Nephrology emergency · KIMS Secunderabad
Hemolytic Uremic Syndrome (HUS and aHUS) — When Blood and Kidneys Are Attacked Simultaneously
Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy — a condition in which small clots form in the tiny blood vessels of the kidneys and other organs, destroying red blood cells as they are forced through narrowed vessels, consuming platelets, and causing acute kidney failure. It manifests as the clinical triad of microangiopathic haemolytic anaemia (red blood cell destruction), thrombocytopaenia (low platelets), and acute kidney injury — three seemingly unconnected laboratory findings that, together, point to a single underlying process: endothelial damage and microvascular thrombosis.
There are two principal forms. Typical HUS — also called STEC-HUS or Shiga toxin HUS — is triggered by infection with Shiga toxin-producing Escherichia coli (most commonly E. coli O157:H7), usually through contaminated food. It primarily affects children and is self-limiting in most cases, though severe cases require dialysis support. Atypical HUS (aHUS) is caused by dysregulation of the alternative complement pathway — a genetic or acquired defect that causes uncontrolled complement activation even without an infectious trigger. aHUS is more severe, more likely to cause permanent kidney damage, has a high relapse rate, and requires specific treatment with eculizumab — a complement inhibitor.
Typical HUS (STEC-HUS) — the infection-triggered form
Typical HUS is triggered by Shiga toxin-producing E. coli, usually after a food-borne outbreak. It predominantly affects young children and is largely managed with supportive care while the kidneys recover.
Cause — Shiga toxin from E. coli
Ingestion of Shiga toxin-producing E. coli (STEC) — most commonly E. coli O157:H7 — through undercooked beef, contaminated water, unpasteurised dairy, or raw vegetables. Shiga toxin is absorbed from the gut, reaches the kidney's endothelial cells, and directly damages the glomerular endothelium — triggering microvascular thrombosis.
Who it affects
Predominantly children under 5 years old. Can affect any age group during food-borne outbreaks.
Symptoms — the diarrhoeal prodrome
The illness begins with 3 to 5 days of bloody diarrhoea (haemorrhagic colitis) — the warning sign that STEC infection has occurred. Approximately 5 to 15% of STEC infections progress to HUS: suddenly, 5 to 10 days after the diarrhoea begins, the urine turns dark (haematuria), urine output falls (oliguria), pallor and jaundice appear (from haemolysis), and the child becomes acutely unwell. Laboratory tests show haemolytic anaemia, thrombocytopaenia, and rising creatinine.
Treatment — supportive care
Primarily supportive — careful fluid and electrolyte management, blood transfusion for severe anaemia, and dialysis (CRRT or intermittent haemodialysis) for kidney failure. Antibiotics are contraindicated — they increase Shiga toxin release and worsen outcomes. Most children recover completely within 2 to 4 weeks with supportive care. Up to 25% develop long-term kidney damage including CKD, hypertension, or proteinuria.
Atypical HUS (aHUS) — the complement-driven form
Atypical HUS is caused by dysregulation of the alternative complement pathway — usually on a genetic background — and can be triggered by relatively minor events. It is more severe than STEC-HUS and requires specific complement-blocking treatment with eculizumab.
Cause — uncontrolled complement activation
Mutations in or antibodies against complement regulatory proteins — most commonly Factor H, Factor I, MCP (CD46), C3, Factor B, or thrombomodulin. These mutations prevent the alternative complement pathway from switching off, causing uncontrolled C3 activation and membrane attack complex deposition on endothelial cells. Unlike STEC-HUS, aHUS is triggered by relatively minor events — pregnancy, infection, drugs, surgery — in a genetically susceptible individual.
Who it affects
All age groups — including adults. Accounts for approximately 10% of all HUS cases but the majority of adult HUS. May present de novo, during pregnancy (usually in the third trimester or postpartum — the most dangerous period), or as a relapse.
Symptoms — same triad, more severe
The same triad — haemolytic anaemia, thrombocytopaenia, AKI — but typically more severe and more likely to cause permanent kidney damage than STEC-HUS. The absence of a diarrhoeal prodrome (or a mild upper respiratory infection as the trigger) in an adult with TMA should prompt aHUS evaluation. Neurological involvement (confusion, seizures, stroke) is more common in aHUS than STEC-HUS.
Treatment — eculizumab
Eculizumab is a monoclonal antibody that blocks complement component C5, preventing the membrane attack complex from forming. It is the specific treatment for aHUS and has transformed the outcome — prior to eculizumab, up to 50% of aHUS patients died or reached end-stage renal disease within 1 year. With eculizumab, remission is achievable in 80 to 90% of patients and kidney function often improves significantly. Eculizumab is initiated at KIMS for confirmed aHUS alongside plasma exchange while genetic testing results are awaited. Long-term eculizumab is required in most patients (indefinite, or for at least 2 years with careful monitoring for relapse if cessation is attempted).
Distinguishing HUS from TTP
Thrombotic thrombocytopenic purpura (TTP) produces an identical clinical picture — microangiopathic haemolytic anaemia, thrombocytopaenia, AKI — but has a different mechanism (ADAMTS13 deficiency) and requires different treatment (plasma exchange is curative for TTP but not for aHUS).
The ADAMTS13 activity level is the critical distinguishing test: severely reduced ADAMTS13 (below 10%) confirms TTP; normal or mildly reduced ADAMTS13 points toward HUS.
At KIMS, ADAMTS13 activity is measured urgently alongside complement studies in every patient presenting with TMA. Plasma exchange is started empirically while the results are awaited — it treats TTP directly and provides complement factors that may modestly benefit aHUS.
CRRT and acute kidney management at KIMS
Severe HUS and aHUS frequently cause oliguric AKI requiring dialysis support while the underlying condition is treated.
At KIMS, CRRT (continuous renal replacement therapy) is available 24/7 in the ICU for haemodynamically unstable patients with severe HUS/aHUS — maintaining fluid balance, electrolyte control, and clearance of uraemic toxins while eculizumab takes effect. Intermittent haemodialysis is used for stable patients.
Most patients with typical HUS recover kidney function fully within 2 to 4 weeks of dialysis support. In aHUS, recovery of kidney function with eculizumab may take 2 to 6 months.
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Frequently Asked Questions — HUS / aHUS
Yes — HUS is a serious condition that can be life-threatening, particularly in its atypical form (aHUS). Severe STEC-HUS can cause acute kidney failure requiring dialysis, neurological complications (seizures, stroke) from microthrombi in brain vessels, and cardiac involvement. Death occurs in approximately 1 to 5% of STEC-HUS cases. aHUS has historically had a much worse prognosis — up to 25% mortality in the acute phase before eculizumab became available. With modern management (CRRT for kidney support, plasma exchange for TTP exclusion, eculizumab for aHUS), outcomes have improved dramatically but the condition remains serious and requires specialist nephrology management.
HUS and TTP (thrombotic thrombocytopenic purpura) are both thrombotic microangiopathies with a similar clinical picture — microangiopathic haemolytic anaemia, thrombocytopaenia, and organ damage. The key differences: TTP is caused by ADAMTS13 deficiency (an enzyme that cleaves von Willebrand factor multimers — without ADAMTS13, large multimers accumulate and cause platelet aggregation). HUS is caused by Shiga toxin (typical) or complement dysregulation (atypical). TTP has more neurological involvement relative to kidney involvement; HUS has more prominent kidney involvement. ADAMTS13 activity below 10% confirms TTP. Normal ADAMTS13 with microangiopathy points to HUS. Plasma exchange treats TTP directly; eculizumab is the specific treatment for aHUS.
Typical HUS (STEC-HUS) is caused by Shiga toxin-producing E. coli — most commonly E. coli O157:H7. The most common food sources: undercooked or raw minced beef (hamburgers — hence the historical name 'hamburger disease' in the USA), unpasteurised milk and dairy products, raw leafy vegetables contaminated by cattle faeces, contaminated drinking water, and direct contact with infected animals (particularly cattle and sheep). Cooking beef thoroughly (internal temperature above 70°C), washing vegetables thoroughly, and avoiding unpasteurised dairy are the principal prevention measures.
Yes — atypical HUS has a genetic basis in the majority of cases. Mutations in complement regulatory genes (Factor H, Factor I, MCP, C3, Factor B, thrombomodulin) are identified in approximately 60 to 70% of aHUS patients. These mutations follow an autosomal dominant inheritance pattern with incomplete penetrance — meaning that carrying the mutation does not guarantee developing aHUS, but significantly increases the risk, particularly when a trigger event occurs. Genetic testing of the patient and first-degree family members is part of the KIMS aHUS workup. Family members who carry the same mutation should be counselled about their risk and the potential triggering events (pregnancy, major surgery, infection) to watch for.
The optimal duration of eculizumab for aHUS is still an area of active research. Most centres, including KIMS, treat for at least 24 months before considering cessation in patients who have achieved sustained remission and have a favourable genetic profile (MCP mutations have a lower relapse rate after cessation than Factor H mutations). Cessation requires very close monitoring — relapses after stopping eculizumab occur in 20 to 30% of patients, and prompt reinitiation of treatment at relapse is essential. Patients with ongoing complement activation (rising C3d or sC5b-9 biomarkers) despite clinical remission are generally continued on eculizumab indefinitely.
Typical STEC-HUS: approximately 25% of children develop long-term sequelae including CKD, proteinuria, or hypertension — even after apparent full recovery. The risk is higher with prolonged oliguria, dialysis dependence during the acute phase, or neurological involvement. Adults with STEC-HUS have worse long-term outcomes than children. Atypical HUS: before eculizumab, 50% of aHUS patients reached end-stage renal disease within 12 months. With eculizumab, the majority avoid permanent dialysis if treatment is initiated promptly. Patients who had aHUS and reached ESRD before eculizumab was available are candidates for kidney transplant — with eculizumab cover to prevent recurrence in the transplanted kidney.
Yes — pregnancy, particularly the third trimester and the postpartum period, is the most common trigger for aHUS in women with underlying complement regulatory gene mutations. Pregnancy activates the alternative complement pathway as part of normal implantation physiology — in women with complement regulatory mutations, this activation is uncontrolled. aHUS in pregnancy must be distinguished from pre-eclampsia, HELLP syndrome, and pregnancy-related TTP — all of which can cause thrombocytopaenia and AKI. ADAMTS13 activity, anti-Factor H antibodies, and complement studies guide the diagnosis. Eculizumab is safe in pregnancy and is used for confirmed aHUS in pregnant patients.
KIMS Secunderabad — Dr. V. S. Reddy and Dr. E. Ravi (senior transplant nephrologists), CRRT 24/7 for acute kidney support, plasma exchange capability, eculizumab administration for confirmed aHUS, ADAMTS13 activity and complement studies, genetic testing coordination for aHUS workup, transplant programme with eculizumab cover for aHUS patients. NABH and NABL accredited. Emergency nephrology 24/7 — call 040-4488-5000.