Nephrotic syndrome (URO) Flashcards
Define nephrotic syndrome.
Defined as the presence of proteinuria (>3.5g/24h), hypoalbuminaemia (<30g/L) and peripheral oedema
What is nephrotic syndrome?
Collection of signs and symptoms indicating damage to the glomerular filtration barrier
What is nephrotic syndrome characterised by? (3)
- massive proteinuria (>3.5g/24hr)
- hypoalbuminaemia (<30g/L)
- peripheral oedema
What causes proteinuria in nephrotic syndrome?
Glomerular damage (injury to podocytes) causes protein leakage into urine
This proteinuria –> hypoalbuminaemia and subsequent oedema due to reduced plasma oncotic pressure
How can nephrotic syndrome be classified?
Primary (idiopathic) or secondary to systemic disease
What are some causes/examples of nephrotic syndrome? (5)
- minimal change disease (primary)
- membranous glomerulonephritis (primary) AKA membranous nephropathy
- focal segmental glomerulosclerosis (primary)
- diabetic nephropathy (secondary)
- amyloid nephropathy (secondary)
In which groups is minimal change disease (nephrotic syndrome) the most common cause of nephrotic syndrome?
Children (young <10)
What does minimal change disease (nephrotic syndrome) commonly present with?
Peri-orbital oedema
What diseases is minimal change disease (nephrotic syndrome) associated with? (3)
- URTI
- non-Hodgkin’s lymphoma
- secondary to Hodgkin’s lymphoma
Describe the pathophysiology of minimal change disease (nephrotic syndrome).
Cytokine-mediated damage of podocytes (role is to prevent protein entering filtrate) - they lose their negatively-charged coat –> proteinuria
What will light microscopy show in minimal change disease (nephrotic syndrome)?
Normal light microscopy
Why is it called ‘minimal change disease’ (nephrotic syndrome)?
‘Minimal change’ refers to light microscopic findings that often reveal normal glomeruli or mild mesangial proliferation with negative immunofluorescence and no immune complex deposition
What will electron microscopy show in minimal change disease (nephrotic syndrome)?
Fusion of podocytes
What is the cause of minimal change disease (nephrotic syndrome)?
Often idiopathic
Describe the clinical picture of minimal change disease (nephrotic syndrome).
Fully nephrotic
What is minimal change disease (nephrotic syndrome) typically responsive to?
Steroids
How do we manage minimal change disease (nephrotic syndrome)?
- prednisolone (corticosteroids) and gradually increase dose
- if resistant to prednisolone –> cyclophosphamide (immunosuppressants)
In which group is membranous glomerulonephritis/nephropathy (nephrotic syndrome) the most common cause of nephrotic syndrome?
Most common cause in older adults
Describe the pathophysiology of membranous nephropathy (nephrotic syndrome).
Deposition of immune complexes on basement membrane –> damage to podocytes and mesangial cells
What diseases is secondary membranous nephropathy (nephrotic syndrome) commonly associated with? (4)
- malignancy
- SLE (lupus nephritis)
- hepatitis B&C
- autoimmune disease
What would a renal biopsy of membranous nephropathy (nephrotic syndrome) show under light microscopy?
Basement membrane thickening (without associated cellular proliferation or infiltration)
What would a renal biopsy of membranous nephropathy (nephrotic syndrome) show under electron microscopy?
Spike and dome appearance
Which antibodies is primary membranous nephropathy (nephrotic syndrome) associated with?
Anti-phospholipase A2 receptor antibodies (PLA2R)
What other blood result might we see in membranous nephropathy (nephrotic syndrome)?
Low T4
How is the response of membranous nephropathy (nephrotic syndrome) to steroids?
Low response to steroids
Give: ACEi/ARBs, immunosuppression
In which group is focal segmental glomerulosclerosis (nephrotic syndrome) the most common cause of nephrotic syndrome?
Common in Afro-Caribbean population
Describe the pathophysiology of focal segmental glomerulosclerosis (nephrotic syndrome).
Sclerosis of glomeruli –> damage and loss of podocytes
What can focal segmental glomerulosclerosis (nephrotic syndrome) be?
Primary (idiopathic), secondary or genetic
Differentiating between primary and secondary FSGS is key in determining management
Primary responds to immunosuppression, while secondary treated by reducing intraglomerular pressure (RAAS blockade)
What does light microscopy show in focal segmental glomerulosclerosis (nephrotic syndrome)?
Segmental areas of mesangial collapse and sclerosis (affecting some but not all glomeruli)
What does electron microscopy show in focal segmental glomerulosclerosis (nephrotic syndrome)?
Effacement of foot processes of podocytes
What is focal segmental glomerulosclerosis (nephrotic syndrome) associated with? (5)
- obesity
- DM
- HIV
- heroin use
- sickle cell
What does focal segmental glomerulosclerosis (nephrotic syndrome) commonly present with? (3)
- haematuria
- hypertension
- reduced renal function
What are patients with focal segmental glomerulosclerosis (nephrotic syndrome) often resistant to?
Steroids
How is focal segmental glomerulosclerosis (nephrotic syndrome) managed?
Corticosteroids +/- immunosuppressants
What additional signs might you see in patients with diabetic nephropathy (nephrotic syndrome)? (2)
- retinopathy
- neuropathy
What is found in urine in diabetic nephropathy (nephrotic syndrome)?
Microalbuminuria (>30mg/day)
What can persistent microalbuminuria in diabetic nephropathy (nephrotic syndrome) lead to?
If left untreated, will progress to frank proteinuria over 10-15y –> at risk of progressing to end-stage renal disease
What will you find on light microscopy in diabetic nephropathy (nephrotic syndrome)? (3)
- mesangial expansion
- GBM thickening
- Kimmelstiel-Wilson nodules
What does kidney USS show in early stages of diabetic nephropathy (nephrotic syndrome)?
Enlarged kidneys (unlike other causes of kidney disease)
What are some causes of enlarged kidneys? (4)
- diabetic nephropathy (nephrotic syndrome)
- autosomal dominant polycystic kidney disease
- amyloidosis
- HIV-associated nephropathy
How is diabetic nephropathy (nephrotic syndrome) managed? (2)
- diabetic control
- ACEi/ARB
In which group of people is amyloidosis (nephrotic syndrome) seen?
Elderly patients
Amyloidosis responsible for 10% of nephrotic syndrome
What diseases is amyloidosis (nephrotic syndrome) associated with? (2)
- multiple myeloma
- chronic inflammatory disease e.g. TB, RA
What is the most commonly affected organ in systemic amyloidosis (nephrotic syndrome)?
Kidney - deposition of amyloid
What are some symptoms of amyloidosis (nephrotic syndrome)? (3)
- breathlessness
- weakness
- can cause hepatosplenomegaly
What will Congo Red staining show in amyloidosis (nephrotic syndrome)?
Apple-green birefringence
What can nephrotic syndrome go on to cause? (2)
- hyperlipidaemia - liver compensates for protein loss by increasing albumin synthesis as well as LDL, VLDL and lipoproteins
- thrombotic disease - loss of antithrombin III, protein C and protein S in urine –> increased hepatic synthesis of procoagulant factors + increased platelet activation
How does nephrotic syndrome compare to nephritic syndrome?
- urine contains few cells/casts vs nephritic syndrome –> active urinary sediment (red cells and red cell casts)
- nephritic syndrome = presence of AKI, hypertension, haematuria
What are the clinical features of nephrotic syndrome?
- massive proteinuria (>3.5g/24hr) - may cause foamy urine
- hypoalbuminaemia (<30g/L)
- oedema (due to hypoalbuminaemia) - begins as periorbital –> peripheral / pulmonary
- hyperlipidaemia (low blood protein increases lipid synthesis)
- hypercoagulable state (loss of ATIII, protein C and protein S and rise in fibrinogen = increased risk of thrombosis)
- increased risk of infection (loss of immunoglobulins)
What are some symptoms of complications of nephrotic syndrome? (3)
- renal vein thrombosis
- loin pain
- haematuria
What does urine dipstick show in nephrotic syndrome?
+++ protein
What does 24-hour urine protein show in nephrotic syndrome?
> 3.5g in 24h (massive proteinuria)
What does urine sediment microscopy show?
Fatty casts (dead epithelial cells)
Describe serum albumin levels in nephrotic syndrome.
Low (leads to oedema)
Describe sodium levels in nephrotic syndrome.
True hyponatraemia + urinary sodium <20mmol/L - primary renal sodium retention in collecting tubules
Describe cholesterol levels in nephrotic syndrome.
High
What do U&Es show in nephrotic syndrome?
Low sodium
What is often needed for diagnosis of nephrotic syndrome?
Renal biopsy –> light and electron microscopy
Compare light and electron microscopy from renal biopsy in minimal change disease vs membranous nephropathy vs focal segmental glomerulosclerosis (nephrotic syndrome).
- minimal change disease: LM normal, EM fusion of podocytes
- membranous nephropathy: LM BM thickening, EM spike and dome
- FSGS: LM segmental mesangial collapse and sclerosis, EM effacement of foot podocytes
What are some differential diagnoses for nephrotic syndrome? (7)
- nephritic syndrome (AKI, hypertension, red cells and casts in urine, haematuria)
- minimal change disease (children, normal creatinine and GFR, podocyte effacement/fusion on electron microscopy)
- membranous nephropathy (PLA2R +ve, thick BM)
- focal segmental glomerulosclerosis (focal and segmental sclerosis of glomeruli)
- diabetic nephropathy
- amyloidosis
- IgA nephropathy (nephritic disease)
What is needed for diagnosis of nephrotic syndrome?
Proteinuria (>3.5g/24hr), hypoalbuminaemia (<30g/L) and peripheral oedema
How is oedema managed in nephrotic syndrome? (3)
- dietary sodium restriction (50mmol/day)
- fluid restriction (1L/day)
- diuretics - spironolactone/furosemide
How is proteinuria managed in nephrotic syndrome?
RAAS inhibitors:
- ACE inhibitors (ramipril)
- ARBs (losartan)
What is given as prophylactic anticoagulation in nephrotic syndrome? (2)
- LMWH
- warfarin
How is infection risk managed in nephrotic syndrome?
Vaccinations
How can we manage minimal change disease?
High-dose prednisolone and gradually increase dose
Cyclophosphamide (immunosuppressant) if no response
How can we manage membranous nephropathy?
ACEi/ARBs, immunosuppression
How can we manage focal segmental glomerulosclerosis?
Steroids +/- immunosuppression
What can we give in early phase of induction therapy (immunosuppression) in nephrotic syndrome?
Prophylactic trimethoprim/sulfamethoxazole to prevent pneumocystis pneumonia
What are some complications of nephrotic syndrome? (5)
- infection - urinary loss of immunoglobulins
- VTE - urinary loss of antithrombin III (and protein C and S)
- hyperlipidaemia - increased hepatic production of lipids (along with albumin) to restore serum oncotic pressure
- pleural effusion (due to proteinuria –> hypoalbuminaemia –> oedema)
- CKD and end-stage kidney disease
What are the main features of nephritic syndrome (low yield)? (4)
- haematuria
- proteinuria
- oedema
- AKI, hypertension, red cell casts in urine
What are some types of nephritic syndrome (low yield)? (2)
- membranoproliferative glomerulonephritis (MPGN)
- rapidly proliferative glomerulonephritis (RPGN)
What causes membranoproliferative glomerulonephritis (low yield)?
- type 1 (90%) - immune complex deposits resulting from chronic infection e.g. hep B/C –> tram track appearance on electron microscopy
- type 2 - complement deposits e.g. in SLE –> low circulating C3, dense deposits on electron microscopy
What is the clinical picture of membranoproliferative glomerulonephritis (low yield)?
Mixed picture of nephrotic and nephritic syndrome
How do we manage membranoproliferative glomerulonephritis (low yield)?
Steroids
What is rapidly proliferative glomerulonephritis (low yield)?
Proliferation of cells in Bowman’s space –> crescent shape (AKA crescenteric glomerulonephritis)
What is type 1 rapidly proliferative glomerulonephritis (low yield)?
Goodpasture’s syndrome:
- mainly nephritic
- anti-GBM antibodies (autoantibodies against type IV collagen)
- Sx - pulmonary features (haemoptysis and SOB), nephritic syndrome
What is type 2 rapidly proliferative glomerulonephritis (low yield)?
Immune-complex mediated:
- post-streptococcal - nephritic, smoky urine, proteinuria, 1-2wk post throat infection/gastroenteritis –> confirm via anti-Streptolysin O titre, immunofluorescence shows starry sky appearance, low C3 levels
- IgA nephropathy - 1-2d post GI/resp infection, IgA +ve bloods, young male, recurrent episodes macroscopic haematuria
- Henoch-Schonlein purpura (IgA vasculitis) - palpable purpuric rash, abdominal pain, polyarthritis, children, IgA +ve bloods
- SLE - immune complex deposits trigger type III hypersensitivity reaction
What diseases come under type 3 rapidly proliferative glomerulonephritis (low yield)?
Pauci-immune:
- cANCA - granulomatosis with polyangiitis (AKA Wegner’s granulomatosis)
- saddle nose shape, epistaxis, sinusitis
- consider if ENT, respiratory and kidney issues present in a patient
- pANCA - microscopic polyangiitis (purpuric rash and pain/numb hands and feet) AND eosinophilic granulomatosis with polyangiitis AKA Churg-Strauss (granulomatous inflammation, asthma-like Sx, eosinophilia)
