Cholemic Nephropathy Causes Acute Kidney Injury and Is... : Hepatology (original) (raw)

Original Articles: AUTOIMMUNE, CHOLESTATIC AND BILIARY DISEASE

Cholemic Nephropathy Causes Acute Kidney Injury and Is Accompanied by Loss of Aquaporin 2 in Collecting Ducts

Bräsen, Jan Hinrich1,†; Mederacke, Young‐Seon2,†; Schmitz, Jessica1; Diahovets, Kateryna1; Khalifa, Abedalrazag1; Hartleben, Björn1; Person, Fermín3; Wiech, Thorsten3; Steenbergen, Eric4; Großhennig, Anika5; Manns, Michael P.2; Schmitt, Roland6; Mederacke, Ingmar*,2

1Institute of Pathology, Nephropathology UnitHannover Medical SchoolHannoverGermany

2Department of Gastroenterology, Hepatology, and EndocrinologyHannover Medical SchoolHannoverGermany

3Institute of Pathology and Nephropathology SectionUniversity Hospital Hamburg EppendorfHamburgGermany

4Department of PathologyRadboud University Medical CenterNijmegenthe Netherlands

5Institute for BiostatisticsHannover Medical SchoolHannoverGermany

6Department of Nephrology and HypertensionHannover Medical SchoolHannoverGermany

* Address Correspondence and Reprint Requests to:
Ingmar Mederacke, M.D.
Hannover Medical School, Department of Gastroenterology, Hepatology, and Endocrinology
Carl‐Neuberg‐Str. 1
30625 Hannover, Germany
E‐mail: [email protected]
Tel: +49‐511‐532‐6619
Fax: +49‐511‐532‐5692

†These authors contributed equally to this work.

Abstract

Impairment of renal function often occurs in patients with liver disease. Hepatorenal syndrome is a significant cause of acute kidney injury (AKI) in patients with cirrhosis (HRS‐AKI, type 1). Causes of non‐HRS‐AKI include cholemic nephropathy (CN), a disease that is characterized by intratubular bile casts and tubular injury. As data on patients with CN are obtained primarily from case reports or autopsy studies, we aimed to investigate the frequency and clinical course of CN. We identified 149 patients who underwent kidney biopsy between 2000 and 2016 at the Department of Gastroenterology, Hepatology and Endocrinology at Hannover Medical School. Of these, 79 had a history of liver disease and deterioration of renal function. When applying recent European Association for the Study of the Liver criteria, 45 of 79 patients (57%) presented with AKI, whereas 34 patients (43%) had chronic kidney disease (CKD). Renal biopsy revealed the diagnosis of CN in 8 of 45 patients with AKI (17.8%), whereas none of the patients with CKD was diagnosed with CN. Univariate analysis identified serum bilirubin, alkaline phosphatase, and urinary bilirubin and urobilinogen as predictive factors for the diagnosis of CN. Histological analysis of AKI patients with normal bilirubin, elevated bilirubin, and the diagnosis of CN revealed loss of aquaporin 2 (AQP2) expression in collecting ducts in patients with elevated bilirubin and CN. Biopsy‐related complications requiring medical intervention occurred in 4 of 79 patients (5.1%). Conclusion: CN is a common finding in patients with liver disease, AKI, and highly elevated bilirubin. Loss of AQP2 in AKI patients with elevated bilirubin and CN might be the result of toxic effects of cholestasis and in part be responsible for the impairment of renal function.