Acute kidney injury and hepatorenal syndrome in cirrhosis

Table 4 The most well-known novel biomarkers being studied for acute kidney injury in cirrhosis

Novel biomarker	Source	Benefits/Clinical uses	Limitations
Cystatin C[62-68]	Plasma, urine	Early biomarker of AKI, potential benefit with severity of disease. Unaffected with age, sarcopenia, gender, or sepsis. Unaffected by malignancy and serum bilirubin level. Multiple studies found it to be an independent risk factor of AKI and mortality	Increased levels in CKD. Influenced by low levels of albumin. Potentially influenced by elevated WBC and CRP. Takes longer time to result when compared to sCr
NGAL[18,67-79]	Urine	Found in kidney tubular cell that is released during damage or injury. Elevated in AKI in cirrhosis and potential predictor of mortality. Markedly elevated in ATN, mildly elevated in prerenal azotemia/CKD/HRS-AKI	Increased levels in CKD. Increased levels in infections, particularly urinary tract infections. Overlap with values in PRA, HRS, and other AKI types of AKI. Small quantities are made in the liver
IL-18[75,78,82-84]	Urine	Very similar to urinary NGAL. Markedly elevated in cirrhotic patients with ATN, in comparison to other AKI types. Found in monocytes and macrophages. A notable proinflammatory marker. Not confounded by CKD, sepsis or UTI	There are increased levels in PRA and HRS but significant overlap in values with limited clinical utility. Levels are increased in levels of inflammation in the kidney other than AKI
Kidney Injury Molecule-1[18,73,84-86]	Urine	Originally found in kidney tubular transmembrane protein. Not expressed in normal kidney tissue. Noted with increased levels in ATN in cirrhosis when compared to the other types of AKI in cirrhosis. High specificity for ischemic or nephrotoxic kidney injury	Elevated from inflammatory conditions. Found to have overlap between different forms of AKI. Confounded by presence of infection
L-FABP[87-93]	Urine	Found in kidney proximal tubule. Levels may be increased in AKI or AKI 2/2 sepsis. Potential utility in predictor in adverse outcomes including AKI in patients with chronic liver disease and other liver disease	Limited studies in cirrhosis. Found to be increased in CKD. Increased in acute liver injury and liver failure as well

AKI: Acute kidney injury; HRS: Hepatorenal syndrome; CKD: Chronic kidney disease; ATN: Acute tubular necrosis; UTI: Urinary tract infection; NGAL: Neutrophil gelatinase-associated lipocalin; PRA: Prerenal azotemia; CRP: C-reactive protein; WBC: White blood cell; sCr: Serum creatinine; IL: Interleukin.