Proteinuria + nephrotic syndrome Flashcards
What is normal urine protein?
<150mg/day (usually 40-80mg/day)
What proteins are present in urine?
albumin
low molecular weight proteins - beta2 microglobulin, polypeptides, RBP
secreted proteins
How does proteinuria present?
asymptomatic and incidental detection on urine dipstick
heavy proteinuria = peripheral oedema, frothy urine
Advantages of urine dipstick
simple bedside test
rapid diagnosis
inexpensive
Disadvantages of urine dipstick
operator dependent
semi-quantitative
insensitive to low level proteinuria
does not detect non-albumin proteinuria
What tests other than dipstick can be used to detect proteinuria?
urine protein creatinine ratio
urine albumin creatinine ratio
24hr urine protein collection
Causes of benign proteinuria
orthostatic proteinuria - children and adolescents, <3.5g/day
transient proteinuria secondary to fever, heavy exercise, vasopressor, IV albumin, usually <1g/day
What is pathological glomerular proteinuria?
disruption to filtration barrier
can be associated with microscopic haematuria
Primary glomerulonephritides
minimal change disease
primary focal segmental
glomerulosclerosis
idiopathic membranous nephropathy
IgA nephropathy
Idiopathic membranoproliferative glomerulonephritis (MPGN)
Secondary glomerulonephritides
diabetes mellitus
systemic amyloidosis
secondary focal segmental glomerulosclerosis (eg. obesity, hypertension, HIV infection)
autoimmune disease (eg. SLE)
secondary membranous nephropathy (eg. cancer, drugs)
MPGN - hepatitis B or C
4 mechanisms of proteinuria
glomerular
tubular
overflow
post-renal
What is tubular proteinuria?
low molecular weight proteins are filtered at the glomerulus and reabsorbed by proximal tubules
Causes of tubular proteinuria
tubulo-interstitial nephritis
drugs eg. antibiotics, NSAIDs, PPIs
autoimmune disease eg. Crohn’s, sarcoidosis, Sjogren’s
infections eg. TB, CMV infection, leptospirosis
What is overflow proteinuria?
excess production of low molecular weight proteins exceed reabsorptive capacity of tubules
Causes of overflow proteinuria
myeloma (free light chains)
rhabdomyolysis (myoglobin)
haemolysis (haemoglobin)
What is post-renal proteinuria?
inflammation of lower urinary tract
Causes of post-renal proteinuria
lower urinary tract infection
stones
What is the clinical significance of proteinuria?
proteinuria is a risk factor for cardiovascular disease
proteinuria is a risk factor for progressive chronic kidney disease
Assessment of a patient with proteinuria
history
examination
urine dipstick + quantification of proteinuria
assessment of renal function - serum creatinine + GFR
renal imaging - ultrasound
bloods - ANA, ANCA, anti-GBM, serum protein electrophoresis, serum free light chain ratio, hep B/C serology, complement, anti-PLA2R
renal biopsy
What is nephrotic syndrome?
urine protein excretion >3.5g/day
hypoalbuminaemia (serum albumin <3g/dL)
oedema
hyperlipidaemia
Clinical significance of nephrotic syndrome
untreated has high mortality:
- infection
- thrombosis
- established renal failure
Renal pathophysiology in nephrotic syndrome
disruption of glomerular filtration barrier with podocyte effacement
nephrotic syndrome is always caused by glomerular disease
Clinical features of nephrotic syndrome
frothy urine
peripheral oedema
pulmonary oedema
pleural effusions
Management of nephrotic syndrome
general measures:
- low sodium diet
- fluid restriction
- diuretics
- renin angiotensin aldosterone inhibition and BP control
- statin
- anticoagulation
Why is inhibiting angiotensin important in nephrotic syndrome?
angiotensin constricts efferent arteriole and increases GFR
inhibition of angiotensin dilates efferent arteriole and decreases GFR
decreases proteinuria
Most common cause of nephrotic syndrome in children?
minimal change disease
Minimal change disease management
steroid-responsive
Causes of secondary focal segmental glomerulosclerosis
obesity
hypertension
HIV
bisphosphonates
What happens in membranous nephropathy?
glomerular basement membrane immune deposits
Causes of primary/idiopathic membranous nephropathy
anti-PLA2R
Causes of secondary membranous nephropathy
hepatitis
malignancy
autoimmune
drugs
Microscopic feature of glomerulosclerosis in diabetic nephropathy
kimmelstein wilson nodules
What is amyloidosis?
extracellular deposition of beta sheet fibrils
