Introduction
Hemosiderin is a compound that stores iron in body tissues. Hemosiderinuria refers to the excretion of hemosiderin in urine. It occurs due to intravascular hemolysis. Intravascular hemolysis is seen in hemolytic anemias. The presence of hemosiderin in urine indicates a recent or ongoing intravascular hemolysis characterized by the presence of excessive hemoglobin filtered via the glomerulus of the kidneys and the loss of hemosiderin-laden necrotic tubular cells.
What Is Hemosiderinuria?
Hemosiderin is a compound that is composed of lysosomes and partially digested ferritin. Biliverdin and iron are produced from the breakdown of red blood cells. The hemoglobin in red blood cells releases iron. The released iron is trapped and stored in the tissues as hemosiderin. Several diseases cause the accumulation of large amounts of hemosiderin in tissues. Hemosiderinuria refers to the excretion of hemosiderin in urine. Intravascular hemolysis causes the excretion of hemosiderin in urine.
What Is the Difference Between Hemoglobinuria and Hemosiderinuria?
Hemoglobinuria is a condition in which excessive hemoglobin is found in urine. Hemosiderinuria is the excretion of hemosiderin in urine. Both conditions are caused by intravascular hemolysis, but hemoglobin disappears quickly, and hemosiderin remains in urine for several weeks. Hence, hemosiderinuria serves as a significant marker for intravascular hemolysis. Hemoglobinuria and hemosiderinuria cause complications like acute tubular necrosis.
What Is Hemosiderosis?
Hemosiderosis is a condition in which excessive hemosiderin is deposited in the tissues. It affects organs like the lungs, liver, brain, skin, and kidneys. Hemosiderosis occurs due to iron overload. It can be due to hemorrhage within an organ or tissue or the destruction of red blood cells. It often remains asymptomatic, and it is difficult to diagnose.
What Are the Causes of Hemosiderinuria?
Hemosiderinuria is caused by intravascular hemolysis in hemolytic anemias. Hemosiderinuria is observed in the following conditions:
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Hemolytic transfusion reactions.
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Cold hemagglutinin disease.
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Thalassemia major (inherited blood disorder).
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Hereditary spherocytosis (a condition characterized by anemia, jaundice and enlarged spleen).
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Disseminated intravascular coagulation (serious blood clotting disorder).
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Trauma during replacement of mechanical heart valves.
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Drug-induced oxidative stress, with or without G6PD (glucose-6-phosphate dehydrogenase) or PK (pyruvate kinase) deficiency.
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Severe burns.
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Infections like hepatitis, malaria, Brucella, cytomegalovirus infections, Epstein-Barr virus infection, Trypanosoma, Treponema, and Rickettsia.
How Does Hemosiderinuria Occur?
Hemosiderinuria is due to the excessive accumulation of hemosiderin in the kidneys. The excessive accumulation of hemosiderin causes hyponatremia, excessive red blood cell destruction (intravascular hemolysis), excessive uptake of iron, or hyperferremia, decreased utilization of iron (anemia of copper toxicity), or decreased uptake of iron (hypofarremia which leads to iron deficiency anemia).
Intravascular hemolysis is characterized by the presence of excessive hemoglobin and hemosiderin-laden necrotic tubular cells. Chronic intravascular hemolysis causes the release of hemoglobin from the red blood cells into the bloodstream. Haptoglobin is the protein that binds the circulating hemoglobin and reduces renal excretion of hemoglobin to prevent injury to the renal tubules. The kidneys filter chelates of hemoglobin that is not bound to haptoglobin, and it is reabsorbed in the proximal convoluted tubule.
In the proximal tubule, the hemoglobin is degraded in the tubular cells, and the free chelatable iron is stored in the form of hemosiderin. The tubular cells of the proximal tubules become damaged and are sloughed off hemosiderin, which is then excreted in the urine. This produces brownish-colored urine, which is usually observed three to four after the onset of intravascular hemolysis.
What Are the Complications of Hemosiderinuria?
Hemosiderinuria can cause complications ranging from reversible kidney injury to irreversible chronic kidney disease. Complications like weakness, the jaundice, and iron deficiency anemia are seen in individuals with long-standing hemosiderinuria due to chronic hemolysis.
The chemically activated iron present in hemosiderin can cause injury to the tubular cells. It causes tubular injury through free radical formation and lipid peroxidation, which may result in tubular necrosis. Chronic persistent hemolysis increases the hemosiderin deposition in the proximal tubules of the kidneys. The excess hemoglobin in the tubules causes cytotoxic effects like the generation of reactive oxygen species, apoptosis, and inflammation. This results in structural changes like tubular atrophy, interstitial fibrosis, and tubular necrosis.
Moderate deposition of hemosiderin in kidneys is mildly toxic under normal conditions. However, hemosiderin can cause hemoglobinuria-associated acute renal failure in the presence of concentrated urine due to fluid volume depletion and hemolysis. Severe deposition of hemosiderin in kidneys results in iron deficiency anemia because iron stored in other sites like nonhematopoietic tissues is not available for the body.
How Is Hemosiderinuria Diagnosed?
Hemosiderinuria is a marker for underlying disease and not a disease by itself. It is formed during the metabolic breakdown of hemoglobin. Hemosiderinuria can be diagnosed with a hemosiderin urine test.
Hemosiderin Urine Test
A hemosiderin urine test detects the presence of hemosiderin in urine. It serves as an important diagnostic tool for detecting hemosiderinuria secondary to hemolytic anemias, incompatible blood transfusions, and hemochromatosis. This test also helps in evaluating and managing the disorders which involve the destruction of red blood cells. It is also used to evaluate chronic venous insufficiency.
The hemosiderin urine test is a simple test in which the patient is asked to urinate in a sterile container. The collected urine is then examined for hemosiderin, and the results are interpreted as positive or negative for hemosiderin.
How Is Hemosiderinuria Treated?
The treatment for hemosiderinuria is usually aimed at managing the underlying cause of hemolysis. Treating the underlying condition by reducing or eliminating the destruction of red blood cells and increasing the red blood cell count eliminates hemosiderinuria. Blood transfusions, medicines like corticosteroids for autoimmune hemolytic anemia, plasmapheresis to remove the antibodies in immune hemolytic anemias, splenectomy (surgical removal of the spleen) to reduce the rate of red blood cell destruction, and blood and bone marrow transplant to replace the damaged cells are the treatment strategies followed to treat hemolytic anemias. Hemosiderinuria stops once the intravascular hemolysis is eliminated.
Conclusion
Hemosiderinuria is not a disease by itself but rather a common symptom of conditions like intravascular hemolysis. It is a useful marker in the diagnosis of intravascular hemolysis. Hemosiderin in urine is a more reliable marker than hemoglobin in urine because hemoglobin disappears soon, but hemosiderin is present in urine for several days. Hemosiderin urine test helps in the detection of recent or ongoing intravascular hemolysis.
