|Classification and external resources|
Photomicrograph of a kidney biopsy from a patient with crescentic glomerulonephritis showing prominent fibrocellular crescent formation and moderate mesangial proliferation in a glomerulus. Hematoxylin and eosin stain.
|ICD-10||N00, N01, N03, N18|
Glomerulonephritis, also known as glomerular nephritis, abbreviated GN, is a renal disease (usually of both kidneys) characterized by inflammation of the glomeruli, or small blood vessels in the kidneys. It may present with isolated hematuria and/or proteinuria (blood or protein in the urine); or as a nephrotic syndrome, a nephritic syndrome, acute renal failure, or chronic renal failure. They are categorized into several different pathological patterns, which are broadly grouped into non-proliferative or proliferative types. Diagnosing the pattern of GN is important because the outcome and treatment differs in different types. Primary causes are intrinsic to the kidney. Secondary causes are associated with certain infections (bacterial, viral or parasitic pathogens), drugs, systemic disorders (SLE, vasculitis), or diabetes.
Thin Basement Membrane Disease
Thin basement membrane disease is an autosomal dominant inherited disease characterized by thin glomerular basement membranes on electron microscopy. It is a benign condition that causes persistent microscopic hematuria. This also may cause proteinuria which is usually mild and overall prognosis is excellent.
This is characterised by absence of increase in the number of cells (lack of hypercellularity) in the glomeruli. They usually cause nephrotic syndrome. This includes the following types:
Minimal change GN (also known as Minimal Change Disease)
This form of GN causes 78.4% of nephrotic syndrome in children, but only 20% in adults. As the name indicates, there are no changes visible on simple light microscopy, but on electron microscopy there is fusion of podocytes (supportive cells in the glomerulus). Immunohistochemistry staining is negative. Treatment consists of supportive care for the massive fluid accumulation in the patients body (= oedema) and as well as steroids to halt the disease process (typically prednisone 1 mg/kg). Over 90% of children respond well to steroids, being essentially cured after 3 months of treatment. Adults have a lower response rate (80%). Failure to respond to steroids ('steroid resistant') or return of the disease when steroids are stopped ('steroid dependent') may require cytotoxic therapy (such as cyclosporin), which is associated with many side-effects.
Focal Segmental Glomerulosclerosis (FSGS)
FSGS may be primary or secondary to reflux nephropathy, Alport syndrome, heroin abuse or HIV. FSGS presents as a nephrotic syndrome with varying degrees of impaired renal function (seen as a rising serum creatinine, hypertension). As the name suggests, only certain foci of glomeruli within the kidney are affected, and then only a segment of an individual glomerulus. The pathological lesion is sclerosis (fibrosis) within the glomerulus and hyalinisation of the feeding arterioles, but no increase in the number of cells (hence non-proliferative). The hyaline is an amorphous material, pink, homogeneous, resulting from combination of plasma proteins, increased mesangial matrix and collagen. Staining for antibodies and complement is essentially negative. Steroids are often tried but not shown effective. 50% of people with FSGS continue to have progressive deterioration of kidney function, ending in renal failure.
Membranous glomerulonephritis (MGN), a relatively common type of glomerulonephritis in adults, frequently produces a mixed nephrotic and nephritic picture. Its cause is usually unknown, but may be associated with cancers of the lung and bowel, infection such as hepatitis and malaria, drugs including penicillamine, and connective tissue diseases such as systemic lupus erythematosus. Individuals with cerebral shunts are at risk of developing shunt nephritis, which frequently produces MGN.
Microscopically, MGN is characterized by a thickened glomerular basement membrane without a hypercellular glomerulus. Immunofluorescence demonstrates diffuse granular uptake of IgG. The basement membrane may completely surround the granular deposits, forming a "spike and dome" pattern. Tubules also display the symptoms of a typical Type III hypersensitivity reaction, which causes the endothelial cells to proliferate, which can be seen under a light microscope with a PAS stain.
Prognosis follows the rule of thirds: one-third remain with MGN indefinitely, one-third remit, and one-third progress to end-stage renal failure. As the glomerulonephritis progresses, the tubules of the kidney become infected, leading to atrophy and hyalinisation. The kidney appears to shrink. Treatment with corticosteroids is attempted if the disease progresses.
In extremely rare cases, the disease has been known to run in families, usually passed down through the females. This condition, similarly, is called Familial Membranous Glomerulonephritis. There have only been about nine documented cases in the world.
This type is characterised by increased number of cells in the glomerulus (hypercellular). Usually present as a nephritic syndrome and usually progress to end-stage renal failure (ESRF) over weeks to years (depending on type).
IgA nephropathy (Berger's disease)
IgA nephropathy is the most common type of glomerulonephritis in adults worldwide. It usually presents as macroscopic haematuria (visibly bloody urine). It occasionally presents as a nephrotic syndrome. It often affects young males within days (24-48hrs) after an upper respiratory tract or gastrointestinal infection. Microscopic examination of biopsy specimens shows increased number of mesangial cells with increased matrix (the 'cement' that holds everything together). Immuno-staining is positive for immunoglobulin A deposits within the matrix. Prognosis is variable, 20% progress to ESRF. ACE inhibitors are the mainstay of treatment.
This is a form of GN characterised by IgA deposits in the mesangial regions and immunocytochemistry is required for definitive diagnosis of the disease.
- Recurrent gross or microscopic hematuria
- gross hematuria occurs post-infection of the respiratory (more common), gastrointestinal, or urinary tract
- mild proteinuria
- occasionally nephrotic syndrome (although it usually has a nephritic presentation)
- rarely, presents with crescentic Rapidly progressive GN
The disease can be primary or secondary to liver and intestinal diseases. It also overlaps with Henoch-Schonlein purpura, a systemic renal disease in children in which similar IgA deposits occur.
Plasma polymeric IgA is increased in IgA Nephropathy, and circulating IgA-containing immune complexes can be found in the blood of some patients. Plasma IgA is usually monomeric and polymeric plasma IgA is broken down in the liver. IgA is normally found in mucus.
There are two forms of IgA and only IgA1 causes nephrogenicity.
- IgA deposition in the mesangium seen by immunofloresence
- Electron dense deposits in electron microscopy
- Absence of early complement components
- normal glomeruli
- mesangioproliferative GN
- focal proliferative GN (healing may cause focal segmental sclerosis)
- overt cresentic glomerulonephritis
- leukocytes in glomerular capillaries
Post-infectious glomerulonephritis can occur after essentially any infection, but classically occurs after infection with Streptococcus pyogenes. It typically occurs 10–14 days after a skin or pharyngeal infection with this bacterium.
Patients present with signs and symptoms of glomerulonephritis. Diagnosis is made based on these findings in an individual with a history of recent streptococcal infection. Streptococcal titers in the blood (antistreptolysin O titers) may support the diagnosis.
Light microscopy demonstrates diffuse endocapillary hypercellularity due to proliferation of endothelial and mesangial cells, as well as an influx of neutrophils and monocytes. The Bowman space is compressed, in some cases to the extent that this produces a crescent formation characteristic of crescentic glomerulonephritis.
Biopsy is seldom done as the disease usually regresses without complications. Treatment is supportive, and the disease generally resolves in 2–4 weeks.
This may be primary, or secondary to SLE, viral hepatitis, or hypocomplementemia. One sees 'hypercellular and hyperlobular' glomeruli due to proliferation of both cells and the matrix within the mesangium. Usually presents with a combined nephritic-nephrotic picture, with inevitable progression to end stage renal failure. The primary form consists of two types:
- Type 1 (Classical and Alternative Complement activation)
- Type 2 (also known as Dense Deposit Disease) Alternative Complement activation only. C3 Nephritic Factor stabilizes C3-convertase, leading to Hypocomplementemia. Unlike Type 1, no IgG is detected.
In both types, the basement membrane may develop a 'tram-track' appearance, due to duplication and splitting.
Rapidly progressive glomerulonephritis
Rapidly progressive glomerulonephritis (Crescentic GN) has a poor prognosis, with rapid progression to kidney failure over weeks. Steroid therapy is sometimes used. Any of the above types of GN can be rapidly progressive. Additionally two further causes present as solely RPGN.
- One is Goodpasture syndrome, an autoimmune disease whereby antibodies are directed against basal membrane antigens found in the kidney and lungs. As well as kidney failure, patients have hemoptysis (cough up blood). High dose immunosuppression is required (intravenous methylprednisolone) and cyclophosphamide, plus plasmapheresis. Immunohistochemistry staining of tissue specimens shows linear IgG deposits.
- The second cause is vasculitic disorders such as Wegener granulomatosis and polyarteritis. There is a lack of immune deposits on staining (pauci-immune), but blood tests are positive for ANCA antibody.
Histopathology: The majority of glomeruli present "crescents". Formation of crescents is initiated by passage of fibrin into the Bowman space as a result of increased permeability of glomerular basement membrane. Fibrin stimulates the proliferation of endothelial cells of Bowman capsule, and an influx of monocytes. Rapid growing and fibrosis of crescents compresses the capillary loops and decreases the Bowman space, which leads to renal failure within weeks or months.
- "glomerulonephritis" at Dorland's Medical Dictionary
- Dr. Zaid G. Nguyen MD. University of Melbourne, Dept of Medicine
- Robbin's Pathology
- Couser WG (May 1999). "Glomerulonephritis". Lancet 353 (9163): 1509–15. doi:10.1016/S0140-6736(98)06195-9. PMID 10232333.