Nephrotic Syndrome Flashcards
What is nephrotic syndrome?
Refers to a group of symptoms without specifying the underlying cause.
Therefore, nephrotic syndrome is not a disease, but is a way of saying “the patient has these symptoms”, which indicates there is an underlying disease present but doesn’t specify the disease.
Describe the pathophysiology behind nephrotic syndrome.
- Damage to glomerulus
- Podocytes or basement membrane aren’t working properly
- Huge amounts of protein, especially albumin, leak into the bowman’s capsule
- Is excreted in the urine
- Loss of albumin = oedema
What 4 signs are needed in order to make a diagnosis of nephrotic syndrome?
- Hypoalbuminaemia (< 25g / L).
- Peripheral Oedema.
- Heavy proteinuria (> 3g / 24 hours).
- Hypercholesterolaemia.
In nephrotic syndrome, what happens to cholesterol and coagulability?
- Albumin is lost.
- So liver increases production of albumin.
- Along with this, the liver increases production of cholesterol (xanthelasma) and coagulation factors (coagulopathy).
Why is someone with nephrotic syndrome at risk of sepsis?
Because you lose immunoglobulins in the urine.
Name 3 primary causes of nephrotic syndrome.
- Minimal change disease
- Focal segmental glomerulosclerosis
- Membranous glomerulonephritis
- Kidney specific (like intrinsic)
Name 3 secondary causes of nephrotic syndrome.
- Diabetic nephropathy.
- Amyloidosis (amyloid deposits).
- Infections - Hep B, Hep C, HIV.
- SLE - lupus symptoms e.g. butterfly rash
- Drugs - some NSAIDs, gold, penicillamine and ACEi
What is the most common cause of nephrotic syndrome in children?
Minimal change disease.
Describe the clinical presentation of nephrotic syndrome.
Due to proteinuria:
1. Frothy urine
2. Infection
Due to hypercholesterolaemia:
3. Xanthelasma (eyes)
4. Xanthomata (joints)
5. Atherosclerosis
Due to hypoalbuminaemia:
6. Oedema - peripheral, ascites, periorbital
7. Fatigue
8. Dyspnoea
9. Leukonychia
General investigations for nephrotic syndromes.
General
1. Bloods: U&E + FBC + LFT + CRP + Ca2+ + glucose
= low serum albumin
2. MSU MCS
3. Urine Dipstick (infection / blood) - lots of protein
4. USS Kidney (ultrasound scan)
5. CXR
6. Screen for HIV, HBV, HCV - serology
- LOOK at past medical history!!
What is the specific gold standard investigation for nephrotic syndromes?
Needle biopsy and microscopy:
- Light microscopy (LM)
- Fluorescence microscopy (FM
- Electron microscopy (EM)
Looking for changes in the glomerulus
Describe the treatment for nephrotic syndrome.
- Treatment of underlying cause – 12wks corticosteroids - prednisolone
- Reduce oedema:
- Loop diuretics e.g. IV FUROSEMIDE - IV since gut oedema may prevent oral absorption
- Thiazide diuretics e.g. IV BENDROFLUMETHIAZIDE
- Fluid and salt restriction while giving diuretics - Reduce proteinuria:
* ACE inhibitor e.g. RAMIPRIL
* Angiotensin receptor blocker e.g. CANDESARTAN
* Eat normal rather than high protein diet - Treatment of complications:
- Prophylactic anti-coagulation:
1) Apixaban
2) LMWH - low molecular weight heparin (immediate effect)
3) Warfarin - delayed effect - especially when albumin is low
(<20g/l)
- Treat infections promtly with antibiotics + vaccines.
Give 2 potential complications of nephrotic syndrome.
- Sepsis.
- Thromboembolism
- E.g. DVT, PE, renal vein thrombosis - Susceptibility to infection
- E.g. cellulitis, Streptococcus infections and spontaneous bacterial peritonitis
Differential diagnosis for nephrotic syndromes.
- Congestive heart failure:
* Where there is oedema and raised jugular venous pressure (JVP)
* In nephrotic syndrome there is normal or low JVP (unless there is renal failure and oliguria) - Cirrhosis:
* Where there is hypoalbuminaemia and oedema
* But there are signs of chronic liver failure e.g. jaundice, fever and loss of body hair
What is minimal change disease?
Disease of the kidney that can cause nephrotic syndrome
What happens in minimal change disease?
T cells release cytokines, which damage podocytes
What would you notice on the electron microscopy taken from someone with minimal change disease?
FUSION of the FOOT PROCESSES of the PODOCYTES is seen, consistent with a disrupted podocyte actin cytoskeleton
Simple terms: fused podocytes
What is the treatment for minimal change disease?
- High dose corticosteroids e.g. PREDNISOLONE
- Can reverse proteinuria in 95% cases - however the majority relapse - Frequent relapse or steroid-dependent disease is treated with
CYCLOPHOSPHAMIDE or CICLOSPORIN/TACROLIMUS
What causes membranous glomerulonephritis (pathophysiology and aetiology)?
Deposition of IgG and C3 along outer aspect of glomerular
basement membrane.
Ab’s against PLA2R, SLE, NSAIDs, HBV/HCV, penicillamine
Diagnosis of membranous glomerulonephritis.
Needle biopsy:
- LM = mesangial expansion, capillary wall thickening
- FM = IgG and complement 3 (C3) staining (granular appearance)
- EM = GBM thickening
What is focal segmental glomerulosclerosis?
Pathophysiology?
Aetiology?
Treatment?
Definition:
Scarring that is focal and only some glomeruli involved and
segmental (only part of glomerulus affected)
Pathophysiology:
CD80 in podocytes resulting in increased permeability in glomeruli.
And, thus proteinuria and haematuria
- Secondary hypertension and renal impairment
Causes:
- The majority (~70%) are idiopathic
- Can be secondary to malignancy, rheumatoid disorders and drugs (e.g. NSAIDS)
- HIV, sickle cell, heroin, interferon treatment
Diagnosis: Needle biopsy
- LM = sclerosis (plaques)
- FM = nothing
- EM = GBM thickening
Treatment:
- Treat with corticosteroids and immunosuppressants e.g.
cyclophosphamide or ciclosporin
