Proposed algorithm for the diagnosis and management of aHUS in the acute phase.^aLow C3 and/or low factor H or I plasma levels are suggestive of complement-mediated aHUS. ^bPositivity at significant titers is diagnostic of autoimmune aHUS. ^cActivity of <10% is diagnostic of ADAMTS13 deficiency TTP. ^dPositivity is diagnostic of Shiga toxin–producing E. coli HUS. ^eLevel of >100 mmol/L is suggestive of cobalamin C deficiency HUS (as well as increased plasma and/or urine methylmalonic acid and low plasma methionine level). Confirmation by genetic testing (MMACHC gene). Cobalamin C deficiency HUS is increasingly diagnosed in young adults. ^fPositivity is suggestive of autoimmune disease–associated HUS. ^gMonoclonal gammopathy–associated TMA carries severe renal and potentially extrarenal (skin and central and peripheral nervous system) involvement, and frequent (up to 75% of cases) features of complement alternative pathway activation. ACEI/ARB, angiotensin converting enzyme inhibitors/angiotensin 2 receptor blocker; AKI, acute kidney injury; BP, blood pressure; dsDNA, double-stranded DNA; ENA, extractable nuclear antigen; FFP, fresh frozen plasma; GPI, glycoprotein I; HD, hemodialysis; PCR, polymerase chain reaction; PE, plasma exchange; Plt, platelet count; PRES, posterior reversible encephalopathy syndrome; SCr, serum creatinine; UPCR, urinary protein/creatinine ratio.