Introduction
Bile cast nephropathy is a condition in which acute kidney injury occurs in the presence of liver injury. It is also referred to as icteric nephrosis, cholemic nephropathy, or cholemic nephrosis. It causes hemodynamic changes in the liver, systemic circulation, and kidneys, resulting in intratubular cast formation and epithelial injury in the tubules. Bile cast nephropathy is common in patients with liver diseases and is associated with morbidity and mortality.
What Is Bile Cast Nephropathy?
Cholestatic liver disease causes various effects on kidney function. Bile cast nephropathy is a condition that occurs in patients with liver diseases. It refers to acute renal dysfunction, including acute kidney injury in the presence of liver injury. It usually occurs secondary to various pre-renal conditions like tubular and interstitial inflammation, bile-salt-induced tubular toxicity, tubular obstruction, and changes in renal hemodynamics.
What Are the Causes of Bile Cast Nephropathy?
-
Bile cast nephropathy is caused by an elevation in the serum bile salts and hyperbilirubinemia. An increase in total bilirubin levels greater than 20 mg/dL (milligrams per deciliter) causes bile cast nephropathy. The increase in bilirubin level is due to hepatocellular dysfunction.
-
Unfavorable factors like hypovolemia, endotoxemia, and exposure to nephrotoxins causes acute kidney injury in cholestatic liver disease. It can also be due to hepatorenal syndrome, which causes alternative intrarenal vasoconstriction and splanchnic vasodilation resulting in functional and hemodynamic alterations in the kidneys.
-
Hepatorenal syndrome is described as type 1 and type 2. Type 1 hepatorenal syndrome causes rapid renal failure, whereas type 2 causes a slow to moderate decline in renal function.
How Does Bile Cast Nephropathy Occur?
Bile cast nephropathy is a broad spectrum of disease that is characterized by the presence of mild reversible changes in patients without underlying renal dysfunction and hyperbilirubinemia of short duration to irreversible disease in patients with underlying renal dysfunction and, severe and prolonged hyperbilirubinemia.
Cholestasis is a condition in which bile flow from the liver is reduced due to liver infection, gallstones, or cancer. Due to the presence of cholestasis, hepatocytes export bile acids and induce basolateral bile acid pumps to prevent intracellular damage. The kidneys undergo alterations in the proximal tube and excrete the excess bile. This excess in bilirubin causes oxidative damage in the cell membranes of the tubules. Further, the sulfated bile salts inhibit the sodium hydrogen, sodium potassium, and sodium chloride pumps and cause changes in pH (potential of hydrogen) in the proximal tubules and loop of Henle, resulting in bile cast formation, tubular toxicity, and injury.
Once the proximal tubules of the kidneys become saturated with bilirubin transport, bile cast formation and tubular obstruction occur. Hemodynamic changes that cause pre-renal azotemia are also observed. An increase in bile salts causes cardiovascular instability and decreases renal perfusion. This further exacerbates due to the presence of endotoxemia, hypoalbuminemia, and nitric-oxide-mediated mechanisms resulting in reduced peripheral vascular resistance and decreased renal perfusion, causing ischemic injury in the kidneys.
What Are the Effects of Hyperbilirubinemia on Kidneys?
Hyperbilirubinemia causes renal tubular hypertrophy, the presence of pigmented bile casts within the tubules, and the absence of glomerular pathology. It causes dilatation of the lumen and cytoplasmic vacuolization, resulting in tubular damage. Severe hyperbilirubinemia is associated with the presence of bile casts in the proximal tubules. It causes histological changes like glomerular congestion, nuclear vacuolization, and necrosis in proximal tubules. It is also associated with the lymphocytic collection, necrosis, interstitial edema, and bile cast deposition.
An increase in bile acids causes cholestatic diseases like obstructive jaundice, primary sclerosing cholangitis, and primary biliary sclerosis. To counteract the increase in bile salts, hepatocytes activate the basolateral hepatocellular transport. This enhances renal filtration and tubular secretion in the proximal tubules. The imbalance in tubular secretion and reabsorption with excessive excretion of bile salts contributes to renal injury.
What Are the Hemodynamic Changes Associated With Hyperbilirubinemia?
Hepatorenal syndrome is a serious complication that affects renal function in patients with advanced liver diseases. Advanced cirrhosis causes severe portal hypertension, splanchnic vasodilation, and vasoconstrictor activation resulting in renal vasoconstriction, hypoperfusion, and eventually acute kidney injury. Excess bilirubin activates the release of systemic endotoxins. This leads to renal blood flow redistribution and results in hypotension and hypoperfusion. These events cause corticomedullary junction ischemia and result in tubular injury.
How Is Bile Cast Nephropathy Diagnosed?
-
Renal Biopsy - Renal biopsy is the major diagnostic criterion for bile cast nephropathy. On histological examination, yellow or green-brown casts are seen obstructing the tubular lamina in the distal tubule. Changes like vacuolization of tubular cells and tubular necrosis are associated with acute kidney injury.
-
Urinalysis - Urinalysis shows an increase in creatinine levels. An increase in bilirubin is associated with a simultaneous increase in creatinine.
-
Urinary Biomarkers - Acute kidney injury due to hyperbilirubinemia causes the release of proteins in urine. Various urinary biomarkers are used to evaluate acute kidney injury. Neutrophil gelatinase-associated lipocalin (NGAL) is a protein excreted in ischemic or nephrotoxic kidney injury. The NGAL levels are used to monitor tubular epithelial damage. Other markers like interleukin 18 and kidney injury molecule (KIM-1) are also seen in kidney injury.
How Is Bile Cast Nephropathy Treated?
No specific guidelines are available for diagnosing, treating, and managing patients with bile cast nephropathy. The treatment for bile cast nephropathy is based on managing the underlying cause of hyperbilirubinemia to prevent renal injury. It includes the following:
-
In the presence of biliary stones or tumors, procedures like endoscopic retrograde cholangiopancreatography, tumor resection, and stent placement are performed to relieve the obstruction.
-
Extracorporeal therapies like hemodialysis and plasma exchange are performed to reduce creatinine and bilirubin levels. Plasmapheresis helps in removing toxins and bilirubin and replenishes factors like albumin, coagulation factors, and hepatic regenerative substances, thereby improving the symptoms of the patients.
-
Drugs like steroids, Cholestyramine, Ursodeoxycholic acid, and Lactulose are also used to treat bile cast nephropathy.
Conclusion
Bile cast nephropathy is a rare condition that is observed in patients with liver disease. It can cause reversible nephropathy or intractable disease that requires liver and kidney transplantation. It is an uncommon finding that usually that requires accurate diagnosis for proper management. Accurate diagnosis and proper management techniques are required to treat bile cast nephropathy.
