Glomerular Diseases

Question 1

Clinical syndromes of glomerular diseases

Answer 1

1. Nephrotic syndrome
2. Nephritic syndrome
3. Microscopic hematuria
4. Acute renal failure
5. Chronic renal failure

Question 2

Features of nephrotic syndrome (5)

Answer 2

• leaky glomerular filter that manifests as
  1. Heavy proteinuria
• 3.5g of protein loss/24h
• selective/non-selective depending on size of protein molecules
  2. Hypoalbuminemia
• albumin loss in urine > liver capacity to maintain normal serum levels
  3. Anasarca
• generalised edema due to decreased plasma oncotic pressure (proteins unable to keep water in vessels)
• marked periorbital edema, pedal edema, facial & abdo swelling
  4. Lipiduria
• leakage of lipoproteins into urine
  5. Hyperlipidemia
• compensatory synthesis of lipoproteins by liver

Question 3

Causes of nephrotic syndrome

Answer 3

1. Glomerular diseases - usually non-proliferative glomerulonephritis
   - commonly also MCD, idiopathic focal segmental glomeruloslcerosis, membranous GN
   - uncommonly membranoproliferative GN, IgA nephropathy
2. Secondary Nephrotic syndrome
   - systemic disease, drugs, infection, malignancies, heterozygous alport disease

Question 4

Clinical features of nephrotic syndrome

Answer 4

• body swelling - face, eyelids, increased abdo girth, ankles
• large urine volumes w frothy urine (proteinuria)
• age is important in diagnosis!! childhood nephrotic syndrome is usually sensitive to steroids, only biopsy if unresponsive

Question 5

Features of nephritic syndrome (6)

Answer 5

• damaged glomeruli (some leaky, some unable to filter) that manifests as
  1. Oliguria
• poor filtration - reduced urine vol
  2. Azotemia
• elevation of serum creatinine levels
  3. Edema
• due to fluid retention
  4. Hypertension
• due to fluid retention
  5. Gross hematuria
• RBCs in urine (red cell casts on urine microscopy)
  6. Proteinuria

Question 6

Causes of nephritis syndrome

Answer 6

1. Primary glomerular disease
   - post streptococcal/infection GN, IgA nephropathy
2. Secondary/Systemic disease
   - Good pasture, SLE, systemic vasculitis, IE, Henoch-Schonlein purpura

Question 7

Outcomes of nephritic syndrome (3)

Answer 7

1. Complete resolution - no residual damage
2. Rapid progression - rapidly progressive GN - ARF
3. Slow progression - CRF

Question 8

Features of microscopic hematuria

Answer 8

• hematuria detected by urinalysis, not visible to the naked eye
• may have some degree of proteinuria, no change in urine vol, no azotemia, no htn

Question 9

Causes of microscopic hematuria

Answer 9

• milder forms of proliferative GNs
• IgA nephropathy
• thin BM syndrome

Question 10

Features of acute renal failure (2)

Answer 10

• associated w severe proliferative GN, often with crescents
  1. Oliguria/anuria
• marked decrease/absence of urine production
  2. Azotemia
• progressive, usually rapid, rise of serum creatinine

Question 11

Causes of acute renal failure (3)

Answer 11

1. Pre-renal - eg blood, fluid
   - hypotension, hemorrhage, severe dehydration, shock, heart disease, liver failure
2. Renal - intrinsic to 4 kidney compartments
   - GN, ATN, AIN, hemolytic uremic syndrome, vasculitis, severe infections
3. Post-renal - urine affected
   - acute urinary tract outlet obstruction eg clots, stones, tumours
   - acute atonia, hypotonia of bladder due to nerve damage

Question 12

Causes of chronic renal failure

Answer 12

• diabetic nephropathy
• glomerulonephritis
• hypertension
• interstitial nephritis
• chronic urinary outflow tract obstruction
• pyelonephritis
• polycystic kidney disease
• other congenital kidney diseases/malformations
• tumours

Question 13

Manifestations/complications of chronic renal failure

Answer 13

1. Fluid & electrolytes - dehydration, anemia, hyperkalemia, metab acidosis
2. Calcium, phosphate, bone
   - hyperphosphatemia, hypocalcemia, 2 hyperparathy, renal osteodystrophy
3. Hematologic
   - anemia, bleeding diathesis
4. Cardiopulmonary
   - htn, heart failure, cardomyopathy, pulm edema, uremic pericarditis
5. GI
   - n/v, bleeding, esophagitis, gastritis, colitis
6. Neuromuscular
   - myopathy, peripheral neuropathy, encephalopathy
7. Skin
   - dermatitis, pruritus, sallow colour

Question 14

Pathology of chronic renal failure

Answer 14

• end stage of many glom/tubular diseases
• diminished renal reserve - renal insufficiency - CRF - ESRD
• bilateral small contracted kidneys
• widespread glomerulosclerosis, tubular atrophy, interstitial fibrosis
• initial polyuria as tubules cannot concentrate glom filtrate
• terminal oliguria when no functioning nephrons left

Question 15

Treatment for chronic renal failure (3)

Answer 15

1. Hemodialysis
2. Peritoneal dialysis
3. Renal transplantation

Question 16

Investigations for renal failure (4)

Answer 16

1. Blood tests: urea, creatinine, electrolytes
2. Urine tests: protein, RBCs, WBCs, Hb, myoglobin
3. Imaging: IVU, US, CT/MRI, CT urogram
4. Kidney biopsy
   - invasive
   - complications - perinephric hematomas, bleeding

Question 17

Features of renal biopsy

Answer 17

1. Light Microscopy - views histological changes
2. Immunofluorescence - detects specific immune complexes and/or antigens
3. Electron Microscopy - examine changes undetectable by LM

Question 18

Histological changes seen on LM

Answer 18

• Non proliferative - MCD, focal glomerulosclerosis, membranous change
• Proliferative - increased numbers of cells in glomeruli
• Distribution: diffuse vs focal (>/<50% of glomeruli involved)
• Extent of glomerular involvement: global vs segmental
• Bad prognosis lesions: crescents, sclerosis/fibrosis - indicate irreversible glomerular damage

Question 19

Changes seen on EM

Answer 19

• changes in thickness of basement membrane
• effacement of foot processes of podocytes
• pattern of immune deposits (subepithelial, mesangial, subendothelial)
• special features eg double contour appearance

Question 20

Features of minimal change disease

Answer 20

• commonest cause of childhood nephrotic syndrome
• good prognosis, curable with steroids
• EM: fusion of foot processes & occasionally detachment from BM, effacement of podocyte foot processes

Question 21

Features of focal segmental glomerulosclerosis

Answer 21

• presents as nephrotic syndrome, steroid resistant
• may progress to chronic renal failure
• LM: some glomeruli show segmental sclerosis, perihilar & tip variants
• IF: sclerotic lesions stain with IgM & C3

Question 22

Features of membranous glomerulonephritis

Answer 22

• most common cause of nephrotic syndrome in adults
• LM: BM thickening, fuchsinophilic spikes seen on MT stain, spikes w silver stain due to protrusion of growth of GBM between sub epithelial deposits
• IF: IgG & C3 on epi-membranous side of BM - spikes/string of pearl appearance

Question 23

Features of post-infectious glomerulonephritis

Answer 23

• classically follows strep pharyngitis
• presents as nephritic syndrome
• almost always resolves, small minority develop RPGN, rarely progresses to chronic renal failure
• LM: diffuse proliferative changes
• IF: granular IgG & C3
• EM: subepithelial humps of large electron dense deposits

Question 24

Features of rapidly progressive glomerulonephritis

Answer 24

• req immunosuppressive treatment, otherwise will progress to renal failure
• IF-positive - usually severe immune complex proliferative GN
• IF-negative - due to systemic vasculitis

Question 25

Features of goodpasture's syndrome

Answer 25

- antiglomerular BM disease - autoantibodies bind to GBM & cause destruction - presents as RPGN, often assoc w pulm hemorrhage as alveolar BM is attacked too - LM: crescents - IF: linear IF for IgG

Question 26

Features of membranoproliferative glomerulonephritis

Answer 26

- can present as nephrotic or nephritic - LM: proliferative changes involving mesangium + thickening of BM - Type 1: subendothelial deposits (EM), IgG & C3 (IF), double contour appearance (mesangial cell grows into capillary loop), immune complex mediated w activation of classical & alternative complement pathways, associated w chronic antigenemia - Type 2: diagnosed by EM, dense deposits in BM, activation of alternative pathway

Question 27

Features of IgA nephropathy

Answer 27

- microscopic proteinuria + hematuria - clinical course waxes & wanes, assoc w URTI - LM: focal mesangial proliferation - IF: IgA in mesangium - EM: mesangial dense deposits of immune complexes

Question 28

Features of lupus nephritis

Answer 28

- 70% of SLE patients will develop renal disease - LM: aggressive forms - proliferative changes, may have crescents - IF: IgG, IgA, IgM, C1q, C3

Question 29

Features of amyloidosis

Answer 29

- proteinuria - amyloid deposits in the glomeruli, interstitium, blood vessel walls - LM: extracellular accumulation of fibrillary proteins which show positive staining w Congo red, apple green birefringence under polarised light examination

Question 30

Features of hypertensive nephrosclerosis

Answer 30

- proteinuria and/or impaired renal function - arterioles show hyalinosis +/- muscular thickening - arteries show arteriosclerosis

Question 31

Features of diabetic nephropathy

Answer 31

- proteinuria, may result in chronic renal failure/ESRD - predisposes to pyelonephritis - glomeruli: GBM thickening (EM), mesangial widening which becomes nodular as the disease progresses, hyalinosis lesions, microaneurysms of glomerular capillary loops, glomerular sclerosis - tubules: thickened BM, tubular atrophy - interstitium: interstitial fibrosis - vessels: arteriolar hyalinosis, arteriosclerosis