Acute Kidney Injury

Definitions

• KDIGO AKI workgroup defined AKI as any of the following:
  • ↑ Cr by 26.5 µmol/L
  • ↑ Cr to ≥ 1.5 x baseline
  • Urine output < 0.5 mL/kg/h for 6 hours
• KDIGO AKI Stages
  • Stage I AKI
    • Cr 1.5-1.9 times baseline over 7 days
    • Cr increase >26.4 µmol/L over 48 hours
    • Urine output <0.5 ml/kg/hr for 6-12 hours
  • Stage II AKI
    • Cr 2-2.9 times baseline
    • Urine output <0.5 ml/kg/hr for 12-24 hours
  • Stage III AKI 
    • Cr >3 times baseline
    • Cr >354 µmol/L
    • Initiation of renal replacement therapy
    • Urine output <0.3 ml/kg/hr for >24 hours
    • Anuria >12 hours
• Other classifications exist (see Deranged Physiology: A comparison of classification systems for acute kidney injury)

Risk Factors

• Age >65
• Infection on admission
• Heart failure
• Cirrhosis
• Respiratory failure
• Haematological malignancy
• Post cardiac arrest
• Pre-existing renal failure

Prevention

• Maintain a Hb > 70
• Ensure intravascular volume is adequate
  • Avoid chloride-rich fluids
  • Avoid using hydroxyethyl starch
• Achieve satisfactory haemodynamic parameters (e.g. MAP > 70 mmHg)
  • In chronically hypertensive septic patients, aim for a higher MAP (eg. 75-80mmg)

Aetiologies

• Medications:
  • Cardiovascular
    • Direct:
      • ACEi & ARBs
    • Indirect:
      • For patients with borderline cardiac output, medications that reduce cardiac output may be nephrotoxic (e.g., beta-blockers, diltiazem).
      • For patients with borderline hypotension, antihypertensives may be nephrotoxic.
  • Antibiotics
    • Aminoglycosides
    • Trimethoprim-Sulfamethoxazole (and other sulfonamides).
    • Vancomycin
    • Beta-lactams rarely cause interstitial nephritis (especially penicillins such as nafcillin, piperacillin, and ampicillin).
  • Antifungals
    • Amphotericin*
  • Antivirals (not exhaustive)
    • Acyclovir, ganciclovir, valacyclovir, valganciclovir (crystal deposition).
    • Indinavir.
    • Tenofovir
  • Chemotherapy
  • Miscellaneous
    • Antiepileptics (topiramate, zonisamide).
    • Bisphosphonates (pamidronate, zoledronic acid).
    • Immunosuppressives:
      • Calcineurin inhibitors (cyclosporine, tacrolimus).
      • mTOR inhibitors (sirolimus, everolimus).
    • Inflammatory bowel disease medications (mesalamine, sulfasalazine).
    • Intravenous immunoglobulin (IVIG).
    • Mannitol
    • NSAIDs

Distinguishing Pre/Intra/Post Renal Failure

	Intra-renal	Pre-renal
Urine osmolality	<400-450 mOsm/kg	>450-500 mOsm/kg
Urine sodium	High (>40 meq/L)	Low (<20 meq/L)
Urea:Cr (mmol:µmol)	<0.04	>0.1
Urine/serum creatinine ratio	>40	<20
Urine/serum osmolality	>1.0	>1.5
Fractional excretion of urea	>25%	<25%
Fractional excretion of sodium1	>2%	<1%
Urine microscopy	Muddy brown granular casts, epithelial casts, epithelial cells	Nothing, hyaline casts

$$\text{Fractional Excretion of }\mathrm{Na}{}^{+}=\left(\frac{\text{Urinary Sodium}}{\text{Serum Sodium}}\right)/\left(\frac{\text{Urinary Creatinine}}{\text{Serum Creatinine}}\right)\times 100$$

Diagnostic Approach

• Labs
  • EUCs
  • CK
  • Urinalysis and sediment analysis
• Additional labs to consider
  • Relevant drug levels (e.g. vancomycin, aminoglycoside, cyclosporine, tacrolimus levels)
  • Uric acid level
  • Plasma-free haemoglobin
  • Urine albumin/creatinine ratio
• Evaluate for post-renal causes
  • POCUS of kidneyes and bladder
  • Flushing or changing IDC
• If oliguric, treat and assess for renal hypoperfusion:
  • History review (e.g. diuresis, fluid balance)
  • Perfusion evaluation (e.g. relative hypoperfusion, shock index, fluid responsiveness, Rush Exam)
  • Resolve renal hypoperfusion:
    • Volume excess + congestive nephropathy → diurese
    • Volume depletion → fluid
    • Cardiogenic shock → trial inotrope or inopressor
    • Hypotension → trial noradrenaline
  • If evaluation doesn’t suggest hypoperfusion or failure to improve urine output consider a furosemide stress test where adequate urine production following a furosemide stress tests suggests pre-renal aetiology and inadequate urine production suggests intrinsic renal failure
• If non-oliguric evaluate for intrinsic renal failure

Furosemide Stress Test

• Administration of a defined dose of furosemide:
  • 1 mg/kg for patients who are furosemide naive.
  • 1.5 mg/kg for patients with prior exposure to furosemide.
• Monitoring urine output

  • More than 200 ml within two hours indicates adequate response.

Management

• Treat the underlying cause as per diagnostic approach (above)
• Discontinue nephrotoxins and dose-adjust renally cleared medications
• Optimise haemodynamics
  • Discontinue anti-hypertensives and negative inotropes
  • Optimise vasopressors (MAP > 65 mmHg and MAP > 80 mmHg in patients with chronic hypertension or hepatorenal physiology)
  • Consider a vasopressor challenge
• Fluids management
  • Fluid is beneficial under the following circumstances:
    • Pre-renal AKI
    • Patient is fluid responsive
    • Patient is hypovolaemic
  • Hypovolaemia + uraemic acidosis give isotonic bicarbonate (5% dextrose with 150 mEq/L sodium bicarbonate)
  • Hypovolaemia + normal bicarbonate give a balancved crystalloid (e.g. hartmann’s or plasmalyte); avoid normal saline
• Potassium management
  • Replace potassium conservatively targeting $\mathrm{K}{}^{+}$ > 3.5 mmol
  • Renal diet to reduce potassium intake
  • Treat hyperkalaemia if present
• Acid-Base support
  • Providing bicarbonate for uraemic acidosis aiming for a pH > 7.2
  • Can be given as:
    • Isotonic bicarbonate (glucose 5% with 150 mEq/L $\mathrm{NaHCO}{}_3$) in patients who are hypovolaemic
    • Hypertonic bicarbonate ampules (50 mL ampules of 1 mEq/mL bicarbonate) in patients who are hyponatraemic
    • Oral bicarbonate tablets
• Phosphate binding
  • If phosphate > 1.94 mmol/L treat with calcium acetate (in hypocalcaemic patients) or sevelamer
• Haemodialysis
  • Indicated for patients with
    • Acidosis refractory to IV bicarbonate
    • Diuresis-refractory electrolyte abnormalities (e.g. hyperkalaemia)
    • Fluid overload refractory to diuretics
    • Symptoms of uraemia (e.g. delirium, asterixis, pericardial effusion)

Hepatorenal Syndrome

• Clinical presentation:
  • Typically in advanced cirrhosis with ascites but also in acute liver failure or alcoholic hepatitis especially those with chronic hypotension and hyponatraemia (i.e. borderline perfusion due to vasodilation)
  • A precipitating factor may be present such as a haemodynamic stressor (e.g. infection, volume depletion or overload) or deterioration in liver function (e.g. acute on chronic liver failure)
  • Presentation is one with oliguria and bland urine sediment findings (i.e. no evidence of glomerulonephritis or tubular necrosis)
• In addition to the above management options consider:
  • Albumin
  • Vasopressors (noradrenaline remains first line)
    • Aim MAP > 15 mmHg above baseline
  • Therapeutic large volume paracentesis

NOTE

• Importantly, these patients have low muscle mass and enhanced renal creatinine secretion leading to artificially low creatinine values; therefore:
  • Creatinine level tends to over-estimate renal function
  • Small changes in creatinine may be significant and meet AKI criteria

Source

• Acute Kidney Injury (including HRS-AKI) - EMCrit Project
• Acute Kidney Injury • LITFL • CCC Renal
• Deranged Physiology:
  • Biochemical indices in diagnosis of pre-renal failure
  • Uraemia; its causes and consequences

Footnotes

1. IBCC says that fractional excretion of sodium performs poorly in differentiating pre-renal and intrinsic renal failure ↩