The Impact of Renal Insufficiency After Liver Transplantation

Cardiovascular mortality and the development of chronic kidney disease are 2 well-known adverse outcomes after liver transplantation; the developments of hypertension, hyperlipidemia, renal insufficiency, and chronic kidney disease have all been associated with liver transplantation, and more specifically, with posttransplant immunosuppression. Renal function is a component of the Model for End-Stage Liver Disease (MELD) score and is a strong predictor of pretransplant mortality. The implementation of MELD to determine liver distribution has resulted in fewer waiting list deaths. However, MELD as a composite score has not been shown to be an accurate predictor of posttransplant mortality.1,2

The present study examines the relationship between renal insufficiency after liver transplant and adverse cardiovascular outcomes.3 The study stratifies and defines cardiovascular outcomes relating to the degree of renal insufficiency in liver transplant recipients at the time of transplant and within the first 30 days after liver transplantation using a large national database and comprehensive single center data, respectively. Importantly, the authors demonstrate that persistent renal dysfunction after transplantation is associated with nonfatal and fatal adverse cardiovascular outcomes even after adjusting for pretransplant renal function, and that patients with a specific pattern of relatively normal kidney function at the time of transplant and rapidly progressing renal insufficiency after transplant suffer some of the most devastating consequences. Without asserting causality, the data presented here proposes an important unifying hypothesis about the relationship between renal dysfunction in liver transplant recipients and the development of posttransplant cardiovascular complications.

There are critical intraoperative variables missing from this study, such as the piggyback versus the caval replacement technique4 and use of vasopressors,5 and donor-related data such as donation after brain death versus donation after circulatory death, cold ischemia time, and percent steatosis, all of which have been established as predictors of renal insufficiency after liver transplantation.6 Furthermore, specific complications classified as cardiovascular disease related may have resulted in misclassification of adverse events. For example, atrial fibrillation and pulmonary embolism are not classically associated with standard cardiovascular complications, such as myocardial infarction, heart failure, and cardiac arrest, but they are included as cardiovascular complications in this study.

In our opinion, the major strength of this study is the investigators’ approach to monitoring the trend in renal function for 30 days posttransplant and identifying patients at risk for future cardiovascular complications according to the trajectory of their renal insufficiency. Indeed, perhaps the most concerning and interesting estimated glomerular filtration rate trajectory group in this analysis is the group entitled “Normal Rapid Decrease,” whose odds ratio for a major cardiovascular complication at 1 year after transplant is 10.55. Unfortunately, however, because the groups are identified in a retrospective manner, it is difficult to know how to incorporate these findings into clinical practice. Though the suggestion of minimizing calcineurin inhibitors is made, we suspect that the introduction of mammalian target of rapamycin inhibitors during the first 30 days posttransplant would raise significant concern for most due to wound healing complications. Based on the data presented in this study, the modifiable factors seem limited; however, with some extrapolation, these results raise important allocation questions. In patients with normal renal function at the time of transplant, should we use fewer donation after circulatory death livers? Should we recommend intraoperative resuscitation with blood products over vasopressors? Should we always strive to use a piggyback technique? Should we abandon the use of calcineurin inhibitors in all patients with any degree of renal insufficiency?

The current system of distribution based on MELD in the United States has led to fewer waiting list deaths and has been embraced by many other countries. Given the weight that the MELD formula gives to creatinine, increasing numbers of patients with renal insufficiency will undergo liver transplantation. As the authors suggest, we should be mindful that decisions made intraoperatively and immediately postoperatively, including those around resuscitation, renal replacement therapy, and initiation of calcineurin inhibitors, may have lasting adverse cardiovascular effects on liver transplant recipients. A more refined understanding of the clinical course patterns in these patients is needed to guide clinical decision making and the rationalization of care. This study provides an important first step toward this understanding.