Clinical Glomerular Disease Flashcards
What is glomerulonephritis?
- A group of inflammatory disorders of the disease and are responsible for almost 30% of ESRD.
- They are classified based on morphology and the majority are attributed to autoimmune aetiologies
What are the features of glomerulonephritis?
- Haematuria
- Proteinuria
- Hypertension
- Renal insufficiency
How does macroscopic haematuria present?
Tea or cola coloured or frank blood
How does microscopic haematuria present?
> 5 RBC per high power field
In what syndrome does haematuria present more often?
Nephritic> nephrotic
What can the source of haematuria be?
- Kidneys
- Ureters
- Bladder
- Prostate
- Urethra
How does haematuria present in glomerulonephritis?
Persistent microscopic haematuria. Microscopy shows dysmorphic RBC (Mickey mouse like)
How does proteinuria present in glomerulonephritis?
Persistent, proteinuria of more than 1 gram /mmol creatinine.
How can proteinuria be investigated?
Urine protein creatinine ratio or 24 hour urine collection
What is considered hypertension?
> 140/80mmHg
Does proteinuria occur more in nephrotic or nephritic syndrome?
Equal
Does hypertension occur more in nephrotic or nephritic syndrome?
Nephritic> nephrotic
What are the features of nephritic syndrome?
- Active urine sediment: haematuria, dysmorphic RBCs and cellular casts
- Hypertension
- Renal impairment
What are the features of nephrotic syndrome?
- Oedema
- Proteinuria >3.5 g/day
- Hypoalbuminemia
- Hyperlipidemia
What can cause nephrotic syndrome?
Primary (idiopathic) glomerular disease or secondary glomerular disease
What is the differential diagnosis for nephrotic syndrome?
- Congestive heart failure (JVP raised, normal albumin, minimal proteinuria)
- Hepatic disease (abnormal LFTs, no proteinuria)
What can glomerulonephritis be classified according to?
- Aetiology
- Primary vs secondary (kidneys alone or multisystem disease)
- Morphological
What is the aetiology of glomerulonephritis?
- Autoimmune
- Infection
- Malignancy
- Drugs
- Others
What is proliferative glomerulonephritis?
Excessive numbers of cells in glomeruli. These include infiltrating leucocytes
What is non-proliferative glomerulonephritis?
Glomeruli look normal or have areas of scarring. They have normal numbers of cells
Define diffuse glomerulonephritis.
> 50% of glomeruli affected
Define focal glomerulonephritis.
<50% of glomeruli affected
Define global glomerulonephritis.
All the glomerulus affected
Define segmental glomerulonephritis
Part of the glomerulonephritis
What glomerulonephritis presents with urinary sediment abnormalities?
IgA nephropathy
What glomerulonephritis presents with proteinuria?
IgA nephropathy
What types of glomerulonephritis present with nephrotic syndrome?
- Minimal change disease
- Membranous nephropathy
What types of glomerulonephritis present with nephritis state?
- Anti-neutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis
- Post infection glomerulonephritis
Give 4 examples of proliferative glomerulonephritis?
- Post infective nephritis
- Mesangial IgA disease
- Focal necrotising (crescentic) nephritis
- Membrano-proliferative nephritiis
What does post-streptococcal glomerulonephritis usually follow?
Follows 10-21 days after infection typically of throat or skin.
What bacteria is post-streptococcal glomerulonephritis most commonly associated with?
Lancefield group A streptococci
What genetic predisposition is associated with post-streptococcal glomerulonephritis?
HLA-DR, -DP, -DP
What is the treatment for post-infective glomerulonephritis?
- Antibiotics for infection, debatable.
- Loop diuretics such as frusemide for oedema
- Vasodilator drugs (e.g. amlodipine) for hypertension
What is the commonest cause of glomerulonephritis?
IgA nephropathy
What is IgA nephropathy characterised by?
Characterized by IgA deposition in the mesangium +mesangial proliferation.
Who is most commonly affected by IgA nephropathy?
Most common in 2nd and 3rd decade of life with males more commonly affected.
What is the prognosis of u[ to 40% of those with IgA nephropathy?
Progress to ESRD
How does IgA nephropathy present?
- Microscopic haematuria.
- Microscopic haematuria + proteinuria
- Nephrotic syndrome
- IgA crescentic glomerulonephritis
What are the causes of crescentic glomerulonephritis?
- Anti-neutrophil cytoplasmic antibody (ANCA)-associated
- Anti-glomerular basement membrane (GBM)
- IgA vasculitis
- Post infection glomerulonephritis
- SLE
What ANCA associated glomerulonephritis is there?
- Microscopic polyangiitis
- Granulomatosis with polyangiitis
- Eosinophilic granulomatosis with polyangiitis
What anti-glomerular basement membrane glomerulonephritis is there?
- Anti-GBM nephritis
- Goodpasture’s syndrome
What is anti-GBM disease?
A rare disease caused by circulating GBM
What can anti-GBM disease present as?
- Nephritis (anti-GBM glomerulonephritis)
- Nephritis+ lung haemorrhage (Goodpasture’s syndrome)
What are the 2 peaks in life for anti-GBM disease?
- 3rd decade
- 6th/7th decade
How is anti-GBM disease diagnosed?
Diagnosed by demonstrating anti-GBM antibodies in serum and kidney
How is anti-GBM disease treated?
- Aggressive immunosuppression
- Steroids
- Plasma exchange
- Cyclophosphamide
What is the management for crescentic glomerulonephritis?
- Immunosuppression
- Corticosteroids
- Plasma exchange
- Cytotoxic e.g. Cyclophosphamide
- B-cell therapy e.g. Rituximab
- Complement inhibitors
What is the prognosis for crescentic glomerulonephritis?
Good provided treatment is started early enough
What syndrome do proliferative glomerulonephritides present with?
Nephritic
Give 3 examples of non-proliferative glomerulonephritis
- Minimal Change Disease
- Focal and segmental glomerulonephritis
- Membranous Nephropathy
What are the general measures in the treatment of nephrotic syndrome?
- 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.
What is the commonest form of glomerulonephritis in children?
Minimal change nephrotic syndrome
How does minimal change disease usually present?
- Sudden onset of oedema
- Complete loss of proteinuria with steroids
What is the initial treatment for minimal change disease?
- Prednisolone – 1mg/kg for up to 16 weeks.
- Once remission achieved , slow taper over 6 months.
- Initial relapse treated with further steroid course.
How are subsequent relapses of minimal change disease treated?
- Cyclophosphamide
- Cyclosporin
- Tacrolimus
- Mycophenolate mofetil
- Rituximab
What is the prognosis of minimal change disease?
- Despite relapsing behaviour, prognosis is favourable.
- Risk of end stage kidney disease is low.
- Steroids toxicity as multiple exposure.
What are the general measures for the management of minimal change disease?
- Salt and fluid restrictions.
- Daily weights.
- Loop diuretic e.g. Furosemide.
- Thromboprophylaxis e.g. low molecular weight heparin.
What does focal and segmental glomerulonephritis present with?
Nephrotic syndrome
What does pathology of focal and segmental glomerulonephritis reveal?
Focal and segmental sclerosis with distinctive patterns e.g. tip lesion, collapsing, cellular, perihilar, and not otherwise specified..
What are focal and segmental glomerulonephritis generally resistant to?
Steroids
What is there a high chance of progression to in focal and segmental glomerulonephritis?
ESRD
How is focal and segmental glomerulonephritis treated?
- General measures
- Trial of steroids, positive response , even partial remission, carries better prognosis.
- Alternative options: cyclosporin, cyclophosphamide, and Rituximab.
What is the commonest cause of nephrotic syndrome in adults?
Membranous nephropathy
What is the cause of the majority of membranous nephropathy cases?
Idiopathic
What are the serological markers for membranous nephropathy?
- Anti-phospholipase A2 receptor (PLA2R) antibody positive in 70% of idiopathic cases
- Thrombospondin type 1 domain containing 7A (THSD7A).
What are secondary causes of membranous nephropathy?
- Malignancies
- SLE
- Rheumatoid arthritis.
- Drugs: NSAIDs, gold, penicillamine.
What is the treatment for membranous nephropathy?
- General measures for at least 6 months.
- Immunosuppression if symptomatic nephrotic syndrome, rising proteinuria or deteriorating renal function.
- Cyclophosphamide and steroids (alternate months) for 6 months.
- Cyclosporine.
- Rituximab.
What is the prognosis of membranous nephropathy?
- Resolves spontaneously in a third.
- Prognosis good in treated patients whose proteinuria resolves
- About 25% are on dialysis at 10 years
- Can recur in renal transplants
What is the key investigation for glomerulonephritis?
Renal biopsy
