Glomerular disease Flashcards
What is the most common cause of nephrotic syndrome in children?
Minimal change glomerulonephritis
Describe the pathophysiology of minimal change glomerulonephritis
Biopsy appears normal under visible light microscopy
Electron microscopy show fusion of podocyte pedicles - this impairs selectivity of GBM, allowing protein to pass into the urine
What problems can occur if the glomerular basement membrane fails and proteins are allowed to leak into the urine?
Albumin - oedema, hyperlipidaemia
Immunoglobulin - increased risk of infection
Anticoagulation factors - hypercoagulability, risk of thromboembolism
How is membranous nephropathy diagnosed?
Biopsy and silver-stain microscopy
- biopsy shows diffuse thickening of the glomerular basement membrane
What is the most common cause of nephrotic syndrome in adults?
Membranous nephropathy (diffusely thickened glomerular basement membrane)
What is meant by “proliferative” glomerulonephritis?
Glomerular disease characterised by excess numbers of cells in glomeruli, including white blood cell infiltration.
What is the major difference between nephritic and nephrotic syndrome?
Nephritic syndrome involves blood loss (haematuria)
Nephrotic syndrome involves protein loss (proteinuria) but not haematuria
(small amount of proteinuria may be seen in nephritic syndrome)
What is the most common cause of nephritic syndrome in children?
Post-infective glomerulonephritis
- diffuse proliferative GN (>50% glomeruli affected)
Describe the pathophysiology of post-infectious glomerulonephritis. Which organism is the most common cause?
Most commonly caused by group A strep (e.g. Strep pyogenes).
Infiltration of inflammatory cells (initially neutrophils) and overproliferation of the endothelial and mesangial cells lead to enlargement of the glomerulus.
Ig and complement are also deposited in the glomerulus (usually IgG.
For which type of glomerular disease is a biopsy usually unnecessary?
Post-infective GN
What is Wegener’s granulomatosis? What type of renal disease is it most associated with?
Granulomatosis with polyangiitis (GPA).
A form of vasculitis that affects small- and medium-size vessels in many organs.
(polyangiitis means inflammation of multiple blood vessels involving more than one type of vessel)
Associated with crescentic glomerulonephritis
What is Churg-Strauss syndrome?
Eosinophilic granulomatosis with polyangiitis (EGPA).
A rare autoimmune condition that causes inflammation of small and medium-sized blood vessels in individuals with a history of airway allergic hypersensitivity.
What is Goodpasture syndrome? Which antibodies are indicative of this disease?
A rare autoimmune disease in which antibodies attack the basement membrane in lungs and kidneys, leading to bleeding from the lungs and kidney failure.
Can cause Crescentic GN. Often also presents with a cough.
Anti-GMB autoantibodies
Which type of glomerulonephritis is associated with the presence of ANCA antibodies in the serum/kidney
Crescentic GN (may present with rapidly progressive GN - RPGN) May be a vasculitic cause, e.g. Wegener's granulomatosis or Churg-Strauss syndrome.
In a patient with crescentic glomerulonephritis, what would a biopsy show?
Endothelial damage and fibrin deposits
Necrotic capillary loops
Cellular proliferation and macrophage infiltration within the Bowman’s space
How is Crescentic glomerulonephritis treated?
Plasma exchange
Immunosuppression (prednisolone, cytotoxic agents)
How is Crescentic glomerulonephritis diagnosed?
Biopsy - bowman’s space infiltration
Serology
- ANCA autoantibodies (vasculitis)
- anti-GBM autoantibodies (Goodpasture’s)
Describe the pathophysiology of IgA nephropathy
IgA deposits are not removed
Mesangium (not the filtration membrane) becomes clogged with IgA
IgA irritates the mesangial cells and causes overproliferation
Glomerular capillaries remain clear and healthy
What is IgA nephropathy?
IgA deposition causes increased proliferation of mesangial cells and over-production and accumulation of mesangial matrix. May be provoked by infection by actual cause is unknown.
Describe the clinical features of nephritic syndrome
Proteinuria (mild) Haematuria Azotaemia (elevated blood nitrogen levels) Red cell casts Oliguria (urine < 300ml/day) Antibodies Hypertension
Describe the clinical features of nephrotic syndrome
Na+ decrease (hyponatraemia) Albumin decrease (hypoalbuminaemia) Proteinuria Hyperlipidaemia Renal vein thrombosis Oedema (orbital) Thromboembolisms Infection risk Coagulability (due to loss of anticoagulation factors)
Which conditions can cause secondary nephrotic syndrome?
Systemic Lupus Erythemus HIV Hepatitis B/C Diabetes mellitus Malignancy
How would you investigate a patient presenting with features of nephritic syndrome?
Urine dipstick
Blood pressure measurement
Assess for oedema
FBC, U&E, ESR, CRP
eGFR (GFR if possible), renal function tests, LFTs
Serology for autoantibodies: ANCA, anti-GBM
Renal biopsy
How would you investigate a patient presenting with features of nephrotic syndrome?
Urine dipstick - followed by urinalysis to quantify proteinuria FBC, U&E, LFTs Bone profile Tests for underlying cause: - ESR, CRP - fasting glucose - immunoglobulins, serum/urine electrophoresis - serology: autoantibodies, hep B/C
How is nephrotic syndrome managed?
Sodium/fluid restriction
High dose diuretic treatment
Treat underlying cause
Prophylaxis against complications (e.g. heparin, penicillin)
Which antibodies are associated with post-infective GN?
Anti-streptolysin O titres (ASOT) if post-streptococcal infection
What are the requirements to ensure a safe renal biopsy?
Blood pressure < 150/90
Platelets > 100x10^9/L
Normal clotting
No low molecular weight heparin in the last 24 hours
