Jennifer Watt. Haemolytic Uraemic Syndrome, Don't Forget the Bubbles, 2020. Available at:
https://doi.org/10.31440/DFTB.26233
What is HUS?
Haemolytic Uraemic Syndrome is a combination of findings which involves the triad of:
- Microangiopathic haemolytic anaemia with red blood cell fragmentation on blood film
- Acute renal failure
- Thrombocytopenia
What causes HUS?
About 90% of cases follow an infection, most commonly with entero-haemorrhagic E. Coli (EHEC). Other infective causes to be considered include Shigella and Streptococcus pneumoniae.
These infections are commonly contracted by the ingestion of contaminated food or water sources. In the US and UK, E. Coli 0.157 forms part of the natural intestinal microflora of cattle and sheep, therefore infection can be caused by direct contact with animal faeces. This can take place at farms or petting zoos, or via undercooked contaminated meat or dairy products.
The other 10-15% of cases represent atypical HUS and are due to a variety of causes, which will not be discussed here.
How do children present?
In children infected with EHEC about 10-15% of them will go on to develop HUS.
The common presentation includes bloody diarrhoea +/- cramping abdominal pain, fever and/or vomiting. The average onset of HUS after development of diarrhoea is about 7-10 days, with children under the age of 5 at highest risk.
Dependent on the extent of HUS progression, children may present with pallor, oedema, lethargy, or reduced urine output.
How to approach the examination
As with any unwell child, an A to E assessment is critical to rule out any immediate, life threatening complications.
Specific attention should be paid to assessing their fluid status, especially for evidence of dehydration.
*Although they may be oedematous, it is important to assess if they are intra-vascularly dry.
Things to examine for:
- Prolonged capillary refill time
- Observations: Tachycardia; hypotension or hypertension
- Are they are cool peripherally?
- Assess fontanelle tension (if applicable)
- Dry mucus membranes/reduced skin turgor
- Oedema (common locations in children include lower limbs, sacral and peri-orbital)
Is there evidence of neurological sequelae?
- Irritable/restlessness
- Confusion
- Reduced GCS
Key investigations to perform
A. Initial blood samples:
- Full blood count with blood film to assess for RBC fragmentation
- Coagulation
- Group and Save +/- cross match if haemoglobin low
- Biochemistry: U&Es, calcium, phosphate, magnesium, bicarbonate
- Glucose
- CRP
- Liver function including albumin
- Amylase/Lipase (hospital dependent)
- LDH
- Blood gas
- Blood cultures
B. Stool MC&S + E. Coli PCR
C. Urinalysis + MC&S
How to approach the management of HUS
Management should always be discussed with your local paediatric nephrologist in order to individualise/optimise management.
This is a generalised framework for the approach to management. Treatment involves supportive therapy to allow time for the infection to clear and the HUS process to cease.
1. Fluid Management:
- IV access
- Assess fluid status
- Monitor for electrolyte disturbances and correct as per local guidelines
- Daily weight, In/Out fluid balance, close monitoring of patient observations
*Fluid rehydration should be administered cautiously and in the setting of oliguria/anuria and oedema, fluids given should not exceed insensible loss + urine output.
*Evidence has shown that children presenting to hospital with dehydration in the prodromal phase of EHEC-induced HUS have a higher risk of developing an oliguric AKI and the requirement for dialysis. The administration of isotonic fluid in this phase has shown to be nephroprotective.
2. Hypertension:
- Can be secondary to fluid overload or as a result of the HUS process
- Trial of diuretics or if receiving dialysis, fluid can be offloaded
- If unresponsive to diuretics, consider a vasodilator (For example, amlodipine/ nifedipine *hospital dependent)
3. Anaemia:
- Target Haemoglobin: 70-100g/L
- Avoid excessive transfusion due to the associated risk of development of hyperkalaemia or fluid overload
4. Thrombocytopenia:
- Consideration for platelet transfusion if platelets <10 x109
- If undergoing surgery may require platelets > 50 x 109
5. Abdominal pain/vomiting:
- Secondary to colitis
- Regular paracetamol for pain relief
- Avoid opiates if possible due to constipating side effects
*NSAIDS like Ibuprofen should not be prescribed*
6. Nutrition:
- All patients should be reviewed by a dietician
- NG tube and feeding regime
7. Dialysis (Peritoneal Dialysis or Haemodialysis) Indications:
- Intractable acidosis
- Diuretic resistant fluid overload
- Electrolyte abnormalities Hyperkalaemia
- Symptoms of uraemia
In children with HUS, peritoneal dialysis is the preferred treatment option as it is a gentler form of dialysis.
Haemodialysis is indicated for children with severe colitis, severe electrolyte abnormalities and those with neurological complications.
HUS Complications
- AKI: Oliguria/anuria; hyperkalaemia; hypertension
- Neurological: Irritable, confusion, seizures
- Bleeding Risk
- Cardiac: Hypertensive cardiomyopathy/myocarditis
- Gastrointestinal: Severe colitis with bleeding/perforation
- Pancreatitis
- Pulmonary oedema
Selected references
Mayer CL, Leibowitz CS, Kurosawa S and Stearns-Kurosawa DJ. Shiga Toxins and the Pathophysiology of Hemolytic Uremic Syndrome in Humans and Animals. Toxins (Basel). Nov 2012. [Cited June 2020]; 4 (11): 1261-1287. doi: 10.3390/toxins4111261
Kausman. J 517 Haemolytic uraemia syndrome. Royal Hospital for Children- Nephrology. Dec 2013. [Cited June 2020]; Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3509707/
Hughes D. Management and investigation of bloody diarrhoea and haemolytic uraemic syndrome [draft]. GG&C Paediatric Guidelines- Kidney Diseases. Oct 30 2019. [Cited June 2020]; Available from: https://www.clinicalguidelines.scot.nhs.uk/ggc-paediatric-guidelines/ggc-guidelines/kidney-diseases/management-and-investigation-of-bloody-diarrhoea-and-haemolytic-uraemic-syndrome-draft/
Balestracci A et al. Dehydration at admission increased the need for dialysis in hemolytic uremic syndrome children. Pediatr Nephrol. 2012. [ Cited June 2020];27: 1407-1410. Doi: 10.1007/s00467-012-2158-0
Scheiring J. Andreoli SP. Zimmerhackl LB. Treatment and outcome of Shiga-toxin-associated hemolytic uremic syndrome (HUS). Ped Neprhrol. 2008. [Cited June 2020]; 23: 1749-1760. Doi: 10.1007/s00467-008-0935-6
Grisaru Silviu. Management of hemolytic-uremic syndrome in children. Int J Nephrol Renovasc Dis. 2014 [Cited June 2020]; 7: 231-239. Doi: 10.2147/IJNRD.S41837.
Nephrotic syndrome
Rachael Kermond. Nephrotic syndrome, Don't Forget the Bubbles, 2021. Available at:
https://doi.org/10.31440/DFTB.31540
Who, when and what…
Nephrotic syndrome is the most common glomerular disorder of childhood, affecting 1-7 children in 100,000 per year. It most typically affects children aged 2- 12 years of age and is characterized by proteinuria, hypoalbuminaemia and oedema.
Why it happens…
The villain of nephrotic syndrome is the glomerular filtration barrier (GFB). If we peer back at our textbooks, we remember the GFB is composed of two cells, the capillary endothelial cells and the podocytes separated by the glomerular basement membrane. The GFB is responsible for the filtration of water and small solutes but the retention of albumin. Defects in this GFB result in increased permeability to albumin and the subsequent proteinuria that defines nephrotic syndrome.
Idiopathic nephrotic syndrome (INS) is the most common cause of nephrotic syndrome in children. The aetiology is unclear however it could be related to circulating factors that, via immune mechanisms, alter the podocyte function and thus the GFB. The underlying histopathology of INS is minimal change disease (MCD) and less frequently focal segmental glomerulosclerosis (FSGS) which carries a poorer prognosis.
Other, less common causes include genetic mutations (with up to 50 genes affecting various components of the GFB identified to date), membranous glomerulopathy and glomerulonephritis (such as systemic lupus erythematous).
How it presents…
Children often present with a history of intermittent periorbital or pedal oedema. It is not commonly diagnosed until the child develops gross oedema with scrotal or labial oedema, ascites and even pleural effusions which prompts presentation.
Other potential presenting features include sepsis, cellulitis related to oedema, spontaneous bacterial peritonitis and complications of a prothrombotic state such as venous sinus thromboses.
How we investigate it…
It’s important to confirm proteinuria with a urine protein:creatinine ratio. Other investigations include a full blood count to evaluate for evidence of haemoconcentration, biochemistry to assess for hyponatraemia, acute kidney injury and serum albumin levels and a urinary sodium to assist in determining the intravascular fluid status of the patient.
Consideration of an immunologic assessment (ANA, complements) should occur if a patient presents with other systemic symptoms or haematuria. Finally, the patient’s immune status to varicella-zoster is important as it will guide prophylaxis if future exposure occurs.
How we treat it…
There are two main arms to the treatment of nephrotic syndrome. Acutely, the management of severe oedema and chronically, the treatment of the disease for which the basis is corticosteroids.
Management of acute presentation:
When assessing oedema in a nephrotic patient, it’s important to evaluate the intravascular fluid status of the patient. Hypotension, cool peripheries, elevated creatinine and a low urinary sodium are all features consistent with intravascular depletion. Whereas those who are oedematous, well-perfused with hypertension and a urinary sodium > 10mmol/L are likely well hydrated.
Management includes a strict fluid balance with a daily weight, a diet low in salt, the introduction of a fluid restriction (unless there is evidence of intravascular depletion) and consideration of IV albumin with frusemide.
If indicated, 1g/kg (5ml/kg) of 20% albumin should be given over 4-6 hours with 1mg/kg IV frusemide dose either halfway through and/or on completion of the infusion (depending on the patient’s fluid status). Those who have evidence of hypervolaemia may be treated with IV frusemide alone. However, this is a short term strategy and they should be closely monitored for evidence of hypovolaemia.
Another component of the acute management is consideration and treatment of the potential complications including sepsis, cellulitis, spontaneous peritonitis and thrombotic sequelae.
Long term management:
Whilst oedema is being treated it is important to instigate the mainstay of nephrotic syndrome therapy, prednisolone. The initial dose is 60mg/m2 for 4-6 weeks followed by a weaning course (alternate daily dosing) for up to 2 months. Previously, this initial course had been as long as 6 months. There is consistent data in the literature that demonstrates that this shorter regime is non-inferior and leads to a reduction in the side effects of steroids, particularly on growth.
The initial presentation is an invaluable opportunity to provide support to these families who are now presented with a chronic medical illness. This is facilitated by intensive education, dietician review and social work (or equivalent) input.
Education:
Dietetics:
Pastoral Care
Gastritis
Infection
Immunisations
The use of aspirin and other anti-thrombotic agents have largely been abandoned given the risks of these therapies. The likelihood of thrombosis is significantly reduced once the child’s oedematous state is appropriately managed
What happens next…
90% of children respond to steroid therapy within 4-6 weeks (i.e. steroid-sensitive). Remission is defined as a negative/trace urine dipstick for three consecutive days. There are a small proportion of children who will not remit in this time period, referred to as steroid-resistant. These children require consideration of a renal biopsy and/or genetic testing (such as rapid genomic sequencing) thus warrant a referral to a paediatric nephrologist.
80% of children with nephrotic syndrome will relapse, often in the context of a concurrent illness. This is the basis for ongoing urine dipstick testing. This will detect a relapse prior to the child becoming oedematous and so may avoid further hospital admission.
Some children will demonstrate steroid-dependence or become frequent relapsers (i.e. ≥2 relapses in the first 6 months following diagnosis or ≥4 in any 12 month period). These patients, in addition to the steroid-resistant group, should be referred to a nephrologist for ongoing management.
Finally, approximately 10% of patients with nephrotic syndrome will continue to relapse in their adult life.
The bottom line…
References