Nephrotic Syndrome Flashcards
Define nephrotic syndrome
Characterised by:
Proteinuria (>3g/24h)
Hypoalbuminaemia (<30g/L)
Peripheral oedema
What are the causes of nephrotic syndrome
Primary:
Steroid-sensitive: minimal change
Steroid-resistant:
- Focal segmental glomerulosclerosis
- Membranous glomerulonephritis/nephropathy
- Membranoproliferative glomerulonephritis (60% nephrotic)
Congenital nephrotic syndrome
Secondary:
Diabetes mellitus
Sickle cell disease
Amyloidosis
Malignancies
Drugs e.g. NSAIDs
Alport’s syndrome
HIV
What are the symptoms and signs of nephrotic syndrome
Swelling (face, abdomen, limbs, genitalia)
- Peri-orbital oedema, especially on waking
- Abdominal swelling → pain
Weight gain (oedema)
Muehrcke’s lines (white bands from hypoalbuminaemia)
Complications:
- pleural effusion → SOB
- Infections
- Renal vein thrombosis → loin pain, haematuria
+ symptoms of underlying cause
What are the features of steroid-sensitive nephrotic syndrome and which syndromes are steroid-sensitive
85-90% of children with nephrotic syndrome have treatment with corticosteroid therapy
Rarely progresses to CKD/ESRF
Often precipitated by respiratory infections
No macroscopic haematuria, normal BP, complement, renal function, biopsy on LM
Electron microscopy: Fusion of specialised epithelial cells that invest the glomerular capillaries (podocytes) on electron microscopy (minimal change disease)
Minimal change
Describe minimal change disease
Most common cause of nephrotic syndrome
Often after a viral infection (→ peri-orbital oedema, abdominal pain)
Steroid-sensitive
What will investigations show for minimal change disease
Complement: normal
Renal function: normal
Renal biopsy (not required for diagnosis):
- LM: normal
- EM: fusion of epithelial cells → loss of foot processes/podocytes in glomerular capillaries
What is the management for minimal change disease
First line: Steroids PO
- Prednisolone for 4 weeks (60mg/m^2)
- Reduce dose to 40 on alternative days for 4 weeks
- Wean and stop steroids
Second line: steroid-sparing Immunosuppressants
- Ciclosporin
- Mycophenolate
- tacrolimus
- Rituximab
+ Make sure up to date with immunisations
± prophylactic Abx (penicillin)
Describe focal segmental glomerulosclerosis (epidemiology, causes, appearance on microscopy, management)
Most common cause of nephrotic syndrome in adults, particularly Afro-Caribbeans and obese pts
May be primary or secondary (heroin, HIV, SCD)
LM: focal and glomerular consolidation → scarring, hyalinosis (NO immune complexes)
EM: loss of foot processes
Management: (1) steroids (2) calcineurin inhibitors
Describe membranoproliferative glomerulonephritis (association, types, investigation)
Can present as nephrotic (60%), nephritic (30%), or rapidly progressive glomerulonephritis
Elderly people
Associated with malignancy, SLE, hep B infection
Type I (90%): Primary or secondary (chronic infection e.g. abscess, IE, HIB )
Type II: Primary or secondary (partial lipodystrophy, factor H deficiency)
Haematuria + low complement
Describe congenital nephrotic syndrome
Presents in the first few months of life
Rare, usually recessive
More common in consanguineous families
Genetic testing recommended: >70% have a genetic defect
The albuminuria can be so severe that unilateral nephrectomy may be necessary
Describe membranous nephropathy (Cause, appearance on microscopy, management)
Primary or secondary (hepatitis B, SLE)
Antibody against Phospholipase A2r (PLA2R) → immune complex formation
LM: diffuse basement membrane thickening
EM: “spike and dome” subepithelial deposits of the entire GBM, loss of foot processes
Management:
ACEi or ARB (reduces proteinuria) ± anticoagulation
Severe: immunosuppression: steroids (but poor response) ± cyclophosphamide
What is the prognosis for membranous glomerulonephritis
1/3 - spontaneous remission
1/3 - remain proteinuric
1/3 - develop end-stage renal failure
What are the complications of nephrotic syndrome
Hypovolaemia (oedema → intravascular compartments become deplete)
thrombosis (loss of Antithrombin in urine)
Infection (loss of Ig in the urine → NHS bacterial infection)
Cholesterolaemia (albumin loss → reduced oncotic pressure → hepatic cholesterol synthesis)
Albumin given for hypovolaemia → fluid overload →
pulmonary oedema and HTN
What is the prognosis for the steroid-resistant nephrotic syndromes
Focal segmental: 30% progress to ESRF, 20% respond to immunosuppressants
Membranoproliferative: decline in renal function over many years, treat with ACEi or immunosuppressants
Membranous: most remit spontaneously within 5 years
