Table 4.

Monitoring disease activity in atypical hemolytic uremic syndrome (aHUS) patients

Characteristics aHUS	Regular workup during eculizumab therapya	Regular workup after therapy withdrawal	Recurrence aHUSb, c
1. (Acute) Kidney injury	Serum creatinine	Serum creatinine	Serum creatinine greater than upper limit of normal per age or increase of > 15% compared with baseline
	Proteinuria (protein–creatinine ratio)	Proteinuria (protein–creatinine ratio)	Increase of > 25% in proteinuria
		Dipstick analyses twice per week at home
	Bloodpressure (aim for P50)	Blood pressure measurement twice per week at home	NA
2. Thrombocytopenia	Platelets	Platelets	Platelet count < 150,000 × 103 μl
3. Mechanical hemolytic anemia			Mechanical hemolysis is defined by the presence of at least 2 or more of the following criteria
	Hemoglobin	Hemoglobin	Below lowest limit of normal per age
	LDH	LDH	Greater than upper limit of normal
	Haptoglobin	Haptoglobin	Undetectable
	Schizocytes	Schizocytes	Appearance of schizocytes

After therapy withdrawal strict monitoring is essential. Regular workup after at least 1,2, 3, 6, 9, and 12 months is required. We would advise to monitor blood pressure at home. We aim for blood pressures around P50 for height and age (children) or < 130/80 mmHg (adults). Urine dipstick analysis at home could be considered, especially in children. Moreover, comprehensible instructions to the patient (and caregivers) when and how to contact their treating physician are essential. In case of signs indicating atypical hemolytic uremic syndrome (aHUS) recurrence such as high blood pressure, petechiae, fatigue, oliguria, jaundice, or a possible triggering event-like infection, the patient has to seek contact immediately. Of note, recurrent aHUS after kidney transplantation can present as a smoldering disease, with a slow increase in serum creatinine without overt systemic hemolysis. A allograft biopsy may disclose only subtle changes, mostly limited to swelling of vascular endothelial cells in capillaries and small arterioles [64]

LDH lactate dehydrogenase, NA not applicable, P50 median percentile for height and age, TMA thrombotic microangiopathy

^aConsider to monitor liver enzymes in light of potential hepatotoxicity, especially in patients with pre-existing liver disease

^bRecurrece of aHUS is defined by the occurrence of all three characteristics of aHUS; acute kidney injury, thrombocytopenia, and mechanical hemolytic anemia

^cA kidney biopsy to detect (smoldering) TMA can be of additional value