📋 Key Information Summary
- Haemolytic uraemic syndrome (HUS) is a thrombotic microangiopathy (TMA) defined by the triad of microangiopathic haemolytic anaemia (MAHA), thrombocytopenia, and acute kidney injury (AKI).
- Typical (diarrhoea-positive) HUS is caused by Shiga toxin-producing Escherichia coli (STEC) — predominantly O157:H7 — and accounts for approximately 90% of paediatric HUS cases in Australia.
- Atypical HUS (aHUS) is caused by uncontrolled complement alternative pathway activation and represents approximately 5–10% of all HUS presentations; it is often diarrhoea-negative and carries significant risk of end-stage kidney disease (ESKD).
- STEC-HUS management is primarily supportive: careful fluid and electrolyte management, avoidance of nephrotoxins, and renal replacement therapy (RRT) when indicated. Antibiotics are generally contraindicated in suspected STEC infection.
- Antibiotic use in STEC may increase the risk of HUS by promoting Shiga toxin release; avoid empirical antibiotics in bloody diarrhoea until STEC is excluded.
- aHUS requires urgent complement inhibition with eculizumab (Soliris®) or ravulizumab (Ultomiris®), which are PBS Authority Required in Australia for complement-mediated aHUS.
- Before initiating complement inhibitor therapy, exclude TTP (ADAMTS13 activity <10%), STEC-HUS (stool PCR/culture for Shiga toxin), drug-induced TMA, and secondary TMA causes.
- Vaccination against Neisseria meningitidis (MenACWY + MenB) is mandatory before starting eculizumab or ravulizumab due to life-threatening meningococcal infection risk.
- Australian STEC notifications have risen in recent years; OzFoodNet reports outbreaks linked to contaminated salad greens, raw milk, and undercooked minced beef.
- Aboriginal and Torres Strait Islander children experience higher rates of infectious gastroenteritis and may present later with more severe STEC-HUS, requiring outreach and telepaediatric support.
- Early nephrology consultation is essential for all suspected HUS; transfer to a paediatric tertiary centre is recommended for children requiring dialysis or suspected aHUS.
- Long-term follow-up is critical: up to 25% of STEC-HUS survivors develop chronic kidney disease (CKD), and aHUS patients on complement inhibitors require lifelong monitoring.
Introduction & Australian Epidemiology
Haemolytic uraemic syndrome (HUS) is a form of thrombotic microangiopathy (TMA) characterised by the clinical triad of microangiopathic haemolytic anaemia (MAHA), consumptive thrombocytopenia, and acute kidney injury (AKI). It is the most common cause of AKI in young children in Australia and other high-income countries.
HUS is broadly classified into two major subtypes:
- Typical HUS (STEC-HUS / diarrhoea-associated HUS): Accounts for approximately 90% of paediatric HUS cases. Caused by Shiga toxin-producing Escherichia coli (STEC), most commonly serotype O157:H7. Preceded by a prodrome of bloody diarrhoea.
- Atypical HUS (aHUS / complement-mediated HUS): Accounts for approximately 5–10% of cases. Driven by dysregulated activation of the complement alternative pathway due to genetic mutations or acquired autoantibodies. Often diarrhoea-negative at presentation.
Australian Epidemiology
In Australia, STEC is a notifiable condition under the National Notifiable Diseases Surveillance System (NNDSS). OzFoodNet data indicate an annual notification rate of approximately 0.5–1.0 per 100,000 population for STEC infection nationally, with seasonal peaks in summer and autumn. The progression rate from confirmed STEC infection to HUS is approximately 8–15% in children under 5 years of age.
Key Australian epidemiological observations include:
- Age distribution: STEC-HUS predominantly affects children aged 6 months to 5 years (median age 2–3 years), though adult cases occur, particularly in the elderly.
- Serotype distribution: While O157:H7 remains the most common STEC serotype in Australia, non-O157 serotypes (O26, O111, O121) are increasingly identified, particularly in South Australia and Queensland.
- Outbreak sources: Documented Australian outbreaks have been linked to contaminated lettuce and salad greens, petting zoos, farm visits, raw milk products, and undercooked minced beef.
- Indigenous considerations: Aboriginal and Torres Strait Islander children in remote communities may experience higher exposure to STEC through environmental water sources and limited food safety infrastructure, with delayed access to specialist nephrology care.
- Regional variation: South Australia has historically reported the highest STEC notification rates in Australia, linked to intensive local surveillance and molecular testing.
Critical distinction: Distinguishing STEC-HUS from aHUS is essential because treatment pathways diverge sharply — supportive care alone for STEC-HUS versus immediate complement inhibition for aHUS. ADAMTS13 activity testing is critical to exclude thrombotic thrombocytopenic purpura (TTP).
Typical HUS (STEC-HUS): Pathophysiology
STEC-HUS follows a well-characterised sequence of events initiated by ingestion of Shiga toxin-producing E. coli, most commonly through contaminated food or water.
Step 1: Colonisation & Shiga Toxin Production
After ingestion, STEC colonises the large intestine using attaching-and-effacing (A/E) lesions mediated by the locus of enterocyte effacement (LEE) pathogenicity island. Intimate attachment to colonic enterocytes triggers local inflammation and bloody diarrhoea. Shiga toxin (Stx1 and/or Stx2) is produced in the gut lumen and released during bacterial lysis.
Step 2: Toxin Translocation & Endothelial Injury
Shiga toxin crosses the intestinal epithelial barrier into the systemic circulation. It binds to globotriaosylceramide (Gb3/CD77) receptors expressed on renal glomerular endothelial cells, and to a lesser extent on intestinal, cerebral, and pancreatic endothelium. The toxin is internalised via receptor-mediated endocytosis, inhibits ribosomal protein synthesis via N-glycosidase activity, and triggers endothelial cell apoptosis and activation.
Step 3: Thrombotic Microangiopathy
Damaged endothelial cells lose their normal antithrombotic surface properties. Consequences include:
- Upregulation of von Willebrand factor (vWF) and tissue factor release.
- Loss of heparan sulfate and thrombomodulin expression.
- Platelet adhesion, activation, and aggregation on exposed subendothelium.
- Fibrin deposition forming microthrombi predominantly in the renal glomerular capillaries.
- Mechanical fragmentation of red blood cells passing through partially occluded vessels → microangiopathic haemolytic anaemia with schistocytes on peripheral blood film.
- Consumptive thrombocytopenia as platelets are consumed in microthrombi.
- Glomerular ischaemia and acute tubular injury → AKI (the dominant clinical feature).
Step 4: Complement Activation (Secondary)
Shiga toxin also directly activates the alternative complement pathway, cleaving factor H binding sites on endothelial cells and amplifying the microangiopathic process. This has led to investigation of complement inhibition as adjunctive therapy in severe STEC-HUS, though current evidence does not support routine use of eculizumab in typical HUS outside clinical trials.
Gb3 receptor distribution explains organ tropism: The kidney (glomerular endothelium) is the primary target. The brain (cortical neurons), pancreas, and colon are secondary sites, explaining the spectrum of extrarenal complications including seizures, stroke-like episodes, pancreatitis, and colonic necrosis.
Atypical HUS (aHUS): Complement Dysregulation
Atypical HUS (aHUS) results from uncontrolled activation of the complement alternative pathway on endothelial surfaces, leading to a complement-mediated thrombotic microangiopathy that is clinically indistinguishable from STEC-HUS and TTP at presentation, but requires fundamentally different treatment.
Genetic & Acquired Causes
A pathogenic complement gene variant or autoantibody is identified in approximately 60–70% of aHUS cases. The major genetic and acquired defects include:
| Defect Type | Gene / Factor | Frequency in aHUS | Mechanism |
|---|---|---|---|
| Loss-of-function (regulators) | Factor H (CFH) | 20–30% | Impaired C3b inactivation on endothelium |
| Loss-of-function | Membrane cofactor protein (CD46/MCP) | 10–15% | Reduced cell-surface complement regulation |
| Loss-of-function | Factor I (CFI) | 5–10% | Impaired C3b/Factor B cleavage |
| Gain-of-function (activators) | Factor B (CFB) | 1–4% | Excessive C3 convertase formation |
| Gain-of-function | C3 (C3) | 5–10% | Resistance to Factor H/mediated inactivation |
| Acquired autoantibody | Anti-Factor H antibodies | 5–10% | Block Factor H regulatory function on endothelium |
| Thrombomodulin | THBD | 3–5% | Impaired protein C activation and complement modulation |
Triggering Events
aHUS may manifest de novo or be triggered by events that stress the complement system:
- Infection (including STEC — so-called "aHUS triggered by STEC")
- Pregnancy (particularly postpartum)
- Surgery or trauma
- Drugs: calcineurin inhibitors (cyclosporin, tacrolimus), anti-VEGF agents (bevacizumab, sunitinib), oral contraceptive pill
- Transplantation (de novo or recurrent aHUS in renal allografts)
- Malignancy
Pathophysiology of Complement-Mediated TMA
Under normal conditions, the alternative complement pathway undergoes continuous low-grade ("tick-over") activation in plasma. Endothelial surfaces are protected by membrane-bound regulators (MCP/CD46) and fluid-phase regulators (Factor H, Factor I). In aHUS, loss of these protective mechanisms — or excessive complement activation — results in:
- Unchecked C3 convertase (C3bBb) activity on the glomerular endothelial surface.
- Massive C3b deposition, membrane attack complex (C5b-9) formation, and endothelial damage.
- Thrombotic microangiopathy identical in histopathology to STEC-HUS but mediated entirely by complement rather than Shiga toxin.
Genetic testing turnaround: Complement gene panel testing in Australia typically takes 4–8 weeks. Do NOT delay eculizumab treatment while awaiting genetic results — treat based on clinical and laboratory exclusion of TTP and STEC-HUS.
Prognosis by Genotype
Better prognosis
MCP/CD46 mutation
~80% survival with native kidneys; recurrent episodes but lower ESKD rate. MCP is membrane-bound and not replaced by eculizumab target (C5); may respond less robustly.
Relapse rate: ~75% but often responds to eculizumab
Moderate prognosis
Factor I or C3 mutation
~50–60% progress to ESKD within 3–5 years without treatment. Good response to complement inhibition.
High post-transplant recurrence risk (Factor I: ~80%)
Worse prognosis
Factor H mutation or anti-Factor H Ab
~60–80% progress to ESKD within 1–3 years without treatment. Excellent response to eculizumab if started early.
Post-transplant recurrence: ~75–90% (Factor H); combined liver-kidney transplant considered
Clinical Features & Laboratory Findings
STEC-HUS — Typical Presentation
The classic presentation follows a predictable sequence:
- Prodrome (Days 1–3): Abdominal cramps, watery diarrhoea progressing to bloody diarrhoea. Low-grade fever may be present. The causative exposure typically occurred 2–8 days earlier.
- HUS phase (Days 3–10): Onset of pallor (anaemia), oliguria or anuria (AKI), and petechiae or purpura (thrombocytopenia). The platelet count nadir typically precedes the peak of AKI by 1–2 days.
Clinical features may include:
- Pallor, jaundice (from haemolysis), fatigue
- Oedema, hypertension, oligoanuria
- Petechiae, purpura, mucosal bleeding (generally mild)
- Abdominal distension, ileus, bloody stools
- Neurological involvement (10–20%): irritability, seizures, altered consciousness, stroke
- Pancreatitis (hyperamylasaemia in ~30%; clinically significant in ~5%)
- Colonic necrosis, perforation (rare but serious)
- Myocardial ischaemia or cardiomyopathy (rare)
Atypical HUS — Presentation
aHUS may present at any age (including neonates and adults). Key distinguishing features from STEC-HUS include:
- Absence of a diarrhoeal prodrome (though preceding infection may be present)
- Insidious onset with progressive AKI, often severe at presentation
- More severe and relapsing course without complement inhibition
- May present in association with pregnancy, postpartum period, or drug exposure
- Family history of HUS or ESKD may be present (~20% have familial disease)
Laboratory Findings — Shared Features
| Investigation | Expected Finding | Clinical Significance |
|---|---|---|
| Full blood count | Hb ↓ (often <80 g/L), Plt ↓ (often <60 × 10⁹/L), WCC ↑ | MAHA + thrombocytopenia = TMA triad components |
| Peripheral blood film | Schistocytes (fragmented RBCs), polychromasia | Confirms microangiopathic haemolysis |
| Reticulocyte count | Elevated | Bone marrow response to haemolysis |
| LDH | Markedly elevated (>500 U/L, often >1000) | Tissue ischaemia + haemolysis marker |
| Haptoglobin | Low / undetectable | Confirms haemolysis |
| Unconjugated bilirubin | Elevated | Haemolysis |
| Coombs test (DAT) | Negative | Distinguishes TMA from autoimmune haemolytic anaemia |
| Creatinine / eGFR | Acute rise (AKI Stage 1–3) | Primary determinant of need for dialysis |
| Electrolytes | Hyperkalaemia, hyperphosphataemia, metabolic acidosis | Urgent correction if severe |
| Coagulation (PT/aPTT/Fibrinogen) | Usually normal or mildly deranged | If markedly abnormal → consider DIC |
| ADAMTS13 activity | >10% in HUS (may be mildly reduced) | <10% = TTP — different emergency treatment pathway |
| C3 / C4 | C3 ↓ in aHUS (especially Factor H, Factor I, C3, Factor B mutations); C4 usually normal | Supports complement-mediated aHUS; normal C3 does not exclude aHUS |
ADAMTS13 is the critical differentiator: ADAMTS13 activity <10% indicates TTP, which requires urgent plasma exchange. In HUS (both STEC and atypical), ADAMTS13 is typically >10%. Request ADAMTS13 urgently in all TMA presentations — do not delay while awaiting other results.
Management
Management of HUS depends critically on the subtype. STEC-HUS requires primarily supportive care, while aHUS mandates early complement inhibition.
STEC-HUS: Supportive Management
Do NOT give antibiotics in suspected STEC: Multiple studies and meta-analyses demonstrate that antibiotic use in STEC infection may increase the risk of HUS by promoting bacterial lysis and Shiga toxin release. Avoid empirical antibiotics in any child or adult presenting with bloody diarrhoea until STEC has been excluded by stool Shiga toxin PCR or culture. If antibiotics are clinically essential (e.g., sepsis), discuss with infectious diseases.
Fluid & Electrolyte Management
- Pre-HUS phase (during diarrhoeal prodrome): Aggressive oral rehydration is recommended. Some evidence suggests early, vigorous intravenous fluid resuscitation during the diarrhoeal prodrome may reduce the severity of subsequent HUS by maintaining renal perfusion. Consider 0.9% NaCl 20 mL/kg bolus followed by 1.5–2× maintenance if oliguric or dehydrated.
- Anuric phase: Restrict fluids to insensible losses (400 mL/m²/day) plus urine output. Avoid fluid overload — pulmonary oedema is a major cause of death in paediatric HUS.
- Electrolytes: Treat hyperkalaemia aggressively (calcium gluconate, insulin-dextrose, resonium). Correct metabolic acidosis with sodium bicarbonate if pH <7.1.
Renal Replacement Therapy (RRT)
Indications for dialysis in STEC-HUS include:
- Refractory hyperkalaemia (>6.5 mmol/L despite medical management)
- Fluid overload with pulmonary oedema or refractory hypertension
- Severe metabolic acidosis (pH <7.1) unresponsive to bicarbonate
- Uraemic symptoms (encephalopathy, pericarditis, bleeding)
- Persistent oligoanuria >48 hours with rising creatinine
Peritoneal dialysis (PD) is the preferred modality in children, particularly in infants, as it is well tolerated and does not require vascular access. PD catheter insertion may be performed at the bedside by experienced paediatric surgeons. Haemodialysis (HD) or continuous renal replacement therapy (CRRT) are used when PD is contraindicated or unavailable.
Blood Product Support
- Packed red blood cells (pRBCs): Transfuse if Hb <60 g/L or symptomatic anaemia. Avoid excessive transfusion to prevent fluid overload. Irradiated and CMV-safe products preferred in paediatric patients.
- Platelets: Do NOT transfuse platelets prophylactically — platelets are consumed in microthrombi and may worsen TMA. Reserve platelet transfusion for active life-threatening haemorrhage or pre-operative (e.g., PD catheter insertion) if platelets <30 × 10⁹/L.
Anti-motility agents: Avoid loperamide and opioids in STEC infection. They increase the risk of HUS by prolonging toxin contact with the gut mucosa.
Antihypertensive Management
Hypertension is common in HUS and may be volume-dependent or renin-mediated:
- First-line: fluid removal via dialysis if volume-overloaded.
- Pharmacotherapy: amlodipine (0.1–0.3 mg/kg/day PO, max 10 mg/day) or nifedipine (0.25–0.5 mg/kg/dose SL for hypertensive urgency). Enalapril (0.1 mg/kg/day PO) if renin-mediated hypertension.
- PBS: Amlodipine — General Benefit; Nifedipine — General Benefit; Enalapril — General Benefit.
Atypical HUS: Complement Inhibition
aHUS requires immediate initiation of complement inhibition once TTP and STEC-HUS have been excluded. Do not delay treatment while awaiting genetic results.
Eculizumab (Soliris®)
Eculizumab
Soliris® · C5 monoclonal antibody · Complement inhibitor
Indication
Complement-mediated aHUS (confirmed or strongly suspected)
Adult induction
900 mg IV weekly × 4 weeks (weeks 1–4)
Adult maintenance
1200 mg IV every 2 weeks (from week 5 onwards)
Paediatric (≥20 kg) induction
600 mg IV weekly × 1, then 900 mg IV weekly × 1, then 1200 mg IV weekly × 1, then 1200 mg IV at week 4
Paediatric (≥20 kg) maintenance
Weight-adjusted: 20–30 kg → 600 mg IV q2w; 30–40 kg → 900 mg IV q2w; >40 kg → 1200 mg IV q2w
Paediatric (5–<20 kg)
Weight-based dosing per product information — consult paediatric nephrology
Route / infusion
IV infusion over 35 minutes (1.5 hours for first dose in some protocols)
Renal adjustment
None required — monoclonal antibody
Hepatic adjustment
None required
PBS status
🔒 PBS Authority Required
Key risks
Meningococcal infection (mandatory vaccination); infusion reactions; risk of HUS relapse on discontinuation
Ravulizumab (Ultomiris®)
Ravulizumab
Ultomiris® · Long-acting C5 inhibitor · Complement inhibitor
Indication
Complement-mediated aHUS (≥10 kg body weight)
Loading dose
Weight-based IV loading on day 1 (e.g., ≥40 kg: 2700 mg; 30–<40 kg: 2400 mg; 20–<30 kg: 2100 mg; 10–<20 kg: 600 mg)
Maintenance
Weight-based IV every 8 weeks (from week 2)
PBS status
🔒 PBS Authority Required
Advantage
Extended dosing interval (q8w vs q2w for eculizumab) — improved quality of life
Meningococcal vaccination — MANDATORY before first dose: All patients must receive MenACWY (Nimenrix®) AND MenB (Bexsero®) vaccination at least 2 weeks before starting eculizumab or ravulizumab. If treatment cannot be delayed, give antibiotics (penicillin V or ciprofloxacin) as chemoprophylaxis concurrently with the first dose and vaccinate as soon as possible. Patients and carers must carry an alert card and have access to emergency antibiotics.
Plasma Therapy in aHUS
Prior to the availability of eculizumab, plasma exchange (PEX) or fresh frozen plasma (FFP) infusion was the standard treatment for aHUS. With the advent of complement inhibitors, plasma therapy is now considered second-line or adjunctive, but remains important in specific scenarios:
- When eculizumab is not immediately available.
- Anti-Factor H antibody-mediated aHUS: PEX combined with immunosuppression (rituximab, mycophenolate) to remove and suppress antibody production.
- Factor H or Factor I mutations: PEX replaces deficient protein (though efficacy is inferior to eculizumab).
- MCP mutations: PEX is generally ineffective (MCP is membrane-bound).
Anti-Factor H Antibody aHUS
This subtype requires a combination approach:
- Plasma exchange: Daily PEX × 5, then taper.
- Immunosuppression: Rituximab (375 mg/m² IV weekly × 4) or mycophenolate mofetil (600 mg/m²/day PO in divided doses) to suppress antibody production.
- Eculizumab: If refractory or relapsing despite PEX + immunosuppression.
Monitoring on Complement Inhibitor Therapy
- Haematological: FBC, LDH, haptoglobin, reticulocytes — weekly during induction, then monthly.
- Renal: Creatinine, eGFR, urine protein:creatinine ratio (uPCR) — weekly during induction, then monthly.
- Complement: CH50 or free C5 level to confirm adequate complement blockade (target CH50 = undetectable).
- Infection surveillance: High index of suspicion for meningococcal disease. Check vaccination status.
- Duration: At least 6–12 months of treatment; consider discontinuation only in patients with MCP mutations or identified trigger (e.g., drug-induced) that has been removed. Genetic counselling for Factor H, Factor I, C3, or Factor B mutations generally recommends lifelong therapy.
Other Therapeutic Considerations
- Anticoagulation: There is no evidence supporting routine anticoagulation (heparin, antiplatelet agents) in HUS. Heparin has been tried historically without benefit and carries bleeding risk.
- Corticosteroids: No established role in STEC-HUS. May have a role in anti-Factor H antibody-mediated aHUS as part of immunosuppressive regimens.
- Dietary management: During acute HUS, appropriate renal diet (potassium and phosphate restriction if anuric). Enteral nutrition is preferred over parenteral where feasible.
Investigations
A systematic diagnostic approach is essential to classify the TMA subtype and guide management. The following investigations should be performed in all patients presenting with suspected HUS:
Essential
Full blood count with blood film
Anaemia, thrombocytopenia, schistocytes. Available at all Australian hospitals. MBS Item 65070.
Essential
Reticulocyte count
Elevated in haemolysis. MBS Item 65090.
Essential
LDH, haptoglobin, unconjugated bilirubin
Haemolysis markers. LDH markedly elevated; haptoglobin undetectable. MBS Items 66524, 66514.
Essential
Direct antiglobulin test (Coombs)
Negative in TMA; positive suggests autoimmune haemolytic anaemia. MBS Item 65116.
Essential
ADAMTS13 activity
CRITICAL — differentiates TTP (<10%) from HUS (>10%). Request as urgent. Available at major hospital laboratories and reference labs. Results may take 24–48 hours; initiate PEX empirically if TTP is suspected while awaiting results.
Essential
Stool Shiga toxin PCR / culture for STEC
PCR for stx1/stx2 genes (preferred — faster, higher sensitivity). Also request E. coli O157 culture. Available at state public health laboratories. Notify to state/territory health department if positive.
Available
Complement studies (C3, C4, CH50)
C3 is often low in aHUS (Factor H, Factor I, C3, Factor B mutations). C4 typically normal. CH50 useful for monitoring on eculizumab. Available at major hospital and reference laboratories.
Referral
Complement gene panel
CFH, CFI, CFB, C3, CD46, THBD — 4–8 week turnaround in Australia. Request through clinical genetics or immunology. Available via Victorian Clinical Genetics Services (VCGS), SA Pathology, and other reference genetics laboratories. Should be sent in all confirmed aHUS cases.
Referral
Anti-Factor H antibody titre
Critical to test in all aHUS — guides therapy (PEX + immunosuppression). Available at reference immunology laboratories.
Available
Renal ultrasound
Assess kidney size, echogenicity, cortical thickness. Rule out obstruction. MBS Item 55010.
Referral
Renal biopsy
Not routinely required for diagnosis of HUS but may be considered if diagnosis uncertain, chronic TMA suspected, or to assess chronicity. Discuss with nephrology.
Risk Stratification & Severity Assessment
Risk stratification in HUS guides the intensity of monitoring, threshold for dialysis, and prognosis:
Lower Risk
Mild STEC-HUS
Age >5 years; presenting Hb >80 g/L; Plt >60 × 10⁹/L; no anuria; no neurological involvement; normal electrolytes at presentation.
Setting: Paediatric ward with nephrology oversight. Monitor UOP, FBC, creatinine daily.
Moderate Risk
Moderate STEC-HUS
Age <2 years; Hb <60 g/L; Plt <30 × 10⁹/L; oliguria >24 hours; rising creatinine; WCC >20 × 10⁹/L (prognostic marker of severity).
Setting: Paediatric nephrology centre. Prepare for dialysis. Consider transfer if at non-tertiary site.
High Risk
Severe STEC-HUS / Suspected aHUS
Anuria >48 hours; neurological involvement (seizures, coma); colonic necrosis/perforation; severe fluid overload; any adult presentation with TMA; any non-diarrhoeal TMA (suspect aHUS).
Setting: PICU / adult ICU. RRT indicated. Urgent complement inhibition for suspected aHUS. Transfer to quaternary centre if needed.
Predictors of poor outcome in STEC-HUS: WCC >20 × 10⁹/L at presentation; age <2 years; anuria >5 days; Hb <60 g/L; neurological involvement. These factors predict higher risk of dialysis dependence, CKD, and death.
Special Populations
Paediatric
General considerations
STEC-HUS is primarily a disease of children <5 years. Peritoneal dialysis is the preferred RRT modality in infants and young children. Transfusion thresholds may be higher to support ongoing haemolysis. Weight-based eculizumab dosing is established for aHUS in children ≥5 kg.
Fluid management
Children are particularly vulnerable to fluid overload during the anuric phase. Strict input/output charting, daily weights, and early RRT initiation are essential. Involve paediatric nephrology early.
Nutrition
Maintain enteral feeding where possible. Potassium and phosphate restriction during anuric phase. Consider paediatric dietitian input.
Pregnancy
Pregnancy-related aHUS
Pregnancy is a known trigger for aHUS, particularly in the postpartum period. Complement activation physiologically increases during pregnancy. Must differentiate from HELLP syndrome, pre-eclampsia with severe features, and TTP.
Eculizumab in pregnancy
Eculizumab crosses the placenta (IgG). Limited safety data — case reports and registries suggest acceptable safety profile. Treatment is indicated if life-threatening aHUS; discuss risks/benefits with maternal-fetal medicine. Monitor neonate for complement inhibition and meningococcal risk.
Elderly
Adult HUS
STEC-HUS can occur in the elderly with higher mortality than in children. Any adult presenting with TMA should be investigated for aHUS, TTP, drug-induced TMA, and malignancy-associated TMA. ADAMTS13 testing is even more critical in adults.
RRT considerations
Haemodialysis is usually preferred in adults. Consider vascular access planning early. Comorbidities (diabetes, CKD) may complicate fluid and electrolyte management.
Renal Impairment
Dialysis and drug dosing
Eculizumab is not dialysable and does not require dose adjustment. Amlodipine and enalapril do not require dose adjustment. Avoid NSAIDs. Monitor drug levels of any renally-excreted medications closely.
Post-HUS CKD surveillance
All HUS survivors require long-term nephrology follow-up. Up to 25% of STEC-HUS survivors develop CKD. Monitor BP, uPCR, eGFR annually for at least 5 years, longer if abnormalities detected.
Immunocompromised
Drug-induced TMA
Calcineurin inhibitors (tacrolimus, cyclosporin) used in transplant immunosuppression can cause TMA that mimics aHUS. Consider drug withdrawal and switching to an alternative immunosuppressant. If TMA persists after drug withdrawal, investigate for de novo or recurrent aHUS.
Complement inhibition and infection
Immunocompromised patients on eculizumab are at particularly high risk for encapsulated organism infections. Ensure comprehensive vaccination and consider prophylactic antibiotics in high-risk patients.
Hepatic Impairment
Eculizumab
No hepatic dose adjustment is required. However, severe hepatic dysfunction may complicate differential diagnosis (TMA vs hepatic coagulopathy). Combined liver-kidney transplant is considered for severe Factor H mutations where post-renal transplant recurrence risk exceeds 75%.
Aboriginal and Torres Strait Islander Health Considerations
Aboriginal and Torres Strait Islander Health
Aboriginal and Torres Strait Islander peoples experience a disproportionate burden of kidney disease, infectious gastroenteritis, and environmental health challenges relevant to HUS epidemiology and outcomes. The following considerations are essential for equitable care.
RACGP & RHDAustralia guidance: Integrate HUS follow-up into Aboriginal and Torres Strait Islander health checks (MBS Item 715). Ensure BP monitoring, urinalysis (albumin:creatinine ratio — MBS Item 69384), and eGFR are documented. Connect families with ACCHOs for ongoing renal surveillance and culturally safe chronic disease management.
📚 References
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