Skip to content

Diagnosing acute post-streptococcal glomerulonephritis

,

SHARE VIA:

A short refresher

This blog will explore clinicians’ processes to diagnose acute post-streptococcal glomerulonephritis (APSGN). Understanding this kidney disorder is crucial to early detection, so we’ll recap the basics before diving into the diagnostics. 

APSGN is an auto-immune response to a Group A Streptococcus (GAS) bacterial infection. The immune system produces antibodies to combat the infection, but they mistakenly attack the inner side of the glomerular tufts, tiny kidney filters. These tufts normally filter plasma proteins into the blood, but now they cannot do their job, so protein is lost in the urine (proteinuria), and fluid leaks out into nearby tissues, causing swelling (oedema) (1-4).

It’s not always the throat!

GAS causes a wide range of clinical diseases.

APSGN commonly presents 1 to 2 weeks after a throat infection (pharyngitis) or six weeks after a skin infection (impetigo or other strep skin infections). These are the two most common infections caused by GAS and the most common in children (1, 5, 6). APSGN has been associated with skin infection following scabies infestation in some populations.

Interestingly, APSGN is often associated with pharyngitis in colder climates and skin infections in warmer climates. Other causes of APSGN include bacterial infections such as endocarditis and pneumonia, viral infections (epatitis, CMV, parvovirus B19), fungal infections (histoplasmosis), and parasitic infections (malaria, toxoplasmosis). 

Globally, the incidence of APSGN is over 470000 cases annually, leading to approximately 5000 deaths (1, 3-5, 10). Putting this figure into perspective, 1.06% of cases lead to death. Approximately 404000 cases occur in children, and 97% occur in less developed countries (1, 4). A higher incidence occurs when overcrowded living spaces mean infections, particularly of the skin, can spread more readily.

In indigenous Australians, APSGN remains the most common cause of renal disease. (1-3, 5, 7, 11, 12). Over the past three decades, the incidence has fallen in the developed world, primarily because of antibiotic therapy and improved living conditions.

APSGN is more common in males than females, although the reasons for this are unknown, and there is no correlation regarding the cause. In three retrospective studies looking at predictors of kidney injury, boys outnumbered girls by 60% to 30% (1, 10, 11).

The disease peaks between 5 and 6 years and rarely occurs in children under 2.

Most children with APSGN make a full recovery without needing admission. The disease is self-limiting, and the long-term prognosis is good. Those who do get admitted are discharged within a few days once their blood pressure (BP) is controlled, and they are monitored as outpatients (3, 4).

Clinical presentation

Alfie, a 6-year-old boy, has been referred to your emergency department (ED) by his GP for review.

He has presented with cola-coloured urine and mild facial oedema.

The GP reports that Alfie is generally fit and well.

His only past medical history was treatment for a throat infection two weeks ago.

He is afebrile. 

The initial diagnostic step is a thorough clinical assessment.

Signs and symptoms appear 1-3 weeks after GAS pharyngitis and 3-6 weeks after GAS pyoderma (1, 4, 5). The classic triad of symptoms – gross haematuria, oedema, and hypertension – is commonly preceded by a recent history of a streptococcal infection. (4, 5, 15)

So far, Alfie has displayed two of these with his dark urine and facial swelling. A sore throat two weeks before suggests GAS pharyngitis. He also has oliguria, seen in 50% of cases (4, 14). 

Other clinical features include hypervolaemia, proteinuria, vomiting, anorexia and malaise.

Elevated serum urea and creatinine are common at presentation, with recovery seen within two weeks.

Red flag symptoms, including anuric renal failure, acid-base disturbance, hyperkalaemia and significant fluid overload, should prompt further evaluation for the need for renal replacement therapy.

Hypertensive encephalopathy (confusion, seizures and coma) can be the presenting feature in up to 10% of cases. However, a proportion of children develop APSGN without experiencing any prior symptoms. 

The next stage in Alfie’s diagnosis is to check his blood pressure.

Hypertension occurs in approximately 65% of cases. In one study looking at the clinical profile of children with APSGN, 87% had hypertension (3, 5, 11). Hypertension and oedema are the main reasons for admission.

Hypertension is defined as a diastolic BP of >90 mmHg in children 13 years and over or >80 below 13 years.

It occurs during the acute stage of APSGN, usually resolving by two weeks and rarely needing long-term treatment.

Clinical Examination

Alfie is hypertensive, with a BP recorded as 150/84. His other observations are normal.

You review the urine microscopy sent by the GP, which shows blood 3+, protein 2+ and leucocytes 1+.

He has periorbital and ankle oedema as well as a soft systolic murmur.

You take some blood tests, including an FBE, U&E, and C3 level.

Laboratory testing

Laboratory tests are instrumental in confirming the diagnosis. The typical findings are:

Urinalysis 

Haematuria is one of the hallmark signs of APSGN. About 30% of children with APSGN have gross haematuria, but sometimes it is microscopic, so it may go unnoticed if not tested. Proteinuria (usually more than 2+) may also be present due to poor renal function. We also look for dysmorphic red cells, red cell casts, and leukocytes. 

Throat or skin swabs 

Throat swabs are commonly negative, but we need to look for the presence of GAS infection. In Alfie’s case, we suspect pharyngitis so we will do a throat swab for culture. 

Blood tests 

Elevated levels of antistreptolysin O (ASO) and anti-DNase B antibodies in the blood suggest a recent GAS infection.

ASO and anti-DNase B are antibodies produced to fight off GAS pharyngitis. If the levels are raised, suspect a GAS infection. Streptococcal antibodies are positive in more than 95% of patients with APSGN from GAS pharyngitis, though this rise may be halted if the patient has received antibiotics

Complement levels, particularly low levels of C3, are also seen in APSGN. Complement C3 protects the body against invasive infections. Low levels of C3 indicate that infection is present, but the levels have been depleted as they work overtime to fight the infection (3-5). 

Kidney function tests: Disproportionately raised urea levels compared to creatinine levels indicate impaired renal function. 

FBC: Normochromic, normocytic anaemia due to haemodilution. 

Acidaemia and hyperkalaemia may occur in those with severe renal injury.

Differential diagnosis

Clinicians must differentiate APSGN from other kidney disorders with similar symptoms, such as IgA nephropathy, Systemic Lupus Erythematosus, and Henoch-Schoenlein Purpura. This is not always easy when the patient is in the ED.

C3 levels, for example, always start low in APSGN but return to normal levels by six to eight weeks. If they remain low after two months, then consider lupus as an alternative diagnosis (3-5).

Indications for renal biopsy

Consider a renal biopsy in the following circumstances. 

  • Persistently low C3 levels beyond eight weeks 
  • Persistent heavy proteinuria after six months 
  • Atypical presentation, including nephrotic syndrome and persistent renal failure beyond 3 weeks. 
  • Other pathologies more likely than APSGN 

Alfie’s blood results are back.

ASO and anti-DNase titres were both high, and C3 was low. Hb was 96 with a normal MCV.

His U&E is slightly more concerning, showing a Urea of 17 and Creatinine of 87.

You discuss him with the Nephrology Registrar, who suggests you admit Alfie under the Renal team, and they will further assess him.

You have successfully diagnosed APSGN.

Later, the Nephrology Registrar tells you they will be keeping Alfie in hospital to monitor him as well treating his hypertension and fluid overload. 

The management of APSGN is usually supportive. The focus is on treating possible complications, including hypertension, volume overload, and electrolyte abnormalities.

The prognosis of APSGN is usually excellent, and children usually recover in 6 to 8 weeks.

Time to resolution of symptoms – adapted from Wong et al., 2013

Take home messages

APSGN can present 1 to 2 weeks following a Group A Streptococcus throat infection or six weeks following a skin infection. 

If GAS pharyngitis is diagnosed and treated while present, it may halt progression to APSGN. 

Males are more commonly affected than females, with a peak age of 5 -6 years. 


‘Cola-coloured’ haematuria is the most common clinical feature, followed by hypertension and oedema. 

Hypertensive encephalopathy is a life-threatening event and should be monitored closely. 

The prognosis for APSGN is good. Most cases resolve completely

References

1. Wan Yusof WA, Yaacob NM, Nasir A, Yusoff S, Ilias MI. Clinical predictors of acute kidney injury in children with acute post-streptococcal glomerulonephritis: a tertiary centre experience. Singapore Medical Journal. 2023. 

2. Kanjanabuch T, Kittikowit W, Eiam-ong S. An update on acute postinfectious glomerulonephritis worldwide. Nature Reviews Nephrology. 2009;5(5):259-69. 

3. Ong LT. Management and outcomes of acute post-streptococcal glomerulonephritis in children. World J Nephrol. 2022;11(5):139-45. 

4. R B. <Acute Poststreptococcal Glomerulonephritis> 2023 [updated 31 OCT 2023. Available from: https://emedicine.medscape.com/article/980685-overview. 

5. Steer AC, Danchin MH, Carapetis JR. Group A streptococcal infections in children. Journal of Paediatrics and Child Health. 2007;43(4):203-13. 

6. Hunt EA, Somers MJ. Infection-related glomerulonephritis. Pediatric Clinics. 2019;66(1):59-72. 

7. Marshall CS, Cheng AC, Markey PG, Towers RJ, Richardson LJ, Fagan PK, et al. Acute post-streptococcal glomerulonephritis in the Northern Territory of Australia: a review of 16 years data and comparison with the literature. The American journal of tropical medicine and hygiene. 2011;85(4):703. 

8. Demuynck M, Lerut E, Kuypers D, Evenepoel P, Claes K, Naesens M, et al. Post-streptococcal glomerulonephritis: not an extinct disease! Acta Clinica Belgica. 2013;68(3):215-7. 

9. VanDeVoorde III RG. Acute post-streptococcal glomerulonephritis: the most common acute glomerulonephritis. Pediatrics in review. 2015;36(1):3-13. 

10. Matsell DG, Cojocaru D, Catapang M. Risk factors associated with short- and long-term kidney injury in children with post-infectious glomerulonephritis. Pediatric Nephrology. 2023;38(10):3309-15. 

11. Dhakal AK, Shrestha D, Singh SK, Acharya S. Clinical profile of children with acute post-streptococcal glomerulonephritis. Pediatric Nephrology. 2023;38(10):3327-36. 

12. Worthing KA, Lacey JA, Price DJ, McIntyre L, Steer AC, Tong SY, et al. A systematic review of group A streptococcal emm types associated with acute post-streptococcal glomerulonephritis. The American journal of tropical medicine and hygiene. 2019;100(5):1066. 

13. Rodriguez-Iturbe B, Haas M. Post-streptococcal glomerulonephritis. 2016. 

14. Rawla P, Padala SA, Ludhwani D. Poststreptococcal glomerulonephritis. 2019. 

15. Pais PJ, Kump T, Greenbaum LA. Delay in diagnosis in poststreptococcal glomerulonephritis. The Journal of Pediatrics. 2008;153(4):560-4. 

16. Demircioglu Kılıc B, Akbalık Kara M, Buyukcelik M, Balat A. Pediatric post‐streptococcal glomerulonephritis: Clinical and laboratory data. Pediatrics International. 2018;60(7):645-50. 

17. Wong W, Lennon DR, Crone S, Neutze JM, Reed PW. A prospective population‐based study on the burden of disease from post‐streptococcal glomerulonephritis of hospitalised children in New Zealand: Epidemiology, clinical features and complications. Journal of paediatrics and child health. 2013;49(10):850-

Authors

  • Tom is a Paediatric Registrar in Melbourne, Australia and research fellow at Murdoch Children’s Research Institute (MCRI) with Interests in sepsis and fluid management. When not at work he can be found at the beach with his biggest life companion Rupert the Labrador. He/Him.

    View all posts

KEEP READING

ENDOCARDITIS HEADER

Infective Endocarditis

, ,
RSV protection HEADER

Protection from RSV

,
Copy of Trial (1)

Bubble Wrap PLUS – July 2024

Copy of Trial (1)

The 82nd Bubble Wrap

BUTTON BATTERY HEADER

Management of Button Battery Ingestion

, ,
PECARN C-spine HEADER (2)

Cervical Spine Imaging in Kids – the PECARN rule

, , ,
HIDDEN C HEADER

The ‘Hidden C’

NEC HEADER

Necrotising Enterocolitis

Copy of Trial (1)

Bubble Wrap PLUS – June 2024

Copy of Trial (1)

The 81st Bubble Wrap

PPHNHEADER

Persistent Pulmonary Hypertension of the Newborn

Diagnosing ASPGN HEADER

Diagnosing acute post-streptococcal glomerulonephritis

,
Not a fever HEADER

When is a fever not ‘just a fever’?

Copy of Trial (1)

Bubble Wrap PLUS – May 2024

Copy of Trial (1)

The 80th Bubble wrap x DFTB MSc in PEM

Leave a Reply

Your email address will not be published. Required fields are marked *

DFTB WORLD

EXPLORE BY TOPIC