Why Do We Need to Change the Diagnostic Criteria of HRS in the Setting of AKI?
A major critical point in the management of AKI in patients with decompensated cirrhosis is whether the diagnostic criteria of type 1 HRS should be revised in light of the new definitions of AKI. The current criteria include a time interval (2 weeks) over which sCr must double to a value >2.5 mg/dL for the diagnosis of type 1 HRS. A revision of these criteria is needed because the current definition of type 1 HRS does not allow physicians to initiate potentially effective treatment, specifically vasoconstrictors and albumin, until the sCr increases to ≥2.5 mg/dL. Since it has been observed that in patients with type 1 HRS, a higher sCr at the beginning of treatment leads to a lower probability of response to terlipressin and albumin, the most investigated and effective treatment of type 1 HRS, it seems prudent not to wait until the sCr increases beyond 2.5 mg/dL before starting the treatment. According to the new proposed algorithm, when AKI is characterised by an initial ICA-AKI stage 2 or 3 or by progression of the initial stage despite general therapeutic measures, patients who meet all other diagnostic criteria of HRS provided by the previous definition should receive vasoconstrictors and albumin, irrespective of the final value of sCr. This makes it possible to remove a barrier to the achievement of a pharmacological response that was linked to the rigid sCr cut-off value of >2.5 mg/dL in the definition of type 1 HRS. The potential advantage of the algorithm is that its application may allow earlier treatment of patients with type 1 HRS, leading to a better outcome as compared with the current approach. However, we lack studies where vasoconstrictors were used in the treatment of HRS with lower values of sCr, and caution should be exercised in the use of vasoconstrictors in these patients pending further controlled trials.
Nevertheless, all the experts agreed on the removal of a fixed cut-off value of sCr from the diagnostic criteria of HRS. This is the only change that they wanted to introduce in the current diagnostic criteria for HRS. As a consequence, all the remaining criteria are maintained ( Box 1 ). However, these criteria do not rule out the possibility of renal parenchymal damage. Thus, all the experts agreed on the potential role of new urinary biomarkers in the differential diagnosis of the different types of AKI in patients with cirrhosis. Several urinary biomarkers of tubular damage, such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), and liver fatty acid-binding protein (L-FABP), have been discovered in recent years. Preliminary experiences from Europe and the USA showed that the use of NGAL and/or the combination of urinary biomarkers (NGAL, KIM-1, IL-18, L-FABP and albuminuria) may be useful in the differential diagnosis of AKI in patients with cirrhosis. These findings need to be confirmed in future studies.
The removal of a fixed cut-off value of sCr from the diagnostic criteria of HRS in the setting of AKI has important implications in the management of these patients. Thus, there is a need to change the definition of response to the pharmacologic treatment of HRS. Full response will be defined by return of sCr to a value within 0.3 mg/dL (26.5 μmol/L) of the baseline value. Partial responses will be defined by a regression of at least one AKI stage with a fall in the sCr value to ≥0.3 mg/dL (26.5 μmol/L) above the baseline value. Nevertheless, we should recognise that preliminary data suggest that even a partial decrease of sCr from baseline may be associated with improved short term survival, irrespective of whether or not the patient achieves HRS reversal (sCr <1.5 mg/dL). These data suggest that the degree of improvement in sCr may be more relevant than achieving a finite level of renal function.