|
|
|
|
Glomerulonephritis
|
| |
|
| |
Glomerulonephritis, also known as glomerular nephritis, abbreviated GN, is a renal disease characterized by inflammation of the glomeruli, or small blood vessels in the kidneys. It may present with isolated hematuria and/or proteinuria (blood resp. protein in the urine); or as a nephrotic syndrome, a nephritic syndrome, acute renal failure, or chronic renal failure. They are categorised into several different pathological patterns, which are broadly grouped into non-proliferative or proliferative types.
Discussion
Ask a question about 'Glomerulonephritis' Start a new discussion about 'Glomerulonephritis' Answer questions from other users |
Encyclopedia
Glomerulonephritis, also known as glomerular nephritis, abbreviated GN, is a renal disease characterized by inflammation of the glomeruli, or small blood vessels in the kidneys. It may present with isolated hematuria and/or proteinuria (blood resp. protein in the urine); or as a nephrotic syndrome, a nephritic syndrome, acute renal failure, or chronic renal failure. They are categorised 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 ones which are intrinsic to the kidney, whilst secondary causes are associated with certain infections (bacterial, viral or parasitic pathogens), drugs, systemic disorders (SLE, vasculitis) or cancers.
Thin Basement Membrane Disease
Thin basement membrane disease is an autosomal dominant inherited disease characterised by thin glomerular basement membranes on electron microscopy. It is a benign condition that causes persistent microscopic haematuria.
Non Proliferative
This is characterised by low numbers of cells (lack of hypercellularity) in the glomeruli. They usually cause nephrotic syndrome. This includes the following types:
Minimal change GN
This form of GN causes 80% 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 to be effective. 50% of people with FSGS continue to have progressive deterioration of kidney function, ending in renal failure.
Membranous glomerulonephritis
Membranous glomerulonephritis (MGN), a relatively common type of glomerulonephritis in adults, frequently produces a mixed nephrotic and nephritic picture. It is usually idiopathic, 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.
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 though the females. This condition, similarliy is called Familial Membranous Glomerulonephritis. There has only been in the ball-park of nine documented cases in the world.
Proliferative
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 world-wide. 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' which holds everything together). Immuno-staining is positive for immunoglobulin A deposits within the matrix. Prognosis is variable, 20% progress to ESRF. Steroids and immunosuppression are not effective treatments for this disease; ACE inhibitors are the mainstay of treatment.
Henoch-Schönlein purpura
Henoch-Schönlein purpura (HSP) is a systemic variant of IgA nephropathy which causes a small-vessel vasculitis and associated glomerulonephritis.
Post-infectious
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 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.
Membranoproliferative/mesangiocapillary GN
This is primary, or secondary to SLE, viral hepatitis, hypocomplementemia. One sees 'hypercellular and hyperlobular' glomeruli due to proliferation of both cells and the matrix within the mesangium. Presents usually with as a nephrotic syndrome but can be nephritic, with inevitable progression to end stage renal failure.
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's syndrome, an autoimmune disease whereby antibodies are directed against basal membrane antigens found in the kidney and lungs. As well as kidney failure, patient have hemoptysis (cough up blood). High dose immunosuppresion 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's granulomatosis and polyarteritis. There is a lack of immune deposits on staining, 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 parietal 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.
See also
|
| |
|
|
