Analysis of a Urinary Biomarker Panel for Clinical Outcomes Assessment in Cirrhosis

Ariza, Xavier; Solà, Elsa; Elia, Chiara; Barreto, Rogelio; Moreira, Rebeca; Morales-Ruíz, Manuel; Graupera, Isabel; Rodríguez, Ezequiel; Huelín, Patrícia; Solé, Cristina; Fernández, Javier; Jiménez, Wladimiro; Arroyo, Vicente; Ginès, Pere

doi:10.1371/journal.pone.0128145

Cited by 106 publications

(159 citation statements)

References 37 publications

(54 reference statements)

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“…chronic liver failure and cirrhosis [49][50][51] . Protein disulfide-isomerase A3 is a biomarker for 327 liver fibrosis caused by CCl4 in rats [52] .…”

mentioning

confidence: 99%

Early urinary candidate biomarker discovery in a rat thioacetamide-induced liver fibrosis model

Zhang

Yuan

et al. 2017

Preprint

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Biomarker is the change associated with the disease. Blood is relatively stable because of the homeostatic mechanisms of the body. However, urine accumulates changes of the body, which makes it a better early biomarker source. Liver fibrosis, which results from the deposition of extracellular matrix (ECM) components, is a reversible pathological condition, whereas cirrhosis, the end-stage of liver fibrosis, is irreversible. Consequently, noninvasive early biomarkers for fibrosis are desperately needed. In this study, differential urinary proteins were identified in the thioacetamide (TAA) liver fibrosis rat model using tandem mass tagging and two-dimensional liquid chromatography tandem mass spectrometry (2DLC-MS/MS). A total of 766 urinary proteins were identified, 143 and 118 of which were significantly changed in the TAA 1-week and 3-week groups, respectively. Multiple reaction monitoring (MRM)-targeted proteomics was used to further validate the abundant differentially expressed proteins in the TAA 1-week, 3-week, 6-week and 8-week groups. A total of 40 urinary proteins were statistically significant (fold change >2 and p<0.05), 15 of which had been previously reported as biomarkers of liver fibrosis, cirrhosis or other related diseases and 10 of which had been reported to be associated with the pathology and mechanism of liver fibrosis. These differential proteins were detected in urine before the alanine aminotransferase (ALT) and aspartate transaminase (AST) changes in the serum and before fibrosis was observed upon hematoxylin and eosin (HE) and Masson’s staining.

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“…chronic liver failure and cirrhosis [49][50][51] . Protein disulfide-isomerase A3 is a biomarker for 327 liver fibrosis caused by CCl4 in rats [52] .…”

mentioning

confidence: 99%

Early urinary candidate biomarker discovery in a rat thioacetamide-induced liver fibrosis model

Zhang

Yuan

et al. 2017

Preprint

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“…However, KIM-1 levels have been shown to predict the development of HRS in patients with advanced cirrhosis. Interestingly, KIM-1 levels are not as accurate as NGAL, oteopontin, albumin and trefoil factor 3 (TTF3) for the diagnosis of ATN in patients with cirrhosis [15]. …”

Section: Discussionmentioning

confidence: 99%

“…In animal models, urinary L-FABPis elevated in kidney disease with tubule-interstitial damage [15]. L-FABP has been evaluated in the diagnosis of AKI and sepsis complicated by AKI [5].…”

Section: Minor Criteriamentioning

confidence: 99%

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Kidney Biomarkers in Hepatorenal Syndrome

Freeman¹

2017

GHOA

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Cirrhosis is the result of advanced liver disease characterized by fibrosis due to increased portal hypertension. Patients with cirrhosis are prone to develop acute kidney injury (AKI) triggered by bacterial infections, hypovolemia, nephrotoxic drugs and intrinsic kidney disease. The diagnostic criteria for the diagnosis of HRS continue to rely on serum creatinine levels which should be interpreted with caution in patients with cirrhosis. To date, accurate biomarkers indicative of renal function are lacking. Further validation with prospective studies is warranted to evaluate the value of novel biomarkers.

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“…The following new kidney biomarkers in urine are investigated in patients with AKI and cirrhosis [19]:…”

Section: Role Of Biomarkersmentioning

confidence: 99%

Renal Failure in Patients with Liver Cirrhosis: Novel Classifications, Biomarkers, Treatment

Appenrodt

Lammert²

2018

Visc Med

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Renal failure is a severe complication in patients with liver cirrhosis. It is associated with increased mortality and morbidity. Diagnosis is a challenge because it is mainly based on serum creatinine, which does not seem to be an ideal measure of renal function in cirrhosis. The definition of renal failure in these patients has been changed for optimizing treatment and for improving outcome and prognosis. The new criteria are based on the adapted KDIGO (Kidney Disease: Improving Global Outcomes) staging system. The diagnosis of acute kidney injury (AKI) is based on an absolute increase of serum creatinine of >0.3 mg/dl from baseline within 48 h or an increase of >50% from baseline. This means smaller changes in serum creatinine in a shorter time frame which may lead to an early identification of renal failure in cirrhotic patients. The former cirrhotic-specific term hepatorenal syndrome (HRS) is now part of the new diagnostic criteria and is called HRS-AKI. The diagnostic criteria of HRS have changed due to the new criteria for AKI. Due to these criteria for HRS, the medical treatment will be started earlier. First-line treatment for renal AKI-HRS is the combination of a vasoconstrictor and albumin. Most data exist for terlipressin, a vasopressin analog, as vasoconstrictor. Besides this medical treatment, there are other options like the placement of a transjugular intrahepatic portosystemic shunt, renal replacement, and artificial extracorporeal liver support systems. However, these alternative treatment options have limitations. Liver transplantation is the treatment of choice for these patients and represents the definitive treatment. Using new biomarkers like urinary neutrophil gelatinase-associated lipocalin or interleukin-18 for renal failure in cirrhosis should help to differentiate the causes of renal failure and provide an indication regarding the prognosis.

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Analysis of a Urinary Biomarker Panel for Clinical Outcomes Assessment in Cirrhosis

Cited by 106 publications

References 37 publications

Early urinary candidate biomarker discovery in a rat thioacetamide-induced liver fibrosis model

Early urinary candidate biomarker discovery in a rat thioacetamide-induced liver fibrosis model

Kidney Biomarkers in Hepatorenal Syndrome

Renal Failure in Patients with Liver Cirrhosis: Novel Classifications, Biomarkers, Treatment

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