Cholemic nephropathy – Historical notes and novel perspectives

• Published in: Biochimica et biophysica acta. Molecular basis of disease 2018-04, Vol.1864 (4), p.1356-1366
• Main Authors: Krones, Elisabeth, Pollheimer, Marion J., Rosenkranz, Alexander R., Fickert, Peter
• Format: Article
• Language: English
• Subjects: Acute kidney injury; Acute Kidney Injury - diagnosis; Acute Kidney Injury - drug therapy; Acute Kidney Injury - etiology; Acute Kidney Injury - pathology; Animals; Bile acids; Bile Acids and Salts - metabolism; Bile Acids and Salts - toxicity; Bile cast nephropathy; Bile Ducts - cytology; Bile Ducts - drug effects; Bile Ducts - metabolism; Bile Ducts - pathology; Bilirubin - metabolism; Bilirubin - toxicity; Cholagogues and Choleretics - pharmacology; Cholagogues and Choleretics - therapeutic use; Cholemic nephropathy; Cholestasis - complications; Cholestasis - drug therapy; Cholestasis - pathology; Disease Models, Animal; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Hepatocytes - drug effects; Hepatocytes - metabolism; Humans; Jaundice, Obstructive - complications; Jaundice, Obstructive - drug therapy; Jaundice, Obstructive - pathology; Kidney Tubules - pathology; Liver - cytology; Liver - drug effects; Liver - metabolism; Liver - pathology; Liver cirrhosis; Renal Elimination; Ursodeoxycholic Acid - analogs & derivatives; Ursodeoxycholic Acid - pharmacology; Ursodeoxycholic Acid - therapeutic use
• ISSN: 0925-4439
• DOI: 10.1016/j.bbadis.2017.08.028

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. •Cholemic nephropathy represents an underestimated cause of renal dysfunction in a wide spectrum of liver disorders with jaundice.•The term cholemic nephropathy encompasses impaired renal function with typical histological changes.•Functional and phenotypical changes of cholemic nephropathy can be modeled in common bile duct ligated mice.•Norursodeoxycholic acid ameliorates the renal phenotype and consequently represents a potential treatment for cholemic nephropathy.•Experimental findings point towards a pivotal pathophysiological role for bile acids in cholemic nephropathy.