Objectives: Acute renal injury is a common complication in liver transplant patients. Acute kidney injury is due to nephrotoxic drugs used after liver transplant, infections, and hemorrhage. Though it is generally reversible, it has effects on grafts and patients survival. In this retrospective observational study carried out at a single center, the effects of acute renal disease on liver recipient’s survival were investigated.

Materials and Methods: Liver transplant recipients of live-donor and deceased-donor transplants between January 2002 and May 2013 were included in this study; there were 310 liver transplant patients (mean age, 28 y; age range, 6 mo-62 y; 165 males, 145 females). The acute kidney disease diagnosis and staging was based on the nephrology department evaluation and daily serum creatinine levels. Patients with acute kidney injury before undergoing liver transplant and those undergoing a transplant for the second time were excluded. Kidney functions were evaluated by the nephrology department 1 week, 3 months, and 1 year after the liver transplant.

Results: Acute kidney disease rates in these patients were 5%, 8%, and 12%. Four patients developed chronic kidney failure during follow-up. The mortality rate was higher (18%) in acute renal failure patients compared with those that did not have acute renal failure. The mortality rate was 11% in patients without acute renal failure.

Conclusions: Acute renal injury is common after liver transplant and has an effect on mortality.

Key words : Renal failure, Mortality

Introduction

Acute kidney injury (AKI) is a frequent complication after a liver transplant, ranging from 17% and 95% in different studies.¹ The cause of AKI after a liver transplant is multifactorial. These factors include surgery-related events, blood loss, hypotension, sepsis, calcineurin inhibitor-induced vasoconstriction, and volume depletion.² At our institution, we tend to target a lower central venous pressure to protect the liver transplant against passive congestion with subsequent worsening of preservation injury in the immediate posttransplant period. Furthermore, renal dysfunction may be present before transplant because of hepatorenal syndrome or other factors such as infections or intravascular volume depletion. A rise in serum creatinine is common after a liver transplant. A high burden of chronic kidney disease and end-stage renal disease has been reported after a liver transplant, most frequently caused by calcineurin inhibitor-induced nephrotoxicity. However, other factors may contribute to this complication.^1,3

There is a convincing body of evidence that AKI is not a transient phenomenon but a complication that may have long-lasting implications on long-term patient outcomes including high mortality. A better definition for early and less severe forms of AKI will assist in designing studies preventing this complication. There is controversy in the literature regarding what is the best definition of AKI. Previous studies have been associated with variable and inconsistent results. We used different levels of severity of AKI, and we excluded AKI requiring renal replacement therapy as it has been extensively studied.⁴

This study sought to determine the optimal definition for AKI after a kidney transplant and its effect on long-term renal function and patient outcomes, and to identify the degree of rise in serum creatinine associated with long-term morbidity and mortality. Considering the high incidence of AKI and the high number of renal replacement therapy procedures in liver transplant recipients, we proposed this observational study to evaluate the effect of time from AKI onset to renal replacement therapy initiation or creatinine peak on survival of patients undergoing liver transplant.

Materials and Methods

Liver transplant recipients of live-donor and deceased-donor transplants between January 2002 and May 2013 were included in this study; there were 310 liver transplant patients (mean age, 28 y; age range, 6 mo-62 y; 165 males, 145 females). Acute kidney disease diagnosis and staging were made based on the nephrology department evaluation and daily serum creatinine levels. Patients with acute kidney injury history before liver transplant and those undergoing transplant for the second time were excluded. The study was approved by the Ethical Review Committee of the institute. All protocols conformed with the ethical guidelines of the 1975 Helsinki Declaration.

The database has information regarding recipient hemodynamic status, cause of liver disease, transplant or retransplant status, Model for End-Stage Liver Disease score, and intraoperative and postoperative clinical data. We used 3 definitions commonly used in the literature to define AKI and evaluated the influence of each on serum creatinine and patient and graft survival. In addition, we evaluated the incidence of acute rejection. Selection of AKI definitions was made to represent changes in renal function from more severe changes in renal function occurring within 1 week at any time during the first 3 months after orthotopic liver transplant.

Cost and these definitions were applied to serum creatinine levels obtained at regular intervals after transplant. The baseline serum creatinine level is the one measured immediately before liver transplant. Patients with AKI were compared with a control group without AKI.

Infection
When patients developed symptoms suggesting infection, blood and urine cultures were obtained. Sepsis was defined as hemodynamic instability associated with a positive blood culture. Positive cytomegalovirus antigenemia or cytomegalovirus polymerase chain reaction was regarded as cytomegalovirus infection. All infections were treated with appropriate therapy.

Rejection
All episodes of acute cellular rejection of the liver were diagnosed on the basis of core needle liver biopsy. Acute cellular rejection was treated with steroid pulse therapy administered as methylprednisolone (1 g daily for 2 days, and then tapered over 5-7 days). Steroid-resistant acute cellular rejection confirmed by biopsy was treated with antithymocyte globulin.

Kidney function
Kidney function was assessed by glomerular filtration rate. Glomerular filtration rate was measured during the initial preoperative evaluation and postoperatively at 1 year, 2 years, 3 years, and 5 years. Serum creatinine in real time was downloaded to the database at defined times.

Preoperative and postoperative data
Database information from pretransplant admission, intraoperative monitoring, and posttransplant care was reviewed. Data included age, sex, serum blood urea nitrogen and creatinine, glomerular filtration rate, stay, rehospitalization, episodes of AKI, incidence of acute rejection, patient and graft survival, calcineurin inhibitor levels, sepsis, infection, use of intravenous contrast, and pretransplant hepatorenal syndrome. All data for this study were obtained from our prospectively maintained database and chart review if necessary. The study was approved by the Ethical Review Committee of the institute. All protocols conformed with the ethical guidelines of the 1975 Helsinki Declaration.

Results

Kidney functions were evaluated by the nephrology department 1 week, 3 months, and 1 year after the liver transplant. Acute kidney disease rates in these patients was 5%, 8%, and 12%. Four patients developed chronic kidney failure during the follow-up. The mortality rate was higher (18%) in acute renal failure patients compared with those that did not have acute renal failure. The mortality rate was 11% in patients without acute renal failure. The incidence of AKI was variable, depending the definition for AKI. The Table shows demographic and outcome data comparing the AKI patients and control group.

Discussion

The incidence of AKI in previous studies after a liver transplant was variable. This variability is caused by different definitions, case mix, and the setting and severity of AKI. Some investigators have suggested applying additional criteria other than serum creatinine to the definition of AKI, such as urine output, age, and sex. In this study, we used changes in serum creatinine from baseline as the main marker for AKI. It is important to note that serum creatinine is less reliable in patients with liver disease in estimating actual renal function. Although a single measurement of serum creatinine is not an accurate reflection of GFR, changes in serum creatinine from baseline reflect changes in renal function. Furthermore, serum creatinine is more reliable than other markers such as urea. Until better markers are discovered and validated, serum creatinine will remain the main criterion used for diagnosing AKI.5 In this study, we have shown higher serum creatinine and lower GFR over the long term in patients with AKI.

A recent consensus conference on AKI has suggested that a milder definition should be used for AKI to detect this problem early and to intervene before it is severe and established.⁶ After a liver transplant, changes in serum creatinine are common because of hemodynamic factors in the peritransplant period. This study shows that AKI has an important effect on long-term renal function and patient and graft survival after a liver transplant. The high incidence of AKI after a liver transplant is an important risk factor for long-term renal dysfunction and associated morbidity and mortality. Using the appropriate definition for AKI after a liver transplant will allow progress preventing the AKI.

References:

1. McCauley J, Van Thiel DH, Starzl TE, Puschett JB. Acute and chronic renal failure in liver transplantation. Nephron. 1990;55(2):121-128.
   CrossRef - PubMed
2. Lima EQ, Zanetta DM, Castro I, et al. Risk factors for development of acute renal failure after liver transplantation. Ren Fail. 2003;25(4):553-560.
   CrossRef - PubMed
3. Gonwa TA, Morris CA, Goldstein RM, Husberg BS, Klintmalm GB. Long-term survival and renal function following liver transplantation in patients with and without hepatorenal syndrome--experience in 300 patients. Transplantation. 1991;51(2):428-430.
   CrossRef - PubMed
4. Johnson JP, Johnston JR, Flick R, Singh A, Angus D, Greenberg A. Acute renal failure in recipients of organ transplantation and nontransplantation patients: comparison of characteristics and mortality. Ren Fail. 1997;19(3):461-473.
   CrossRef - PubMed
5. Paramesh AS, Roayaie S, Doan Y, et al. Post-liver transplant acute renal failure: factors predicting development of end-stage renal disease. Clin Transplant. 2004;18(1):94-99.
   CrossRef - PubMed
6. Sanchez EQ, Gonwa TA, Levy MF, et al. Preoperative and perioperative predictors of the need for renal replacement therapy after orthotopic liver transplantation. Transplantation. 2004;78(7):1048-1054.
   CrossRef - PubMed