Atypical Hemolytic Uremic Syndrome (
aHUS) is a rare, life-threatening disease characterized by the triad of hemolytic anemia, thrombocytopenia, and acute kidney injury. Unlike typical HUS, which is often associated with infections like
Shiga toxin-producing Escherichia coli (STEC), aHUS is primarily linked with genetic mutations affecting the complement system.
Histological Features of aHUS
In aHUS, histological examination of kidney biopsies reveals distinctive changes. These include
glomerular and arteriolar
thrombotic microangiopathy (TMA). The glomeruli often exhibit endothelial swelling, mesangiolysis, and the presence of fibrin-rich thrombi in the capillary loops. In the arterioles, there can be fibrinoid necrosis and mucoid intimal thickening.
Role of Endothelial Cells
Endothelial cells play a crucial role in the pathology of aHUS. These cells are essential for maintaining the balance between thrombosis and fibrinolysis. In aHUS, mutations in genes regulating the complement system lead to uncontrolled activation of the complement pathway, resulting in endothelial cell injury. This injury is pivotal in the formation of microthrombi, which can be observed in histological sections.
Complement System and aHUS
The complement system is a part of the immune system that enhances the ability of antibodies and phagocytic cells to clear microbes and damaged cells. In aHUS, mutations in genes like
CFH,
CFI,
MCP, and others lead to dysregulation of the complement pathway. Histologically, this dysregulation is manifested by the deposition of complement components, such as C3, in the glomeruli and arterioles.
Diagnostic Histological Techniques
Several histological techniques are employed to diagnose aHUS. Hematoxylin and eosin (H&E) staining is used to evaluate the general architecture of the kidney and identify thrombi. Immunofluorescence can be employed to detect the deposition of complement components. Electron microscopy is helpful in visualizing endothelial cell injury and the presence of subendothelial electrondense deposits.
Differences Between aHUS and Other TMAs
It is essential to differentiate aHUS from other forms of thrombotic microangiopathies (TMAs), such as
thrombotic thrombocytopenic purpura (TTP) and typical HUS. While TTP is characterized by a deficiency in the ADAMTS13 enzyme, aHUS involves complement dysregulation. Histologically, TTP often shows more prominent platelet aggregation without the extensive complement deposition seen in aHUS.
Therapeutic Implications
The histological findings in aHUS have significant therapeutic implications. The identification of complement deposition in kidney biopsies supports the use of complement inhibitors like
eculizumab, which has revolutionized the treatment of aHUS. By inhibiting the complement pathway, these drugs help to prevent further endothelial damage and thrombus formation.
Conclusion
Histology plays a vital role in the diagnosis and understanding of atypical hemolytic uremic syndrome (aHUS). The examination of kidney biopsies reveals critical changes such as glomerular and arteriolar thrombotic microangiopathy, endothelial cell injury, and complement deposition. Recognizing these histological features is essential for differential diagnosis and guiding appropriate therapy for affected individuals.
