Glomerular Disease Flashcards
What is glomerulonephritis?
Disease of glomerulus
- inflammatory or non-inflammatory
Can be primary (only glomerulus affected) or secondary to a wider condition e.g. SLE)
What are the general causes of glomerulonephritis?
Autoimmune
Infection
Malignancy
Drugs
What are the two different classes of glomerulonephritis, and what are some examples of each type?
Proliferative
- post-infective (diffuse)
- mesangial IgA disease (focal)
- crescentic nephritis (focal necrotising)
- membrano-proliferative nephritis
- diabetic nephropathy
Non-proliferative
- minimal change disease
- focal segmental glomerulonephritis
- membranous nepropathy
What are the two general forms of glomerulonephritis presentation, and with which types of the disease do they correlate? Which type can present with both?
Proliferative generally presents with nephritic state
Non-proliferative generally with nephrotic syndrome
Membrano-proliferative can present as combined nephrotic/nephritic
What is the commonest type of glomerulonephritis?
IgA nephropathy in general
Membranous is commonest nephrotic syndrome cause
Minimal change commonest in children
What are the 4 common symptoms/signs presenting in glomerulonephritis?
Haematuria
Heavy proteinuria (nephrotic syndrome)
Slowly increasing proteinuria
Acute renal failure
Hypertension also common co-morbidity
What is the common presentation of IgA nephropathy?
Microscopic haematuria
Proteinuria
Nephritic, sometimes nephrotic
What features may suggest minimal change disease
Sudden onset of oedema
Complete loss of proteinuria with steroids
How does focal segmental glomerulosclerosis generally present?
Nephrotic syndrome
Distinct patterns of sclerosis
Generally steroid resistant
High chance of end-stage kidney disease
What are the features of nephritic state?
Active urine sediment - haematuria, dysmorphic RBCs, cellular casts
Hypertension
Renal impairment
What are the features of nephrotic syndrome?
Oedema
Proteinuria >3.5g/day
Hypoalbuminaemia
Hyperlipidaemia
What are the 4 main pathological types of glomerulonephritis? (By Paul Brown’s standards)
IgA nephropathy
Membranous glomerulonephritis
Diabetic nephropathy
Crescentic glomerulonephritis
What investigations might be performed in suspected glomerulonephritis?
Renal biopsy is key Dipstick Urine culture USS Usual bloods e.g. serum albumin, creatinine (eGFR)
Specific serological markers
- anti-GBM antibodies in serum/kidney = anti-GBM disease (type of crescentic)
- anti phospholipase A2 receptor antibody positive in 70% of idiopathic causes of membranous nephropathy
- ANCA serum test (Wegener’s/microscopic polyarteritis)
What are some other causes of haematuria (not glomerulonephritis)?
UTI
Urinary tract stone
Urinary tract tumour
How is glomerulonephritis differentiated as diffuse/focal and global/segmental?
Diffuse = >50% of glomeruli affected Focal = <50%
Global = the entire of the affected glomeruli are affected Segmental = only part of each affected glomerulus is affected
How is post-infective nephropathy treated?
Possible antibiotics
Loop diuretics (e.g. furosemide)
Vasodilators (amlodipine) for hypertension
How is IgA nephropathy treated?
Hypertension treatments - ACEi/ARB
Immunosuppressants - cortisol
Consider statins
How is crescentic nephropathy treated?
Immunosuppression - corticosteroids, plasma exchange, cytotoxic (cyclophosphamide), rituximab, complement inhibitors
Anti-GBM - aggressive immunosuppression
What are the general measures of treatment in nephrotic syndrome?
Treat oedema - salt/fluid restriction and loop diuretics
Treat hypertension - RAAS blockade
Reduce thrombosis risk - warfarin/heparin
Reduce infection risk - pneumococcal vaccine
Treat lipidaemia - statins
How is minimal-change disease treated?
General measures if required
Prednisolone
Slowly taper once remission achieved
Treat initial relapse with prednisolone, further relapses with cyclophosphamide, cyclosporin, tacrolimus, mycophenolate mofetil, rituximab
How is focal segmental glomerulosclerosis treated?
General measures
Steroids
Alternatives - cyclosporin, cyclophosphamide, rituximab
How is (non-proliferative) membranous nephropathy treated?
General measures for 6 months
Immunosuppression if symptomatic nephrotic syndrome/rising proteinuria/deteriorating renal function
Cyclophosphamide and steroids (alternating) for 6 months
Cyclosporin, rituximab
Why does IgA deposition cause proliferation?
Mesangium, NOT filter membrane, clogged with IgA
IgA irritates mesangial cells, causes them to proliferate and produce more matrix
What are the pathological features of membranous glomerulonephritis, why does this cause nephrotic syndrome?
Thickened glomerular basement membrane
Spikes of new basement membrane matrix material underneath podocytes
Deposit of IgG within thickened membrane
Basal lamina spike (matrix which tries to surround and remove IgG deposit)
IgG deposits itself from plasma to between basal lamina and podocyte buy cannot go further and is not filtered into urine - too big
But IgG activates complement (C3), which punches holes in filter
Leaky filter now allows albumin to be filtered into urine > nephrotic syndrome
