Nephrotic Syndrome Flashcards
Clinical presentation of nephrotic syndrome
- Oedema - usually over lower limbs, some may progress to anasarca and periorbital oedema prior to presentation
(painless, symmetric) - Frothy bubbly urine
- Reduced urine output - severe involvement
Rarely presents as:
4. Peritonitis
5. Thromboembolic events
6. Premature atherosclerosis and cardiovascular disease
Examination findings of nephrotic syndrome
Features of hypoalbuminaemia with fluid retention and ascites
- Peripheral oedema
- Periorbital oedema
- Leukonychia and Muehrcke’s lines over nail beds
- Possible splinter haemorrhages and nailfold infarcts (thromboembolism)
- No other stigmata of chronic liver disease
- No lymphadenopathy
- Elevated JVP
- Abdomen distended with ascites
- No hepatosplenomegaly
- No hepatic encephalopathy
Wishlists:
1. Urine dipstick - confirm proteinuria
2. Measure blood pressure - hypertension
3. Chest examination - pleural effusions
4. Underlying etiologies
Peripheral oedema in renal disease first occurs in tissues with low resistance such as periorbital region, scrotal and labia
This is in contrast to right sided heart failure with generalised oedema
Muehrcke’s lines vs Mee’s lines
Muehrcke’s lines - twin transverse lines involving vascular bed (NOT nail matrix)
- No nail surface irregularities
- Blanchable on pressure
- Do not move with nail growth
- Reversible with rise of albumin levels
Mee’s lines - true leukonychia involving nail matrix
- Usually no nail surface irregularity
- DO not disappear with nail bed pressure (can be seen, but not felt)
- Lines progress with the growth of the nail
In nephrotic syndrome, oedema can develop by 2 distinct hypothesised mechanisms:
- Underfill hypothesis
- Hypoalbuminaemia -> decreased oncotic pressure
- Reduced effective intravscular compartment size
- Activation of RAAS and renal sodium resorption - Overfill hypothesis
- Corin mediated activation of epithelial sodium channel causes abnormal sodium retention
Assessment of JVP in differentiating causes of oedema
(However overtly overloaded patients are unlikely to appear in PACES - thus skewed may not be useful)
What are the presentation of glomerular disease?
- Nephrotic syndrome
- Focal nephrotic syndrome - < 1/3 glomeruli involvement on LM. UFEME haematuria, mild proteinuria, red cell casts
- Diffuse nephritic syndrome - affects most/all of glomeruli
Nephrotic syndrome is a cluster of abnormal findings:
- Physical sign (1), laboratory abnormalities (3+1)
Contrary to popular belief, __ or __ are NOT defining feature of nephrotic syndrome in any age group
Oedema
Massive proteinuria
Hypoalbuminaemia
Hypercholesterolaemia
Hypercoagulable state
Not defining feature:
Reduced eGFR
Azotemia
Hypercoagulable state in nephrotic syndrome is due to (3)
1. Urinary loss of antithrombin III
2. Increased platelet aggregation
3. Endothelial dysfunction
Complications of nephrotic syndrome
- Oedema
- Hypertension
- Hypercholesterolaemia
- Thrombosis
- Recurrent infection
Diagnosis of nephrotic syndrome
- Massive proteinuria
- uPCR > 2g/day in adults (some suggests 3.5g) - Excluded cirrhosis, congestive heart failure and protein losing enteropathy/malabsorption
Causes of nephrotic syndrome
A. Primary
1. Minimal change disease (MCD)
2. Focal segmental glomerulosclerosis (FSGS)
3. Membranous nephropathy (MN)
4. Membranoproliferative (mesangiocapillary) GN (MPGN)
B. Secondary
1. Post-infectious GN
2. SLE
3. HSP
4. Medications
5. Infections - Hep B, Hep C, HIV
6. Malignancy - HL
7. Amyloidosis
8. Diabetes, hypertension
AKI in nephrotic syndrome can be due to (3)
1. Intra-renal oedema
2. Tubular obstruction
3. Severe contraction of effective intravascular compartment (reduced perfusion)
Natural progression of nephrotic syndrome depends on primary etiology
MCD: excellent long term prognosis, responsive to therapy. Occasional relapse, with eventual outgrow without permanent kidney injury
FSGS: 50% progress to ESRF over 5-10 years, and 25-50% recurrence after kidney transplant
MPGN: 50% progress to ESRF over 10-20 years, 20-25% recurrence after kidney transplant
Membranous: variable, 1/3 remission, 1/3 persistent proteinuria with stable function, 1/3 steady decline
Nephrotic syndrome workup
UFEME: proteinuria +/- haematuria, red cell casts
A. Quantitation of urine protein
1. Urine protein:creatinine ratio (uPCR) > 2mg/mg (or 15mg/mmol)
2. 24H urine collection > 2g/day (or 3.5g/day)
B. Metabolic profile
1. Renal function test - urea, creatinine
2. Ca Mg Phos, albumin, PTH
3. FBC - anaemia
C. Secondary workup
1. HIV, Hep B, Hep C - membranous, cryo, medication side effect, screening pre-treatment
2. Anti-streptolycin O titre - post-strep GN
3. ANA, dsDNA, C3, C4 - post-infx, SLE, MPGN
4. C3 nephritic factor - MPGN
5. Anti-PLA2R, phospholipase A M-type - idiopathic MN
6. Anti-thrombospondin (sent to Mayo) - malignancy immune mediated MN
7. US renal veins TRO renal vein thrombosis
D. Kidney biopsy - for definitive diagnosis
- See subsequent card for indications
Benefits and possible limitations of spot uPCR
Benefits:
1. Correlates with daily protein excretion
2. Significantly less cumbersome than 24 hour collection
Limitations:
1. Variations of result with time of day, race, body mass
Orthostatic proteinuria is a benign condition in young adults under 30 years old with abnormal proteinuria in the day, but overnight urine collection shows normal excretion
What should we perform kidney biopsy to assess nephrotic syndrome?
Criteria for children:
1. Age < 6 months, or adolescent onset Tanner 3 or more
2. Low C3 levels
3. Unusual clinical features
4. Resistance to steroids
Criteria for adults:
1. Done prior to initiation of steroids - due to diverse pathology and reduced tolerance to steroids
2. Distinguish between different causes of nephrotic syndrome
What should kidney biopsy samples be sent for?
- Light microscopy (LM)
- Eletron microscopy (EM)
- Immunofluorescence
- Special staining for synaptopodin, dystroglycan
Management of nephrotic syndrome
A. Supportive care
1. Sodium and fluid restriction
2. Judicious use of diuretics (furosemide +/- metolazone) - aim for weight loss 0.5-1kg/day
3. Monitor for hyponatraemia, hypokalaemia, metabolic alkalosis
4. Statins for hypercholesterolaemia
5. Immunisations
B. Definitive treatment
First Line
1. Corticosteroids - MCD and FSGS
2. ACEi/ARBs only in MN
Second Line - steroid resistant
1. MMF
2. Cyclophosphamide
3. CNI - ciclosporin, tacrolimus
Emerging
1. Eculizumab - for type II MPGN
2. Rituximab (CD20i) + CNI - for MN
3. Abatacept (B7.1 Ab) - for FSGS
4. Thiazolidinediones (rosiglitazone) and adalimumab (anti-TNF) - prevention of kidney fibrosis
C. Explore on kidney transplant if progression to ESRF
