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dx.
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Hemolytic Uremic Syndrome (HUS)
Cardiovascular Presentations
Abdominal aortic aneurysm
Acute coronary syndrome (NSTEMI)
Acute coronary syndrome (STEMI)
Acute decompensated heart failure
Acute limb ischemia
Acute mesenteric ischemia
Aortic dissection
Aortic stenosis
Atrial fibrillation and flutter
Bradyarrhythmia and heart block
Cardiac arrest
Deep vein thrombosis
Myocarditis
Pericarditis
Pulmonary embolism
Stable angina
Superficial thrombophlebitis
Superior vena cava syndrome
Supraventricular tachycardia
Syncope (cardiogenic)
Unstable angina
Ventricular tachycardia
Respiratory Presentations
Acute bronchitis
Acute respiratory failure
Aspiration pneumonia
Asthma exacerbation
Bronchiolitis
Community-acquired pneumonia
COVID-19 pneumonia
COPD exacerbation
Croup
Croup (laryngotracheobronchitis)
Epiglottitis
Hemothorax
Hospital-acquired pneumonia
Pleural effusion
Pneumothorax (traumatic)
Pulmonary contusion
Spontaneous pneumothorax
Neurological Presentations
Bell's palsy
Benign paroxysmal positional vertigo
Brain abscess
Cauda equina syndrome
Cervical radiculopathy
Concussion (mild traumatic brain injury)
Encephalitis
Guillain-Barré syndrome
Hemorrhagic stroke (intracerebral)
Ischemic stroke
Lumbar radiculopathy
Malignant spinal cord compression
Migraine
Peripheral neuropathy (acute)
Retropharyngeal abscess
Schizophrenia (acute exacerbation)
Seizure (breakthrough:known epilepsy)
Seizure (first-time)
Spinal cord injury
Status epilepticus
Subarachnoid hemorrhage
Tension headache
Transient ischemic attack
Traumatic brain injury (moderate-severe)
Vestibular neuritis
Viral meningitis
Gastrointestinal Presentations
Acute appendicitis
Acute cholecystitis
Acute diverticulitis
Acute pancreatitis
Anal fissure
Choledocholithiasis and cholangitis
Clostridioides difficile colitis
Gastritis
Gastroenteritis (viral and bacterial)
Gastroesophageal reflux disease
Incarcerated or strangulated hernia
Inflammatory bowel disease flare
Large bowel obstruction
Lower GI hemorrhage
Peptic ulcer disease
Perforated viscus
Small bowel obstruction
Upper GI hemorrhage
Genitourinary and Reproductive Presentations
Acute prostatitis
Acute urinary retention
Ectopic pregnancy
Epididymitis
Orchitis
Ovarian torsion
Paraphimosis
Pelvic inflammatory disease
Priapism
Pyelonephritis
Renal laceration
Ruptured ovarian cyst
Testicular torsion
Tubo-ovarian abscess
Urinary tract infection (uncomplicated)
Urolithiasis (renal colic)
Vaginal bleeding (non-pregnant)
Infectious Disease Presentations
Acute sinusitis
Acute tonsillitis
Acute upper respiratory infection
Animal bite
Bacterial meningitis
Cellulitis
Conjunctivitis (bacterial)
Dental abscess
Endocarditis
Febrile neutropenia
Fournier gangrene
Hand-foot-mouth disease
Hepatitis (acute)
Herpes zoster
HIV-related illness
Human bite
Impetigo
Infected diabetic foot ulcer
Infectious mononucleosis
Influenza
Necrotizing fasciitis
Osteomyelitis
Otitis externa
Parasitic infection
Periorbital cellulitis
Peritonsillar abscess
Scabies
Sepsis
Septic arthritis
Spontaneous bacterial peritonitis
Tick-borne illness (Lyme disease)
Tinea infection
Tuberculosis
Viral exanthem
Wound infection
Trauma Presentations
Achilles tendon rupture
ACL and mceniscus tear
Ankle fracture
Ankle sprain
Burn
Calcaneus fracture
Cervical spine fracture
Clavicle fracture
Dental avulsion
Distal radius fracture
Drowning
Elbow fracture and dislocation
Electrical injury
Facial bone fracture
Facial laceration
Femur fracture
Fingertip amputation
Forearm fracture (radius and ulna)
Frostbite
Hand:finger laceration
Heat exhaustion
Heat stroke
Hip fracture
Humeral shaft fracture
Knee dislocation
Knee sprain
Lightning injury
Mandible fracture
Metacarpal fracture
Metatarsal fracture
Muscle strain
Nasal fracture
Non-accidental trauma
Orbital fracture
Patella fracture
Phalanx fracture (finger)
Proximal humerus fracture
Pulmonary contusion
Rib fracture
Rotator cuff tear (acute traumatic)
Scalp laceration
Scaphoid fracture
Shoulder dislocation
Skull fracture
Splenic laceration
Sternal fracture
Supracondylar pediatric fracture
Tendon laceration (hand:wrist)
Thoracic and lumbar spine fracture
Tibia:fibula fracture
Tibial plateau fracture
Toe fracture
Traumatic epistaxis
Traumatic hyphema
Toxicologic Presentations
Acetaminophen toxicity
Alcohol intoxication
Alcohol withdrawal
Anticholinergic toxicity
Anticoagulant overdose
Benzodiazepine overdose
Benzodiazepine:sedative overdose
Beta-blocker and calcium channel blocker toxicity
Carbon monoxide poisoning
Caustic ingestion
Digoxin toxicity
Drug eruption
Foreign body ingestion
Opioid intoxication
Opioid overdose
Opioid withdrawal
Organophosphate
Salicylate toxicity
Serotonin syndrome
Stimulant intoxication (cocaine, methamphetamine)
Tricyclic antidepressant overdose
Psychiatric Presentations
Acute anxiety
Acute psychosis
Agitation:behavioral emergency
Bipolar disorder
Conversion disorder
Major depressive episode
Neuroleptic malignant syndrome
Suicidal ideation and attempt
Musculoskeletal and Rheumatologic Presentations
Acute low back pain (mechanical)
Bursitis
Cervical radiculopathy
Costochondritis
Gout (acute)
Lumbar radiculopathy
Pseudogout
Tendinitis
Dermatology Presentations
Acute eczema (Eczema acute flare)
Allergic contact dermatitis
Erythema multiforme
Henoch-Schönlein purpura
Pressure injury
Psoriasis (acute flare)
Stevens-Johnson syndrome
Toxic epidermal necrolysis
Urticaria (acute)
Environmental and Exposure Presentations
Envenomation (snake, spider, insect)
High-altitude illness
Hypothermia
Hematologic and Oncologic Presentations
Acute chest syndrome
Coagulopathy
Hyperviscosity syndrome
Sickle cell crisis (vaso-occlusive)
Symptomatic anemia
Thrombocytopenia (severe)
Tumor lysis syndrome
Pediatric-Specific Presentations
Bronchiolitis
Croup
Emergency delivery
Febrile seizure
Kawasaki disease
Neonatal jaundice
Neonatal sepsis
Nursemaid's elbow
Pediatric fever 0 to 28 days
Pediatric fever 29 to 60 days
Pediatric fever 61 to 90 days
Pyloric stenosis
Slipped capital femoral epiphysis
Intussusception
Endocrine and Metabolic Presentations
Adrenal crisis
Diabetic ketoacidosis
Hypercalcemia
Hyperosmolar hyperglycemic state
Hypertensive emergency
Hypertensive urgency
Hypoglycemia
Myasthenia gravis crisis
Myxedema coma
Severe hyperkalemia
Severe hyponatremia
Thyroid storm
ENT and Maxillofacial Presentations
Acute laryngitis
Acute otitis media
Acute pharyngitis
Cerumen impaction
Epistaxis (anterior)
Nasal foreign body
Otitis externa
Tympanic membrane perforation
Ophthalmologic Presentations
Acute angle-closure glaucoma
Central retinal artery occlusion
Chemical eye injury
Corneal abrasion
Corneal ulcer
Globe rupture
Ocular foreign body
Orbital cellulitis
Retinal detachment
Obstetric Presentations
Hyperemesis gravidarum
Painful vaginal bleeding in pregnancy
Placenta previa
Placental abruption
Preeclampsia:eclampsia
Preterm labor
Threatened:inevitable:incomplete abortion
Systemic and Miscellaneous Presentations
Anaphylaxis
Angioedema
Cannabis-induced hyperemesis
Hemolytic Uremic Syndrome (HUS)
POCUS
Procedures
Calculators
Resuscitation
ECG Guide
Back
Clinical Assessment Checklist
Browse categories and answer follow-up questions to refine your symptom profile.
Approach to the Critical Patient
Immediate resuscitation priorities
Airway and fluid status
▶
Volume depletion from diarrheal illness
▶
Isotonic IV fluid resuscitation with normal saline
Target urine output 1–2 mL/kg/hour in children
If anuric, avoid aggressive fluid loading to prevent pulmonary edema
▶
Restrict to insensible losses plus prior output
Early nephrology consultation
Respiratory distress from fluid overload
▶
Supplemental oxygen
Diuretic caution — may worsen AKI
Hemodynamic monitoring
▶
Continuous cardiac monitoring
▶
Hyperkalemia-related arrhythmia risk
QTc prolongation monitoring
Blood pressure targets
▶
MAP >= 65 mmHg in adults
Hypertensive emergency threshold — diastolic >= 120 mmHg
If hypertensive emergency, initiate antihypertensive therapy within 1 hour
▶
Nicardipine or labetalol IV preferred
Avoid ACE inhibitors in acute AKI with hyperkalemia
Escalation triggers
Indications for ICU or high-acuity care
▶
Anuria or rapidly rising creatinine
▶
Dialysis preparation
Nephrology at bedside
Neurological deterioration
▶
Seizures — benzodiazepine first-line
Altered consciousness — emergent brain MRI
Severe thrombocytopenia with bleeding
▶
Platelet count < 20 × 10^9/L with active bleeding
Hematology consultation
Cardiac involvement
▶
Troponin elevation
Echocardiography urgently
Key early decisions
▶
STEC-HUS vs aHUS distinction
▶
Stool Shiga toxin PCR as first step
ADAMTS13 activity to exclude TTP
Avoid antibiotics and antimotility agents in suspected STEC-HUS
▶
Associated with increased HUS progression risk
Class I recommendation to withhold
If aHUS suspected, initiate eculizumab without delay
▶
Do not wait for genetic results
Class I recommendation
Immediate consults
Mandatory consultation triggers
▶
Nephrology — all confirmed or suspected HUS
▶
Dialysis planning
Complement workup guidance
Hematology — if TTP cannot be excluded
▶
ADAMTS13 result pending
Therapeutic plasma exchange consideration
Pediatric critical care or PICU — all pediatric HUS with severe AKI
▶
Weight-based fluid and dialysis management
Seizure threshold lower in children
History
Presenting symptoms
Gastrointestinal prodrome
▶
Diarrhea character
▶
Watery onset progressing to bloody diarrhea
Hemorrhagic colitis in approximately 90% of STEC-HUS
3 to 8 days after contaminated food ingestion
Abdominal pain
▶
Cramping, often severe
Right lower quadrant predominance
Vomiting
▶
Associated with abdominal pain
Limits oral hydration
Systemic and renal symptoms
▶
Decreased urine output
▶
Oliguria or anuria developing as diarrhea resolves
HUS develops approximately 7 days after diarrhea onset
Pallor and fatigue
▶
Hemolysis markers — jaundice, tea-colored urine
Petechiae from thrombocytopenia
Edema
▶
Facial and peripheral from AKI
Fluid retention marker
Exposures and triggers
Food and environmental exposures
▶
Undercooked ground beef — O157:H7 most common STEC
▶
3 to 8 day incubation period
Restaurant cluster or home exposure
Unpasteurized dairy products or juice
Contaminated produce — leafy greens, sprouts
Contaminated recreational water
Petting zoo or farm animal contact
Daycare exposure or sick contacts with bloody diarrhea
Non-STEC triggers for aHUS
▶
Upper respiratory or other viral illness preceding episode
Pregnancy or postpartum state
Medication exposure
▶
Calcineurin inhibitors — cyclosporine, tacrolimus
Quinine, gemcitabine, oral contraceptives
Transplantation — solid organ or stem cell
Alarm features
High-acuity historical red flags
▶
Anuria — severe AKI, dialysis likely needed
Neurological symptoms
▶
Irritability, altered consciousness, seizures in 10 to 25% of STEC-HUS
Focal neurological deficits — worse prognosis
Severe hypertension with headache
Severe abdominal distension — toxic megacolon concern
Cardiac chest pain or dyspnea — myocardial involvement ~7% of pediatric aHUS
Prior similar episodes — relapsing course strongly suggests aHUS
Past medical and family history
Relevant past history
▶
Prior episodes of TMA or HUS
Kidney disease or unexplained chronic kidney failure
Autoimmune disease — SLE, antiphospholipid syndrome
Transplant history
Malignancy or active chemotherapy
Pregnancy — current or recent postpartum
Family history
▶
HUS or TMA in first-degree relatives — strongly suggests complement-mediated aHUS
Consanguinity
Unexplained renal failure in family members
Known complement gene mutations — CFH, CFI, MCP, C3, CFB
Physical Exam
Vitals and hemodynamic assessment
Vital sign abnormalities
▶
Blood pressure
▶
Hypertension — often severe, may be malignant
Systolic > 180 mmHg or diastolic > 120 mmHg in crisis
Heart rate
▶
Tachycardia from anemia, volume depletion, or pain
Temperature
▶
Fever variable — may be absent or mild in STEC-HUS
Respiratory rate
▶
Tachypnea from metabolic acidosis or fluid overload
Skin and general appearance
Integument findings
▶
Pallor — from microangiopathic hemolytic anemia
Jaundice — hemolysis byproduct
Petechiae or purpura — thrombocytopenia
Peripheral edema — AKI and fluid retention
Tea-colored or cola-colored urine — hemoglobinuria
Peripheral gangrene — rare but severe microvascular occlusion in aHUS
Abdominal and gastrointestinal exam
Abdominal findings
▶
Tenderness
▶
Right lower quadrant or diffuse
Guarding or rigidity — concern for perforation
Distension
▶
Toxic megacolon concern
Hypoactive bowel sounds in severe cases
Rectal exam
▶
Gross blood on examination
Heme-positive stool
Neurological examination
CNS status
▶
Mental status
▶
Irritability in children
Lethargy, confusion, or coma in severe cases
Seizure activity
▶
Focal or generalized
Postictal state
Focal deficits
▶
Motor weakness
Cranial nerve palsies
Fundoscopy
▶
Flame-shaped hemorrhages
Optic disc edema particularly in aHUS
Cardiovascular and fluid status
Fluid overload signs
▶
Elevated JVP
Pulmonary crackles from volume overload
S3 gallop
Peripheral pitting edema
Signs of cardiac involvement
▶
Troponin elevation — order if myocardial involvement suspected
New murmur
Differential Diagnosis
Thrombotic microangiopathy spectrum
Key TMA diagnoses
▶
Thrombotic thrombocytopenic purpura — TTP
▶
ICD-10 M31.1
ADAMTS13 activity < 10% — diagnostic
More severe thrombocytopenia — platelets < 30 × 10^9/L
Relatively mild renal dysfunction — creatinine often < 180 mmol/l
Prominent neurological features
STEC-HUS — diarrhea-associated
▶
ICD-10 D59.3
Stool Shiga toxin positive
Diarrheal prodrome
Self-limited in most cases
Atypical HUS — complement-mediated
▶
ICD-10 D59.3
No diarrheal prodrome
Complement gene mutation or anti-factor H antibody
Recurrent episodes possible
Coagulopathy mimics
DIC and immune hemolysis
▶
Disseminated intravascular coagulation
▶
Prolonged PT, PTT — normal in HUS
Low fibrinogen
Elevated D-dimer
Underlying sepsis or malignancy
Evans syndrome
▶
Autoimmune hemolytic anemia plus ITP
Direct Coombs test positive — negative in HUS
No renal involvement typically
Severe vitamin B12 deficiency
▶
MAHA-like picture
Elevated MCV, very high LDH
Low reticulocyte count
Obstetric and systemic mimics
Pregnancy-related TMA
▶
HELLP syndrome
▶
ICD-10 O14.2
Second or third trimester
Elevated liver enzymes
Resolves with delivery
Preeclampsia with severe features
▶
Proteinuria, hypertension, endothelial dysfunction
Systemic diseases with TMA
▶
Malignant hypertension
▶
Severe diastolic hypertension > 120 mmHg
End-organ damage — papilledema, AKI, cardiac
SLE — antiphospholipid syndrome
▶
Positive ANA, anti-dsDNA
Complement consumption
Scleroderma renal crisis
▶
Rapid onset hypertension
Diffuse skin thickening history
Laboratory Tests
Core diagnostic labs
Complete blood count with peripheral smear
▶
Anemia
▶
Hemoglobin typically < 100 g/L
Rapidly falling hemoglobin a key severity marker
Thrombocytopenia
▶
Platelets < 150 × 10^9/L at diagnosis
Sentinel hematologic abnormality heralding HUS
Schistocytes on peripheral smear
▶
>= 2% confirms microangiopathic hemolytic anemia
Helmet cells, fragmented red cells
Hemolysis markers
▶
LDH — lactate dehydrogenase
▶
Markedly elevated — earliest marker of HUS progression
Trending LDH guides disease activity
Haptoglobin
▶
Low or undetectable — confirms intravascular hemolysis
Indirect bilirubin
▶
Elevated from RBC breakdown
Reticulocyte count
▶
Elevated — compensatory erythropoiesis
Direct Coombs test
▶
Negative — critical to exclude immune-mediated hemolysis
Renal and metabolic labs
Kidney function and electrolytes
▶
Serum creatinine and BUN
▶
Rapidly rising creatinine — severe AKI indicator
Serial measurements every 12 to 24 hours
Electrolytes
▶
Hyperkalemia — AKI-related, arrhythmia risk
Hyperphosphatemia — phosphate binders needed
Hyponatremia — dilutional from fluid overload
Bicarbonate
▶
Metabolic acidosis — anion gap elevated
Bicarbonate < 15 mmol/L suggests severe AKI
Urinalysis
▶
Hematuria — microscopic or gross
Proteinuria — glomerular injury marker
Hemoglobinuria — tea-colored urine
Etiology-specific labs
Stool and microbiological testing
▶
Stool Shiga toxin assay — PCR preferred over culture
▶
Sensitivity higher for Stx2 producing O157:H7 and O104:H4
Obtain before antibiotics
Stool culture for STEC
▶
Sorbitol MacConkey agar for O157:H7
Serotyping if positive
TTP exclusion
▶
ADAMTS13 activity
▶
< 10% diagnostic of TTP
Obtain before plasma exchange if TTP considered
Results may take 48 to 72 hours
Complement workup for aHUS
▶
Serum C3 and C4
▶
Low C3 with normal C4 — alternative pathway activation
Normal levels do not exclude aHUS
Factor H, factor I levels
Anti-factor H antibodies
▶
Present in ~10% of pediatric aHUS
Genetic testing for complement mutations
▶
CFH, CFI, MCP/CD46, C3, CFB — send early, results delayed
Additional markers
▶
Amylase and lipase
▶
Pancreatic involvement in up to two-thirds of STEC-HUS
Elevated amylase with abdominal pain
Troponin — cardiac involvement screen in aHUS
ANA, anti-dsDNA — if autoimmune TMA suspected
Diagnostic Tests
Scoring Systems
TMA classification and severity tools
▶
French score for HUS severity in children
▶
Age, anuria duration, WBC count, hematocrit at admission
Predicts need for dialysis and neurological complications
Platelet and creatinine nadir tracking
▶
Daily trending guides escalation decisions
Rising platelet count signals recovery
PLASMIC score — for TTP probability
▶
Platelet count, combined hemolysis variables, no active cancer, no stem cell transplant, MCV, INR, creatinine
High score (>= 6) favors TTP
Low score (0 to 4) supports HUS over TTP
Guides urgency of ADAMTS13 and plasma exchange decision
MRI
Brain MRI indications
▶
Neurological symptoms present
▶
Seizures, altered consciousness, focal deficits
10 to 25% of STEC-HUS have neurological involvement
Findings in HUS-associated encephalopathy
▶
Posterior reversible encephalopathy syndrome — PRES
Hyperintense lesions on T2/FLAIR
Thalami, brainstem, basal ganglia involvement in TMA-specific injury
Diffusion restriction indicates cytotoxic edema — worse prognosis
MRI preferred over CT for brain parenchyma evaluation
▶
No ionizing radiation — important in pediatric patients
Better posterior fossa visualization
Contraindications
▶
Unstable patient — CT head as bridge
Non-compatible implants
Renal MRI
▶
Limited acute utility
▶
Renal ultrasound preferred first-line
MRI for complex renal anatomy or research protocols
CT
Abdominal CT indications
▶
Surgical abdomen concern
▶
Toxic megacolon suspected
Free perforation — peritoneal signs
Transmural necrosis
CT findings in STEC-HUS colitis
▶
Colonic wall thickening — right colon predominance
Pericolonic fat stranding
Pneumatosis intestinalis in severe cases
Free air indicates perforation
Contrast considerations
▶
Avoid contrast if creatinine markedly elevated
Non-contrast CT still useful for free air and pneumatosis
CT head
▶
Bridge imaging if MRI not immediately available
▶
Hemorrhage, mass, herniation exclusion
Lower sensitivity for posterior fossa pathology than MRI
Ultrasound
Renal ultrasound — first-line imaging
▶
Indications
▶
All confirmed or suspected HUS
AKI characterization
Obstruction exclusion
Findings in HUS
▶
Increased renal echogenicity — cortical injury
Normal or enlarged kidneys
Reduced or absent corticomedullary differentiation in severe AKI
Absence of hydronephrosis — distinguishes from obstructive uropathy
Doppler assessment
▶
Elevated resistive index — microvascular disease
Absent or reversed diastolic flow — severe ischemia
Cardiac POCUS
▶
Myocardial function assessment
▶
Estimated LV systolic function
Pericardial effusion screen
Volume status
▶
IVC collapsibility in fluid-managed patients
Integrate with clinical exam
Abdominal POCUS adjunct
▶
Free fluid screen
Bowel wall assessment — limited compared to CT
Disposition
Admission and level of care
All patients with confirmed HUS require hospital admission
▶
No safe outpatient management for established HUS
Minimum general ward with renal monitoring capability
ICU indications
▶
Anuria or rapidly rising creatinine requiring dialysis
▶
Continuous renal replacement therapy in hemodynamically unstable
Intermittent hemodialysis if hemodynamically stable
Neurological involvement
▶
Seizures requiring anticonvulsant infusions
Deteriorating consciousness
Hypertensive emergency uncontrolled on oral agents
Cardiac involvement with hemodynamic compromise
Respiratory failure from fluid overload
PICU indications for pediatric patients
▶
Anuria lasting > 24 hours
Severe neurological symptoms
Inability to maintain minimal IV access or monitoring on ward
Transfer and consultation
Transfer criteria
▶
aHUS requiring eculizumab — transfer to center with complement expertise
Surgical abdomen — transfer if no surgical coverage
Dialysis not available at receiving facility
Pediatric patient at adult center without PICU
Mandatory consultations before discharge
▶
Nephrology follow-up arranged
Genetics referral for aHUS — complement mutation testing
Gastroenterology if ongoing GI complications
Discharge criteria
Copy
Clinical stability requirements
▶
Platelet count trending up and stable
Creatinine stable or improving
No new neurological symptoms
Able to maintain adequate oral hydration
Blood pressure controlled on oral medications
Follow-up plan
▶
Nephrology in 1 to 2 weeks
Urinalysis and blood pressure at each follow-up
Long-term CKD risk monitoring — up to 25% develop CKD after STEC-HUS
Treatment
Supportive care — STEC-HUS
IV fluid management — cornerstone of STEC-HUS treatment
▶
Early aggressive isotonic fluid resuscitation
▶
Normal saline 0.9% — 10 to 20 mL/kg boluses in children
Reduces adverse outcomes when started during bloody diarrhea phase
Class I recommendation based on observational evidence
Volume monitoring
▶
Strict fluid balance every 8 hours
Weight daily
Restrict fluids if anuric to insensible losses + prior output
Avoid hypotonic fluids
▶
Hyponatremia risk
Cerebral edema risk particularly in children
Red blood cell transfusion
▶
Threshold
▶
Hemoglobin < 70 g/L or symptomatic anemia
Avoid arbitrary restrictive threshold in cardiac disease
Packed RBC 10 to 15 mL/kg in pediatric patients
Monitor for fluid overload — transfuse slowly if anuric
Platelet transfusion generally avoided
▶
May worsen microvascular thrombosis
Reserve for active life-threatening bleeding only
Renal replacement therapy
Dialysis indications
▶
Anuria despite adequate hydration
▶
Most common indication in STEC-HUS
Up to 50% of hospitalized STEC-HUS require dialysis
Severe hyperkalemia unresponsive to medical management
▶
Potassium > 6.5 mmol/L with ECG changes
Fluid overload causing respiratory compromise
Severe metabolic acidosis
▶
Bicarbonate < 10 mmol/L unresponsive to bicarb therapy
Uremic encephalopathy
Modality selection
▶
Peritoneal dialysis — preferred in children < 10 kg
▶
Avoids large venous access in small children
Continuous gentle fluid removal
Continuous renal replacement therapy — hemodynamically unstable
▶
CVVH or CVVHDF
Flow rate 20 to 25 mL/kg/hour
Intermittent hemodialysis — hemodynamically stable adults
▶
4-hour sessions as needed
Hypertension management
Acute hypertensive emergency
▶
Nicardipine IV
▶
5 mg/hour initial infusion
Titrate by 2.5 mg/hour every 5 to 15 minutes
Maximum 15 mg/hour
Labetalol IV
▶
0.25 mg/kg IV bolus — maximum 20 mg per dose
Infusion 0.5 to 3 mg/kg/hour
Avoid in bradycardia or heart block
Hydralazine IV — alternative in children
▶
0.2 to 0.6 mg/kg IV per dose
Onset 10 to 20 minutes
Oral antihypertensive maintenance
▶
Amlodipine PO
▶
Adults 5 to 10 mg daily
Children 0.1 to 0.3 mg/kg/day
Avoid ACE inhibitors and ARBs acutely
▶
Hyperkalemia risk in AKI
May use in recovery phase for proteinuria reduction
Treatment of aHUS — complement inhibition
Eculizumab — anti-C5 monoclonal antibody
▶
First-line therapy for complement-mediated aHUS
▶
Class I recommendation
Initiate without waiting for genetic test results
Dosing — adults
▶
Induction: 900 mg IV weekly for 4 weeks
Maintenance: 1200 mg IV every 2 weeks from week 5 onward
Dosing — pediatric weight-based
▶
5 to < 10 kg: 300 mg weekly x 1, then 300 mg every 3 weeks
10 to < 20 kg: 600 mg weekly x 1, then 300 mg every 2 weeks
20 to < 30 kg: 600 mg weekly x 2, then 600 mg every 2 weeks
30 to < 40 kg: 900 mg weekly x 2, then 900 mg every 2 weeks
>= 40 kg: adult dosing
Mandatory pre-treatment meningococcal vaccination
▶
MenACWY and MenB vaccines required
If urgent initiation before vaccination, prophylactic penicillin V or amoxicillin
Ravulizumab — longer-acting C5 inhibitor
▶
Alternative to eculizumab — 8-week dosing interval after loading
▶
Same efficacy and safety profile
Preferred for long-term maintenance due to convenience
Loading dose based on weight, then maintenance every 8 weeks
Duration of complement inhibition
▶
Complement factor mutation — indefinite therapy usually required
Anti-factor H antibody mediated — immunosuppression may allow discontinuation
Trial of discontinuation only with specialist guidance
Plasma exchange — selected indications
Plasma exchange role in HUS
▶
Not first-line for STEC-HUS — no proven benefit
Use if TTP cannot be excluded pending ADAMTS13
▶
Empirical plasma exchange for severe undifferentiated TMA
Bridging therapy for aHUS when eculizumab unavailable
▶
Fresh frozen plasma 30 to 40 mL/kg exchange
Daily exchanges until eculizumab available
Contraindications and risks
▶
Citrate toxicity — hypocalcemia
Sepsis risk from central access
Not a substitute for eculizumab in aHUS
Drugs to avoid
Contraindicated agents in STEC-HUS
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Antibiotics
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Fluoroquinolones and TMP-SMX increase Shiga toxin release
Multiple meta-analyses confirm HUS risk increase
Class I recommendation to avoid
Antimotility agents
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Loperamide, diphenoxylate, opioids
Reduce colonic STEC excretion
Increase neurological complication risk
NSAIDs
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Worsen AKI
Avoid in all phases of HUS
Special Populations
Pregnancy
Pregnancy-associated HUS
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Epidemiology
▶
Postpartum HUS most common — days to weeks after delivery
aHUS is the dominant form — complement dysregulation triggered by pregnancy
HELLP syndrome must be distinguished — resolves with delivery
Diagnostic approach
▶
ADAMTS13 to exclude TTP
Complement studies — C3, C4, factor H
LDH, haptoglobin, peripheral smear
Treatment
▶
Eculizumab safe in pregnancy and postpartum
Limited data — case series support use
Delivery does not reliably resolve complement-mediated HUS
Avoid ACE inhibitors in pregnancy — teratogenic
Imaging
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Renal ultrasound preferred — avoid CT radiation
MRI without gadolinium if neurological symptoms
Geriatric
Older adult considerations
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Atypical HUS presentations
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STEC-HUS less common — more often complement-mediated or drug-induced
Drug-induced TMA — quinine, calcineurin inhibitors, chemotherapy
Malignancy-associated TMA
Comorbidity burden
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Pre-existing CKD amplifies AKI severity
Cardiovascular disease increases risk of fluid overload
Hypertension often pre-existing and difficult to control
Medication adjustments
▶
Eculizumab dosing unchanged by age
Antihypertensive selection — avoid severe hypotension
Renal dosing for all cleared renally
Prognosis
▶
Higher mortality from STEC-HUS in adults > 65 years
Epidemic O104:H4 outbreak in Germany 2011 showed higher adult mortality
Pediatrics
Pediatric epidemiology and features
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STEC-HUS is the most common cause of AKI in children
Age < 5 years — highest risk group for HUS after STEC infection
Risk factors for progression
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WBC > 13 × 10^9/L during diarrheal illness
Stx2-producing strains
Antibiotic or antimotility agent exposure
Neurological complications in 10 to 25% of pediatric STEC-HUS
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Seizures, coma, stroke-like presentations
MRI indicated for any neurological change
Fluid management in children
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Early isotonic fluid resuscitation during bloody diarrhea phase
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10 to 20 mL/kg NS boluses
Reduces need for dialysis when started early
Strict fluid balance — weigh diapers, measure output
Electrolyte monitoring every 6 to 12 hours in severe AKI
Dialysis in pediatrics
▶
Peritoneal dialysis preferred in infants and small children
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Avoids large bore venous access
Continuous gentle fluid and solute clearance
Hemodialysis in older children who are hemodynamically stable
aHUS in pediatrics
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Anti-factor H antibodies — found in ~10% of pediatric aHUS
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Treat with plasma exchange plus immunosuppression — steroids, mycophenolate
Monitor antibody titers to guide therapy
Genetic complement mutations — account for majority of remaining pediatric aHUS
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Eculizumab first-line — same dosing schedule weight-based as above
Prognosis — 50% progress to end-stage kidney disease without complement inhibition
Background
Epidemiology
Incidence and demographics
▶
STEC-HUS
▶
Approximately 90% of all HUS cases
Most common cause of AKI in children < 5 years
Annual incidence 1 to 3 per 100,000 children in developed countries
O157:H7 responsible for majority of cases in North America
O104:H4 caused large outbreak in Germany 2011 — predominantly adults
Atypical HUS
▶
5 to 10% of all HUS cases
Incidence approximately 0.1 to 0.5 per million population per year
Complement gene mutations identified in 60 to 70% of cases
Anti-factor H antibodies in ~10% of pediatric aHUS
Outcomes
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STEC-HUS mortality — 1 to 3% in high-resource settings
Neurological complications increase STEC-HUS mortality to 3 to 5%
Long-term CKD in 25% of STEC-HUS survivors
aHUS without complement inhibition — 50% progress to ESKD within 1 year
Recurrence rate in aHUS — up to 50% within 3 years without ongoing complement inhibition
Pathophysiology
Shiga toxin-mediated mechanism — STEC-HUS
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Shiga toxin production
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Stx1 and Stx2 — Stx2 more nephrotoxic
Binds globotriaosylceramide Gb3 receptor on endothelial cells
Particularly high Gb3 receptor density in glomerular endothelium
Endothelial injury cascade
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Protein synthesis inhibition by toxin
Apoptosis and endothelial cell death
Platelet adhesion and microvascular thrombosis
Fibrin-platelet thrombi in glomerular capillaries
Systemic amplification
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Inflammatory cytokines amplify vascular injury
Complement activation as secondary phenomenon
Neurological injury via Gb3 on brain endothelium
Complement dysregulation — aHUS
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Alternative complement pathway
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Continuous low-level activation normally controlled by factor H
Loss-of-function mutations in CFH, CFI, MCP reduce regulation
Gain-of-function mutations in C3, CFB increase activation
Anti-factor H antibodies mimic loss-of-function
Uncontrolled complement activation
▶
C3 deposition on endothelium
Membrane attack complex formation
Endothelial injury and platelet activation
Microvascular thrombosis in kidney, brain, heart
Therapeutic Considerations
STEC-HUS management principles
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Supportive care is the evidence-based standard
▶
IV hydration, dialysis, transfusion, blood pressure control
No specific antitoxin therapy available in routine practice
Antibiotic avoidance
▶
Meta-analyses associate antibiotics with increased HUS risk
Fluoroquinolones induce SOS response amplifying toxin release
Withhold in all suspected STEC gastroenteritis
Early hydration timing critical
▶
Fluid resuscitation during diarrheal prodrome reduces dialysis need
Mechanism — improved glomerular blood flow before thrombosis established
aHUS treatment rationale
▶
Terminal complement inhibition with eculizumab
▶
Prevents C5 cleavage into C5a and C5b
Blocks membrane attack complex formation
Platelet and endothelial injury reversed within days of initiation
Genetic testing guides prognosis and treatment duration
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CFH mutations — highest recurrence risk — indefinite therapy
MCP/CD46 mutations — lower recurrence — discontinuation may be considered
Plasma exchange mechanism
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Removes anti-factor H antibodies
Provides normal factor H in fresh frozen plasma
Temporary bridging effect — not definitive therapy
Patient Discharge Instructions
copy discharge instructions
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Hemolytic uremic syndrome — home care after hospital discharge
▶
Rest and gradual return to normal activities
Adequate fluid intake — target 6 to 8 glasses per day unless restricted by kidney team
Follow all medication instructions exactly
▶
Blood pressure medications as prescribed
Eculizumab infusion appointments if on complement inhibitor therapy
Weigh yourself every morning — report gain of > 1 kg in one day to your doctor
Food safety if HUS was caused by E. coli
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Cook ground beef to 71 degrees C internal temperature
Avoid unpasteurized milk, juice, or cheese
Wash hands thoroughly after handling raw meat or animals
Wash produce carefully before eating
Warning signs — return to ER immediately
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No urine output for 8 hours
Sudden severe headache or confusion
Seizure or loss of consciousness
Severe weakness or inability to walk
Chest pain or difficulty breathing
Urine appearing red, brown, or tea-colored again
Marked swelling of the face, hands, or feet
Blood pressure reading above 180/110 mmHg at home
Fever above 38.5 degrees C
Follow-up appointments
▶
Nephrology (kidney specialist) within 1 to 2 weeks
Blood tests — kidney function, blood count — at every follow-up visit
Urine test — protein and blood — at each follow-up
If on eculizumab — keep all infusion center appointments
Genetics appointment if atypical HUS — complement mutation testing
Long-term kidney health
▶
Up to 1 in 4 patients develop chronic kidney disease after HUS
Blood pressure monitoring is lifelong
Low-sodium diet helps protect kidneys
Avoid NSAIDs — ibuprofen, naproxen — they can harm kidneys
References
Guidelines and key sources
Society guidelines
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European HUS registry and European Renal Association recommendations on aHUS management
American Society of Nephrology consensus on TMA classification and treatment
ACEP clinical policy references for TMA in the emergency setting
Surviving Sepsis Campaign — sepsis and AKI management principles
Landmark studies and evidence base
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Bell et al. — antibiotic use and HUS risk in STEC infection
Garg et al. — early hydration reducing adverse outcomes in STEC-HUS
Legendre et al. — eculizumab for atypical HUS (NEJM 2013)
Loirat and Fakhouri — comprehensive review of aHUS pathophysiology and genetics
German O104:H4 outbreak 2011 — TMA epidemiology and adult HUS outcomes
Diagnostic coding
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ICD-10 D59.3 — hemolytic uremic syndrome
ICD-10 M31.1 — thrombotic thrombocytopenic purpura
SNOMED CT — hemolytic uremic syndrome disorder concept
SymptomDx is an educational tool for medical professionals. It does not replace clinical judgment. Verify all clinical data and drug dosages with authoritative sources.
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Management Protocols
Hemolytic Uremic Syndrome (HUS)