What is the recommended anti-tuberculous treatment regimen for a patient with Acute Kidney Injury (AKI)?

Anti-Tuberculous Treatment in Acute Kidney Injury

In patients with AKI, immediately discontinue rifampicin if it is the suspected cause of AKI, substitute with levofloxacin, continue isoniazid, pyrazinamide (with dose adjustment), and ethambutol (with dose adjustment), and consider short-term corticosteroids if acute interstitial nephritis is confirmed or strongly suspected. 1, 2

Immediate Assessment and Drug Discontinuation

When AKI develops during anti-TB treatment, rifampicin is the leading cause in 80-100% of cases, typically presenting 21-54 days after treatment initiation with acute interstitial nephritis, crescentic glomerulonephritis, or acute tubular necrosis. 1, 3

• Stop all anti-TB drugs immediately when AKI is detected, as this is the most critical first step—restarting rifampicin after AKI has resulted in death from severe renal failure in documented cases. 1
• Monitor serum creatinine every 12-24 hours during the acute phase, as creatinine typically peaks at 3.0-5.1 mg/dL from baseline of 0.5-1.4 mg/dL. 1, 4
• Obtain renal biopsy if clinically feasible to confirm acute interstitial nephritis, as pathological confirmation guides corticosteroid use. 1, 2

Corticosteroid Administration

• Administer corticosteroids in all pathologically confirmed acute interstitial nephritis cases (100% received steroids in the largest case series). 1
• Consider corticosteroids in clinically diagnosed AIN even without biopsy confirmation (42.8% received steroids with good outcomes). 1
• Use oral prednisolone at standard immunosuppressive doses until renal function stabilizes, then taper. 5

Modified Anti-TB Regimen After AKI

Replace rifampicin with levofloxacin as the cornerstone of the modified regimen, as this substitution achieved renal function normalization in 80% of patients and allows continuation of effective TB treatment. 1, 2

Specific Drug Dosing in AKI:

• Levofloxacin: Use standard dose (750-1000 mg daily) as rifampicin replacement—this drug is both safe and potent in AKI. 1, 2
• Isoniazid: Continue at standard dose (5 mg/kg daily, maximum 300 mg) with prophylactic pyridoxine 10 mg/day, as isoniazid rarely causes AKI and does not require dose adjustment. 6, 7
• Pyrazinamide: Reduce dosing frequency to 25-35 mg/kg three times weekly (not daily) in patients with creatinine clearance <30 mL/min, as pyrazinamide can accumulate and cause hyperuricemia. 6, 7
• Ethambutol: Reduce to 15-25 mg/kg three times weekly (not daily) in renal impairment, as ethambutol accumulation causes optic neuritis—give dose 8 hours before hemodialysis if on dialysis. 6, 7
• Streptomycin: If aminoglycoside is absolutely necessary, reduce frequency to 12-15 mg/kg two to three times weekly (maintaining the mg/kg dose but reducing frequency), give after dialysis, and monitor serum drug concentrations—however, aminoglycosides increase AKI odds by 53% and should be avoided. 6, 4

Concurrent AKI Management

While modifying the TB regimen, simultaneously address the AKI itself:

• Discontinue all nephrotoxic medications immediately: NSAIDs, ACE inhibitors, ARBs, diuretics, and contrast media—the "triple whammy" combination is particularly dangerous. 4
• Provide isotonic crystalloid resuscitation (preferably lactated Ringer's over 0.9% saline) targeting mean arterial pressure ≥65 mmHg if volume depleted. 4
• Avoid furosemide in hemodynamically unstable patients, as it worsens volume depletion and reduces renal perfusion. 4
• Consider renal replacement therapy only for refractory hyperkalemia, severe acidosis, or life-threatening fluid overload—not for creatinine elevation alone. 6, 4

Critical Monitoring During Modified Therapy

• Measure serum creatinine every 2-4 days during hospitalization and every 2-4 weeks for the first 6 months after discharge. 4
• Monitor for proteinuria monthly, as all rifampicin-induced AKI cases presented with proteinuria. 2
• Perform baseline and monthly audiograms if using streptomycin, as ototoxicity risk increases with renal impairment. 6
• Check uric acid levels if continuing pyrazinamide, as reduced renal excretion can precipitate acute gout. 3

Common Pitfalls to Avoid

• Never restart rifampicin after rifampicin-induced AKI—two patients died from severe renal failure after rifampicin rechallenge in the largest case series. 1
• Do not use eGFR equations (MDRD, CKD-EPI) to assess renal function in AKI—these require steady-state creatinine and are inaccurate in acute settings; use actual creatinine trends instead. 4
• Do not delay steroid administration while waiting for biopsy if clinical presentation strongly suggests acute interstitial nephritis (fever, rash, eosinophilia, sterile pyuria). 1
• Avoid combining multiple nephrotoxic agents, as each additional nephrotoxin increases AKI odds by 53%, and combinations more than double the risk. 4

Special Populations

In cirrhotic patients with AKI during TB treatment:

• Discontinue both diuretics AND beta-blockers (not just diuretics). 4
• Administer IV albumin 1 g/kg bodyweight (maximum 100g) for two consecutive days to differentiate prerenal AKI from hepatorenal syndrome. 4
• Monitor closely for fluid overload, as albumin administration carries risk of pulmonary edema. 6

Treatment Duration

Continue the modified rifampicin-free regimen (levofloxacin + isoniazid + pyrazinamide + ethambutol) for extended duration—typically 12-18 months total instead of the standard 6 months, as fluoroquinolone-based regimens without rifampicin require longer treatment to prevent relapse. 7