Glomerulonephritis

Question 1

What is glomerulonephritis (GN)?

Answer 1

Glomerulonephritis (GN) denotes 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). The injury can involve a part or all of the glomeruli or the glomerular tuft. The inflammatory changes are mostly immune mediated.

Question 2

What is interstitial nephritis?

Answer 2

Interstitial nephritis is a term to describe a situation where there is inflammation of the space between cells and tubules (the interstitium) within the kidney.

It is important not to confuse this with glomerulonephritis. Under the umbrella term of interstitial nephritis, there are two key specific diagnoses: acute interstitial nephritis and chronic tubulointerstitial nephritis.

Question 3

What can cause glomerular injury?

Answer 3

Infections (group A beta-haemolytic Streptococcus, respiratory and gastrointestinal infections, hepatitis B and C, endocarditis, HIV, toxaemia and syphilis).

Systemic inflammatory conditions such as vasculitides (SLE, rheumatoid arthritis and anti-glomerular basement membrane disease).

Drugs (penicillamine, gold sodium thiomalate, non-steroidal anti-inflammatory drugs, captopril, heroin, cocaine and anabolic steroids).

Metabolic disorders (diabetes mellitus, hypertension and thyroiditis).

Malignancy (lung and colorectal cancer, melanoma, and Hodgkin’s lymphoma).

Question 4

Give examples of diseases which are included in GN

Answer 4

Diseases include membranous GN:

• Minimal change disease
• Focal and segmental glomerulosclerosis
• Membranous glomerulonephritis
• IgA nephropathy (Berger’s disease)
• Forms of rapidly progressive GN (vasculitis and anti-GBM disease)
• Lupus nephritis
• Post streptococcal glomerulonephritis
• Goodpasture syndrome

Question 5

Briefly describe the pathophysiology of glomerular disease

Answer 5

Glomerular injury may be caused by inflammation due to leukocyte infiltration, antibody deposition, and complement activation.

Question 6

What is glomerulosclerosis?

Answer 6

Glomerulosclerosis is a term to describe the pathological process of scarring of the tissue in the glomerulus. It is not a diagnosis in itself and is more a term used to describe the damage and scarring done by other diagnoses.

Glomerulosclerosis can be caused by any type of glomerulonephritis or obstructive uropathy (blockage of urine outflow), and by a specific disease called focal segmental glomerulosclerosis.

Question 7

What are the risk factors for GN?

Answer 7

Risk factors include 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 lymphoma, lung cancer, colorectal cancer, non-Hodgkin’s lymphoma, leukaemia, thymoma), haemolytic uraemic syndrome, and drugs.

Question 8

What are the signs of GN?

Answer 8

• Oedema
• Hypertension

Question 9

What are the symptoms of GN?

Answer 9

• Haematuria
  *

Question 10

What investigations should be ordered for GN?

Answer 10

• Urinalysis and urine microscopy
• Metabolic profile
• GFR
• FBC
• Lipid profile
• Urine creatinine: albumin ratio (ACR)
• Ultrasound of kidneys
• Renal biopsy

Question 11

Why investigate urinalysis and urine microscopy?

Answer 11

Dysmorphic red blood cells (RBCs), sub-nephrotic proteinuria, and active sediment points to the presence of GN.

Question 12

Why investigate metabolic panel?

Answer 12

Elevated creatinine (indicates severe or advanced disease). Normal creatinine does not exclude significant renal pathology.

Elevated liver enzymes may be seen if aetiology is related to hepatitis C virus or hepatitis B virus.

Patients with nephrotic syndrome have hypoalbuminaemia.

Question 13

Why investigate GFR?

Answer 13

Determined by mathematical equations such as the Modification of Diet in Renal Disease formula or CKD-EPI formula, the GFR gives an indication of the severity and stage of chronic kidney disease.

Question 14

Why investigate FBC?

Answer 14

Anaemia is a feature of several systemic diseases that are associated with GN.

Question 15

Why investigate lipid profile?

Answer 15

May reveal hyperlipidaemia.

Question 16

Why investigate urine albumin:creatinine ratio (ACR)?

Answer 16

Quantifies proteinuria reasonably accurately and much more easily than a 24-hour urine collection, and should always be ordered as a follow-up to urinalysis showing proteinuria.

If ACR is >220 mg/mmol, patients are classified as having nephrotic-range proteinuria and may have full nephrotic syndrome (hyperlipidaemia, hypoalbuminaemia, oedema, nephrotic-range proteinuria).

Question 17

Why investigate using ultrasound of the kidneys?

Answer 17

Thinning of the cortico-medullary junction and shrunken kidneys indicate a chronic process, thereby reducing the chances of treatment success.

Helps differentiate from other causes of acute renal failure such as obstructive uropathy.

Question 18

Why investigate using renal biopsy?

Answer 18

Should be urgently performed if glomerulonephritis is suspected.

Core-needle biopsy remains the most sensitive and specific test for diagnosis. Light and electron microscopy will reveal pattern of cellular proliferation and number of glomeruli involved.

Immunofluorescence and electron microscopy may show patterns of immune complex deposition.

Question 19

What is the overarching treatment used for GN?

Answer 19

Immunosuppression (e.g. steroids) and blood pressure control by blocking the renin-angiotensin system (i.e. ACE inhibitors or angiotensin-II receptor blockers).

Question 20

Are the glomerulonephritides nephrotic or nephritic?

Answer 20

The glomerulonephritides classically present on a spectrum ranging from nephrosis to nephritis. However, if GN causes scarring, then proteinuria can occur. Proteinuria can therefore complicate the longer-term picture of any GN, including those that are classically ‘nephritic’.

Question 21

Briefly differentiate between nephrotic and nephritic syndrome

Answer 21

Nephrotic: proteinuria due to podocyte damage

Nephritic: haematuria due to inflammatory damage

Question 22

What differentials should be considered for GN?

Answer 22

1. Nephrolithiasis
2. Bladder cancer
3. Renal cancer

Question 23

How does GN and nephrolithiasis differ?

Answer 23

Differentiating signs and symptoms:

• Patients usually have severe pain in addition to haematuria
• The site and radiation of pain depend on the position of the stone

Differentiating investigations:

• Urinalysis shows haematuria, but no dysmorphic red blood cells (RBCs) or casts
• CT KUB (kidney, ureter, bladder) or renal ultrasound reveals the stone

Question 24

How does GN and bladder cancer differ?

Answer 24

Differentiating signs and symptoms:

• Important cause of painless haematuria
• Patients are older and mostly have a history of smoking

Differentiating investigations:

• Urinalysis shows haematuria, but no dysmorphic RBCs or casts
• Diagnosis is made by cystoscopy and biopsy of the lesion

Question 25

How does GN and renal cancer differ?

Answer 25

Differentiating signs and symptoms:

• A triad of flank pain, fever, and haematuria is typical
• Many cases are detected incidentally when a CT is done for other purposes

Differentiating investigations:

• Urinalysis shows haematuria, but no dysmorphic RBCs or casts
• Imaging by CT would reveal a renal mass

Question 26

Which diseases of GN cause nephritic syndrome?

Answer 26

• IgA nephropathy
• Henoch-Schonlein purpura
• Post-streptococcal GN
• Anti-GBM disease
• Rapidly progressive GN

Question 27

Which diseases of GN cause nephrotic syndrome?

Answer 27

• Minimal change disease
• Focal segmental glomeulosclerosis
• Membranous nephropathy
• Membranoproliferative glomerulonephritis