What is the next step for a patient with Acute Kidney Injury (AKI) and normalized liver enzymes after being switched to a modified Anti-Tuberculosis Treatment (ATT) regimen due to deranged liver enzymes?

Management of AKI in a Patient with Normalized Liver Enzymes After Modified Anti-TB Treatment

The next step for a patient with AKI and normalized liver enzymes after being switched to modified anti-tuberculosis treatment (ATT) is to reintroduce first-line anti-TB drugs sequentially, starting with isoniazid at low doses, followed by rifampicin, and then pyrazinamide if needed, with careful monitoring of renal function.

Assessment of Current Status

• The patient developed deranged liver enzymes on standard ATT regimen
• Was switched to a modified ATT regimen (likely containing non-hepatotoxic drugs)
• Now has normalized liver enzymes but has developed AKI
• Renal function needs to be addressed while maintaining effective TB treatment

Management Algorithm

Step 1: Address the AKI

• Identify and remove potential nephrotoxic agents from the current regimen
• Assess volume status and provide appropriate fluid management 1
• If hypovolemic: administer isotonic crystalloids (500-1000 mL initial bolus)
• If patient has cirrhosis with ascites: consider albumin 1 g/kg/day for two consecutive days 2
• Monitor renal function daily with serum creatinine, BUN, and electrolytes 1

Step 2: Reintroduce First-Line Anti-TB Drugs

Once AKI is stabilizing (no further deterioration in renal function), begin sequential reintroduction of first-line ATT drugs 2:

1. Start with isoniazid:

   • Begin at 50 mg/day
   • Increase to 300 mg/day after 2-3 days if no adverse reaction
   • Continue for 2-3 days at full dose

2. Add rifampicin (if no reaction to isoniazid):

   • Begin at 75 mg/day
   • Increase to 300 mg after 2-3 days
   • Further increase to weight-appropriate dose (450-600 mg) after another 2-3 days
   • Continue for 2-3 days at full dose

3. Add pyrazinamide (if no reaction to rifampicin):

   • Begin at 250 mg/day
   • Increase to 1.0 g after 2-3 days
   • Further increase to weight-appropriate dose (1.5-2.0 g) after another 2-3 days

Step 3: Adjust Dosing Based on Renal Function

• For patients with AKI, adjust medication dosages according to estimated GFR 2
• Drugs requiring adjustment in renal impairment include:
  • Pyrazinamide: 25-35 mg/kg/dose three times weekly (not daily)
  • Ethambutol: 20-25 mg/kg/dose three times weekly (not daily)
  • Streptomycin and other aminoglycosides: 15 mg/kg/dose 2-3 times weekly

Step 4: Monitoring During Reintroduction

• Daily monitoring of renal function (serum creatinine, BUN, electrolytes)
• Monitor liver function tests every 2-3 days during drug reintroduction
• Watch for clinical signs of drug toxicity (nausea, vomiting, abdominal pain, jaundice)
• If AKI worsens or liver enzymes become deranged again, stop the most recently added drug

Important Considerations

Risk Factors for Recurrent Hepatotoxicity

• Female gender is associated with higher risk of positive rechallenge 3
• First episode of TB treatment carries higher risk of rechallenge reactions 3
• Pyrazinamide rechallenge has the highest risk of recurrent hepatotoxicity 3

Alternative Regimens if Rechallenge Fails

If reintroduction of standard ATT is not tolerated, consider these options 2:

1. Without pyrazinamide: Isoniazid, rifampicin, and ethambutol for 2 months, followed by 7 months of isoniazid and rifampicin
2. Without isoniazid: Rifampicin, pyrazinamide, and ethambutol with or without a fluoroquinolone for at least 6 months
3. Without rifampicin: Isoniazid, ethambutol, pyrazinamide, and a fluoroquinolone for 12-18 months

Pitfalls to Avoid

• Do not reintroduce all drugs simultaneously, as this prevents identification of the offending drug
• Do not use nephrotoxic drugs (aminoglycosides) in patients with unstable renal function
• Avoid excessive fluid administration in euvolemic or hypervolemic patients 1
• Do not use diuretics to treat AKI except for managing volume overload 1
• Avoid restarting rifampicin without careful monitoring, as it has been associated with mortality in patients with previous ATT-induced AKI 4

By following this systematic approach to reintroducing anti-TB medications while monitoring renal function, you can optimize the treatment of tuberculosis while minimizing the risk of recurrent hepatotoxicity or worsening kidney injury.