A cut-off serum creatinine value of 1.5 mg/dl for AKI – To be or not to be
Authors: Florence Wong, Jacqueline G. O’Leary, K. Rajender Reddy, Patrick S. Kamath, Guadalupe Garcia-Tsao, Benedict Maliakkal, Ram Subramanian, Leroy Thacker, Jasmoham Bajaj
Journal: Journal of Hepatology (2014)

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: "A cut-off serum creatinine value of 1.5 mg/dl for AKI – To be or not to be"Journal of HepatologyVol. 62Issue 3PreviewWe 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]. 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. Full-Text PDF Open AccessReply to: "A cut-off serum creatinine value of 1.5 mg/dl for AKI – To be or not to be"Journal of HepatologyVol. 62Issue 3PreviewA cut-off creatinine value of 1.5 mg/dl for AKI: sometimes "the question" does not concern "the being", but "the meaning"To the Editor: Full-Text PDF Open Access Acute renal failure (ARF) is a common problem in patients with decompensated cirrhosis and ascites [[1]Garcia-Tsao G. Parikh C.R. Viola A. Acute kidney injury in cirrhosis.Hepatology. 2008; 48: 2064-2077Crossref PubMed Scopus (451) Google Scholar]. 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]Salerno F. Gerbes A. Ginès P. Wong F. Arroyo V. Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis.Gut. 2007; 56: 1310-1318Crossref PubMed Scopus (77) Google Scholar]. More recently, it has been recognized in non-cirrhotic patients that smaller increases in serum creatinine also have a negative impact on survival [[3]Lassnigg A. Schmidlin D. Mouhieddine M. Bachmann L.M. Druml W. Bauer P. et al.Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: a prospective cohort study.J Am Soc Nephrol. 2004; 15: 1597-1605Crossref PubMed Scopus (1105) Google Scholar]. 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 [4Bellomo R. Ronco C. Kellum J.A. Mehta R.L. Palevsky P. Acute Dialysis Quality Initiative workgroup. Acute renal failure – definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group.Crit Care. 2004; 8: R204-R212Crossref PubMed Google Scholar, 5Mehta R.L. Kellum J.A. Shah S.V. Molitoris B.A. Ronco C. Warnock D.G. et al.Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury.Crit Care. 2007; 11: R31Crossref PubMed Scopus (5313) Google Scholar, 6KDIGO Clinical Practice Guideline for Acute Kidney Injury. AKI definition.Kidney Int. 2012; : 19-36PubMed Google Scholar]. The degree of AKI severity is also defined by stages [4Bellomo R. Ronco C. Kellum J.A. Mehta R.L. Palevsky P. Acute Dialysis Quality Initiative workgroup. Acute renal failure – definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group.Crit Care. 2004; 8: R204-R212Crossref PubMed Google Scholar, 5Mehta R.L. Kellum J.A. Shah S.V. Molitoris B.A. Ronco C. Warnock D.G. et al.Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury.Crit Care. 2007; 11: R31Crossref PubMed Scopus (5313) Google Scholar, 6KDIGO Clinical Practice Guideline for Acute Kidney Injury. AKI definition.Kidney Int. 2012; : 19-36PubMed Google Scholar]. The most commonly reported classification used to diagnose AKI is that of the Acute Kidney Injury Network (AKIN), which set forth specific serum creatinine and urine output changes to define stages of AKI, without setting a fixed serum creatinine level in its diagnostic criteria [[5]Mehta R.L. Kellum J.A. Shah S.V. Molitoris B.A. Ronco C. Warnock D.G. et al.Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury.Crit Care. 2007; 11: R31Crossref PubMed Scopus (5313) Google Scholar]. Comparison of results from various studies in patients with cirrhosis has been difficult, as these studies assessed cirrhotic patients of various disease severities, in different hospital settings, using different methodologies to calculate the change in serum creatinine [7Altamirano J. Fagundes C. Dominguez M. García E. Michelena J. Cárdenas A. et al.Acute kidney injury is an early predictor of mortality for patients with alcoholic hepatitis.Clin Gastroenterol Hepatol. 2012; 10: 65-71Abstract Full Text Full Text PDF PubMed Scopus (125) Google Scholar, 8de Carvalho J.R. Villela-Nogueir C.A. Luiz R.R. Guzzo P.L. da Silva Rosa J.M. Rocha E. et al.Acute kidney injury network criteria as a predictor of hospital mortality in cirrhotic patients with ascites.J Clin Gastroenterol. 2012; 46: e21-e26Crossref PubMed Scopus (72) Google Scholar, 9Scott R.A. Andrew S. Austin A.S. Nitin V. Kolhe N.V. Chris W. et al.Acute kidney injury is independently associated with death in patients with cirrhosis.Frontline Gastroenterol. 2013; 4: 191-197Crossref PubMed Google Scholar]. Emerging from these studies are the findings that both the severity of AKI, as well as the progression of AKI have a negative impact on patient survival. In two recent articles by Fagundes et al. [[10]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], and Piano et al. [[11]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], published in the Journal of Hepatology, which evaluated the impact of AKI on short-term mortality in patients with decompensated cirrhosis, admitted to the hospital for various reasons, similar trends were reported. Both studies incorporated parts of the AKIN criteria using the conventional criteria for the diagnosis of AKI. Fagundes et al. found that patients with stage 1 AKI (increase in serum creatinine by either 0.3 mg/dl or by 50% irrespective of the final serum creatinine) and peak serum creatinine of ⩽1.5 mg/dl had a very good survival, similar to that of non-AKI patients [[10]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 et al. found that the conventional diagnostic criteria, using a cut-off serum creatinine of 1.5 mg/dl was better than the AKIN criteria in the prediction of survival. This is not surprising, as the conventional diagnostic criteria tend to select out patients with more severe kidney injury. Furthermore, a serum creatinine of ⩾1.5 mg/dl was able to predict progression of AKI [[11]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]. Based on these two studies, Fagundes et al. proposed instituting a new classification of AKI in cirrhosis, separating cirrhotic patients with AKI into 3 subgroups: (i) stage 1 with a final serum creatinine of ⩽1.5 mg/dl, (ii) stage 1 with a final serum creatinine of >1.5 mg/dl, and (iii) combined stages 2 and 3. Piano et al. suggested that future interventional trials should incorporate certain aspects of the AKIN criteria, namely, small increment of 0.3 mg/dl in serum creatinine and staging, to allow assessment of progression, while maintaining the conventional diagnostic criteria, requiring a minimum serum creatinine of ⩾1.5 mg/dl. Therefore, these two studies seem to suggest a serum creatinine cut-off value of 1.5 mg/dl is important in the management of AKI and the prediction of patient outcome in cirrhosis. These studies also imply that AKI episodes with a lower peak serum creatinine may not be clinically important., and may not require intervention However, as Thalheimer and Burroughs pointed out, AKI with a peak serum creatinine of <1.5 mg/dl is not a benign condition [[12]Thalheimer U. Burroughs A.K. To close the stable door before the horse has bolted.J Hepatol. 2014; 60: 678-679Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar]. One has to emphasize that the above two studies were designed specifically to evaluate the impact of AKI on short-term survival in a very specific population of cirrhotic patients, namely hospitalized cirrhotic patients. They did not set out to evaluate the impact of AKI on other events that could be important in the natural history of cirrhosis, such as recurrence of AKI, the development of future complications, or future hospitalizations. In light of the marked variation in baseline creatinine between cirrhotic patients, using a specific serum creatinine cut-off value could potentially result in the late diagnosis of AKI, and delay interventions. In a totally different setting of outpatient decompensated cirrhotics, Tsien et al. reported that patients with AKI, defined as a rise in serum creatinine by either 0.3 mg/dl within <48 h or an increase of 50% from a stable value in the previous 6 months, and a mean peak serum creatinine within the normal laboratory range had a worse prognosis compared to those without AKI when followed for 12 months [[13]Tsien C.D. Rabie R. Wong F. Acute kidney injury in decompensated cirrhosis.Gut. 2013; 62: 131-137Crossref PubMed Scopus (178) Google Scholar]. In another cohort of hospitalized decompensated cirrhotic patients with infection (n = 337) [[14]Wong F. O'Leary J.G. Reddy K.R. Patton H. Kamath P.S. Fallon M.B. et al.New consensus definition of acute kidney injury accurately predicts 30-day mortality in patients with cirrhosis and infection.Gastroenterology. 2013; 145: 1280-1288Abstract Full Text Full Text PDF PubMed Scopus (193) Google Scholar], a higher percentage of those who developed AKI (n = 166) died within 30 days, despite receiving the standard of care for their AKI plus prompt antibiotic treatment. Re-analysis of the data showed that of the 166 patients who developed AKI, there were 31 patients whose peak serum creatinine was ⩽1.5 mg/dl (group A), and 135 patients whose peak serum creatinine was >1.5 mg/dl (group B). 81% of group A patients survived 30 days vs. 93% of control subjects, p = 0.038 (Fisher's exact test) (Fig. 1). Interestingly, the 30 day survival of group B (63%) was statistically similar to that of group A (p = 0.09) despite group B having significantly more organ failures (group A: median number of organ failure = 1, interquartile range 0:1; group B: median number of organ failure = 1, interquartile range 1:2) (p = 0.008, Mann-Whitney U test). Therefore, in different clinical settings to those of Fagundes et al., and Piano et al., using the conventional criteria of serum creatinine of ⩾1.5 mg/dl to diagnose AKI may lead to clinical decisions that could be detrimental to these patients. The diagnosis of AKI in cirrhosis is currently still a matter under discussion. We have borrowed the AKIN criteria from nephrologists [[5]Mehta R.L. Kellum J.A. Shah S.V. Molitoris B.A. Ronco C. Warnock D.G. et al.Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury.Crit Care. 2007; 11: R31Crossref PubMed Scopus (5313) Google Scholar], but do not really adhere strictly to the diagnostic criteria of AKIN for the diagnosis of AKI, as no study to date has incorporated the urine output criteria of the AKIN definition. This is reasonable because cirrhotic patients have issues that are particular to themselves, such as lower urine output even without AKI, due to avid sodium and water retention. Cirrhotic patients also have malnutrition, leading to lower muscle mass, thereby artificially lowering the serum creatinine [[15]Sherman D.S. Fish D.N. Teitelbaum I. Assessing renal function in cirrhotic patients: problems and pitfalls.Am J Kidney Dis. 2003; 41: 269-278Abstract Full Text PDF PubMed Scopus (273) Google Scholar]. This is particularly problematic in female patients, whose serum creatinine significantly overestimates renal function; utilization of a 1.5 mg/dl cut-off for diagnosing clinically significant AKI may discriminate against women [[16]Bajaj J.S. O'Leary J. Reddy K.R. Wong F. Fallon M. Biggins S. et al.Differences in creatinine between genders could disadvantage infected cirrhotic women: the NACSELD experience.J Hepatol. 2014; 60: S389-S390Abstract Full Text PDF Google Scholar]. Therefore, academic societies are working together to try to identify the best unified diagnostic criteria for AKI in cirrhosis. Although Fagundes et al. and Piano et al. have provided robust results for their particular sets of patients, their results may not be generalizable and equitable to other patients with cirrhosis. Therefore, to use results of selected individual studies to propose widespread changes in diagnostic criteria for AKI may be premature. Rather, these studies should stimulate the performance of prospective trials that will clarify the best timing to initiate therapy for renal dysfunction that will prevent its progression, thereby improving the survival of this fragile population of patients with decompensated cirrhosis. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.