Natural history, spectrum and outcome of stage 3 AKI in patients with acute‐on‐chronic liver failure

Abstract

Background and Aim There is limited data on natural course and interventions in stage‐3 acute kidney injury (AKI‐3) in patients with acute‐on‐chronic liver failure (ACLF). We studied the factors of AKI‐3 reversal and outcomes of dialysis in ACLF patients. Methods Consecutive patients with ACLF were prospectively enrolled (n = 1022) and variables determining AKI and its outcomes were analysed. Results At 1 month, 337 (33%) patients had AKI‐3, of which, 131 had AKI‐3 at enrolment and 206 developed AKI‐3 during hospital stay. Of patients with AKI‐3 at enrolment, 18% showed terlipressin response, 21% had AKI resolution and 59% required dialysis. High MELD (≥35) (model 1), serum bilirubin (≥23 mg/dL) (model 2) and AARC score (≥11) (model 3) were independent risk factors for dialysis. Dialysis was associated with worse survival in all AKI patients but improved outcomes in patients with AKI‐3 (p = .022, HR 0.69 [0.50–0.95]). Post‐mortem kidney biopsies (n = 61) revealed cholemic nephropathy (CN) in 54%, acute tubular necrosis (ATN) in 31%, and a combination (CN and ATN) in 15%. Serum bilirubin was significantly higher in patients with CN, CN and ATN compared with ATN respectively ([30.8 ± 12.2] vs. [26.7 ± 12.0] vs. [18.5 ± 9.8]; p = .002). Conclusion AKI‐3 rapidly increases from 13% to 33% within 30 days in ACLF patients. Histopathological data suggested cholemic nephropathy as the predominant cause which correlated with high bilirubin levels. AKI‐3 resolves in only one in five patients. Patients with AARC grade 3 and MELD >35 demand need for early dialysis in AKI‐3 for improved outcomes.

APASL clinical practice guidelines on the management of acute kidney injury in acute-on-chronic liver failure

“…In patients on dialysis, complete recovery could be defined as a sustained recovery of kidney functions with non-requirement of dialysis for > 14 days with the return of serum creatinine to below 1.5 mg/dl and urine output to more than 0.5 ml/kg/h CN was identified in almost two-thirds of patients who died of stage 3 AKI [13]. Further, data from critically ill patients suggests a poor agreement between urine output and sCr.…”

“…Traditionally, kidney diseases are categorized into acute and chronic at a 3-month cutoff. The mortality risk in AKI is associated with severity of liver disease (higher grade of ACLF) and more severe renal dysfunction (higher stage of AKI) [13]. AKI can evolve to acute kidney disease (AKD) or to CKD if the renal injury persists for more than 7 or 90 days, respectively.…”

“…They are also considered an organ of immense utility, and therefore the approach and management of AKI could improve the overall outcomes in these patients [10][11][12]. Interestingly, patients with ACLF more frequently have stage 3 AKI which in the majority responds poorly to the current modalities [13].…”

Austrian consensus on the diagnosis and management of portal hypertension in advanced chronic liver disease (Billroth IV)

“…Pathophysiologically, HRS-AKI results from compromised renal perfusion caused by systemic vasodilatation in patients with ascites and is often aggravated by infections and systemic inflammation [ 146 , 147 ]. AKI induced by acute tubular necrosis (ATN-AKI) is primarily caused by shock [ 148 ] and/or cholemic nephropathy (also known as bile cast nephropathy) [ 149 – 152 ]. Finally, less common causes of AKI such as glomerulonephritis and postrenal obstruction should be considered as differential diagnoses [ 148 ].…”