Atypical hemolytic uremic syndrome (aHUS) is characterized by hemolytic anemia, thrombocytopenia and kidney failure. Unlike typical HUS which is usually caused by infection with certain strains of E.Coli, a-HUS is caused by abnormalities in complement system, triggered by certain environmental factors or genetic mutations. aHUS can be genetic, acquired, or idiopathic. Mutations in at least 10 genes identified so far (C3, CD46, CFB, CFH, CFHR1, 3, 4 and 5, CFI and THBD) appear to increase the risk of developing aHUS. CFH mutation is the most common accounting for approximately 30 percent of all cases. Pathophysiology is proposed to be microangiopathic in nature, where platelet thrombi occlude microcirculation resulting in organ dysfunction. It is believed that aHUS causes renal dysfunction but we propose that either condition can precede the other. Lucio et al (2013) followed patients who had biopsy-proven diagnosis of glomerulonephritis and found that significant number of them developed aHUS over a period of time.

A 26-year old male with no past medical history presented to E.D. with malaise for one week. He denied any fever or chills, recent or remote diarrheal illness or any upper respiratory symptoms. Initial diagnostics revealed hemoglobin 6.8, hematocrit 19.7, WBC 9.2, platelets 79 with peripheral blood smear showing schistocyte, BUN 109, creatinine 28.6, LDH 813, and haptoglobin<10 consistent with hemolytic anemia, thrombocytopenia and renal insufficiency prompting the presumptive diagnosis of TTP/HUS. He was treated with emergent plasmapheresis and hemodialysis. ADAMTS13, complement C3and C4 levels were normal. Renal ultrasound discovered atrophic kidneys consistent with severe chronic kidney disease and kidney biopsy revealed focal segmental collapsing glomerulosclerosis without any evidence of microthrombi. Testing for HIV and hepatitis A, B, C and D were also negative. Given the absence of any preceding diarrheal illness, patient’s age at presentation, and triad of thrombocytopenia, hemolytic anemia and renal insufficiency prompted the diagnosis of a-HUS. Genetic studies for CFH, C3, CFB and CFI mutations were sent, which are still pending. Patient condition remained critical with ongoing hemolysis needing regular plasma exchange therapy and hemodialysis for over period of one month, consistent with aHUS refractory or dependent to plasma therapy. Patient was subsequently referred to a specialized center for treatment with Eculizumab and possible renal transplant.

The sequence of events and kidney biopsy findings for our patient suggest that he had an underlying chronic glomerulonephritis which was complicated by aHUS, which has been reported previously. We propose that some common genetic mutations may predispose patients to glomerulonephritis and development of aHUS. Till now it has been postulated that underlying pathophysiology in aHUS is chronic, uncontrolled activation of the complement system. In this case normal complement levels and underlying chronic glomerulonephritis suggests an alternate mechanism for development of aHUS. We emphasizes the importance of further testing and research into the mechanism of aHUS and possible genetic linkage of chronic glomerulonephritis to aHUS.


No relevant conflicts of interest to declare.

Author notes


Asterisk with author names denotes non-ASH members.