Acute Glomerulonephritis

Epidemiology

Acute post-infectious glomerulonephropathy is the most common worldwide, accounting for approximately 80% of cases.¹

Recently, ASPGN has been grouped under the term post-infectious GN (PIGN), as Streptococcal species account for <50% of this type of nephritis. Staphylococcus infection-associated GN (SAGN) is now the most prevalent cause of PIGN in developed countries; however, it predominantly affects the elderly population in the UK.²

As Streptococcal sp. remains the most prevalent cause in the paediatric population, APSGN will be the focus in this article.

Greater disease incidence is reported in East Asian and indigenous island populations. This is partially influenced by poor access to healthcare. It is also evident that individuals from poorer socioeconomic groups are more likely to develop PSGN, compared to those from wealthier backgrounds.

Pathophysiology

Pathophysiology largely depends upon the underlying cause, though many are thought to involve immune complex depositions and/or autoantibodies (including systemic diseases such as SLE or vasculitis). However, more research is needed into the exact mechanisms which lead to glomerulonephritis. Idiopathic disease is rare.³

Causes of acute glomerulonephritis include¹:

Post-infectious GN

An infection with group A β-haemolytic Streptococci leads to circulating antibodies that bind to antigens (from the bacteria), which subsequently become trapped in the glomerulus and lead to inflammation within the nephron due to deposition of IgG ± C3 and the release of cytokines^3,4

Other bacteria that cause GN via this mechanism include Staphylococcus aureus and Staphylococcus epidermidis.

IgA nephropathy

This is often idiopathic but can follow infections that lead to an increase in circulating IgA, resulting in mesangial deposition and glomerular inflammation⁵

Henoch-Schönlein Purpura (HSP)

HSP is an IgA-mediated small vessel vasculitis. The renal findings are identical to those seen in IgA nephropathy. HSP, however, will present with renal signs plus involvement from any of the following systems: skin, GI tract, joints.

Alport’s

Alport’s is an X-linked genetic condition. You should consider a family history of renal +/- ear disease (it more likely to present with chronic renal impairment but can present with haematuria acutely).

Anti-glomerular basement membrane (anti-GBM) disease

AKA Goodpasture’s is an “extremely rare” cause of GN in children. It does, however, carry a high rate of morbidity and mortality due to its high rate of progression to rapidly progressive glomerulonephritis (RPGN).⁶

Risk Factors

• Recent URTI or pyoderma (less common in Western countries).
  • Pyoderma carries a 5x greater risk of developing nephropathy²
• Age 3-15
• Asian ancestry (especially East-Asian)
• Presence of atrioventricular or ventriculoperitoneal shunts (specific sub-classification of post-infectious GN, due to bacteria that can grow in the shunts – usually Staphylococcus species).⁷

Clinical Features

PIGN may occur at any age but is most common between the ages of 3 and 15 years (median age at presentation is 6–8 years old).⁸

PIGN can present in various ways, from being asymptomatic to severe nephritic syndrome.⁹

You should also consider if there is a history of recent pharyngitis or staphylococcal skin infection^7,9:

• pharyngitis 1-2 weeks ago
• impetigo 4-6 weeks ago

“IgG takes weeks” ~ post-infectious GN
”IgA takes dAys” ~ IgA nephropathy

Differentials (8,9)

Investigations

• Urinalysis plus MC&S
  • Morning sample for accurate protein: creatine ratio (if raised, ↑ likelihood of nephrotic syndrome)
  • Proteinuria (of varying severity)
  • RBC casts (only seen in fresh samples; sign of microscopic haematuria)
• Stool sample (if hx of diarrhoea for E. coli)
• Blood tests:
  • Paediatric renal profile: U&Es, creatinine, calcium, phosphate, chloride, bicarbonate, and albumin⁸
  • FBC – inflammatory markers and Hb
  • Consider capillary blood gas if concerned about electrolytes and acid-base status
• Specific tests:
  • Immunoglobulins
  • Complement proteins – hypocomplementemia (low C3 level)^9,10
  • Antibodies – antistreptolysin O titers in PIGN¹⁰
  • Kidney biopsy in children
    • Performed if the less invasive tests/scans have been unable to provide sufficient information to make a safe diagnosis. Biopsies can confirm the diagnosis, rule out other diagnoses and assess the degree of inflammation/presence of necrosis.^7,11
  • IgG and C3 complex deposits in PIGN

Management

Specific treatments are dependent on the underlying causes. The main aims of treatment are usually to control blood pressure, proteinuria and prevent further deterioration of renal function.

Post-infectious GN

• Antibiotics: 10-day course of Phenoxymethyl Penicillin or Clarithromycin (if penicillin allergy)
  • Limited impact of course of illness and prognosis, but will limit spread of B-haemolytic Group A streptococcus
• Largely supportive care, with monitoring of BP, urine output and electrolytes for complications.
• Fluid balance monitoring (the aim is to have input = total output, including insensible losses).
  • Daily weights
  • Salt restriction
  • Input-output measurements (can catheterise if necessary)
  • Furosemide (if signs of fluid overload)

If hypertensive (>95^th centile), amlodipine is 1st line; can consider ACEi/ARB if proteinuria present and discussed with nephrologist (not first line due to increased risk of AKI).⁸

IgA Nephropathy

• BP control: ACEi or ARB blockade, advice on a low-sodium diet, optimal lifestyle and blood pressure monitoring (systolic blood pressure [SBP] <90th percentile for age, sex, and height).
• In children with proteinuria >1 g/day, steroid therapy is often used. Typically, high-dose oral prednisolone for 4 weeks (then tapered over 4-6 months). IV methylprednisolone can also be used, though less commonly.⁷

Nephrologist Referral

• Consider referring to a paediatric nephrologist for children and young people who have recovered from an episode of acute kidney injury but have hypertension, impaired renal function or 1+ proteinuria on dipstick testing of an early morning urine sample.
  • hypertensive
  • urinary PCR >50mg/mmol (early morning specimen)
  • Alb <30g/dl
  • eGFR <90ml/min/1.73m2⁸
• Need for RRT [when the below are refractory to medical treatment]¹²
  • Metabolic acidosis
  • Hyperkalaemia
  • Pulmonary oedema
  • Persistent fluid overload
  • Symptoms or complications of uraemia (for example, pericarditis or encephalopathy)
• The indications for RRT can be remembered with AEIOU
  • A – Acidosis
  • E – electrolytes
  • I – Intoxicants (drug ingestion)
  • O – Overload and Oedema
  • U – Uraemic Complications

Prognosis & Complications

• PIGN typically has a very positive prognosis; approximately 95% of cases are self-limiting and rarely progress to renal failure/RPGN.¹⁰
• However, it is important to note that other causes of acute glomerulonephritis have less favourable prognoses and may frequently require early nephrology input.
• Complications that can occur following acute nephritis consist of:
  • Hypertension
  • Hyperkalaemia
  • Persistent/recurrent haematuria (<10%)
  • Rapidly progressive glomerulonephritis (RPGN) – very rare for PIGN to progress
  • CKD

References

1. Glomerulonephritis, Renal Unit, Paediatrics (494) | Right Decisions [Internet]. Scot.nhs.uk. 2018 [cited 2024 Dec 28]. Available from: https://rightdecisions.scot.nhs.uk/shared-content/ggc-clinical-guidelines/paediatrics/kidney-diseases/glomerulonephritis-renal-unit-paediatrics-494/
2. Satoskar AA, Parikh SV, Nadasdy T. Epidemiology, pathogenesis, treatment and outcomes of infection-associated glomerulonephritis. Nature Reviews Nephrology, 2020 01;16(1):32-50.
3. Glomerulonephritis – Aetiology | BMJ Best Practice [Internet]. com. 2022 [cited 2024 Oct 29]. Available from: https://bestpractice.bmj.com/topics/en-gb/207/aetiology
4. Couser WG, Johnson RJ. The etiology of glomerulonephritis: roles of infection and autoimmunity. Kidney International, 2014;86(5):905–14. Available from: https://www.kidney-international.org/article/S0085-2538(15)30397-5/fulltext
5. IgA nephropathy – Aetiology | BMJ Best Practice [Internet]. com. 2014 [cited 2024 Oct 29]. Available from: https://bestpractice.bmj.com/topics/en-gb/480/aetiology
6. Dowsett T, Oni L. Anti-glomerular basement membrane disease in children: a brief overview. Pediatric Nephrology, 2021 Nov 12;37(8):1713–9. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC8586640/
7. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases.
8. Glomerulonephritis UHL Children’s Hospital guideline (20 January 2023) UHL Policies and Guidelines. Available at: https://secure.library.leicestershospitals.nhs.uk/PAGL/Shared Documents/Glomerulonephritis UHL Childrens Hospital Guideline.pdf (Trust ref: E5/2019) (Accessed: 29 October 2024).
9. Viteri B, Reid-Adam J. Hematuria and Proteinuria in Children. Pediatrics In Review. 2018 Dec 1;39(12):573–87. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC6494107/
10. VanDeVoorde RG. Acute Poststreptococcal Glomerulonephritis: The Most Common Acute Glomerulonephritis. Pediatrics in Review. 2015 Jan;36(1):3–13. Available from: https://pubmed.ncbi.nlm.nih.gov/25554106/
11. Kidney biopsy. Great Ormond Street Hospital for Children hospital site. 2019 [cited 2024 Oct 29]. Available from: https://www.gosh.nhs.uk/conditions-and-treatments/procedures-and-treatments/kidney-biopsy/
12. National Institute for Health and Care Excellence (2019) Recommendations | Acute kidney injury: prevention, detection and management | Guidance | NICE. [cited 2024 Oct 29]. Available from: https://www.nice.org.uk/guidance/ng148/chapter/Recommendations#managing-acute-kidney-injury