D-minus hemolytic uremic syndrome

D-minus hemolytic uremic syndrome (D-HUS), also known as atypical hemolytic uremic syndrome (aHUS), is a rare, life-threatening medical condition characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Unlike the more common D+HUS, which is typically caused by infection with Shiga toxin-producing Escherichia coli (STEC), D-HUS does not follow an infectious trigger and is instead associated with genetic mutations affecting the complement system, a part of the body's immune system that helps fight infections.

Etiology and Pathophysiology

D-HUS results from dysregulation of the complement system, leading to uncontrolled complement activation. This activation causes damage to the endothelial cells lining the blood vessels, particularly in the kidneys, resulting in the characteristic symptoms of HUS. Several genetic mutations have been identified that predispose individuals to D-HUS, including mutations in factors H, I, B, and components of the membrane attack complex (MAC).

Clinical Presentation

Patients with D-HUS typically present with symptoms of anemia, such as fatigue and pallor, due to the destruction of red blood cells. Thrombocytopenia can lead to bleeding tendencies, including purpura, petechiae, and bleeding from mucous membranes. The acute kidney injury associated with D-HUS may manifest as reduced urine output, fluid overload, hypertension, and in severe cases, anuria requiring dialysis.

Diagnosis

The diagnosis of D-HUS is based on the clinical triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury, in the absence of a preceding diarrheal illness. Laboratory tests will show evidence of hemolysis, such as elevated lactate dehydrogenase (LDH), low haptoglobin, and the presence of schistocytes on a peripheral blood smear. Kidney function tests will indicate impaired renal function. Genetic testing may be performed to identify mutations in complement regulatory proteins.

Treatment

Treatment of D-HUS focuses on supportive care, including management of acute kidney injury and hypertension. Plasma exchange or infusion may be used to remove or replace defective complement proteins in some cases. Eculizumab, a monoclonal antibody that inhibits the complement protein C5, has shown efficacy in treating D-HUS by preventing further complement-mediated damage to the endothelium.

Prognosis

The prognosis of D-HUS varies, with some patients experiencing full recovery while others may have persistent renal impairment or progress to end-stage renal disease requiring long-term dialysis or kidney transplantation. Early diagnosis and treatment are critical to improving outcomes.