Flashcards in Conditions that results in proteinuria Deck (37):
What are transient causes for proteinuria?
How do you quantify proteinuria?
Urine dipstick > +3 proteinuria
24 hour urine collection
- >4mg/m2/hr is abnormal
Early morning Urine protein to creatine excretion ratio
- >0.5 in children under 2 is abN
- >0.2 in older children is excessive
- test may OVERestimate protein excretion in individuals with low muscle mass
What is the difference between glomerular vs tubular proteinuria?
Glomerular proteinuria is due to increased permeability of glomerular capillary wall
- major protein loss is albumin
Tubular proteinuria is due to diminished reabsorptive capacity
- loss of lower molecular weight protein than albumin like light chains of Ig, insulin, growth hormone, lysozyme
- not assoc w oedema
- loss rarely exceeds 1g/24hr
What is one factor that increases the likelihood of corticosteroid responsiveness?
- loss of plasma proteins of molecular wt up to and including albumin (not larger molecules like IgG)
- occurs primarily in minimal-change nephrotic syndrome
What are causes of nephrotic syndrome?
Idiopathic nephrotic syndrome
- minimal change (85%)
- focal segmental glomerulosclerosis (10%)
- mesangial proliferation (5%)
- membranous glomuerlonephrits
- membranoproliferative glomerulonephritis (low C3)
- other forms less common include lupus, HSP, hep B, chronic infection including schistosomiasis and malaria
- Minimal change disease seen in lymphomas
- Lithium, NSAID, penicillamine, ethosuximide
Is nephrotic syndrome more common in boys or girls?
M: F ratio = 2: 1
What is nephrotic syndrome?
A clinical syndrome characterised by heavy proteinuria, hypoalbuminaemia (albumin < 25g/l), oedema and hypercholesterolemia.
Nephrotic range proteinuria is >40mg/hr/m2 or a first morning urine protein/creatinine ratio >200mg/mmol (normal <20).
What is the outcome of nephrotic syndrome?
More than 90% steroid sensitive
- best prognosis assoc with minimal change
Prognostic indicator includes
- Non-selective proteinuria
- Development of HTN
Rarely leads to chronic renal failure
What does the light microscope / immunofluorescence / electron microscope show in minimal change nephrotic syndrome?
- Normal glomerulus
- Increased mesangial cells
- fusion of podocytes foot processes (not specific but frequently only change found)
What is the relapse rate of minimal change nephrotic syndrome ?
- most likely to occur during URTI
- Can be prevented by prophylactic prednisolone 5-15mg alt days
Is it common to see haematuria w nephrotic syndrome?
- up to 70% of MCD
- 48% of FSGS.
- common in FSGS.
What atypical features would make you want to check ANA / complement levels in a patient w nephrotic syndrome?
- age <12 months or >12 years
- persistent hypertension
- impaired renal function
- macroscopic haematuria,
- signs of systemic illness
What are complications of nephrotic syndrome?
- present as acute abdomen, tachycardia, raised haemoglobin/haematocrit, hypertension
- postural blood pressure change should be assessed
- hypotension as a late sign
- FeNA < 1 supports this
- encapsulated bacterial organisms (Pneumococcus, H. Influenzae) therefore penicillin prophylaxis indicated
- gram negative organisms and Varicella zoster more severe in those on steroids
- DVT, PE, renal vein thrombosis
Chronic renal failure
- more common in focal segmental glomerulosclerosis
What does remission in nephrotic syndrome mean?
- Urine protein excretion <4mg/hr/m2 or albustix is negative/trace for 3 consecutive days
- Average time approx 10 days
What does relapse in nephrotic syndrome mean?
- Proteinuria on dipstick 3+ for 3 consecutive days after having been previously in remission. This is common, occurring in up to 75% of patients.
What does frequent relapse in nephrotic syndrome mean?
- 2 or more relapses within 6 months OR
- more than 4 relapses in 12 months.
What does steroid dependence in nephrotic syndrome mean?
- 2 consecutive relapses occurring during steroid treatment OR
- within 14 days of steroid therapy cessation
What does steroid resistance in nephrotic syndrome mean?
Steroid Resistance (7%)
- Failure to achieve response after 28 days of steroid at 60mg/m2/day followed by 3 pulses of intravenous methylprednisolone (10mg/kg/dose to maximum 700mg on alternate days).
NOTE - some experts define steroid resistance after 8 weeks of daily high dose prednisone.
Discussion with Nephrology should be made if no response at 28 days to arrange for biopsy within 8 weeks from onset; esp to exclude FSGN
When is cyclophosphamide indicated in nephrotic syndrome?
When steroid side effects with multiple relapses became an issue.
2.5-3mg/kg/day for 8 weeks
What are indications for renal biopsy in nephrotic syndrome?
Impaired renal function with normal volume status.
Initial macroscopic haematuria.
Persistent microscopic haematuria if associated with hypertension.
Onset less than 6 months of age.
What is the dietary management of nephrotic syndrome?
NORMAL protein intake.
Salt restriction during relapses.
How can oedema from nephrotic syndrome be managed?
Fluid restriction (e.g. 70% maintenance
What's the role of albumin infusion in nephrotic syndrome?
Used in hypovolaemia or severe oedema.
- Maximum dose 1g/kg of 20% albumin over minimum of 4 hours.
- If given for severe oedema, follow with IV frusemide 2-3 mg/kg/dose.
- HypoNa / K,
- pulmonary oedema.
What may be the cause of low creatinine clearance when nephrotic syndrome is first diagnosed?
Reduced intravascular volume due to diminished renal perfusion; should return to normal once volume is restored
What are the causes of nephrotic syndrome in first 6 months of life?
Congenital nephrotic syndrome
- toxoplasmosis, CMV, syphilis
- Nephropathy, Wilm's tumour, genital abnormalities
What is the pathology / inheritance pattern in congenital nephrotic syndrome?
Pathology described as 'microcytic' resulting in dilation of the proximal convoluted tubules
- Gene is on 19q
Most common in Finland, now seen in descendent of other european communities
What are clinical features of congenital nephrotic syndrome?
Oedema noted in the first week of life
Death likely by age of 5 y
Are steroids effective in congenital nephrotic syndrome?
Transplant patients do well with no recurrence of glomerulopathy
How is the prenatal diagnosis of congenital nephrotic syndrome made?
Elevated AFP in amniotic fluid at 16-20 wks gestation
What is focal segmental glumerulosclerosis?
Cause of nephrotic syndrome where plasma factor increases permeability to proteins
Biopsy shows segmental sclerosis and hyalinosis
- may be mesangial proliferation
- IgM and IgG in affected segmental lesions
What's the difference between minimal change nephrotic syndrome and focal segmental glomulerosclerosis?
- 85% of nephrotic syndrome
- 20% has microscopic haematuria
- 5-10% of nephrotic syndrome
- 80% has microscopic haematuria
- 70% steroid resistant
- 60% progress to ESRF over 10 years
- 30% recurrence risk in transplanted kidney
(highest in older age of onset / shorter time from onset to ESRF)
What are clinical features of membranoproliferative GN (aka mesangiocapillary GN)?
Most common cause of chronic glomerulonephritis in older children and adults.
- Often secondary to other causes like hepatitis
- Presents with proteinuria, haematuria, HTN
- Can be similar in Px to PSGN but doesn't improve in 2 months
Progresses to renal failure
Virtually non are steroid responsive
What are ix findings of membranoproliferative GN?
- type 1: increase mesangial cells / matrix +/- crescents
- type 2: dense deposit disease
Serum C3 decreased
What is the membranous GN?
Membranous glomerulonephritis is the most common nephrotic syndrome in adults
A/w hepatitis B and C, malaria, syphilus in children
- membrane thickening due to epimembranous immune complex
What is mesangial proliferative GN?
Makes up of 5% idiopathic nephrotic syndrome
Poorly defined entity
- minimal change disease with mesangial proliferation
- resolving PSGN
50-60% steroid responsive
What is persistent asymptomatic proteinuria?
proteinuria in an apparently normal child that occurs w/o haematuria > 3 months
Occurs up to 6% of children
Needs annual physical exam / BP / urinalysis / cr clearance and 24 hour urine protein