Reply to: “A cut-off serum creatinine value of 1.5 mg/dl for AKI – To be or not to be”
Authors: Claudia Fagundes, Rogelio Barreto, Ezequiel Rodríguez, Isabel Graupera, Esteban Poch, Elsa Solà, Javier Fernández, Pere Ginès
Journal: Journal of Hepatology (2014)

A cut-off serum creatinine value of 1.5 mg/dl for AKI – To be or not to beJournal of HepatologyVol. 62Issue 3PreviewAcute renal failure (ARF) is a common problem in patients with decompensated cirrhosis and ascites [1]. Traditionally, the diagnosis of ARF is made using the conventional criteria of a 50% increase in serum creatinine with the final serum creatinine reaching ⩾1.5 mg/dl [2]. More recently, it has been recognized in non-cirrhotic patients that smaller increases in serum creatinine also have a negative impact on survival [3]. This has led various learned societies to re-define ARF as acute kidney injury (AKI), incorporating even small changes in serum creatinine either in absolute or percentage terms in the diagnostic criteria [4–6]. Full-Text PDF Open AccessA modified acute kidney injury classification for diagnosis and risk stratification of impairment of kidney function in cirrhosisJournal of HepatologyVol. 59Issue 3PreviewThe Acute Kidney Injury Network (AKIN) criteria are widely used in nephrology, but information on cirrhosis is limited. We aimed at evaluating the AKIN criteria and their relationship with the cause of kidney impairment and survival. Full-Text PDF We really appreciate the interest of Wong and colleagues, from the North American Consortium in the Study of End-Stage Liver Disease (NACSELD) group, on our study published in the Journal of Hepatology in late 2013 [[1]Fagundes C. Barreto R. Guevara M. Garcia E. Solà E. Rodríguez E. et al.A modified acute kidney injury classification for diagnosis and risk stratification of impairment of kidney function in cirrhosis.J Hepatol. 2013; 59: 474-481Abstract Full Text Full Text PDF PubMed Scopus (206) Google Scholar]. As a research group interested in kidney dysfunction in cirrhosis, we share the concerns of our American colleagues about improving the diagnosis and management of kidney dysfunction in cirrhosis. Needless to say, we agree on their comments about the need for improving the interpretation of the relationship between glomerular filtration rate and serum creatinine values in women. This is particularly important in the application of the MELD score for organ allocation in liver transplantation. We would be willing to join efforts with our American colleagues to further investigate this issue. That said, we would like to highlight 4 important issues related to their letter:(1)The study of Fagundes et al. [[1]Fagundes C. Barreto R. Guevara M. Garcia E. Solà E. Rodríguez E. et al.A modified acute kidney injury classification for diagnosis and risk stratification of impairment of kidney function in cirrhosis.J Hepatol. 2013; 59: 474-481Abstract Full Text Full Text PDF PubMed Scopus (206) Google Scholar] was a prospective evaluation of all patients requiring hospital admission for an acute decompensation of cirrhosis, during a 26-month period, with the only exceptions of patients with large hepatocellular carcinoma, previous solid organ transplantation, and those on renal replacement therapy. Therefore, our study population included "all comers" to a tertiary hospital. We do not know whether our results apply to similar populations of patients with cirrhosis in other tertiary hospitals or to different populations in other settings. The new classification proposed (categorizing AKI stage 1 in two subgroups-A and B- and combining stages 2 and 3) was internally validated, but we obviously stated in the manuscript that it would require external validation in future studies before it could be widely applicable. Nonetheless, it is important to remark that in the same issue of the Journal, in which our study was published, Piano et al. reported amazingly similar results in a population of "all comers" with decompensated cirrhosis, in a tertiary hospital in Northern Italy [[2]Piano S. Rosi S. Maresio G. Fasolato S. Cavallin M. Romano A. et al.Evaluation of the Acute Kidney Injury Network criteria in hospitalized patients with cirrhosis and ascites.J Hepatol. 2013; 59: 482-489Abstract Full Text Full Text PDF PubMed Scopus (190) Google Scholar].(2)Wong et al. disapprove of our proposal for this modified AKI classification that uses the cut-off value of serum creatinine of 1.5 mg/dl, to categorize patients with AKI stage 1. In our opinion, as well as that of others, the use of a cut-off of serum creatinine makes perfect pathophysiological sense because it helps put into perspective the relative increase in serum creatinine used in the AKIN classification. In this regard, it is clear that a 50% increase in serum creatinine is markedly dependent on the baseline creatinine value. In fact, a 50% increase does not have the same significance in a patient with a baseline serum creatinine level of 0.6 mg/dl, compared to that of a patient with a baseline level of 1.2 mg/dl. In the first case, the final value is 0.9 mg/dl, which despite the 50% raise still represents a relatively preserved glomerular filtration rate. By contrast, in the second case the final value is 1.8 mg/dl, which corresponds to a very low glomerular filtration rate, indicating the presence of significant organ failure. If we translate this example to the liver using serum bilirubin as marker of liver function, it is clear that a 50% increase in serum bilirubin does not represent the same degree of liver failure when the final value of bilirubin is 3 mg/dl or 12 mg/dl.(3)Another argument used by Wong et al. to refute our classification based on a cut-off level of serum creatinine of 1.5 mg/dl, is that it could result in late diagnosis of AKI and delayed interventions. We disagree with this interpretation of our findings. Nowhere in our study it is stated that patients with AKI stage 1A should not be treated for AKI. In fact, all patients diagnosed at AKI stage 1A (serum creatinine <1.5 mg/dl) were investigated to determine the cause of AKI and received immediate treatment, whenever a cause of AKI was identified. Moreover, with our approach, the majority of patients (77%) were diagnosed at AKI stage 1, while only 12% were diagnosed at stage 3, which clearly seems to indicate that there was no delay in the diagnosis of AKI. By comparison, figures reported in a multicenter study performed in several North American hospitals were 48% for stage 1 and 23% for stage 3 [[3]Belcher J.M. Garcia-Tsao G. Sanyal A.J. Bhogal H. Lim J.K. Ansari N. et al.Association of AKI with mortality and complications in hospitalized patients with cirrhosis.Hepatology. 2013; 57: 753-762Crossref PubMed Scopus (253) Google Scholar]. Moreover, in our study, progression from stages 1 and 2 to higher stages occurred in only 22% of patients, a figure much lower than the 44% reported in the former study [[3]Belcher J.M. Garcia-Tsao G. Sanyal A.J. Bhogal H. Lim J.K. Ansari N. et al.Association of AKI with mortality and complications in hospitalized patients with cirrhosis.Hepatology. 2013; 57: 753-762Crossref PubMed Scopus (253) Google Scholar]. Therefore, it appears as though that the use of a 1.5 mg/dl cut-off, to identify patients with greater kidney dysfunction and worse prognosis, neither delayed the diagnosis of AKI nor resulted in a higher rate of progression, compared to other published reports.(4)Finally, recent studies from the EASL-CLIF Consortium highlight the importance of considering, not only kidney failure, but also the potential co-existence of other organ failures in patients hospitalized for acute decompensation of cirrhosis [[4]Moreau R. Jalan R. Gines P. Pavesi M. Angeli P. Cordoba J. et al.Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis.Gastroenterology. 2013; 144: 1426-1437Abstract Full Text Full Text PDF PubMed Scopus (1888) Google Scholar]. In this regard, a recent study has shown that the use of the ACLF classification has a higher predictive accuracy than the AKI classification in predicting 28-day and 90-day mortality in cirrhosis [[5]Angeli P. Rodríguez E. Piano S. Ariza X. Morando F. Solà E. et al.Acute kidney injury and acute-on-chronic liver failure classifications in prognosis assessment of patients with acute decompensation of cirrhosis.Gut. 2014; https://doi.org/10.1136/gutjnl-2014-307526Crossref PubMed Scopus (78) Google Scholar]. Therefore, these results suggest that the ACLF classification should be used in patients with cirrhosis hospitalized for acute decompensation to assess prognosis and also guide specific therapies aimed at improving function of multiple organs. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.