glomerulonephritis (GN)

see also:

• nephrotic syndrome
• renal medicine (nephrology)

• inflammation of the renal glomeruli with virtually all forms being mediated by an immune process (except for Alport's syndrome and TGBM disease)
• spectrum ranges from:
  • asymptomatic cases
  • isolated microhaematuria without proteinuria - which is usually benign but may become progressive
  • chronically progressive renal impairment associated with haematuria and proteinuria
  • acute nephrotic syndrome
  • acute nephritic syndrome

• anaphylactoid purpura with nephritis
• chronic GN with an acute exacerbation
• idiopathic hematuria
• familial nephritis

• usually autosomal dominant but may be sporadic
• aka benign familial hematuria
• it appears to be due to a missense mutation in the COL4A4 gene that codes for the alpha-4 chain of type IV collagen, resulting in a glycine to glutamic acid substitution producing defective collagen that interferes with the normal meshwork architecture of the GBM, in a similar manner to Alport's syndrome leading many to postulate that it is a heterozygous form of autosomal recessive Alport's syndrome but it could represent a different type of mutation
• one of the most common causes of glomerular microhaematuria - may account for almost 30% of the cases of glomerular hematuria ¹⁾
• frequency of TGBM nephropathy may be as high as 5% to 9% of the general population, according to studies on kidneys used for renal transplantation ²⁾
• most cases are benign but some may develop ESRF - particularly those who have proteinuria and hypertension
• most cases are asymptomatic but some develop loin pain
• unlike Alport's syndrome, there are no ocular associations of thin basement membrane disease

• rare heterogeneous collagen disorder syndrome affecting 1 in 5000 people
• accounts for 1-2% of all patients who start renal replacement therapy
• 85% are familial X-linked semi-dominant syndrome
  • primary abnormality appears to be due to mutations in the COL4A5 gene (OMIM #305010) on the X chromosome (Xq22 region) that codes for the alpha-5 chain of type IV collagen
  • females are generally less affected than males, microhematuria being the only sign present throughout life, although approximately 30% can progress to end-stage renal disease
  • affected males develop renal failure and usually have a high-tone sensorineural deafness by the age of 20 and:
    • glomerular haematuria and often thinning of glomerula basement membrane
    • high-tone sensorineural hearing loss in the 2000 to 8000 Hz range
    • ocular defects:
      • ant. lenticonus (in 25%), and retinal flecks in the macula and mid periphery (in ~85%) - these may be specific for Alport's
      • retinopathy similar to that of fundus albipunctatus
      • lens opacities are common
      • corneal erosions from mild trauma such as riding a bike without goggles
      • rarely, posterior polymorphous corneal dystrophy which is highly suggestive the patient has Alport's
      • other ocular abnormalities occur sporadically
    • may progress to ESRF
    • truncating mutations, comprising nonsense mutations, frame-shifts, and larger structural rearrangements, were found to cause a juvenile form of the disease with a mean age at ESRD of 21.6 years, compared to 33.1 years in patients with a non-truncating mutation. No significant differences in the presence of hearing defects or ocular manifestations between patients with the different types of mutations ³⁾
  • a subtype of X-linked Alport syndrome (XLAS) in which diffuse leiomyomatosis is an associated feature reflects deletion mutations involving the adjacent COL4A5 and COL4A6 genes
• 10-14% are due to the rare autosomal recessive form (ARAS)
  • due to homozygous mutations in either alpha-3 (COL4A3 gene region) and alpha-4 (COL4A4 gene region) chains of type IV collagen
  • boys and girls will develop kidney failure and hearing loss by their teens or young adult years.
• 1-5% are due to the rare “autosomal dominant form”
  • this form has only recently been identified in some families
  • this has been mapped to chromosome 2q in the region of COL4A3 and COL4A4
  • presumably heterozygous mutation and may be part of a spectrum along with TGBM disease
  • have a relatively mild phenotype, indicated by a slower rate of progression to ESRF than most patients with X-linked Alports
  • high clinical variability from complete asymptomatic state, to non-progressive isolated microhaematuria, to those developing ESRF in their 5th decade
  • usually well into middle age before kidney failure develops
  • the determinants of the phenotype remain largely unknown, so that it may be risky to predict renal prognosis in the individual with a single COL4A3/A4 mutation and an isolated microhematuria at the time of examination.⁴⁾
• the ocular and other clinical features of autosomal recessive Alport syndrome are identical to those seen in X-linked disease, while retinopathy and cataracts are the only ocular abnormalities described in the rare autosomal dominant form of Alport syndrome.
• there are no specific therapies for AS at present although gene therapy in the future may hold promise
• hearing aids are usually very effective for patients with hearing loss caused by Alport Syndrome
• see also: wikipedia

• results from an antecedent infection of the skin (develops 3-6 weeks after episode of pyoderma) or throat (develops 1-2 weeks after episode of pharyngitis) caused by nephritogenic strains of group A beta-hemolytic streptococci
• risk of APSGN following infection with these nephritogenic strains is 5% if throat infection (this is more common in temperate zones) and 25% if skin infection (this is more common in tropics and sub-tropics)
• most frequent in children 2-12 years old, peak at 5-6 years old but may affect any age persons
• 50% may be sublinical
• nearly all children recover fully
• elderly have high mortality rate of 20-25%
• children develop:
  • proteinuria which may take months to resolve and may recur over the next 2 years
  • haematuria which usually settles within 1-3 weeks
  • gross oedema which usually resolves within 5-10 days
  • hypertension which usually settles within 2-3 weeks but may take 6 weeks resolve
  • 5% may develop hypertensive encephalopathy
  • dilutional anaemia is common early
• Mx in ED:
  • antibiotics to eradicate Strept.
  • have a low threshold for admitting patients with suspected acute glomerulonephritis
  • admit if present with oliguria, renal failure, nephrotic syndrome, massive proteinuria, significant hypertension, or pulmonary symptoms
  • see emedicine - emergent Mx of acute GN
• DDx includes:
  • IgA nephritis
  • membranoproliferative GN
  • lupus nephritis (but gross haematuria is unusual)
  • GN of chronic infection
  • vasculitis
  • predominantly non-glomerular diseases such as haemolytic uraemic syndrome (HUS), thrombotic thrombocytopenic purpura (TTP), atheroembolic renal disease, acute hypersensitivity interstitial nephritis
  • irradiation of Wilm's tumour
• see emedicine - APSGN

• usually associated with a rapid decline in renal function (eg. 50% in GFR over 3 months)
• idiopathic primary type (>10% of all primary GN) is classified into 5 types
  • type I is associated with IgG anti–glomerular basement membrane [GBM] disease and mainly affects young adults
  • type II is immune complex mediated
  • type III is pauci-immune and associated with ANCA
  • type IV are combinations of I and III
  • type V accounts for 5-10% and is ANCA-negative renal vasculitis
  • type II and III mainly occur in middle age
• 40% are secondary to multisystem disease such as Goodpasture syndrome, Wegener granulomatosis, systemic lupus erythematosus
• over half present with nephritic syndrome and rapidly deteriorating GFR
• ~70% will either die or require dialysis
• DDx includes haemolytic uraemic syndrome (HUS), thrombotic thrombocytopenic purpura (TTP)
• emedicine

• an histologic form seen in patients with multisystem disorders such as Wegener granulomatosis, systemic lupus erythematosus, polyarteritis nodosa (PAN), Henoch-Schonlein purpura (HSP), vasculitis and infections.
• most cases are associated with immune complex deposition

• an uncommon cause of chronic nephritis that occurs primarily in children and young adults
• 7% of children and 12% of adults with idiopathic nephrotic syndrome
• 3 idiopathic primary types
• most are secondary to diseases such as systemic lupus erythematosus (SLE), chronic infections (eg. hepatitis B virus, hepatitis C virus, mycoplasma, malaria, infective endocarditis (including SBE))
• hypocomplementemia is a characteristic finding with all types but bears no prognostic value nor indicator of severity

• the most common single form of nephrotic syndrome in children accounting for 85-95% of cases
• 80% are younger than 6 years old at presentation with peak incidence in 2 year olds
• in adults, the mean age of onset is 40 years
• corticosteroids are the treatment of choice, leading to complete remission of proteinuria in most cases.
• ~90% of children respond within 2 weeks to prednisone at a dose of 60 mg/msq/d. Rx is continued for another 6 weeks, at lower doses of prednisone, after the remission of proteinuria.
• emedicine

• aka Berger disease
• the most common cause of glomerulonephritis in the world, being found in 40% of renal biopsies performed for GN in Asia, 20% in Europe and 10% in USA
• highly variable ranging from asymptomatic haematuria to rapidly progressive glomerulonephritis
• usually sporadic with onset often preceded by resp. tract infection (has been linked to H. parainfluenzae in some cases), but familial forms have been reported
• many have sporadic, transient frank haematuria within the 1st 72 hours of onset of pharyngitis, but may be associated with other infections, strenuous physical exercise and trauma.
• mesangial IgA deposits also occur in other conditions such as Henoch-Schonlein purpura (HSP), systemic lupus erythematosus (SLE), cirrhosis, coeliac disease, HIV / AIDS, dermatitis herpetiformis and ankylosing spondylitis
• usually benign course but 20% may develop ESRD over 20 years, and 1-2% of all patients with IgA nephropathy develop ESRD each year.
• 80% are diagnosed at age range 16-35years but can affect all ages
• emedicine

• a rare form of glomerulonephritis with pulmonary hemorrhage due to an anti-GBM disease of complex pathogeneses
• note that cases where there is no pulmonary involvement are usually just called anti-GBM disease (10-40% may be ANCA positive)
• 1-2% of all cases of crescentic rapidly progressive glomerulonephritis are secondary to this disorder
• 1st described in 1919 by Goodpasture who documented 3 cases in the influenza epidemic
• a classic type II reaction in the Gell and Coombs classification of antigen-antibody reactions
• an initial insult to the pulmonary vasculature is required for exposure of the alveolar capillaries to the anti-GBM antibodies.
• predisposing factors for such exposure include the following:
  • association with HLA-DR2
  • exposure to organic solvents or hydrocarbons
  • smoking
  • infection (eg, influenza A2)
  • cocaine inhalation
  • exposure to metal dusts
• emedicine