Cholemic Nephropathy as Cause of Acute and Chronic Kidney Disease. Update on an Under-Diagnosed Disease

Francesca Tinti; Ilaria Umbro; Mariadomenica D'Alessandro; Silvia Lai; Manuela Merli; Annalisa Noce; Nicola Di Daniele; Sandro Mazzaferro; Anna Paola Mitterhofer

doi:10.3390/life11111200

Cholemic Nephropathy as Cause of Acute and Chronic Kidney Disease. Update on an Under-Diagnosed Disease

Life (Basel). 2021 Nov 6;11(11):1200. doi: 10.3390/life11111200.

Authors

Francesca Tinti¹, Ilaria Umbro¹, Mariadomenica D'Alessandro², Silvia Lai¹, Manuela Merli³, Annalisa Noce⁴, Nicola Di Daniele⁴, Sandro Mazzaferro¹, Anna Paola Mitterhofer⁵

Affiliations

¹ Nephrology Unit, Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy.
² Clinical Pathology Unit, Department of General Surgery "P.Stefanini", Sapienza University of Rome, 00161 Rome, Italy.
³ Gastroenterology Unit, Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy.
⁴ UOC of Internal Medicine-Center of Hypertension and Nephrology Unit, Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.
⁵ Nephrology and Dialysis Unit, Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.

Abstract

Cholemic nephropathy (CN) is a recognized cause of acute kidney injury (AKI) in patients with severe hyperbilirubinemia (sHyb) and jaundice. Pathophysiological mechanisms of CN are not completely understood, but it seems caused both by direct toxicity of cholephiles and bile casts formation in nephrons enhanced by prolonged exposure to sHyb, particularly in the presence of promoting factors, as highlighted by a literature reviewed and by personal experience. The aim of our update is to retrace CN in its pathophysiology, risk factors, diagnosis and treatment, underlining the role of sHyb, promoting factors, and CN-AKI diagnostic criteria in the different clinical settings associated with this often-concealed disease. Our purpose is to focus on clinical manifestation of CN, exploring the possible transition to CKD. Cholemic nephropathy is an overlooked clinical entity that enters differential diagnosis with other causes of AKI. Early diagnosis and treatment are essential because renal injury could be fully reversible as rapidly as bilirubin levels are reduced. In conclusion, our proposal is to introduce an alert for considering CN in diagnostic and prognostic scores that include bilirubin and/or creatinine with acute renal involvement, with the aim of early diagnosis and treatment of sHyb to reduce the burden on renal outcome.

Keywords: acute kidney injury; acute on chronic liver failure; bile casts; cholemic nephropathy; chronic kidney disease; liver transplantation; promoting factors.