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Bile Acids as Potential Biomarkers to Assess Liver Impairment in Polycystic Kidney Disease.

ABSTRACT: Polycystic kidney disease is characterized by the progressive development of kidney cysts and declining renal function with frequent development of cysts in other organs including the liver. The polycystic kidney (PCK) rat is a rodent model of polycystic liver disease that has been used to study hepatorenal disease progression and evaluate pharmacotherapeutic interventions. Biomarkers that describe the cyst progression, liver impairment, and/or hepatic cyst burden could provide clinical utility for this disease. In the present study, hepatic cyst volume was measured by magnetic resonance imaging in PCK rats at 12, 16, and 20 weeks. After 20 weeks, Sprague Dawley (n = 4) and PCK (n = 4) rats were sacrificed and 42 bile acids were analyzed in the liver, bile, serum, and urine by liquid chromatography coupled to tandem mass spectrometry. Bile acid profiling revealed significant increases in total bile acids (molar sum of all measured bile acids) in the liver (13-fold), serum (6-fold), and urine (3-fold) in PCK rats, including those speciated bile acids usually associated with hepatotoxicity. Total serum bile acids correlated with markers of liver impairment (liver weight, total liver bile acids, total hepatotoxic liver bile acids, and cyst volume [ r > 0.75; P < 0.05]). Based on these data, serum bile acids may be useful biomarkers of liver impairment in polycystic hepatorenal disease.

SUBMITTER: Brock WJ

PROVIDER: S-EPMC5877312 | biostudies-literature | 2018 Mar/Apr

REPOSITORIES: biostudies-literature

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Bile Acids as Potential Biomarkers to Assess Liver Impairment in Polycystic Kidney Disease.

Brock William J WJ Beaudoin James J JJ Slizgi Jason R JR Su Mingming M Jia Wei W Roth Sharin E SE Brouwer Kim L R KLR

International journal of toxicology 20180301 2

Polycystic kidney disease is characterized by the progressive development of kidney cysts and declining renal function with frequent development of cysts in other organs including the liver. The polycystic kidney (PCK) rat is a rodent model of polycystic liver disease that has been used to study hepatorenal disease progression and evaluate pharmacotherapeutic interventions. Biomarkers that describe the cyst progression, liver impairment, and/or hepatic cyst burden could provide clinical utility ...[more]

PMID: 29587557

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Project description:Background & aimsPolycystic liver disease (PLD), the most common extrarenal manifestation of autosomal-dominant polycystic kidney disease (ADPKD), has become more prevalent as a result of increased life expectancy, improved renal survival, reduced cardiovascular mortality, and renal replacement therapy. No studies have fully characterized PLD in large cohorts. We investigated whether liver and cyst volumes are associated with volume of the hepatic parenchyma, results from liver laboratory tests, and patient-reported outcomes.MethodsWe performed a cross-sectional analysis of baseline liver volumes, measured by magnetic resonance imaging, and their association with demographics, results from liver laboratory and other tests, and quality of life. The data were collected from a randomized, placebo-controlled trial underway at 7 tertiary-care medical centers to determine whether the combination of an angiotensin I-converting enzyme inhibitor and angiotensin II-receptor blocker was superior to the inhibitor alone, and whether low blood pressure (<110/75 mm Hg) was superior to standard blood pressure (120-130/70-80 mm Hg), in delaying renal cystic progression in 558 patients with ADPKD, stages 1 and 2 chronic kidney disease, and hypertension (age, 15-49 y).ResultsWe found hepatomegaly to be common among patients with ADPKD. Cysts and parenchyma contributed to hepatomegaly. Cysts were more common and liver and cyst volumes were greater in women, increasing with age. Patients with advanced disease had a relative loss of liver parenchyma. We observed small abnormalities in results from liver laboratory tests, and that splenomegaly and hypersplenism were associated with PLD severity. Higher liver volumes were associated with a lower quality of life.ConclusionsHepatomegaly is common even in early stage ADPKD and is not accounted for by cysts alone. Parenchymal volumes were larger, compared with liver volumes of patients without ADPKD or with those predicted by standardized equations, even among patients without cysts. The severity of PLD was associated with altered biochemical and hematologic features, as well as quality of life. ClinicalTrials.gov identifier: NCT00283686.

Dataset Information

Bile Acids as Potential Biomarkers to Assess Liver Impairment in Polycystic Kidney Disease.

Publications

Bile Acids as Potential Biomarkers to Assess Liver Impairment in Polycystic Kidney Disease.

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