L77: Diseases Of Kidneys 2

Question 1

***Tubular, Tubulointerstitial, Vascular renal disease

Answer 1

Tubular
1. Acute tubular injury (ischaemia)

Tubulointerstitial

1. Drugs
2. Pyelonephritis (infection)
3. Neoplasm (myeloma, light chain cast nephropathy)

Vascular

1. Hypertensive nephrosclerosis
2. Malignant hypertension (ACUTE renal failure)
3. Diabetic nephropathy
4. ANCA-associated vasculitis (Type III rapidly progressive glomerulonephritis)

Question 2

Diseases of renal tubules and interstitium (2 major groups)

Answer 2

1. Acute tubular injury (mostly tubular: ischaemic / toxic injury)
2. Tubulointerstital nephritis (inflammation of both tubules + interstitium)

Question 3

Acute renal failure

Answer 3

• Most common cause: Tubular injury
• acute deterioration of renal function
• Causes:
  1. Ischaemia (FAR MORE COMMON)
• Shock (pre-renal, involve blood cirulation)
• Diffuse involvement of intravenous blood vessel (malignant hypertension)
• thrombosis
  2. Direct toxic injury (nephrotoxic drug, heavy metals etc.)
  3. Tubulointerstitial nephritis
  4. Prostatic hypertrophy / tumour / blood (post-renal, involve urinary tract)

LM: dilated tubules, necrotic tubular epithelium sloughed in tubules

Question 4

Acute tubular injury

Answer 4

3 stages:

• Initiation phase (36 hours, ↓ urine, ↑ blood urea and creatinine)
• Maintenance phase (oliguria, salt and water overload, hyperkalaemia, metabolic acidosis)
• Recovery phase (steady ↑ urine, loss of large amount of water, Na, K —> may cause electrolyte imbalance) (Tubular epithelium can regenerate)

Outcome:
- most patient recover within 1-2 weeks, up to 4-6 weeks

Question 5

Tubulointerstitial nephritis

Answer 5

• Inflammatory of tubules + interstitium
• glomerulus NOT affected
• Present as acute / subacute ↓ renal function
• ↑ urea + creatinine
• 2 weeks after drugs exposure

Features:

• Interstitial inflammation (abundant eosinophil)
• Interstitial oedema (loose space in between interstitium)
• Interstitial fibrosis
• Tubulitis (lymphocyte in between tubular cells)
• NO immune complex

Causes:

• **- DRUGS (NSAIDs, hypersensitivity, withdrawal is key)
• Infections (pyelonephritis)
• Metabolic diseases (uric acid nephropathy)
• Neoplasm (myeloma, light chain cast nephropathy)
• Physical factor (UT obstruction)
• Immunologic reactions (sarcoidosis)

Question 6

Pyelonephritis

Answer 6

• Infection in kidney
• affect TUBULES, INTERSTITIUM, RENAL PELVIS
• Acute / Chronic

Acute:

• Ascending route (most common) (bladder —> ureter —> renal pelvis —> collecting duct —> proximal tubule)
• Haematogenous route

Chronic:
- Scarred kidney by repeated bacterial infections

Question 7

Acute pyelonephritis

Answer 7

• Ascending route most common
• E. coli, Proteus mirabilis, Klebsiella, Enterobacteriaceae, Mtb, Candida spp. etc
• large amount of neutrophil
• Glomerulus usually UNAFFECTED (end stop is Bowman’s capsule)
• pus / microabscess
• Renal biopsy CI

Causes:

• Lower UTI
• Urinary tract obstruction
• Vesico-ureteric reflux
• Pregnancy

Symptoms:

• High fever
• Loin pain
• Failure to thrive (children)

Treatment:
- Antibiotic (IV)

Outcome:

• symptoms disappear in a few days
• complete resolution without leaving significant effects
• neutrophils replaced by macrophage, plasma cells, lymphocytes
• scattered scar

Complications:

• Pyelonephrosis (pus in pelvic, calyces, ureter)
• Perinephric abscess (pus in perinephric tissue)

Question 8

Chronic pyelonephritis

Answer 8

• Chronic inflammation in tubules and interstitium (exclude Mtb)
• Scarred kidney by repeated infections
  —> Glomeruli: sclerosed, ↓ functional number, compensated hypertrophy, progressive fibrosis (FSGS) (glomerulus AFFECTED in LONG TERM)
  —> Fibrosis
  —> Tubular atrophy
  —> Thinning of cortex
  —> Unequal on 2 sides of kidneys

Causes:

• Vesico-ureteric reflux
• UT obstruction

Symptoms:

• Recurrent acute pyelonephritis (high fever, loin pain)
• NO symptoms in early stage
• Polyuria / Nocturia
• Uraemia —> chronic / end stage renal failure

Diagnosis:
Microscopic finding NOT useful since non-specific

Treatment:

• Underlying cause
• Antibiotic

Outcome:
- depend on scarring —> significant: end stage renal disease

Question 9

Light chain cast nephropathy

Answer 9

• Tubulointerstitial nephritis
• Multiple myeloma (plasma cell cancer)
• > 50 years old
• present as acute renal failure
• kappa, lambda light chain of antibiotics

Treatment:

• Treat plasma cell neoplasm
• Hematopoietic stem cell transplantation

Outcome:
- 20-25% 5 year survival rate (poor prognosis)

Question 10

Vascular disease of kidney

Answer 10

1. Hypertensive nephrosclerosis
2. Malignant hypertension (ACUTE renal failure)
3. Diabetic nephropathy
4. ANCA-associated vasculitis (Type III rapidly progressive glomerulonephritis)

Question 11

Hypertensive nephrosclerosis

Answer 11

• strongly associated with Hypertension
• Sclerosis of renal arterioles
  —> Hyalinization
  —> Intimal fibrosis
  —> Medial thickening (thickened walls, narrowed lumen)
  —> Ischaemia —> Glomerulosclerosis —> Chronic Tubulointerstitial injury
  —> GRADUAL decline in renal function —> end stage renal failure

Question 12

Malignant nephrosclerosis

Answer 12

• Associated with Malignant/ accelerated hypertension
• Systolic >200, Diastolic > 120
• Present as ACUTE renal failure
• Retinal haemorrhage, encephalopathy, papilloedema
  —> Fibrinoid necrosis of arteriole
  —> Hyperplastic arteriolitis (onion-skin lesion)

Treatment:
- aggressive antihypertensive

Question 13

Diabetic nephropathy

Answer 13

Type I and Type II DM

1. Hyalinization of arterioles, Arteriolosclerosis
   - Glomeruli affected:
2. Thickened GBM (deposit of ground substance)
3. Mesangial matrix increase
4. Kimmelstiel-Wilson nodules
   —> Ischaemia —> Glomerulosclerosis —> Chronic Tubulointerstitial injury
   —> GRADUAL decline in renal function —> end stage renal failure

Treatment:
- Diabetes

Question 14

ANCA-associated vasculitis

Answer 14

• Type III RPGN
• Severe glomerular injury
• Inflammation of vessels —> fibrosis of interlobular artery
• Pauci-immune (cannot be detected in IF/EM: lack of detectable anti-GBM antibody / Immune complex)
  —> differ from Goodpasture (Anti-GBM antibody: detectable)
• Circulating antineutrophil cytoplasmic antibodies (ANCA)
  —> c-ANCA (cytoplasmic)
  —> p-ANCA (perinuclear)

Disease:

• Granulomatosis with polyangiitis
• Microscopic polyangiitis

Treatment:
- Immunosupression (cyclophosphamide)