Glomerulonephritis, Postinfectious

Basics

Description

Postinfectious glomerulonephritis (PIGN) is an immune complex disease associated with nonrenal infection by certain strains of bacteria, most commonly Streptococcus and Staphylococcus. The most common form of PIGN, poststreptococcal glomerulonephritis (PSGN), is preceded by infection with Streptococcus spp. and predominantly affects children. The clinical presentation can be asymptomatic or with an acute nephritic syndrome, characterized by gross hematuria, proteinuria, edema, hypertension (HTN), and acute kidney injury.

Epidemiology

PIGN is declining globally, especially in developed countries, in large part due to better hygiene and a decreased incidence of streptococcal skin infections. There are an estimated 470,000 new cases per annum of PSGN worldwide, and it remains the most common cause of acute nephritis in children globally, with 97% of cases occur in developing countries. PSGN is primarily a pediatric disease, but a recent increase in cases has been seen in nonstreptococcal GN in adults.

Incidence

  • New cases of PSGN in developing countries ranges from 9.5 to 28.5 per 100,000 persons per year.
  • Pediatrics: 24.3 cases/100,000 persons per year in developing countries; 6 cases/100,000 persons per year in developed countries
  • Adults: 2 cases/100,000 persons per year in developing countries; 0.3 cases/100,000 persons per year in developed countries
  • Worldwide: 34% of cases are now seen in adults with a global burden of 68,000 cases per year.
  • Estimated incidence of 470,000 and 5,000 deaths per year globally
  • Male > female (2:1)

Etiology and Pathophysiology

  • Glomerular immune complex disease induced by specific nephritogenic strains of bacteria:
    • >95% of cases are caused by group A β-hemolytic Streptococcus (GAS) (1)
    • Staphylococcus (predominantly Staphylococcus aureus; more commonly methicillin-resistant S. aureus [MRSA], occasionally coagulase-negative Staphylococcus)
    • Gram-negative bacteria including Escherichia coli, Yersinia, Pseudomonas, and Haemophilus (2)
    • Occasionally viral, fungal, helminthic or protozoal causes
  • Proposed mechanisms for the glomerular injury (3):
    • Deposition of circulating immune complexes with streptococcal or staphylococcal antigens—while these complexes can be detected in patients with streptococcal- or staphylococcal-related GN, they do not correlate to disease activity.
      • Note: IgG is the most frequent immunoglobulin in PSGN (2).
    • In situ immune complex formation from deposition of antigens within the glomerular basement membrane (GBM) and subsequent antibody binding
    • In situ glomerular immune complex formation promoted by antibodies to streptococcal or staphylococcal antigens
    • Alteration of normal renal antigen leading to molecular mimicry that elicits an autoimmune response
  • Glomerular immune complex causing complement activation and inflammation:
    • Nephritis-associated plasmin receptor (NAPlr): activates plasmin, contributes to activation of the alternative complement pathway
    • Streptococcal pyrogenic exotoxin B (SPE B): binds plasmin and acts as a protease; promotes the release of inflammatory mediators
  • Activation of the alternative complement pathway causes initial glomerular injury as evidenced by C3 deposition and decreased levels of serum C3. The lectin pathway of complement activation has also been recently implicated in glomerular injury (1),(4).

Risk Factors

  • Children 5 to 12 years of age
  • Older patients (>65 years of age):
    • Patients with immunocompromising comorbid conditions
    • Diabetes
    • Alcohol abuse

General Prevention

  • Early antibiotic treatment for streptococcal and staphylococcal infections, although efficacy in preventing GN is uncertain
  • Improved hand hygiene and respiratory etiquette
  • Prophylactic penicillin treatment to be used in closed communities and household contacts of index cases in areas where PIGN is prevalent

Commonly Associated Conditions

Streptococcal or staphylococcal infection

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