Current knowledge about biomarkers of acute kidney injury in liver cirrhosis

Abstract

Acute kidney injury (AKI) is common in advanced cirrhosis. Prerenal azotemia, hepatorenal syndrome, and acute tubular necrosis are the main causes of AKI in patients with cirrhosis.Evaluation of renal function and differentiation between functional and structural kidney injury are important issues in the management of cirrhosis. However, AKI in cirrhosis exists as a complex clinical spectrum rather than concrete clinical entity. Based on current evidence, changes in serum creatinine (Cr) levels remain the most appropriate standard for defining AKI in cirrhosis. However, serum Cr has a limited role in assessing renal function in this population.This review examines previous studies that investigated the ability of recent biomarkers for AKI in cirrhosis from the perspective of earlier and accurate diagnosis, classification of AKI phenotype, and prediction of clinical outcomes. Serum cystatin C and urine neutrophil gelatinase-associated lipocalin have been extensively studied in cirrhosis, and have facilitated improved diagnosis and prognosis prediction in patients with AKI. In addition, urine N-acetylβ-D-glucosaminidase, interleukin 18, and kidney injury molecule 1 are other promising biomarkers for advanced cirrhosis. However, the clinical significance of these markers remains unclear because there are no cut-off values defining the normal range and differentiating phenotypes of AKI. In addition, AKI has been defined in terms of serum Cr, and renal biopsythe gold standard-has not been carried out in most studies. Further discovery of innovate biomarkers and incorporation of various markers could improve the diagnosis and prognosis prediction of AKI, and will translate into meaningful improvements in patient outcomes.

Influence of fluid balance on postoperative outcomes after hepatic resection in patients with left ventricular diastolic dysfunction

“…Data regarding the nature and incidence of postoperative complications, intensive care unit (ICU) admission, and length of postoperative hospitalization were also collected. Acute kidney injury (AKI) was defined in accordance with the 2012 Kidney Disease Improving Global Outcomes guidelines ( 15 ) which had higher predictability than other criteria for assessing prognosis ( 16 ): increase in serum creatinine by ≥0.3 mg/dl within 48 h; increase in serum creatinine to ≥1.5 times baseline within 7 days before surgery; or urine volume <0.5 ml/kg/h for 6 h. Pulmonary effusion or edema was diagnosed by radiologist that showed a costophrenic angle blunting with abnormal accumulation of fluid in the extravascular compartments of the lung on x-ray findings in postoperative period. We used a term pulmonary effusion or edema because it cannot be distinguished without clinical evaluation.…”

Influence of perioperative fluid balance on clinical outcomes after hepatic resection in patients with left ventricular diastolic dysfunction

“…Data regarding the nature and incidence of postoperative complications, intensive care unit (ICU) admission, and length of postoperative hospitalization were also collected. Acute kidney injury (AKI) was de ned in accordance with the 2012 Kidney Disease Improving Global Outcomes guidelines (Khwaja A, 2012) which had higher predictability than other criteria for assessing prognosis (Lee HA et al, 2022): increase in serum creatinine by ≥ 0.3 mg/dL within 48 hours; increase in serum creatinine to ≥ 1.5 times baseline within 7 days before surgery; or urine volume < 0.5 mL/kg/h for 6 hours. Postoperative liver insu ciency was de ned as a peak postoperative TB level of > 7 mg/dL and/or the presence of ascites > 500 mL/day based on a previous study (Mullen JT et al, 2007).…”

Novel biomarkers of acute kidney injury in chronic liver disease: Where do we stand after a decade of research?

“…Novel kidney injury biomarkers that have transitioned from preclinical models to clinical studies are broadly classified into three groups 39,40 (iii) markers of cell-cycle arrest, which detect cellular stress for example, insulin-like growth factor binding protein-7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2).…”

“…Detection of these biomarkers reflects various underlying pathophysiological mechanisms affecting renal tubules such as tubular injury, cell damage, diminished tubular reabsorption, and inflammatory cell recruitment. 38,39 Neutrophil gelatinase-associated lipocalin This is the prototype biomarker of tubular injury in cirrhosis with promising results across studies conducted over the last decade.…”

“…Novel kidney injury biomarkers that have transitioned from pre‐clinical models to clinical studies are broadly classified into three groups 39,40 : (i) markers of renal function for example, cystatin‐C, β 2 ‐microglobulin; (ii) markers of renal tubular injury, which reflect various pathophysiological mechanisms affecting renal tubules such as (a) tubular proteins upregulated by injury for example, neutrophil gelatinase‐associated lipocalin (NGAL), liver‐type fatty‐acid binding protein (L‐FABP), kidney injury molecule (KIM‐1), (b) tubular proteins released due to cell damage for example, N ‐acetyl‐β‐ d ‐glucosaminidase (NAG), α‐glutathione‐ S ‐transferase, (c) plasma proteins due to diminished tubular reabsorption for example, α 1 ‐microgobulin, β 2 ‐microglobulin, retinol‐binding protein, and (d) markers released by recruited inflammatory cells for example, interleukin‐18 (IL‐18); and (iii) markers of cell‐cycle arrest, which detect cellular stress for example, insulin‐like growth factor binding protein‐7 (IGFBP7) and tissue inhibitor of metalloproteinases‐2 (TIMP‐2).…”