Cholemic nephropathy – Historical notes and novel perspectives

Acute kidney injury is common in patients with liver disease and associated with significant morbidity and mortality. Besides bacterial infections, fluid loss, and use of nephrotoxic drugs AKI in liver disease may be triggered by tubular toxicity of cholephiles. Cholemic nephropathy, also known as bile cast nephropathy, supposedly represents a widely underestimated but important cause of renal dysfunction in cholestasic or advanced liver diseases with jaundice. Cholemic nephropathy describes impaired renal function along with characteristic histomorphological changes consisting of intratubular cast formation and tubular epithelial cell injury directed towards distal nephron segments. The underlying pathophysiologic mechanisms are not entirely understood and clear defined diagnostic criteria are still missing.This review aims to summarize (i) the present knowledge on clinical and morphological characteristics of cholemic nephropathy, (ii) available preclinical models, (iii) potential pathomechanisms especially the potential role of bile acids, and (iv) future diagnostic and therapeutic strategies for cholemic nephropathy. This article is part of a Special Issue entitled: Cholangiocytes in Health and Disease edited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.     

Unusual Constriction Zones in the Major Porins OmpU and OmpT from Vibrio cholerae

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Diet,Genetics, and the Gut Microbiome Drive Dynamic Changes in Plasma Metabolites

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Exogenously Hypercholesterolemic Rats, Compared with Their Progenitor Sprague-Dawley Rats, Have Altered mRNAs for Cholesterol 7α-Hydroxylase and Low-Density-Lipoprotein Receptor and Activities of Cholesterol 7α-Hydroxylase and Acyl-CoA:Cholesterol Acyltransferase in the Liver in Response to Dietary Cholesterol

Exogenously hypercholesterolemic (ExHC) rats promptly increase serum cholesterol concentration in response to dietary cholesterol. To examine underlying mechanism(s) for this susceptibility, responses of mRNAs for cholesterol metabolism-related proteins and their activities in the liver to dietary cholesterol were compared between ExHC rats and their progenitor Sprague-Dawley rats. ExHC rats slightly decreased the abundance of low-density-lipoprotein (LDL) receptor mRNA in response to dietary cholesterol, although the amount of LDL receptor was not influenced. The abundance of cholesterol 7α-hydroxylase mRNA and the enzyme activity in response to dietary cholesterol were greater in ExHC rats, but the fecal excretion of bile acid was comparable between the strain. Dietary cholesterol-dependent elevation of acyl-CoA:cholesterol acyltransferase activity was greater in ExHC rats. The concentration of liver triacylglycerols was markedly lower in ExHC rats. These results suggest that ExHC rats may increase serum cholesterol by increasing hepatic secretion of cholesteryl ester-rich particles.     

Exogenous hypercholesterolemic rats, compared with their progenitor, Sprague-Dawley rats, promptly alter cholesterol metabolism in the liver and secrete cholesterol-rich particles in response to dietary cholesterol

Early responses of cholesterol metabolism to dietary cholesterol were compared between exogenous hypercholesterolemic (ExHC) and Sprague-Dawley rats. Both strains had a similar radioactivity of [¹⁴C]cholesterol in the serum half a day after the oral administration, but thereafter the radioactivity disappeared slowly in ExHC rats. ExHC rats promptly altered in response to the dietary cholesterol, activities of cholesterol 7α-hydroxylase and cholesterol synthesis in the liver and fecal excretion of bile acids derived from [¹⁴C]cholesterol administered orally. Lymphatic transport for 24 hr of [¹⁴C]cholesterol was similar between the strains. Triton administration resulted in a marked accumulation of cholesterol in serum d > 1.006 g/ml lipoproteins in ExHC rats; in addition, the formation of cholesteryl esters from [¹⁴C]oleic acid intravenously infused was greater in ExHC rats. These results indicate that ExHC rats increase serum cholesterol in response to exogenous cholesterol by decreasing the liver uptake and enhancing the secretion in the liver.     

广东眼镜蛇蛇胆的鉴别及质量控制的研究Ⅳ：广东眼镜蛇蛇胆中牛磺酸、甘氨酸、牛磺胆酸和甘氨胆酸的测定

本文采用日立８３５－５０型氨基酸自动分析仪测定比较了广东眼镜蛇蛇胆及牛、猪、兔、鸡胆中牛磺酸、甘氨酸和其他氨基酸的成分与含量,并间接测定了牛磺胆酸与甘氨胆酸的含量和比值。结果表明广东眼镜蛇蛇胆中牛磺酸（６．６６７ｇ／１００ｇ干重）与牛磺胆酸（２７．４７ｇ／１００ｇ干重）的含量最高,而甘氨酸（０．５９８ｇ／１００ｇ干重）与甘氨胆酸（３．７０ｇ／１００ｇ干重）的含量最低,其他氨基酸的含量甚微。实验结果为蛇胆的真伪鉴别及内在质量控制提供了有实用价值的科学依据,同时也提供了一个准确、灵敏、微量的测定方法。     

Expression of fibroblast growth factor 21 in patients with biliary atresia

Fibroblast growth factor 21 is a critical circulating adipokine involving in metabolic disorders and various liver diseases. This study was performed to investigate whether FGF21 is also associated with the pathophysiology of biliary atresia. Serum FGF21 levels were measured in 57 BA patients and 20 age matched healthy controls. We also examined hepatic FGF21 mRNA expression and FGF21 protein levels in liver tissues obtained from 15 BA patients undergoing liver transplantation and 5 cases of pediatric donation after cardiac death donor without liver diseases by RT-PCR and Western blotting. Patients with BA showed significantly higher serum FGF21 levels than those without BA (554.7 pg/mL [83–2300] vs. 124.5 pg/mL [66–270], P < 0.05). Patients with BA also had significantly higher FGF21 mRNA and protein levels in hepatic tissues than control subjects. Serum FGF21 expression increased corresponding to the severity of liver fibrosis. Furthermore, serum FGF21 levels dropped significantly in BA patients within 6 months after liver transplantation and approached baseline in healthy controls (P > 0.05). In vivo, FXR knockout could significantly abrogate cholestasis induced FGF21 expression. FGF21 levels in serum and liver tissue increased significantly in BA patients. In vivo, cholestasis could induce FGF21 expression in FXR dependent manner.