To close the stable door before the horse has bolted
Authors: Ulrich Thalheimer, Andrew K. Burroughs
Journal: Journal of Hepatology (2013)

Evaluation of the Acute Kidney Injury Network criteria in hospitalized patients with cirrhosis and ascitesJournal of HepatologyVol. 59Issue 3PreviewFor several years hepatologists have defined acute renal failure in patients with cirrhosis as an increase in serum creatinine (sCr) ⩾50% to a final value of sCr >1.5 mg/dl (conventional criterion). Recently, the Acute Kidney Injury Network (AKIN) defined acute renal failure as acute kidney injury (AKI) on the basis of an absolute increase in sCr of 0.3 mg/dl or a percentage increase in sCr ⩾50% providing also a staging from 1 to 3. AKIN stage 1 was defined as an increase in sCr ⩾0.3 mg/dl or increase in sCr ⩾1.5-fold to 2-fold from baseline. Full-Text PDF A 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 Reply to: “To close the stable door before the horse has bolted”Journal of HepatologyVol. 60Issue 3PreviewTo the Editor: Full-Text PDF Open AccessReply to: “To close the stable door before the horse has bolted”Journal of HepatologyVol. 60Issue 3PreviewWe read with great interest the letter by Thalheimer and Burroughs in relation to our study and that of Piano et al. [1,2] recently published in Journal of Hepatology. We appreciate their interesting and stimulating comments as they contribute to scientific interaction on a very important topic. We absolutely agree with their comment that the results of our study should be interpreted in the perspective that patients were hospitalized in a Liver Unit and complications of cirrhosis were managed according to international guidelines [3]. Full-Text PDF Open Access We read with interest the studies by Fagundes and colleagues [[1]Fagundes C. Barreto R. Guevara M. Garcia E. Sola E. Rodriguez 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], Piano and colleagues [[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] and the accompanying editorial [[3]Arroyo V. Acute kidney injury (AKI) in cirrhosis: should we change current definition and diagnostic criteria of renal failure in cirrhosis?.J Hepatol. 2013; 59: 415-417Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar]. Both studies evaluated large numbers of patients with cirrhosis (375 and 233, respectively) and assessed the impact of acute kidney injury (AKI), assessed both by AKIN criteria and the more conventional finding of a creatinine level of ⩾1.5 mg/dl. Piano and colleagues only included patients with hospital acquired AKI, thus excluding patients who already had renal impairment on admission. In this study, all patients had ascites, while in the study by Fagundes and colleagues this was present in two thirds. In both studies, patients with stage 1 AKI with a peak creatinine <1.5 mg/dl did not have an increased mortality as compared to patients without AKI. The accompanying editorial therefore suggests the conclusion that stage 1 AKI with a peak creatinine of <1.5 mg/dl is a benign condition. The importance of renal failure in cirrhosis is well established. It increases the risk of dying 7-fold and carries a 1 month mortality of up to 50% [[4]Fede G. D’Amico G. Arvaniti V. Tsochatzis E. Germani G. Georgiadis D. et al.Renal failure and cirrhosis: a systematic review of mortality and prognosis.J Hepatol. 2012; 56: 810-818Abstract Full Text Full Text PDF PubMed Scopus (210) Google Scholar], an impact on the natural history of a magnitude similar to that of bacterial infections [[5]Arvaniti V. D’Amico G. Fede G. Manousou P. Tsochatzis E. Pleguezuelo M. et al.Infections in patients with cirrhosis increase mortality four-fold and should be used in determining prognosis.Gastroenterology. 2010; 139: 1256Abstract Full Text Full Text PDF Scopus (798) Google Scholar]. Creatinine as an indicator of renal function is an essential component of prognostic scores such as MELD and UKELD. Both the stage of AKI and the peak creatinine level are associated with increased mortality [[6]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]. Tsien and colleagues [[7]Tsien C.D. Rabie R. Wong F. Acute kidney injury in decompensated cirrhosis.Gut. 2013; 62: 131-137Crossref PubMed Scopus (178) Google Scholar] recently published a prospective study on 90 outpatients with cirrhosis and ascites. Episodes of AKI (as per AKIN criteria) were common, and the mean peak creatinine value was within normal laboratory values. Importantly, patients with an episode of AKI had decreased survival on follow up. While widely used, creatinine remains an imperfect marker of renal function in cirrhosis. Not only can high levels of bilirubin interfere with creatinine measurements, but levels also correlate with total muscle mass, which is often markedly reduced in patients with cirrhosis and ascites [[8]Cholongitas E. Xirouchakis E. Garcovich M. Burroughs A.K. Evaluation of renal function in patients with cirrhosis.J Hepatol. 2010; 53: 589Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar]. As a consequence, baseline creatinine levels in patients with cirrhosis are frequently substantially lower than the upper limit of normal used by laboratories, and substantial increases in creatinine level may not exceed the “normal values” and may thus not be spotted by the non-hepatologist. We would therefore like to disagree with the conclusion that stage 1 AKI with a peak creatinine of <1.5 mg/dl is a “benign” condition. Both Fagundes’ and Piano’s study had standard interventions for patients whose creatinine increased (even if below 1.5 mg/dl), and these measures were implemented rapidly since all patients were in hospital. These included such crucial measures as withdrawal of diuretics and nephrotoxic drugs, diagnosis and treatment of bacterial infections and fluid challenges with crystalloids or albumin. In Tien’s study, blood tests were taken every 4–6 weeks but clinical evaluation for assessment of AKI only occurred every 4 months – this raises the question whether interventions in patients with increasing renal markers were not carried out in a similarly timely fashion. This is in line with a recently published trial reporting improved survival in patients with cirrhosis and ascites who were allocated to closely monitored outpatient management under the care of a specialised clinical team at a dedicated Hepatology centre [[9]Morando F. Maresio G. Piano S. Fasolato S. Cavallin M. Romano A. et al.How to improve care in outpatients with cirrhosis and ascites: a new model of care coordination by consultant hepatologists.J Hepatol. 2013; 59: 257-264Abstract Full Text Full Text PDF PubMed Scopus (121) Google Scholar]. In our opinion, the correct conclusion from the current evidence should be that stage 1 AKI with a peak creatinine of <1.5 mg/dl in patients with cirrhosis is a potentially benign condition if promptly treated and correctly managed. If ignored and untreated, it is likely to progress to higher stages of AKI and carry an increased mortality. Our vigilance should therefore be aimed at the timely detection of renal impairment in patients with cirrhosis and ascites, in order to intervene early and prevent further deterioration to a point where resolution becomes less certain and prognosis adverse. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.