Kidney nontumor
Tubulointestitial disease
Drug and toxin related tubulointerstitial injury
Bile cast nephropathy


Topic Completed: 9 April 2020

Minor changes: 24 September 2020

Copyright: 2019-2020, PathologyOutlines.com, Inc.

PubMed Search: Bile cast nephropathy

Sittipong Wangsawibul, M.D.
Jonathan E. Zuckerman, M.D., Ph.D.
Page views in 2020 to date: 402
Cite this page: Wangsawibul S, Zuckerman J. Bile cast nephropathy. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/kidneybilecastnephropathy.html. Accessed October 24th, 2020.
Definition / general
  • Acute or chronic renal tubular injury secondary to bile containing casts in the setting of hyperbilirubinemia
Essential features
  • Presence of intratubular bile stained casts, especially in distal tubules / collecting ducts with acute tubular injury
  • Associated with various hepatic diseases resulting in cholestasis and hyperbilirubinemia
Terminology
  • Also called cholemic nephrosis, cholemic nephropathy, bile nephrosis, jaundice related renal insufficiency, jaundice associated acute kidney injury, bile acid nephropathy and bile nephropathy
  • Bile cast nephropathy is a pathologic term that emphasizes the severe end of the spectrum of the renal injury in this unique clinical situation (Kidney Int 2013;84:192)
    • Emphasizes the findings that can be directly observed on histologic examination of the renal tissue (bile casts)
  • Bile salts can also cause tubular injury (tubulopathy) in the absence of bile cast (J Nephrol 2006;19:229)
    • However, there is no characteristic biopsy finding in this setting
    • In the absence of bile casts, the term cholemic nephropathy may be more appropriate
    • May be difficult to distinguish from other causes of hepatorenal syndrome
ICD coding
  • ICD-10: N28.9 - Disorder of kidney and ureter, unspecified
Epidemiology
Sites
  • Renal tubules
Pathophysiology
  • Direct tubular toxicity (J Nephrol 2006;19:229)
    • Excess bilirubin believed to cause oxidative damage of the tubular cell membranes and uncoupling of mitochondrial phosphorylation (Hepatology 2013;58:2056)
    • Sulfated bile salt inhibit Na-H, Na-K, Na-Cl pumps in proximal tubules and loop of Henle causing pH changes enhance bile cast deposition (Am J Physiol 1990;258:F986)
  • Tubular obstruction
    • Saturated bilirubin due to limited transportation in the proximal tubules leads to cast formation and tubular obstruction
    • Bile acids are poorly water soluble which may also contribute to cast formation within the low pH microenvironment of the distal nephron
Etiology
  • Any insult leading to profound bilirubinemia, usually > 20 mg/dL (Kidney Int 2013;84:192)
  • Hepatic or extrahepatic causes including:
    • Cirrhosis of any cause (e.g., alcohol, drug)
    • Acute hepatitis
    • Obstructive jaundice
  • However, some etiologies of hyperbilirubinemia including cirrhosis due to hepatitis C virus infection and nonalcoholic steatohepatitis (NASH) show a lower propensity for bile casts (Kidney Int 2013;84:192)
  • Hemolytic jaundice generally does not show bile casts formation (Kidney Int 2019;96:1400)
Clinical features
  • Symptoms related to hepatic dysfunction including jaundice, pruritus, scleral icterus and abdominal distension (J Nephrol 2006;19:229)
  • Acute or chronic renal dysfunction including oliguria, anuria and urine discoloration
Diagnosis
  • Presence of bile stained tubular casts with acute tubular injury
Laboratory
  • Increased serum creatinine, blood urea nitrogen, aspartate transaminase, alanine transaminase and bilirubin (elevated total bilirubin levels, typically > 20 mg/dL) (Kidney Int 2013;84:192)
  • Presence of urinary muddy brown granular casts with bile staining and bile casts
Prognostic factors
  • Reversibility of liver failure
  • Reduction in serum bilirubin and bile acids might result in cessation of renal injury and renal recovery (World J Gastroenterol 2016;22:6328)
Case reports
Treatment
  • Supportive treatment to reduce bilirubin burden and improve renal function including endoscopic retrograde cholangiopancreatography with stent replacement in case of biliary obstruction, plasmapheresis and hemodialysis
  • Medical therapies including the use of steroids, cholestyramine, ursodeoxycholic acid and lactulose have shown minimal benefit (J Nephrol 2006;19:229)
  • Liver or kidney transplantation
Gross description
  • Yellowish discoloration of the renal cortex and medulla and green discoloration due to conversion of bilirubin to biliverdin after formalin fixation (renal medulla may show deeper green color due to higher concentration of bilirubin in distal nephron segments) (Kidney Int 2013;84:192)
Gross images

Contributed by Jonathan E. Zuckerman, M.D., Ph.D.

Bile stained kidney

Microscopic (histologic) description
  • Pigmented greenish yellow or dark red granular cast material in tubular lumens (Kidney Int 2013;84:192)
  • Pigmented casts more prominent in distal nephron segments
  • Proximal tubules and Bowman space involvement in severe cases
  • Casts associated with variable acute tubular injury
  • Pigmented material in cytoplasmic tubular resorption droplets
  • Mononuclear inflammatory cells in the vasa recta may be seen
  • Bile does not polarize (Nephrol Dial Transplant 2010;25:1909)
Microscopic (histologic) images

Contributed by Jonathan E. Zuckerman, M.D., Ph.D.

Bile casts in collecting ducts

Bile casts in proximal tubules

Hall bile stain

Cytology images

Images hosted on other servers:

Bile case

Immunofluorescence description
  • Bile cast should be negative by immunofluorescence
Positive stains
  • Hall (Fouchet) stain reveals yellow or grayish green color intratubular casts
Negative stains
Electron microscopy description
  • No specific findings
Sample pathology report
  • Kidney, biopsy:
    • Acute tubular injury with increased bile stained casts consistent with bile cast nephropathy
Differential diagnosis
Board review style question #1
A patient with alcoholic cirrhosis has acute kidney injury. At autopsy their kidneys show numerous red-brown colored tubular casts most notably in distal tubules and collecting ducts. The casts stain positively on Hall stain. What do these renal histology findings represent?



  1. Myoglobin casts nephropathy
  2. Hemoglobin casts nephropathy
  3. Bile cast nephropathy
  4. Light chain cast nephropathy
  5. Oxalate nephropathy
Board review answer #1
C. Bile cast nephropathy

Reference: Bile cast nephropathy

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Board review style question #2
A pretransplant renal deceased donor allograft biopsy shows numerous red-brown colored tubular casts. The casts stain positively on Hall stain. Hemoglobin and myoglobin immunostains are negative. These histologic findings might indicate what disease in the donor?

  1. Fulminant hepatic failure in the setting of drug toxicity
  2. Rhabdomyolysis
  3. Hemolytic anemia
  4. Multiple myeloma
Board review answer #2
A. Fulminant hepatic failure in the setting of drug toxicity

Reference: Bile cast nephropathy

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