What is the pathogenesis and management of post-streptococcal glomerulonephritis (PSGN)?

From the Guidelines

Post-streptococcal glomerulonephritis (PSGN) is an immune-mediated kidney disease that develops following a streptococcal infection, and its management is primarily supportive, focusing on controlling hypertension and fluid overload, with antibiotics given to eradicate any remaining streptococcal infection, as recommended by the KDIGO 2021 clinical practice guideline for the management of glomerular diseases 1.

Pathogenesis of PSGN

The pathogenesis of PSGN involves immune complex formation when streptococcal antigens trigger antibody production, leading to deposition of these complexes in the glomerular basement membrane. This activates complement, attracts inflammatory cells, and damages the glomeruli, resulting in reduced kidney filtration.

Management of PSGN

Management of PSGN is primarily supportive as the condition is usually self-limiting.

• Treatment focuses on controlling hypertension with antihypertensives like ACE inhibitors or calcium channel blockers,
• restricting sodium and fluid intake if edema is present,
• and using diuretics such as furosemide 20-40mg daily to manage fluid overload.
• Antibiotics like penicillin or amoxicillin should be given to eradicate any remaining streptococcal infection, though they don't alter the course of established PSGN. Most patients, especially children, recover completely within weeks to months with normal kidney function. However, adults may have a higher risk of developing chronic kidney disease, necessitating long-term monitoring of blood pressure, urinalysis, and kidney function tests. Severe cases with significant kidney dysfunction, persistent heavy proteinuria, or rapidly progressive disease may require nephrology consultation to consider immunosuppressive therapy, though this is uncommon, as noted in the KDIGO 2021 guideline 1 and the executive summary of the KDIGO 2021 guideline for the management of glomerular diseases 1.

Key Considerations

• The utility of immunosuppression, even in cases of crescentic GN, is uncertain and carries substantial potential risks, in particular in the elderly, as mentioned in the executive summary of the KDIGO 2021 guideline for the management of glomerular diseases 1.
• Persistently low C3 in serum beyond week 12 may be an indication for kidney biopsy to particularly exclude complement C3 glomerulonephritis (C3GN), as noted in the executive summary of the KDIGO 2021 guideline for the management of glomerular diseases 1.

From the Research

Pathogenesis of Post-Streptococcal Glomerulonephritis (PSGN)

• PSGN is primarily associated with preceding group A streptococcal skin or throat infections, and its pathogenesis is multifactorial 2.
• The formation of antigen-antibody immune complexes, causing inflammatory damage to renal glomeruli, is a key mechanism in the development of PSGN 2, 3.
• Deposition of circulating immune complexes or in situ formation of immune complexes in glomeruli, or both, results in glomerulonephritis 2.
• Molecular mimicry is hypothesized as a mechanism, wherein cross-reactivity between anti-streptococcal antibodies and glomerular intrinsic matrix proteins leads to glomerulonephritis 2.
• Streptococcal pyrogenic exotoxin B and nephritis-associated plasmin receptor are identified nephritogenic antigens (nephritogens) involved in the pathogenesis of PSGN 2, 3.

Management of PSGN

• The management of PSGN is symptomatic, and the main way to prevent PSGN is to treat group A streptococcal (GAS) infections with antibiotic therapy 4.
• If PSGN is not treated, the patient may develop chronic kidney disease 4.
• There is no specific therapy for PSGN, but its morbidity and mortality are drastically reduced by the prevention and/or treatment of complications 3.
• The prognosis is generally good, but some cases may evolve into chronic kidney disease 3.

Key Factors Involved in PSGN Pathogenesis

• Renal glomerular immune complex deposition is critical in the initiation of APSGN 5.
• Mechanisms previous to immune complex formation could modulate the initiation and the progression of the disease 5.
• Initial and late renal events involved in the nephritis can also be related to host factors and streptococcal factors 5.
• The possibility that APSGN is not just due to a single streptococcal antigen and its antibody, but instead, kidney damage may be the result of different factors acting at the same time related to both streptococcus and host factors 5.