Acute kidney injury

• functions of the kidney include:

  • salt and water balance
  • potassium excretion
  • acid-base balance
  • vitamin D metabolism
  • EPO production
• normal renal structure:

  • glomeruli - filtering units
  • tubules - reabsorption tubes
  • interstitial - comprised of microvascular capillaries that
• definition of AKI:

  • increase in serum creatinine by >26.5 µmols/l in 48 hours or,
  • increase in serum creatinine by >1.5x baseline creatinine within last 7 days or
  • urine volume <0.5ml/kg/hr for 6 hours
• AKI staging:

  • AKIN 1 - increased serum creatinine > 26.5 µmol/l in 48 hrs or increased serum creatinine > 1.5 - 1.9 fold over baseline
  • AKIN 2 - increases serum creatinine > 2 - 2.9 fold over baseline
  • AKIN 3 - increased serum creatinine >3 fold over baseline or increased serum creatinine >394 µmol/l or started on dialysis
• severe AKI is independently associated with adverse renal outcomes:

  • increased incidence of chronic kidney disease
  • increased incidence of end-stage renal disease
• all patients with significant acute kidney injury must have an ultrasound scan to exclude or demonstrate obstruction to the renal tract
• renal causes of AKI can be split into:

  • tubulointerstitial (tubules and the bit ‘in between’)
  • glomerular
  • vascular
• tubulointerstitial causes of AKI:

  • acute allergic interstitial nephritis
  • drug-related (e.g., PPI’s omeprazole, antibiotics, diuretics, NSAID’s)
  • may have an eosinophilia (infiltration of kidneys by eosinophils, may respond to steroids)
  • often respond well to steroids
• glomerular causes of AKI:

  • rapidly progressive glomerulonephritis (RPGN): immune aetiology and characterised by ‘glomerular crescents’
  • mass of inflammatory cells in the Bowman’s space
• examples of causes of cresentic rapidly progressive glomerulonephritis:

  • Goodpasture’s syndrome: anti-GBM antibody (targets collagen in GMB)
  • Wegener’s granulomatosis: PR3 antibody (perinuclear pattern, myeloperoxidase
  • Microscopic polyarteritis (MPA): MPO antibody (cytoplasmic pattern, proteinase-3)
  • SLE: anti-nuclear antibody(ANA), anti-dsDNA antibody
• vascular causes of AKI:

  • haemolytic uraemia syndrome (HUS) (leads to glomerular microvascular thrombosis)
  • E coli related (E coli O157)
  • familial cases (genetic aetiology)
• acute tubular injury (ATI) is the commonest causes of AKI in hospitals
• ATI can be caused by:

  • tubular toxin (e.g., gentamicin, cisplatinum, NSAID’s radio-contrast dye)
  • sever prolonged hypotension (sepsis, MI)
  • renal hypoperfusion e.g., elderly patient on ACEI, diuretic who has D&V
• ATI causes initial oliguria (low urine output) then may exhibit polyureic recovery phase (watch electrolysis)
• ischaemia is a very important part of the aetiology of patients who have acute kidney injury, nephron is partially hypoxic (medullary area) and thus is very susceptible to ischaemia
• pathogenesis of AKI:

  • ischaemia insult (haemodynamic injury leading to decreased filtration pressure)
  • systemic inflammation
  • sepsis
• differential diagnosis of AKI can be split into pre-renal, renal, and post-renal
• pre-renal differential diagnosis of AKI include:

  • reduced renal or ‘effective’ blood volume
  • hypovolaemic (e.g., bleeding, 3rd space fluid losses, over-enthusiastic diuretic therapy)
  • hypotension e.g., septic/cardiogenic shock, liver failure
  • reduced renal blood supply secondary to severe renovascular disease (± ACEI), dissection of the abdominal aorta etc.
• renal differential diagnosis of AKI include issues with glomerulus, tubules and interstitial
• post-renal differential diagnosis of AKI include obstruction at multiple levels (e.g., ureter, bladder etc.)
• post-renal differential diagnosis of AKI can be caused by:

  • prostate- hypertrophy (common), cancer
  • bladder lesions - tumour
  • ureter - calculi, tumour, extrinsic compression (retroperitoneal fibrosis, tumour)
  • myeloma kidney- internal obstruction of the lumen of the nephron, para protein precipitates in the nephron creating a myeloma cast
• bilateral obstruction or obstruction of a single kidney transplant is required is order to result in AKI
• clinical history in AKI:

  • renal history- pre-existing renal disease, diabetes, famiy history
  • urine volume- acute oliguria
  • drug history- new drugs, nephrotic drugs (NSAID’s, ACEI, antibiotics)
  • systemic symptoms- diarrhoea, rashes, etc.
• clinical examination in AKI:

  • fluid status (JVP, postural BP) dehydration?
  • evidence of infection?
  • rash, joint pathology?
  • arterial burits? underlying reno-vascular disease
  • palpable bladder (obstruction)
  • check drug chart
• investigations in AKI

  • urine dipstick - simple but important (blood protein)
  • urine culture
  • renal ultrasound - if obstructed then decompress
  • renal biopsy (AKI and normal sized kidney)
  • angiography ± intervention
  • blood tests
  • immunological tests
  • other tests
• blood tests for AKI investigation include:

  • FBC, blood film, clotting screen
  • biochemistry including calcium, phosphate, LFT’s and albumin
  • creatinine kinase (rhabdomyolysis)
  • blood cultures
  • virology and serology (e.g., Hep B, ASOT)
• immunological tests for AKI include:

  • IgG’s and serum electrophoresis (myeloma)
  • complement levels (SLE, post strep GN)
  • autoantibodies
• autoantibodies to check for AKI:

  • anti-nuclear factor (ANA) - SLE
  • anti-neutrophil antibody (ANCA) - vasculitis
  • anti-GBM antibody - Goodpasture’s syndrome
• other tests to do for AKI:

  • urine: Bence Jones protein = light chains (myeloma)
  • chest X-ray (cardiac size, pulmonary oedema or haemorrhage)
  • ECG especially if hyperkalaemia
• general treatment for AKI:

  • optimise fluid balance and circulation
  • stop exacerbating factors (e.g., nephrotoxic drugs- check drug chart)
  • appropriate prescribing (check BNF, discuss with pharmacist) e.g., opiates accumulate in AKI
  • supportive treatment (e.g., dialysis, nutrition)
• specific treatment of AKI:

  • obstruction - drain renal tract
  • sepsis - effective antibiotics
  • RPGN (e.g., SLE) - immunosuppression
  • Goodpasture’s syndrome - plasma exchange
  • compartment syndrome - fasciotomy
• criteria of initiating haemodialysis:

  • severe ‘uraemia’ (no prospect of immediate improvement/uraemia encephalopathy or seizures/uraemic pericarditis)
  • hyperkalaemia unresponsive to medical treatment (>6.5)
  • fluid overload, especially pulmonary oedema, resistant to treatment with diuretics/fluid restriction
  • severe acidosis (results in myocardial depression and hypotension
• haemodialysis (long-term dialysis) for AKI can cause vascular access related complications (pneumothorax, infection, bleeding)
• for haemodialysis anticoagulation may be required which could be problematic in patients with bleeding, and hypotension may be troublesome in some patients (sepsis, IHD, diabetes)