Glomerulonephritis

Question 1

Define glomerulonephritis

Answer 1

An immunological mediated inflammation of the renal glomeruli and nephrons

Glomerulonephritis denotes (mostly immune related) glomerular injury and applies to a group of diseases that are generally, but not always, characterised by inflammatory changes in the glomerular capillaries and the glomerular basement membrane (GBM).

Question 2

What are the common risk factors for GN?

Answer 2

• infections
  
  • group A beta-haemolotyic streptococci
  • hepatitis B and C
  • respiratory and gastrointestinal infections
  • infective endocarditis
  • HIV
• connective tissue diseases
  
  • systemic lupus erythematosus
  • systemic vasculitides
• malignancy
  
  • Hodgkin’s + non-Hodgkin’slymphoma
  • lung cancer
  • colorectal cancer
  • leukaemia
  • thymoma
• haemolytic uraemic syndrome
• drugs
  
  • ​gold
  • penicillinamin

Question 3

Briefly explain how glomerular injury may occur in immune-mediated GN

Answer 3

Most human glomerulonephritides are triggered by immune-mediated injury exhibiting both humoral and cellular components.

• cellular response: infiltration of glomeruli by circulating mononuclear inflammatory cells (lymphocytes and macrophages)
• humoral response: leads to immune deposit formation and complement activation in glomeruli. Circulating antibodies react with:
  
  • intrinsic autoantigens (anti-glomerular basement membrane disease membranous nephropathy)
  • extrinsic antigens (post-infectious GN)
• Injury usually occurs as a consequence of the activation and release of a variety of inflammatory mediators (complement activation, cytokines, growth factors, and vasoactive agents)

Question 4

Give examples of some non-immunological causes of GN

Answer 4

A variety of non-immunological metabolic, haemodynamic, and toxic stresses can also induce glomerular injury:

• Hyperglycaemia (diabetic nephropathy)
• Lysosomal enzyme defects
• High intraglomerular pressure (systemic hypertension and overload of functioning nephrons following loss of other nephrons due to other causes)
• Hereditary defects resulting in deformity of the glomerular basement membrane (e.g., type IV collagen).

Question 5

GN can be classified into which 2 syndromes? State associated clinical signs

Answer 5

Nephrotic syndrome - increased permeability of the glomerulus leading to loss of proteins into the tubules – LOSS OF A LOT OF PROTEIN (NO BLOOD)

• nephrotic-range proteinuria > 3.5 g/24 hr
• hypoalbuminaemia <24 g/L
• hyperlipidaemia
• oedema

Nephritic syndrome - thin glomerular basement membrane with pores that allow protein and blood into the tubule – LOSS OF A LOT OF BLOOD

• haematuria
• non-nephrotic range proteinuria
• hypertension
• oligouria

Question 6

State some common primary and secondary causes of nephrotic syndrome

Answer 6

PRIMARY

• Membranous nephropathy
• Minimal change disease
• Mesangiocapillary nephropathy

SECONDARY

• Diabetes
• Amyloid
• Hep B/C

Question 7

State some common primary and secondary causes of nephritic syndrome

Answer 7

PRIMARY

• Immunoglobulin A nephropathy
• Mesangiocapillary
• Rapidly progressive GN
  
  • Vasculitis
  • Anti-glomerular basement membrane (GBM) GN.

SECONDARY

• Post-infectious- streptococcal
• Vasculitis
• SLE
• Cryoglobinaemia

Question 8

Summarise the epidemiology of glomerulonephritis

Answer 8

• GN is the third commonest cause of end-stage renal disease (ESRD), after diabetes and hypertension- accounts for 25% cases of CKD
• For every patient with clinically apparent GN, approximately 5 to 10 patients have undiagnosed subclinical disease.

Question 9

What are the presenting symptoms of glomerulonephritis?

Answer 9

• Polyuria or oliguria
• Haematuria- microscopic common, macroscopic seen with some forms
• Anorexia, weight loss
• Nausea
• Malaise
• Fever- may occur with infectious aetiology, for example, post-streptococcal GN.
• Skin rash, arthralgia- vascular aetiology
• Haemoptysis
• Abdominal pain- in post-streptococcal GN and Henoch-Schonlein purpura.
• Sore throat- post-streptococcal GN and IgA nephropathy.

Question 10

Why do you see hyperlipidaemia in nephrotic GN?

Answer 10

due to the hypoalbuminaema, the liver tries to compensate and increases production of lipids, causing hyperlipidaemia

In nephrotic syndrome, only PROTEINS are moving into the urine

Question 11

Identify appropriate investigations for, and state what you would see, in GN

Answer 11

1. urinalysis and urine microscopy
   
   • haematuria, proteinuria, dysmorphic RBCs, leukocytes, and RBC casts
   • 24 hr collection: creatinine clearance and protein
2. comprehensive metabolic profile
   
   • Creatinine and liver enzymes
   • Normal or renal failure, elevated liver enzymes (if HBV/HCV), hypoalbuminaemia (nephrotic)
3. glomerular filtration rate (GFR)
   
   • normal or reduced
4. full blood count, inc antibodies-
   
   • ANA
   • Anti-dsDNA
   • ANCA
   • Anti-GBM antibody
   • Cryoglobulins
5. lipid profile
6. ​​Renal tract USS
   
   • ​​thinning of the cortico-medullary junction and shrunken kidneys = chronic process → reduced chances of treatment success.
   • Helps differentiate from other causes of acute renal failure such as obstructive uropathy.
7. Renal biopsy
   
   • Should be urgently performed if glomerulonephritis is suspected.
   • Core-needle biopsy remains the most sensitive and specific test for diagnosis.
8. Investigations for associated conditions (e.g. HBV, HCV and HIV serology)