Chronic Kidney Disease in Cirrhosis: Emerging Complication With Negative Impact in the Liver Transplant Setting

Potential conflict of interest: Nothing to report. See Article on Page 498 Some of the investigators involved have been supported by grants from Instituto de Salud Carlos III (ISCIII), project PI18/00727 and PI16/00043, cofunded by the European Regional Development Fund, Agencia de Gestió d'Ajuts Universitaris i de Recerca (2017‐SGR‐01281) and the EU Horizon 20/20 Programme (H2020‐SC1‐2016‐RTD); LIVERHOPE (731875). Pere Ginès is a recipient of an Institució Catalana de Recerca i Estudis Avançats (ICREA) Academia Award. Impaired renal function is common in patients with advanced cirrhosis and is associated with poor outcomes. There is a large amount of evidence about the impact of acute kidney injury (AKI) in patients with decompensated cirrhosis.1 In addition, pretransplant kidney dysfunction adversely affects posttransplantation outcomes.4 Recent studies in hospitalized patients with cirrhosis indicate that chronic kidney disease (CKD) is common in this population, ranging from 20% to 46%. This is explained, at least in part, by the increase in the prevalence of nonalcoholic steatohepatitis (NASH)–related cirrhosis and associated comorbidities, such as diabetes mellitus and arterial hypertension.1 However, information on the burden of CKD in patients with cirrhosis is still limited. In the current issue, Cullaro et al. evaluated the prevalence of CKD among patients with cirrhosis awaiting liver transplantation (LT) and its impact on post‐LT outcomes.8 This is a retrospective analysis of a large cohort of patients with cirrhosis included on the waiting list for LT in the United States from 2002 to 2017. The study includes 78,640 LT candidates with these major findings: The prevalence of CKD defined as eGFR <60 mL/minute for ≥90 days or ≥42 days in hemodialysis is high and increased significantly from 8% in 2002 to 15% in 2017 (P < 0.001). Pre‐LT CKD was associated with increased post‐LT mortality (12% versus 9% at 1 year in patients with and without CKD, respectively; P < 0.001). Not only CKD but any type of pre‐LT kidney failure, including AKI on CKD, was associated with increased post‐LT mortality. Overall, the prevalence of CKD among LT candidates was 16%. As compared with patients without CKD, those with CKD were older and had significantly higher frequency of NASH‐related cirrhosis and diabetes mellitus. These results are in keeping with those from a recent study indicating that CKD in cirrhosis is common and that NASH as the etiology of cirrhosis with accompanying diabetes mellitus are risk factors to the development of CKD.7 The authors compared the frequency of CKD between different time periods showing that although the prevalence of CKD was 8% in 2002, it increased up to 15% in 2017. Two factors may explain this significant increase over time. First, as the authors point out in their study, the progressive increase in patients with NASH‐related cirrhosis and associated comorbidities may lead to the increase in patients with some degree of parenchymal kidney injury. Second, it has to be taken into consideration that the definition of kidney failure in cirrhosis has recently been modified with the use of dynamic changes in serum creatinine rather than a cutoff value for the diagnosis of AKI.9 This leads to a better distinction between AKI and CKD in cirrhosis and could account, at least in part, for the apparent increased recognition of CKD. A major issue of the study by Cullaro et al. is that patients on the waiting list who received extra points (ie, for hepatocellular carcinoma) were excluded from the analysis, which may have carried a major bias. We agree with the authors’ argument that those patients may have different baseline characteristics as compared with the whole population. However, patients with exception points represented a large proportion of patients from those listed (53,089 out of 148,143; 36%). Therefore, excluding these patients may lead to either overestimation or underestimation of the frequency of CKD among patients awaiting LT. In addition, to our knowledge, there are no data to support the fact that these patients may behave differently in terms of risk for CKD development, and thus, there was probably no need to exclude them from the analysis. Importantly, the study shows that 1‐year and 5‐year post‐LT mortality was significantly increased in patients with pre‐LT CKD compared with patients without CKD. It is important to remark that although the severity of CKD correlated with the increase in post‐LT mortality, any degree of CKD was associated with impaired post‐LT outcome. Finally, authors investigated not only the effect of CKD but also the effect of AKI alone and AKI on CKD at the time of LT on post‐LT outcomes. Using the new definition of AKI in cirrhosis, AKI can complicate preexisting CKD in cirrhosis. However, to date there are no data on the frequency and impact of acute‐on‐chronic kidney disease in cirrhosis. In this study, 3% of listed patients had AKI on CKD at the time of LT. Although the frequency is low, these patients had significantly higher post‐LT mortality compared with patients with normal renal function at the time of LT. However, there were no differences on post‐LT survival between patients with CKD alone and those with AKI on CKD. In conclusion, despite the limitations inherent to the retrospective nature of the study, the manuscript raises the point that CKD is emerging as a frequent complication in patients with advanced cirrhosis and that this is particularly relevant in patients on the waiting list for LT in terms of post‐LT outcomes. Further studies are needed to better characterize CKD and its impact on patients with advanced cirrhosis. Nonetheless, the results of this study indicate that efforts should be made to identify patients at risk and detect CKD early in order to closely monitor these patients and prevent the progression of kidney disease, if possible.