Glomerular Disease Flashcards
What are the pathological consequences of glomerular disease?
Leakage of cells and macromolecules across the glomerular filtration barrier
- Proteinuria: characteristic of podocyte diseases or of alteration of the architecture by scarring or deposition of foreign material
- Haematuria: characteristic of inflammatory and destructive processes
Loss of filtration capacity (GFR)
Hypertension
What is meant by the term glomerulonephritis?
This means “inflammation of the glomeruli” and although inflammation is not apparent in all varieties (“glomerulopathy” is a term used to denote this), the name sticks.
What is the pathogenesis of glomerulonephritis?
Most types of GN are immunologically mediated and several respond to immunosuppressive drugs.
Deposition of antibody occurs in many types of GN but frequently th presumed mechanisms involve cellular immunity, which is more difficult to investigate.
Most granular deposts are formed “in situ” rather than by circulating immune complexes”, by antibodies which complex about glomerular antigens or about other antigens that have localised in the glomerulus.
Which forms of glomerulonephritis cause nephrotic syndrome predominantly?
Mechanisms in nephrotic syndrome - injury to podocytes, changed architecture (scarring, deposition of matrix or other elements)
1) Minimal change nephropathy
2) FSGC
3) Membranous nephropathy
4) Amyloid
5) Diabetic nephropathy
6) SLE spectrum
What is minimal change nephropathy?
This is a primary GN and occurs at all ages but accounts for nephrotic syndrome in most children, and about 25% of adults.
Proteinuria usually remits on high dose corticosteroid therapy (1mg/kg prednisolone for 6 weeks), although some patients who respond incompletely or relapse frequently need maintenance steroids, cytotoxic therapy or other agents.
The main problems are those of the nephrotic syndrome and complications of treatment.
What is the histology in minimal change disease?
Normal, except on electron microscopy where fusion of podocyte foot processes is seen (non specific finding).
Are there any associations with minimal change disease?
Atopy
HLA-DR7
Drugs
What is FSGS?
Focal segmental glomerulosclerosis.
This is another primary GN that presents with the nephrotic syndrome.
It is a histological term with many causes. As it is a focal process, abnormal glomeruli may not be seen on renal biopsy if only a few are sampled, leading to an initial diagnosis of minimal change disease. Juxtaglomerular glomeruli are more likely to be affected early in the disease.
How does primary FSGS present?
There are two types of presentation with FSGS:
1) Idiopathic nephrotic syndrome and no other cause of renal disease - little response to steroid treatment and progress to renal failure. Frequently recurrs after renal transplantation (proteinuria can recur almost immediately). Proportion of patients do respond to steroids (good prognostic sign)
2) Histological appearance of FSGS but less protenuria (secondary FSGS) Focal scarring reflects healing of previous focal glomerular injury, such as HUS, cholesterol embolism or vasculitis. In others it seems to represent particular types of nephropathy (e.g. those associated with HIV, some podocyte toxins and massive obesity). Associated with numerous other forms of injury and renal disorders; no specific treatment
What is membranous nephropathy?
This is the most common cause of nephrotic syndrome in adults and presents with proteinuria.
Some cases are associated with known causes, but most are idiopathic.
What is the histology of membranous nephropathy?
Thickening of GBM progressing to increased matrix deposition and glomerulosclerosis.
Granular subepithelial deposits of IgG.
What are the associations of membranous nephropathy?
HLA-DR3 (or idiopathic) Drugs - gold, penicillamine, NSAIDs Mercury, heavy metals Hepatitis B virus, malaria, syphilis Malignancy Autoimmune disease - SLE (type V), RA
What is the underlying abnormality in idiopathic nephrotic syndrome?
Anti-phospholipase A2 antibodies
How is membranous nephropathy managed?
1) All patients should receive an ACE inhibitor or an angiotensin II receptor blocker (ARB): these have been shown to reduce proteinuria and improve prognosis
2) Immunosuppression: as many patients spontaneously improve only patient with severe or progressive disease require immunosuppression.
Corticosteroids alone have not been shown to be effective. A combination of corticosteroid + another agent such as cyclophosphamide is often used.
Consider anticoagulation for high-risk patients
What is the prognosis in membranous nephropathy?
Rule of thirds
1/3 - spontaneous remission
1/3 - remain proteinuric
1/3 - ESRF
Good prognostic features - female sex, young age at presentation, asymptomatic proteinuria
What forms of glomerulonephritis present predominantly with nephritic syndrome?
MCGN (variable proteinuria) IgA nephropathy Post-streptococcal GN Small vessel vasculitis Anti-GBM disease
What is IgA nephropathy?
This is the most commonly recognised type of GN and can present in many ways.
Haematuria is the earliest sign and is almost universal, proteinuria a later feature and hypertension very common.
There may be severe proteinuria or in some cases progressive loss of renal function.
It is a common cause of ESRD.
How does IgA nephropathy present?
A hallmark in young adults is acute self limiting exacerbations often with gross haematuria in association with minor respiratory infections in the preceeding days.
This may be so acute as to resemble acute post infectious glomerulonephritis, with fluid retention, hypertension and oliguria with dark or red urine.
Occasionaly, IgA nephropathy progresses rapidly and crescent formation may be seen. The response to immunosuppression is usually poor.
