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The ability to estimate rather than measure the glomerular filtration rate (GFR) in patients before and after liver transplantation would be helpful in estimating risk, dosing drugs, and assessing long-term toxicity of calcineurin

The incidence of acute kidney injury (AKI) has been reported to vary between 17% and 95% post-orthotopic liver transplantation. This variability may be related to the absence of a uniform definition of AKI in this setting. The purpose of this study was to identify the degree of AKI that is associated with long-term adverse outcome. Furthermore, to determine the best definition (for use in future studies) of AKI not requiring dialysis in post-liver transplant patients, we retrospectively reviewed the effect of 3 definitions of AKI post-orthotopic liver transplantation on renal and patient outcome between 1997 and 2005. We compared patients with AKI to a control group without AKI by each definition. AKI was defined in 3 groups as an acute rise in serum creatinine, from the pretransplant baseline, of Ͼ0.5 mg/dL, Ͼ1.0 mg/dL, or Ͼ50% above baseline to a value above 2 mg/dL. In all groups, the glomerular filtration rate was significantly lower at both 1 and 2 years post-transplant. Patient survival was worse in all groups. Graft survival was worse in all groups. The incidence of AKI was highest in the group with a rise in creatinine of Ͼ0.5 mg/dL (78%) and lowest in patients with a rise in creatinine of Ͼ50% above 2.0 mg/dL (14%). Even mild AKI, defined as a rise in serum creatinine of Ͼ0.5 mg/dL, was associated with reduced patient and graft survival. However, in comparison with the other definitions, the definition of AKI with the greatest impact on patient's outcome post-liver transplant was a rise in serum creatinine of Ͼ50% above baseline to Ͼ2 mg/dL. See Editorial on Page 455Acute kidney injury (AKI) is a frequent complication post-liver transplantation. The incidence has been reported to range between 17% and 95% in different studies. [1][2][3][4] The etiology of AKI post-liver transplantation is usually multifactorial. These factors include surgeryrelated events, blood loss, hypotension, sepsis, calcineurin inhibitor (CNI)-induced vasoconstriction, and volume depletion. 4 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 prior to transplantation because of hepatorenal syndrome or other factors such as infections or intravascular volume depletion. [5][6][7] Therefore, a rise in serum creatinine is common post-liver transplantation. A high burden of chronic kidney disease (CKD) and end-stage renal disease (ESRD) has been reported postliver transplantation, most frequently due to CNI-induced nephrotoxicity.8 However, other factors may contribute to the development of this complication. 8,9 A report from our institution has shown that the incidence of ESRD is 9.5% after 13 years of follow-up postliver transplantation.10 AKI has been proposed to be an important risk factor for the long-term development of CKD and ESRD.9 However, most of the studies have been limited to AKI requiring renal replacement the...

Nonalcoholic steatohepatitis (NASH) may account for many cases of cryptogenic cirrhosis. If so, then steatosis might recur after liver transplantation. Two thousand fifty-two patients underwent primary liver transplantation for chronic liver disease between 1986 and 2004. Serial liver biopsy samples were assessed for steatosis and fibrosis. Two hundred fifty-seven patients (12%) had a pretransplant diagnosis of cryptogenic cirrhosis (239) or NASH (18). Fatty liver developed in 31% and was more common when the pretransplant diagnosis was NASH (45% at 5 years versus 23% for cryptogenic cirrhosis, P ¼ 0.007). NASH developed in only 4% and occurred exclusively when steatosis had already occurred. Steatosis after liver transplantation was associated with the baseline body weight and body mass index by univariate analyses, but no pretransplant or posttransplant characteristic independently predicted steatosis after liver transplantation because obesity was so common in all groups. Five percent and 10% developed bridging fibrosis or cirrhosis after 5 and 10 years, respectively, and this was more common after NASH (31%) than in those who developed steatosis alone (6%) or had no fat (3%, P ¼ 0.002). One-, 5-, and 10-year survival was the same in patients who underwent transplantation for cryptogenic cirrhosis or NASH (86%, 71%, and 56%) and in patients who underwent transplantation for other indications (86%, 71%, and 53%; not significant), but death was more often due to cardiovascular disease and less likely from recurrent liver disease. In conclusion, fatty liver is common after liver transplantation for cryptogenic cirrhosis or NASH but is twice as common in the latter group; this suggests that some cryptogenic cirrhosis, but perhaps not all, is caused by NASH. Posttransplant NASH is unusual, and steatosis appears to be a prerequisite. Advanced fibrosis is uncommon, and survival is the same as that of patients who undergo transplantation for other causes. Liver Transpl 16:431-439,

The role of de novo donor-specific HLA antibodies (DSA) in liver transplantation remains unknown as most of the previous studies have only focused on preformed HLA antibodies. To understand the significance of de novo DSA, we designed a retrospective cohort study of 749 adult liver transplant recipients with pre-and posttransplant serum samples that were analyzed for DSA. We found that 8.1% of patients developed de novo DSA 1 year after transplant; almost all de novo DSAs were against HLA class II antigens, and the majority were against DQ antigens. In multivariable modeling, the use of cyclosporine (as opposed to tacrolimus) and low calcineurin inhibitor levels increased the risk of de novo DSA formation, while a calculated MELD score >15 at transplant and recipient age >60 years old reduced the risk. Multivariable analysis also demonstrated that patients with de novo DSA at 1-year had significantly lower patient and graft survival. In conclusion, we demonstrate that de novo DSA development after liver transplantation is an independent risk factor for patient death and graft loss.