Glomerulonephritis Flashcards
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
