Glomerular disease - pathology and clinical aspects Flashcards
What is Glomerulonephritis?
Glomerulonephritis (GN) is an umbrella term applying to a number of different conditions that cause inflammation and damage in or around the glomeruli.
This allows protein (+/- blood) to leak out into the urine.
The conditions are generally categorised into either proliferative or non-proliferative.
Clinical features of Nephrotic syndrome (4)
If patient is in a nephrotic state they must have the following features:
Proteinuria > 3g in 24 hr
Peripheral oedema
Low serum albumin due to leakage
hypercholesterolaemia
Difference between nephritic syndrome and nephrotic syndrome?
Nephrotic syndrome involves the loss of a lot of protein (albumin) from the urine
Whereas nephritic syndrome involves the loss of a lot of blood (and less protein). There is no set criteria for symptoms unlike that of nephrotic syndrome.
What is proliferative glomerulonephritis
Excessive numbers of cells in glomeruli.
These include infiltrating leucocytes
Early diagnosis is necessary to save nephrons
Can cause rapid decline in renal function leading to dialysis.
Present with nephritic state
What is non-proliferative glomerulonephritis
Glomeruli look normal or have areas of scarring - Minimal change disease
Present with nephrotic syndrome
They have normal numbers of cells
Renal biopsy is key investigation
Focal and segmental glomerulonephritis
Descriptive terms relating to renal pathology
Diffuse >50% of glomeruli affected
Focal <50% of glomeruli affected
Global: all the glomerulus affected
Segmental: part of the glomerulus affected
Membraneous nephropathy
What is IgA nephropathy/Berger’s disease?
Commonest cause of glomerulonephritis world-wide.
IgA antibody deposition in the mesangium (middle part of kidney between capillaries) + mesangial cell proliferation
M>F
Up to 30% of cases can progress to end stage kidney disease or halving eGFR at 10 years.
How does IgA Nephropathy present?
Microscopic haematuria (non-visible)
Micoscopic haematuria + proteinuria
Nephrotic syndrome
IgA crescentic glomerulonephritis
Post-streptococcal glomerulonephritis
Follows 10-21 days after infection typically of throat or skin.
Most commonly with Lancefield group A Streptococci.
Genetic predisposition: HLA-DR, -DP, -DP.
What is Crescentic glomerulonephritis?
characterised by the presence of extensive glomerular crescents (usually greater than 50%) in histology
Associated with rapid decline in kidney function
Primary or idiopathic crescentic glomerulonephritis is classified into the following types
Anti-neutrophil cytoplasmic antibody (ANCA)-associated
Anti-glomerular basement membrane
Others: IgA vasculitis, post-infection glomerulonephritis or SLE
Examples of Anti-neutrophil cytoplasmic antibody associated small vessel vasculitis (ANCA)
Microscopic polyangiitis.
Granulomatosis with polyangiitis.
Eosinophilic granulomatosis with polyangiitis.
What is Goodpasture syndrome/ Anti-glomerular basement membrane (GBM) disease
Anti GBM antibodies attack the glomerulus and the pulmonary basement membrane
So if given a case of a patient presenting with acute renal failure and haemoptysis this would be Goodpasture syndrome
How is anti-GBM disease diagnosed?
Demonstrating anti-GBM antibodies in serum and kidney
Treatment of anti GBM
Aggressive immunosuppression by steroid, plasma exchange, and cyclophosphamide.
Management of nephrotic syndrome
General:
Treat oedema: salt and fluid restriction and loop diuretics.
Hypertension: use Renin-Angiotensin-Aldosterone-blockade.
Reduce risk of thrombosis: Heparin or Warfarin.
Reduce risk of infection e.g. pneumococcal vaccine.
Treat dyslipidemia e.g. statins.
Specific therapy - target cause
What is Minimal change disease
Type of glomerulonephritis
It is the commonest cause of nephrotic syndrome. Commonest form in children.
Sudden onset of oedema, low albumin and proteinuria (days)
Responds well to treatment with steroids
Treatment of minimal change disease
Prednisolone – 1mg/kg for up to 16 weeks.
Once remission achieved, slow taper over 6 months.
Initial relapse of minimal change disease is treated with what?
A further steroid course
Subsequent relapses of minimal change disease is treated with what?
Cyclophosphamide Cyclosporin Tacrolimus Mycophenolate mofetil Rituximab
What does the term Focal segmental glomerulosclerosis mean?
Not a single disease, rather a syndrome with multiple causes. Commonest cause of nephrotic syndrome in adults.
Presents with nephrotic syndrome.
Pathology reveals focal and segmental sclerosis (scarring/damage) with distinctive patterns
Can be primary (idiopathic) or secondary
Steroid treatment
High chance of progression to end stage kidney disease
Membranous Glomerulonephritis
Commonest type of glomerulonephritis overall. 2 peaks of presentation - in your 20s and 60s
70% cases are idiopathic but secondary causes include: Malignancies, Rheumatoid arthritis and medication like NSAIDs.
The glomerular basement membrane becomes thickened by IgG deposits - this activates Complement system (C3) which punches holes in the filter making it leaky. It now allows albumin to be filtered into urine => nephrotic syndrome
Serological markers
PLA2R antibody positive in 70% of idiopathic cases
(THSD7A) in ~2%.
Treatment of membranous nephropathy
General measures for at least 6 months. Immunosuppression (steroids and cyclophosphamide) if symptomatic nephrotic syndrome, rising proteinuria or deteriorating renal function.
Tacrolimus.
Rituximab.
Prognosis of membranous nephropathy
Resolves spontaneously in a third.
Prognosis good in treated patients is proteinuria resolves
About 25% are on dialysis at 10 years
Can recur in renal transplants
Give examples of non-proliferative glomerulonephritis
Minimal change disease
Focal segmental glomerulosclerosis
Membranous glomerulonephritis
Give examples of proliferative glomerulonephritis
IgA nephropathy
Post infectious streptococcal
Crescentic - Rapidly progressive glomerulonephritis (think crescendo)
Features of Nephritic syndrome
No set criteria of symptoms:
Haematuria
Oliguria
Proteinuria
Oedema - peripheral and pulmonary
Aetiology of glomerulonephritis
Some are due to immunoglobulin deposition
Some are diseases with no immunoglobulin deposition – for example – diabetic glomerular disease
What are mesangial cells?
A ‘tree-like’ group of cells that support renal capillaries.
What are podocytes?
Cells in the Bowman’s capsule in the kidneys that wrap around capillaries of the glomerulus.
Podocyte cells make up the epithelial lining of the Bowman’s capsule, the third layer through which filtration of blood takes place.
Main causes of Haematuria
UTI
Stone
Urinary tract Tumour
In IgA nephropathy (type of glomerulonephritis) where does the IgA antibody get deposited? What is the result of this?
In the mesangium - the cells in between the capillaries. This irritates them and causes them to proliferate and produce more matrix
Example case presentation of patient with nephrotic syndrome (ie they have specific features but the underlying cause is not clear from these)
50 y/o M - 3 weeks of feeling unwell and swollen legs
Blood biochemistry and haematology tests show low serum albumin and a urine dipstick test shows proteinuria.
He’s referred to see a nephrologist who measures the protein level (albumin) in his urine – very heavy loss
After diagnosis do clotting screen (prevent risk of bleeding to death) and then do a renal biopsy if okay
Diabetes and glomerulonephritis
Glycated molecules cause matrix deposition in the basal lamina underlying the endothelium and in the mesangial matrix
Results in thickened but leaky glomerular basement membranes and the thickened mesangial matrix compresses capillaries
Continued poor glycaemic control causes an inevitable decline
What is Granulomatosis with polyangiitis (formerly called Wegener’s)?
A rare disease of uncertain cause that can affect people of all ages. Lethal if not correctly diagnosed or treated.
It is caused by autoantibodies against proteinase 3
c-ANCA test (positive if you detect these autoantibodies)
It is characterised by vasculitis mainly in the respiratory tract and the kidneys
