Renal Pathology

Urinary Tract Obstruction

• Obstruction increases susceptibility to infection and stone formation
• Unrelieved obstruction leads to renal atrophy
• Hydronephrosis = dilation of renal pelvis and calyces associated with atrophy of kidney due to obstruction
• Causes:
  • Congenital = posterior urethral valves, urethral strictures, meatal stenosis, BOO, severe vesico-ureteral reflux, ureteropelvic junction narrowing
  • Urinary calculi
  • BPH
  • Tumours
  • Inflammation = prostatitis, urethritis
  • Sloughed papillae and blood clots
  • Pregnancy
  • Uterine prolapse and cystocele
  • Functional = neurogenic bladder

Urolithiasis

• Four main types of calculi
  • Calcium oxalate and phosphate 70% (radio-opaque)
    • Idiopathic hypercalciuria
    • Hypercalcaemia due to hyperparathyroidism, bone disease, sarcoidosis
    • Hyperoxaluria
  • Magnesium ammonium phosphate (struvite) 15-20% (radio-opaque)
    • Post infection by Proteus/ staphylococci that convert urea to ammonia. Alkaline urine causes precipitation of salts
    • Large “staghorn” calculi
  • Uric acid 5-10% (radiolucent on XR but visible on CT KUB)
    • Hyperuricaemia such as gout, leukaemia
  • Cystine 1-2%
    • Genetic defects in renal absorption of amino acids
• Morphology: unilateral 80% patients, in renal calyces, pelvis or bladder
• Clinical features: asymptomatic, haematuria, pain, obstruction

Acute kidney injury

Acute diminution of renal function often with morphologic evidence of tubular injury

Reversible

Causes:

• Ischaemia due to decreased or interrupted blood flow
  • Microscopic polyangiitis
  • Malignant HTN
  • Decreased effective circulating blood volume
  • Thrombosis in setting of disseminated intravascular coagulation (DIC, haemolytic uraemic syndrome (HUS) or thrombotic thrombocytopaenic purpura (TTP)
• Direct toxic injury to tubules
  • Drugs
  • Radiocontrast dye
  • Myoglobin, haemoglobin
  • Radiation
• Acute tubulointerstitial nephritis
  • Hypersensitivity to drugs
• Urinary obstruction
  • Tumours
  • Prostatic hypertrophy
  • Blood clots

Types:

Ischaemic AKI

= Arises due to period of inadequate blood flow to peripheral organs, accompanied by marked hypotension and shock

Nephrotoxic AKI

= Caused by drugs such as gentamicin, radiocontrast, poisons and heavy metals

Combination of ischaemic and nephrotoxic = mismatched blood transfusions, myoglobinuria or haemoglobinuria, result in characteristic intratubular casts

Pathogenesis:

1. Tubule cell injury
2. Structural changes of reversible injury = cellular swelling, loss of brush border, blebbing and cell detachment (causing luminal obstruction)
3. Depletion of ATP, increased in intracellular calcium, activation of proteases causing cytoskeletal disruption
4. Loss of cell polarity -> abnormal ion transport across cell -> increased sodium delivery to distal tubule-> vasoconstriction via tubuloglomerular feedback mechanism
5. Disturbance in blood flow
6. Intrarenal vasoconstriction resulting in reduced glomerular blood flow and reduced oxygen delivery to outer medulla
7. Activation of renin-angiotensin-aldosterone system

Morphology:

Ischaemic AKI

• Focal tubular epithelial necrosis at multiple points along nephron, with large skip areas in between
• Rupture of basement membrane
• Occlusion of tubular lumen by casts
• Interstitial oedema
• Leukocytes within dilated vasa recta

Nephrotoxic AKI

• Marked in PCT
• Tubular necrosis may be non specific
• Distinctive patterns with certain agents

Clinical course: 3 stages

1. Initiation
2. Lasts 36 hours
3. Slight decline in urine output, rise in BUN
4. Maintenance
5. Sustained decreases in urine output between 40-400 mL/day, salt and water overload, rising BUN concentrations, hyperkalaemia, metabolic acidosis, uraemia
6. Recovery
7. Steady increase in urine volume up to 3L/day
8. Large amount of sodium, potassium, water are lost in flood of urine
9. Hypokalaemia
10. BUN and creatinine levels begin to return to normal
11. Prognosis depends on clinical setting

Tubulointerstitial nephritis

= Group of renal diseases characterised by histologic and functional alterations that involve the tubules and interstitium

Can be acute or chronic:

• Acute = rapid clinical onset, interstitial oedema, leukocytic infiltration of interstitium and tubules with focal tubular necrosis
• Chronic = infiltration of mononuclear leukocytes, interstitial fibrosis, widespread tubular atrophy

Causes:

• Infections
  • Acute bacterial pyelonephritis
    • Organisms = E coli, Proteus, Klebsiella, Enterobacter, Strep faecalis, Staphylococci
    • Two routes = haematogenous or ascending infection (from urinary tract)
    • More common in females
    • Predisposing conditions = urinary tract obstruction, instrumentation, vesico-ureteral reflux, pregnancy, pre-existing renal lesions, diabetes or immunosuppression
    • Characterised by acute suppurative inflammation, complications are papillary necrosis/ pyonephrosis/ perinephric abscess
  • Chronic pyelonephritis (including reflux nephropathy)
    • Chronic inflammation and renal scarring
  • Viral or parasitic infection
• Toxins
  • Drugs
  • Acute hypersensitivity interstitial nephritis
  • Analgesics
  • Heavy metals Lead, cadmium
• Metabolic diseases
  • Urate nephropathy
  • Nephrocalcinosis
  • Acute phosphate nephropathy
  • Hypokalaemic nephropathy
  • Oxalate nephropathy
• Physical factors
  • Chronic urinary tract obstruction
• Neoplasms
  • Multiple myeloma
• Immunologic
  • Transplant rejection
  • Sjogren syndrome
  • Sarcoidosis
• Vascular Diseases
• Miscellaneous
  • Idiopathic
  • Balkan nephropathy
  • Medullary cystic disease complex

Last Updated on August 25, 2021 by Andrew Crofton