Cholemic nephrosis

We recently saw a 37 year old gentlemen with his second bout of acute alcoholic hepatitis that presented with altered mental status, elevated bilirubin/transaminases, and non-oliguric acute kidney injury. We were consulted as the primary team was concerned about hepatorenal syndrome. We decided that the patient didn’t have HRS given that he had almost 900 mg proteinuria/day, enlarged kidneys at 16 cm each, and was found to have multiple (bright yellow stained) cast on microscopy. Given the patients protracted course of bilirubinemia with serum bilirubins >30 during the hospitalization that this was like like cholemic-induced. Today I’d like to review quickly how cholestasis and elevated bilirubin cause acute renal tubular injury. According to Shimizu et al.  acute hepatic failure (AHF) associated AKI has multiple mechanisms for injury. From the Am J Nephrol 2013 article on Renal Inflammatory Changes in Acute Hepatic Failure-Associated Acute Kidney Injury:
 

AHF-associated AKI seems to be mediated by renal tubular epithelial cell injury with bile pigment accumulation, impaired microcirculation caused by PTC endothelial cell injury with depletion of endothelial nitric oxide synthase and angiogenic factors, and by a decrease in RBC velocity and renal inflammation. Multiple mechanisms including tubular and PTC injuries and renal inflammation may be involved in the development of AHF-associated AKI.

Here is another great case report of high bilirubin (>20) in two patients that had renal biopsies that showed normal renal architecture but extensive tubular damage.  There is also the evidence that there is a spectrum with cholemic nephrosis that starts with just tubular damage (as seen in the previous case report)  and ends with bile cast nephropathy. I first read about this from renalfellow.blogspot.com several years ago and looks like there hasn’t been any big changes since.