 (8e106) 15 (2e166) .24 In-hospital mortality 0 (0%) 11 (18.97%) .029 Renal replacement 0/23 (0%) 7/58 (12.07%) .18 therapy 1-y mortality 1/23 (4.3%) 5/47 (10.64%) .66 Creatinine > 2 mg/dL 0/22 (0%) 4/42 (9.52%) .29 at 1 y Long-term renal 0/22 (0%) 1/42 (2.38%) >.99 replacement therapy Abbreviation: ARF, acute renal failure.
transfused in the postoperative period as the risk factors of ARF after OLT (Table 5). The logistic regression multivariate analysis found that intraoperative hypotension longer than 30 minutes and presence of postoperative hypotension were independent signiﬁcant risk factors of ARF after OLT (Table 6).
ARF is a serious complication after OLT. The incidence varies and intercenter comparisons are difﬁcult due to the absence of universal criteria for diagnosis. The etiology of ARF is multifactorial, involving preoperative, intraoperative, and postoperative factors. There are many well-established risk factors such as unstable hemodynamic status, preoperative renal insufﬁciency, diabetes mellitus, immunosuppressive and nephrotoxic drugs, graft dysfunction, and sepsis. In this study, we identiﬁed the risk factors of ARF after OLT in Siriraj Hospital. Preoperative renal insufﬁciency is usually considered an important risk factor of ARF after OLT in several studies but it is not identiﬁed as a risk factor in this study because we excluded the patient who had impaired renal function before OLT (serum creatinine more than 2.0 mg/dL). The hemodynamic status of a patient may be affected by multiple factors such as intraoperative and postoperative bleeding, which also had many confounding factors including coagulation disturbance and hypotension after graft reperfusion. The incidence of ARF from this study was 71.60%, and the result demonstrated that patients who developed ARF after OLT had higher short-term and long-term morbidity Table 6. Logistic Regression Multivariate Analysis of the Risk Factors of Acute Renal Failure After Liver Transplantation Factors
Crude OR (95% CI)
Adjusted OR (95% CI)
Intraoperative hypotension > 30 min Presence of postoperative hypotension
Abbreviations: CI, conﬁdence interval; OR, odds ratio.
RENAL DYSFUNCTION AFTER OLT
and mortality. Preoperative coagulopathy, prolonged intraoperative hypotension, massive intraoperative blood loss, presence of postoperative hypotension, and greater volume of postoperative blood transfusion were associated with the occurrence of ARF after OLT. These data were conﬁrmed by multivariate analysis, in which intraoperative hypotension longer than 30 minutes and presence of postoperative hypotension were identiﬁed as the 2 independent risk factors of ARF. Identiﬁcation of these risk factors could develop the patient management guideline to reduce ARF and the morbidity and mortality after OLT. REFERENCES  Alvares-da-Silva MR, Waechter FL, Francisconi CF, et al. Risk factors for postoperative acute renal failure at a new orthotopic liver transplantation program. Transplant Proc 1999;31: 3050e2.  Cabezuelo JB, Ramirez P, Acosta F, et al. Prognostic factors of early acute renal failure in liver transplantation. Transplant Proc 2002;34:254e5.
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