Gn causes

• Overview of the pathogenesis and causes of glomerulonephritis in children
• Glomerulonephritis (GN)


  Presents as a constellation of findings that include hematuria, proteinuria, edema, and, often, hypertension
• GN


  Caused by a number of disorders that are all characterized by glomerular injury accompanied by inflammation
• GN may progress to kidney failure
• Pathogenesis of GN


  1. Autoimmune response, which is modified by genetic factors, to a variety of different etiologic agents including infectious agents

  2. Immunologic response activates complement activation, leukocyte recruitment, and release of growth factors and cytokines resulting in glomerular inflammation and injury
• GN


  • May be isolated to the kidney (primary GN) or be a component of a systemic disorder (secondary GN)
• Immunologic damage in GN


  1. Humoral (T helper cell 2-regulated) immune response results in immunoglobulin deposition and complement activation within the glomeruli

  2. Immune complex deposition is an active process caused by in situ binding of antibodies to antigens localized within the glomeruli

  3. Antigens may be structural glomeruli components or trapped/deposited within the glomerulus

  4. Autoantibodies to complement factors can induce C3 GN through complement activation

  5. Passive process of trapping circulating immune complexes within the glomeruli
• GN due to antibody formation


  • Requires the presence of T lymphocytes
  • CD4+ T lymphocytes specific for nephritogenic autoantigens are present in the circulation of patients
  • T lymphocytes may also cause GN in the absence of antibodies
• Secondary processes in GN


  1. Complement system activation

  2. Coagulation system activation

  3. Leukocyte recruitment

  4. Injury to glomerular cells

  5. Growth factors and cytokines production
• Etiologic classification of GN


  • Clinical presentation
  • Histopathology
• Acute nephritic syndrome


  Sudden onset of hematuria, proteinuria, decreased glomerular filtration rate, and retention of sodium and water, usually resulting in an elevated blood pressure and edema
• Causes of acute nephritic syndrome in children

  • Poststreptococcal GN
  • Other infectious agents
  • IgA vasculitis
  • Nephritis associated with subacute bacterial endocarditis
  • Shunt nephritis
  • Chronic GN presenting as acute nephritic syndrome (IgA nephropathy, membranoproliferative GN, lupus nephritis)
• Rapidly progressive glomerulonephritis (RPGN)


  Clinical syndrome manifested by features of subacute nephritic syndrome with a progressive loss of kidney function over a comparatively short period of time, characterized morphologically by extensive crescent formation
• Causes of pediatric RPGN


  • Primary GN (IgA nephropathy, membranoproliferative GN, anti-glomerular basement membrane disease)
  • Secondary GN (ANCA-associated vasculitis, lupus nephritis, poststreptococcal GN, IgA vasculitis nephritis)
• Recurrent macroscopic hematuria


  Commonly caused by IgA nephropathy or Alport syndrome
• Chronic glomerulonephritis


  • Patients may have few overt symptoms, with asymptomatic hematuria or proteinuria as the only presenting sign
  • May present as acute nephritic syndrome initially
  • Includes both primary GN (membranoproliferative GN, IgA nephropathy, anti-GBM disease) and secondary GN (lupus nephritis, ANCA-associated vasculitis)
• Kidney biopsy may be needed to determine the histologic etiology of GN or confirm the diagnosis
• Urinalysis may be the only presenting sign. In addition, causes of chronic GN may present as acute nephritic syndrome and may be initially indistinguishable clinically from acute disorders
• In some cases, patients are diagnosed in a late stage of disease and present with hypertension, kidney impairment, and proteinuria with or without hematuria. The kidney biopsy at this stage may only demonstrate nonspecific and nondiagnostic findings of fibrosis, glomerular sclerosis, and tubular atrophy on light microscopy
• Immunofluorescence microscopy may be more helpful in making a diagnosis
• Chronic GN that presents in childhood includes


  • Primary GN (eg, MPGN, IgA nephropathy, and anti-GBM disease)
  • Secondary GN (eg, lupus nephritis and ANCA-associated vasculitis)
• Histopathology


  • A kidney biopsy may be needed to determine the histologic etiology of GN or confirm the diagnosis
  • In some cases, the diagnosis can be made clinically and a biopsy is not required (eg, poststreptococcal GN)
  • Histopathology also allows to diagnose active lesions potentially reversible with therapeutic interventions or chronic and irreversible lesions
• Histopathologic evaluation consists of


  • Light microscopy
  • Immunofluorescence examination
  • Electron microscopy
• Light microscopy


  • The light microscopic findings generally are not specific, as the same morphological pattern may be produced by a number of different diseases
  • A specific disease may present with several different histologic patterns
• Despite the diagnostic limitation of light microscopy, it is a generally useful tool because histologic findings often correlate with the clinical status and prognosis of the patient
• Immunofluorescence microscopy


  • Demonstrates the pattern of immunoglobulin and complement glomerular deposition, which is helpful in identifying specific kidney disorders among the different causes of GN
• Histologic patterns of lupus nephritis

  • Minimal mesangial lupus nephritis (class I)
  • Mesangial proliferative lupus nephritis (class II)
  • Focal lupus nephritis (class III)
  • Diffuse lupus nephritis (class IV)
  • Membranous lupus nephropathy (class V)
  • Advanced sclerosing lupus nephritis (class VI)
• Diffuse proliferative GN


  • Associated with inflammatory lesions in most or all of the glomeruli
  • Patients may have significant and serious clinical findings, including nephrotic range proteinuria, edema, hypertension, and impaired kidney function
• Focal GN


  • Associated with inflammatory lesions in less than one-half of the glomeruli
  • Patients with focal involvement generally do not have serious clinical findings and have a better prognosis
• Linear deposition of IgG along the GBM

  • Diagnostic for anti-GBM GN
• Granular deposits


  • Characteristic of immune complex diseases
  • The pattern of deposition is based on the immunosera used (eg, anti-IgG, anti-IgA, anti-C3) and is used to diagnose specific GN
• Electron microscopy may be useful in confirming or making a specific diagnosis of an underlying kidney disorder
• Electron microscopy demonstrates the characteristic subepithelial "humps" seen in patients with poststreptococcal GN
• Primary glomerulonephritides in children


  • Membranoproliferative GN (MPGN)
  • IgA nephropathy
  • Anti-glomerular basement membrane (GBM) disease
• Secondary glomerulonephritides in children


  • Idiopathic crescentic GN
  • Poststreptococcal GN
  • IgA vasculitis (Henoch-Schönlein purpura [HSP])
  • Systemic lupus erythematosus nephritis
  • Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis
  • Nephritis associated with infective endocarditis