Bile Cast Nephropathy

Bile cast nephropathy (cholaemic nephrosis) is acute kidney injury occurring in patients with severe cholestatic jaundice, characterised by bile stained casts in the distal tubules and tubular epithelial injury. It is under recognised and often misattributed to hepatorenal syndrome. It typically occurs when serum bilirubin exceeds 200 to 340 micromol/L (12 to 20 mg/dL), although injury has been described at lower levels.

Mechanisms:

• Direct tubular toxicity of conjugated bilirubin and bile acids, with oxidative and inflammatory injury
• Obstruction by bile casts in distal tubules
• Associated vasodilation and renal hypoperfusion in advanced liver disease
• Superimposed endotoxaemia, sepsis, gastrointestinal bleeding and nephrotoxins

Settings:

• Decompensated cirrhosis with alcoholic hepatitis
• Acute liver failure
• Obstructive jaundice (choledocholithiasis, pancreatic or biliary malignancy, strictures)
• Sepsis related cholestasis
• Drug induced liver injury
• Hepatitis A, B or E with cholestasis, malaria, leptospirosis, sickle cell hepatopathy

It is distinguished from hepatorenal syndrome by the presence of tubular injury (granular casts, high urinary sodium) and a poor response to vasoconstrictors and albumin.

• Deep jaundice, dark urine, pale stools in obstruction, pruritus
• Oliguria or non-oliguric rise in creatinine
• Features of chronic liver disease (ascites, spider naevi, encephalopathy) or acute liver injury
• Fever and right upper quadrant pain in cholangitis (Charcot triad: fever, jaundice, pain)
• Coagulopathy, hepatic encephalopathy, hypotension

Red flags: bilirubin above 200 micromol/L with rising creatinine, cholangitis with shock, hepatic encephalopathy grade 2 or higher, INR above 2.0, potassium above 6.0 mmol/L, anuria.

• Liver tests (bilirubin predominantly conjugated, alkaline phosphatase, gamma glutamyl transferase, transaminases), INR, albumin, creatinine, urea, electrolytes, lactate
• Urinalysis: bilirubinuria (dark yellow urine, positive bile on dipstick), granular and bile stained casts, tubular epithelial cells
• Urine indices: urine sodium above 40 mmol/L and fractional excretion of sodium above 1% favour tubular injury; urine sodium below 10 mmol/L with bland sediment favours hepatorenal syndrome
• Liver and biliary ultrasound, magnetic resonance cholangiopancreatography; CT where appropriate
• Cultures; ascitic tap for spontaneous bacterial peritonitis (neutrophils above 250/mm3)
• Biopsy (transjugular if coagulopathic) shows bile stained casts in distal tubules and tubular injury

Differentials: hepatorenal syndrome, prerenal azotaemia from bleeding or diuretics, sepsis related injury, glomerulonephritis in hepatitis B or C, nephrotoxic injury, post-obstructive uropathy.

First line

• Treat the cause of cholestasis: relieve biliary obstruction by endoscopic retrograde cholangiopancreatography with sphincterotomy and stenting, or percutaneous transhepatic drainage, within 24 hours for cholangitis with shock.
• Antibiotics for cholangitis or spontaneous bacterial peritonitis: piperacillin-tazobactam 4.5 g every 8 hours or ceftriaxone 2 g daily with metronidazole 500 mg every 8 hours; dose adjust after 48 hours.
• Stop nephrotoxins, NSAIDs, diuretics and lactulose induced dehydration.
• Volume: albumin 20% 1 g/kg (maximum 100 g) daily for 2 days, then reassess; balanced crystalloid for bleeding or sepsis.
• Alcohol associated hepatitis (Maddrey discriminant function 32 or above): prednisolone 40 mg daily for 28 days if no infection or bleeding, with assessment at day 7 (Lille score).

If hepatorenal syndrome is possible

• Terlipressin 0.85 mg intravenously every 6 hours (increase to 1.7 mg every 6 hours after day 3 if creatinine has not fallen by 25%), with albumin 20 to 40 g daily, for up to 14 days; or noradrenaline 0.5 to 3 mg/h infusion with albumin. Stop in ischaemic events or hypoxia.

Extracorporeal measures

• Renal replacement therapy for refractory hyperkalaemia, acidosis, overload or uraemia; continuous therapy is preferred in unstable patients, using regional citrate cautiously because of impaired citrate metabolism in liver failure.
• Plasma exchange (1 to 1.5 plasma volumes) or albumin dialysis can lower bilirubin and has been used in bile cast injury, but benefit is unproven.

Transplantation. Liver or combined liver kidney transplantation is considered in acute liver failure and end stage liver disease with dialysis for 6 weeks or more.

Follow up. Renal function usually improves with falling bilirubin, over weeks; monitor creatinine and urine protein at 3 months.