Acute kidney injury and post-reperfusion syndrome in liver transplantation

Abstract

In the past decades liver transplantation (LT) has become the treatment of choice for patients with end stage liver disease (ESLD). The chronic shortage of cadaveric organs for transplantation led to the utilization of a greater number of marginal donors such as older donors or donors after circulatory death (DCD). The improved survival of transplanted patients has increased the frequency of long-term complications, in particular chronic kidney disease (CKD). Acute kidney injury (AKI) post-LT has been recently recognized as an important risk factor for the occurrence of de novo CKD in the long-term outcome. The onset of AKI post-LT is multifactorial, with pre-LT risk factors involved, including higher Model for End-stage Liver Disease score, more sever ESLD and pre-existing renal dysfunction, either with intra-operative conditions, in particular ischaemia reperfusion injury responsible for post-reperfusion syndrome (PRS) that can influence recipient’s morbidity and mortality. Post-reperfusion syndrome-induced AKI is an important complication post-LT that characterizes kidney involvement caused by PRS with mechanisms not clearly understood and implication on graft and patient survival. Since pre-LT risk factors may influence intra-operative events responsible for PRS-induced AKI, we aim to consider all the relevant aspects involved in PRS-induced AKI in the setting of LT and to identify all studies that better clarified the specific mechanisms linking PRS and AKI. A PubMed search was conducted using the terms liver transplantation AND acute kidney injury; liver transplantation AND post-reperfusion syndrome; acute kidney injury AND post-reperfusion syndrome; acute kidney injury AND DCD AND liver transplantation. Five hundred seventy four articles were retrieved on PubMed search. Results were limited to title/abstract of English-language articles published between 2000 and 2015. Twenty-three studies were identified that specifically evaluated incidence, risk factors and outcome for patients developing PRS-induced AKI in liver transplantation. In order to identify intra-operative risk factors/mechanisms specifically involved in PRS-induced AKI, avoiding confounding factors, we have limited our study to “acute kidney injury AND DCD AND liver transplantation”. Accordingly, three out of five studies were selected for our purpose.

Molecular profiling of postreperfusion milieu determines acute kidney injury after liver transplantation: A prospective study

“…(31,32,35) Current clinical trials are evaluating the use of IL18 binding protein as well as neutralizing antibodies to IL18 in treating several human diseases including AKI. (36) Postreperfusion syndrome and hemodynamic instability have been associated with the development of AKI after LT. (1,37) However, similarly to other studies, (38,39) we did not find a significant difference in postreperfusion syndrome and hemodynamic instability between the AKI and non-AKI groups. Furthermore, despite previous studies suggesting that peak transaminases are an independent predictor of AKI after LT, (4,38) our study suggests that the ET-1 and IL18 serum levels outperform peak ALT for prognostic determination of AKI after LT.…”

“…Postreperfusion syndrome and hemodynamic instability have been associated with the development of AKI after LT . However, similarly to other studies, we did not find a significant difference in postreperfusion syndrome and hemodynamic instability between the AKI and non‐AKI groups.…”

“…Acute kidney injury (AKI) is a well‐recognized problem after liver transplantation (LT) and is associated with significant morbidity and mortality . AKI after LT is also known to be a risk factor for the development of chronic renal failure, which is associated with inferior longterm survival .…”

Liver Grafts From Donors After Circulatory Death on Regional Perfusion With Extended Warm Ischemia Compared With Donors After Brain Death

“…These findings add further support to the hypothesis that DCD livers, once reperfused, trigger a systemic inflammatory response that ultimately causes renal dysfunction. (30) In these transplants, it thus seems advisable to opt for immunosuppression regimens that offer reduced nephrotoxicity and to explore strategies to limit the inflammatory response.…”

A severely cholestatic liver graft can be successfully used in deceased donor liver transplantation

“…A renal‐sparing immunosuppressive regimen, consisting of basiliximab and mycophenolate mofetil, was introduced to avoid administration of a calcineurin inhibitor (CNI), as grafts from ECDs often provoke ischemia–reperfusion injury (IRI) and occasionally acute kidney injury (AKI) . The patient unfortunately required relaparotomy for intra‐abdominal bleeding on post‐operative day (POD) 1.…”