Glomerulonephritis Flashcards
(29 cards)
What percentage of glomerulonephritis causes end stage kidney disease?
25%
What is the glomerulus?
Site of ultrafiltration within the kidneys
What is the filtration barrier made up of?
- Endothelium
- Basement membrane
- Foot processes of the podocytes
What are the hallmarks of glomerular disease?
Leakage of blood and protein.
Effects of glomerulonephritis?
- Leaky glomeruli - haematuria and proteinuria
- High blood pressure
- Deteriorating kidney function (eGFR)
How can damage to the glomerulus occur?
Can be secondary to deposition of immune or non-immune material or direct immune attack of components of the glomerular structure.
Diabetes and amyloid: deposition of non-immune material
Anti-glomerular basement membrane disease - antibodies directed to proteins on the basement membrane and this initiates a pro-inflammatory response.
Usually damage to the glomerulus is immune mediated and we can see immunoglobulin deposits and if we suppress the immune system, patients get better.
What is the triad of nephrotic syndrome?
Massive proteinuria (>3.5g per day or A:CR >250mg/mmol)
Hypoalbuminemia (<30g/L serum albumin)
Oedema
Can present with hypercholesterolemia and haematuria is usually absent or mild
Causes of nephrotic syndrome
Either primary renal disease or secondary due to systemic disorder
Primary
- primary renal pathology. causing glomerular disease
- minimal change disease (children)
- membranous nephropathy (caucasian adults)
- focal segmental glomerulonephrosis (black adults)
- membranoproliferative GN
Secondary
- disease process involved injury to the renal glomeruli
- diabetes
- lupus nephritis
- malignancy
- amyloid
- pre-eclampsia
- drugs - gold and penicillinamine
Describe the pathophysiology of nephrotic syndrome including how nephrotic syndrome causes an increased risk of infection, increased risk of clots, oedema and hyperlipidemia.
- The filtration barrier of the kidney is formed by podocytes, the glomerular basement membrane and endothelial cells.
- Nephrotic syndrome is a consequence of structural changes in the glomeruli in response to glomerular injury. It causes excessive leakage of key plasma molecules including albumin.
- This leads to the typical features of heavy proteinuria and hypoalbuminaemia.
- The reduction in serum albumin causes a lowering of oncotic pressure which can lead to oedema.
- Patients with nephrotic syndrome are more at risk of infections due to the loss of immunoglobins from the glomerulus.
- Hyperlipidemia is another common feature of nephrotic syndrome due to loss of oncotic pressure which leads to elevated levels of cholesterol, LDL and triglycerides in serum
- A hypercoagulable state may also be developed most likely due to loss of anti-clotting factors such as antithrombin III, plasminogen, protein C and S.
Presentation or clinical features of nephrotic syndrome
- Generalised, pitting oedema which can be rapid and severe (ankles, if mobile, sacral pads, elbows if bed bound)
- Ask about systemic symptoms (joint, skin, consider malignancy and chronic infection)
- Episodic macroscopic haematuria
How do we manage nephrotic syndrome? (Oedema, proteinuria & complications)
- *Reduce oedema**
- Fluid and salt restriction
- Diuretics (furosemide)
- *Treat underlying cause**
- Renal biopsy for adults
- Treat any underlying malignancy, infection or systemic disease
- Children - minimal change disease is the most common aetiology and steroids induce remission in majority - biopsy not needed usually in children
- *Reduce proteinuria**
- ACE-i or ARB as they reduce proteinuria
Manage complications
- Thromboembolism: hypercoaguable state due to increased clotting factors and platelet abnormalities
→ Increased risk of DVT and PE and renal thrombosis
→ Treat with heparin and warfarin
- Infection: urine losses of immunoglobulins and immune mediators lead to increased risk of urinary, CNS and respiratory infection
→ Can also cause peritonitis, empyema, cellulitis
→ Ensure pneumococcal vaccine given
- Hyperlipidemia: Increased cholesterol, increased LDL and triglycerides and low HDL.
→ Thought to be due to hepatic synthesis in response to low oncotic pressure and defective lipid breakdown
What is minimal change disease? Who is it most commonly seen in? How is it diagnosed and treated?
Minimal change disease is a kidney disorder that can lead to nephrotic syndrome.
When a kidney biopsy is examined under the microscope, it appears normal = minimal change seen but symptoms of glomerulonephritis can still be present.
- Common type of glomerulonephritis in children
- 25% of adult nephrotic syndrome
- Idiopathic (most) or in association with drugs (NSAIDs, lithium)
- Does not cause renal failure
Diagnosis
- Light microscopy is normal (hence the name)
- Electron microscopy shows effacement (thinning, reduction) of podocyte foot processes
Treatment
- Prednisolone for 4-16 weeks.
- Frequent relapses are managed with immunosuppression - (cyclophosphamide, calcineurin inhibitors)
What is nephritic syndrome, what are the characteristics?
Inflammation of the kidney. Clinica presentation characterised by: 1. haematuria (nv or v) 2. proteinuria 3. oliguria 4. hypertension
symptoms of nephritic syndrome
haematuria - nv or v
oedema
reduced urine output (oliguria)
uremic symptoms - reduced appetite, fatigue, pruritis, nausea)
Causes of acute nephritic syndrome?
- ANCA associated vasculitis
- Goodpastures disease - ab to glomerular basement membrane
- SLE, systemic sclerosis
- Post-streptococcal infection = antibodies formed and immune deposits in kidneys
- Crescentic IgA nephropathy or Henoch
What would we see on urinalysis/diagnosing nephritic syndrome?
- Urine microscopy: Red cell casts on urine microscopy are characteristic of glomerular bleeding (glomerulonephritis), leucocytes, sub-nephrotic range proteinuria and dysmorphic red cells (nephritic urinary sediment)
- Haematuria (blood +++)
- Proteinuria (mild protein)
- Red cell casts
- Linear deposits of antibody along basement membrane
- Serology: anti-glomerular basement membrane antibodies
- Hypertension
Treatment of acute nephritic syndrome?
Remove antibody - plasma exchange
Immunosuppression using steroids or cyclophosphamide
What is ANCA associated vasculitis? When do they present, name a few conditions which fall under ANCA associated, what is the pathophysiology?
- Umbrella term for a group of multi-system autoimmune small vessel vasculitides
- They can present at any age
- ANCA includes miscroscopic polyangitis, granulomatosis with polyangitis, eosinophilic granulomatosis with polyangitis
- The conditions are characterised by formation of granulomas and inflammation of small arteries, arterioles, venules and capillaries
- Inflamed vessels may rupture or become occluded giving rise to a broad array of clinical symptoms and signs related to systemic inflammatory response, end organ microvascular injury or the mass effect of granulomas
What would a biopsy of ANCA associated vasculitis show?
Biopsy
- Segmental glomerular necrosis with crescent formation
- Degree of active lesions, fibrosis and tubular atrophy are important prognostic markers
Why do we change patients from high dose immunosuppressants to lower dose in ANCA?
- Disease related complications are bad but the treatments themselves also have very bad effects
- This is why we swap them from higher immunosuppressants to weaker ones
What is the most common cause of glomerulonephritis world wide? At what age is this most common? What is the pathophysiology of this condition?
IgA nephropathy
50% cases occur in 20s/30s and is uncommon before 10.
IgA antibodies deposit in the kidney’s mesangium leading to inflammation, scarring and damage.
Presentation/clinical features of IgA nephropathy?
- Non visible haematuria or episodic visible haematuria which may be ‘synpharyngitic’ within 12-72h of infection
- Can be asymptomatic but urine shows erythrocytes, casts and proteinuria
- Most patients have a history of upper respiratory tract infection either at the onset or within first 24-48h there is gross haematuria that lasts for less than 3 days. Urine is brown and there may be loin pain ‘coca cola urine’.
- Illnesses that can precipitate haematuria: include urinary tract infection, pneumonia, staphylococcal infection, acute gastroenteritis, influenza and glandular fever.
- Increased BP
- Proteinuria usually <1g
- Nephrotic syndrome occurs in only 5% of all cases
How do we diagnose IgA nephropathy?
- Asymptomatic urine testing identifies 30-40% of cases
- Urine dipstick: light to moderate albumin and blood presence
- Urine microscopy needed for red blood cells, leukocytes and casts
- Renal Biopsy: showing diffuse mesangial IgA deposits, subendothelial and sub epithelial deposits on EM is not uncommon
Treatment of IgA nephropathy?
- ACE-i or ARB reduce proteinuria and protect renal function and lower BP.
- HTN needs early and aggressive management, ACEi are drugs of choice and ARB are reserves.
- Corticosteroids and fish oil can be used in persistent proteinuria >1g despite 3-6m of ACE-i and ARB and GFR >50.
- If there are crescents on biopsy and the patient is deteriorating, can use steroids.
