Atypical hemolytic uremic syndrome (aHUS) is a rare and severe form of thrombotic microangiopathy (TMA) characterized by the clinical triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Unlike typical HUS, which is usually caused by Shiga toxin-producing Escherichia coli (STEC), aHUS is primarily mediated by the excess activation or dysregulation of the alternative complement pathway [3]. While various triggers such as pregnancy, drugs, and other infections exist, colitis caused by Clostridioides difficile is identified as an exceptionally rare precipitant of this syndrome [2]. Very few adult cases have been documented in the medical literature, particularly following abdominal surgery.

Clinical manifestations typically begin with gastrointestinal symptoms, including diffuse abdominal pain and diarrhea, which can range from watery to bloody stools. As the syndrome progresses, patients often develop severe acute renal failure, frequently presenting with anuria or oliguria and moderate to accelerated hypertension [3]. Extra-renal involvement is also common, affecting 10% to 30% of patients; this most frequently manifests as neurological complications such as encephalopathy, delirium, confusion, and severe headaches [1].

In terms of biology and laboratory findings, a diagnosis is established through evidence of mechanical hemolysis, including the presence of schistocytes (fragmented red blood cells) on a peripheral blood smear and an acute drop in hemoglobin. Other hallmark markers include a severely low platelet count, significantly elevated Lactate Dehydrogenase (LDH), and undetectable or very low haptoglobin levels. Renal function tests show a sudden and sharp rise in serum creatinine and blood urea nitrogen (BUN) [2]. To confirm aHUS and rule out other TMAs, it is essential to demonstrate normal ADAMTS13 activity (typically >5-10%) and the absence of Shiga toxins in stool samples. Stool studies must be positive for C. difficile toxins A or B or the GDH antigen to confirm the infection as the trigger [4].

Colonoscopy and rectosigmoidoscopy serve as useful tools to document the severity of the underlying colitis and assist in differential diagnosis. These procedures may reveal signs of pseudomembranous colitis, characterized by diffuse erythema, multiple superficial ulcerations, and a complete loss of healthy mucosa. Such findings correspond to high endoscopic severity scores and help distinguish C. difficile infection from other inflammatory or infectious causes of hemorrhagic diarrhea [4].

Imaging and radiology provide critical insights into organ involvement and complications. Renal ultrasound often shows normal-sized kidneys, which helps rule out obstructive causes like stones or hydronephrosis, though bilateral cortical thinning may be seen in cases with underlying chronic disease. Abdominal CT scans are vital for detecting acute renal infarctions secondary to branch artery thrombosis or evidence of severe colitis. For patients with neurological symptoms, head CT or MRI is necessary to identify chronic vascular ischemic changes, lacunar infarcts, or cerebral edema [1].

The treatment of C. difficile-associated aHUS requires a multifaceted approach, starting with aggressive supportive care, including hemodialysis for renal failure and blood transfusions for anemia. Specific antimicrobial therapy with oral vancomycin or metronidazole is mandatory to eradicate the C. difficile infection [5]. While plasma exchange and corticosteroids have historically been used, eculizumab—a monoclonal antibody that inhibits the C5 complement fraction—has emerged as a highly effective first-line therapy. The prognosis is generally favorable with early intervention, often leading to complete renal recovery and dialysis independence.