P82 Proteomics in inpatients with decompensated cirrhosis and ascites to identify novel biomarkers to diagnose acute kidney injury. A pilot study

<h3>Introduction</h3> Serum creatinine (sCr) overestimates glomerular filtration rate in patients with advanced liver cirrhosis. Only one small study employed proteomics in cirrhotic patients and found the maltase glucoamylase was increased in the urinary exosomes of patients with decompensated cirrhosis compared to compensated cirrhosis and healthy controls and it was higher in those with acute kidney injury (AKI). Thus, more sensitive markers of renal dysfunction in patients admitted with decompensated cirrhosis are needed. <h3>Methods</h3> One plasma sample during the admission was taken in patients admitted with decompensated cirrhosis and clinical ascites, with and without AKI, defined as increased in sCr ≥50% from baseline levels, and stored at -80°C. The top 14 abundant proteins (including albumin/immunoglobulins) were depleted followed by mass spectrometry based proteomic analysis. Protein identification and quantification was done by Spectronaut (version 19.9) software from Biognosys AG. Univariate logistic regression models were fitted with each protein variable as predictor, and AKI group as the outcome. <h3>Results</h3> 14 patients admitted with acute decompensated cirrhosis were included. 4 patients had samples considered of inadequate quality because less than 400 proteins were identified. In the 10 remaining patients, 5 with and 5 without AKI, the range of proteins identified were 591 and 2934. In the AKI group there were more male patients: 4(80%) vs 2(40%), more were taking nephrotoxic medication (carvedilol or diuretics): 4(80%) vs 2(40%), and mean age: 62±14 vs 53±8 years and creatinine levels at inclusion: 202±41 vs 65±14, p&lt;0.001 were higher. The AKI group had higher levels of inflammation as per white cell count: 11.4±7.4 vs 8.5±3.0 cellsx109/L and C-reactive protein: 46±31 vs 26±16 mg/L; and had worse liver function according to bilirubin: 156±185 vs 91±37 μmol/L and INR: 1.9±0.6 vs 1.2±0.1, p=0.03. However, Child-Pugh score: 11±2 vs 10±1; albumin 32±9 vs 27±6 g/L; sodium 130±6 vs 131±7; hepatic encephalopathy 2(40%) vs 0; and presence of infection: 3(60%) vs 4(80%) were similar in both groups. We selected and quantify 881 proteins on the basis of their presence across the groups. The univariate logistic regression model identified some potential novel markers of AKI (24 of the proteins had a p-value &lt; 0.1). The volcano plot shows 5 of the top biomarkers. <h3>Conclusion</h3> This pilot study demonstrated the feasibility of a proteomics study in patients with decompensated cirrhosis and identified potential new biomarkers of AKI.

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Published
2025-10-01
DOI
https://doi.org/10.1136/gutjnl-2025-basl.98
Primary Topic
Acute Kidney Injury Research
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article
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article

P82 Proteomics in inpatients with decompensated cirrhosis and ascites to identify novel biomarkers to diagnose acute kidney injury. A pilot study

Mahmoud Gouda, Joe Lomax, Kris Bennett, Joanne Hosking et al.
Acute Kidney Injury Research
article

P82 Proteomics in inpatients with decompensated cirrhosis and ascites to identify novel biomarkers to diagnose acute kidney injury. A pilot study

Mahmoud Gouda, Joe Lomax, Kris Bennett, Joanne Hosking, Paula Boeira, Prebashan Moodley, Huey Tan, Juan Acevedo Haro, Rhys Williams, Vikram Sharma, A. Abdulgader, Mumbe Miyanza, Steren Mottart, George Mawson
article en

Abstract

<h3>Introduction</h3> Serum creatinine (sCr) overestimates glomerular filtration rate in patients with advanced liver cirrhosis. Only one small study employed proteomics in cirrhotic patients and found the maltase glucoamylase was increased in the urinary exosomes of patients with decompensated cirrhosis compared to compensated cirrhosis and healthy controls and it was higher in those with acute kidney injury (AKI). Thus, more sensitive markers of renal dysfunction in patients admitted with decompensated cirrhosis are needed. <h3>Methods</h3> One plasma sample during the admission was taken in patients admitted with decompensated cirrhosis and clinical ascites, with and without AKI, defined as increased in sCr ≥50% from baseline levels, and stored at -80°C. The top 14 abundant proteins (including albumin/immunoglobulins) were depleted followed by mass spectrometry based proteomic analysis. Protein identification and quantification was done by Spectronaut (version 19.9) software from Biognosys AG. Univariate logistic regression models were fitted with each protein variable as predictor, and AKI group as the outcome. <h3>Results</h3> 14 patients admitted with acute decompensated cirrhosis were included. 4 patients had samples considered of inadequate quality because less than 400 proteins were identified. In the 10 remaining patients, 5 with and 5 without AKI, the range of proteins identified were 591 and 2934. In the AKI group there were more male patients: 4(80%) vs 2(40%), more were taking nephrotoxic medication (carvedilol or diuretics): 4(80%) vs 2(40%), and mean age: 62±14 vs 53±8 years and creatinine levels at inclusion: 202±41 vs 65±14, p&lt;0.001 were higher. The AKI group had higher levels of inflammation as per white cell count: 11.4±7.4 vs 8.5±3.0 cellsx109/L and C-reactive protein: 46±31 vs 26±16 mg/L; and had worse liver function according to bilirubin: 156±185 vs 91±37 μmol/L and INR: 1.9±0.6 vs 1.2±0.1, p=0.03. However, Child-Pugh score: 11±2 vs 10±1; albumin 32±9 vs 27±6 g/L; sodium 130±6 vs 131±7; hepatic encephalopathy 2(40%) vs 0; and presence of infection: 3(60%) vs 4(80%) were similar in both groups. We selected and quantify 881 proteins on the basis of their presence across the groups. The univariate logistic regression model identified some potential novel markers of AKI (24 of the proteins had a p-value &lt; 0.1). The volcano plot shows 5 of the top biomarkers. <h3>Conclusion</h3> This pilot study demonstrated the feasibility of a proteomics study in patients with decompensated cirrhosis and identified potential new biomarkers of AKI.

University Hospitals Plymouth NHS Trust (GB), Peninsula College of Medicine and Dentistry (GB), University of Plymouth (GB)
Openalex Percentile: Top 70%
Acute Kidney Injury Research
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