Hemoglobinuria is a condition in which the oxygen transport protein hemoglobin is found in abnormally high concentrations in the urine. The condition is caused by excessive intravascular hemolysis, in which large numbers of red blood cells (RBCs) are destroyed, thereby releasing free hemoglobin into the plasma. Excess hemoglobin is filtered by the kidneys, which excrete it into the urine, giving urine a discolored appearance.
Pathophysiology
When red blood cells are lysed, cell-free hemoglobin will bind to hemoglobin binding protein known as haptoglobin in order to prevent it from reaching the kidneys' filtration system, instead forming large complexes to be targeted and cleared by macrophages. In the absence of adequate defenses to remove hemoglobin in excess, hemoglobin can cause damage to the kidneys due to direct cytotoxic effects, oxidative stress, and endothelial dysfunction. PNH produces red blood cells with defective genes for CD55 and CD59 surface proteins, destroying the blood cells and leading to the classical appearance of dark urine in the morning. SCD patients have red blood cells that are constantly destroyed due to sickled membrane abnormalities. One acquired etiology is autoimmune hemolytic anemia (AIHA) which was shown to be the most common cause of hemoglobin cast nephropathy; causing nearly 30% of total cases studied, AIHA may cause intravascular hemolysis in severe cases. Other acquired causes include medication induced hemolysis and acute hemolytic transfusion reactions. Typically seen in runners and military persons, an example of this was first noted in 1881 where a German soldier passed dark urine after prolonged marching. Abdominal pain, esophageal spasm, dysphagia, and sternal pain occur with intravascular hemolysis in a dose-dependent manner. LDH levels will be much higher than in extravascular hemolysis. Hemosiderinuria, or iron-containing cells in the urine, occurs only with severe intravascular hemolysis and indicates recurrent or chronic hemoglobinuria.
Treatment
Appropriate treatment for hemoglobinuria requires treating of the underlying cause of hemolysis; in the study that had 27 patients with biopsy-proven hemoglobin cast nephropathy, 78% regained normal renal function after treatment of their respective causes.
Some conditions will also require adjunct therapies or treatments specific to the underlying cause. Corticosteroids and monoclonal antibodies like rituximab are used to treat AIHA with initial response rates up 80 percent. Discontinuation or removal of the offending agent is the mainstay of treatment for acute hemolytic transfusion reaction and medication induced hemolysis. Complement inhibitors like eculizumab are used to treat PNH, with hematopoietic stem cell transplant reserved for refractory cases or patients with severe bone marrow failure.