Can anti-tuberculosis (TB) therapy and steroids be given simultaneously in a patient with Acute Kidney Injury (AKI)?

Can Anti-TB Therapy and Steroids Be Given Simultaneously in AKI?

Yes, anti-tuberculosis therapy and steroids can and should be given simultaneously in patients with AKI, with specific modifications to the TB regimen—most importantly, rifampicin should be discontinued or avoided as it is the primary nephrotoxic culprit, while steroids are indicated for managing drug-induced acute interstitial nephritis and can facilitate renal recovery. 1, 2

Understanding TB Drug-Induced AKI

The incidence of AKI during anti-TB treatment ranges from 1-10% in prospective studies, which is higher than previously recognized. 1, 3 Rifampicin is the leading cause of AKI among first-line TB drugs, typically manifesting as acute interstitial nephritis (AIN) with a median onset of 45 days after treatment initiation. 1, 4

Key Clinical Features of TB Drug-Induced AKI:

• Rifampicin-induced AIN presents with fever, chills, and proteinuria in most cases 1, 4
• Peak serum creatinine typically reaches 4.0 mg/dL (range 3.08-5.12 mg/dL) 1
• Risk factors include older age, higher baseline eGFR, and blood eosinophil count >350 (10⁹/L) 3
• AKI can occur at both initial administration and readministration of rifampicin 4

Management Algorithm for Simultaneous TB Treatment and AKI

Step 1: Immediate Drug Modification

Stop all anti-TB drugs immediately when AKI develops, then restart a modified regimen without rifampicin. 1 This approach achieved renal function normalization in 80% of patients and allowed completion of TB treatment. 1

Step 2: Steroid Administration

Administer corticosteroids for confirmed or clinically suspected acute interstitial nephritis. 1, 2 In case series, steroids were given to 100% of pathologically confirmed AIN cases and 42.8% of clinically diagnosed cases, with successful outcomes. 1

The FDA label for prednisolone explicitly states: "The use of prednisolone in active tuberculosis should be restricted to those cases of fulminating or disseminated tuberculosis in which the corticosteroid is used for the management of the disease in conjunction with an appropriate antituberculous regimen." 5 This confirms steroids and TB drugs can be given together when medically indicated.

Step 3: Modified TB Regimen

Replace rifampicin with levofloxacin as the alternative backbone drug. 1, 4 The modified regimen typically includes:

• Isoniazid (continue if not causative)
• Pyrazinamide (adjust dosing interval to three times weekly in severe AKI) 6
• Ethambutol (adjust to three times weekly dosing in creatinine clearance <30 mL/min) 6
• Levofloxacin (as rifampicin substitute, with dose adjustment for renal function) 1, 4

Step 4: Dose Adjustments for Renal Impairment

For patients with creatinine clearance <30 mL/min or on hemodialysis: 6

• Isoniazid: 300 mg once daily or 900 mg three times weekly (no change needed)
• Rifampicin: Avoid due to nephrotoxicity risk in AKI context
• Pyrazinamide and Ethambutol: Increase dosing interval to three times weekly rather than reducing dose
• Levofloxacin: Requires dose adjustment based on creatinine clearance 6

Critical Considerations and Pitfalls

Nephrotoxin Management Principles

The KDIGO guidelines emphasize that potentially nephrotoxic agents should not be withheld in life-threatening conditions (such as active TB), but kidney function must be monitored regularly. 6, 7 However, when AKI develops, the decision to discontinue a nephrotoxin should be made when evaluation indicates it is the potential cause. 6

Avoiding Fatal Errors

Do not restart rifampicin after AKI develops. Two patients in one case series died from severe renal failure after rifampicin was restarted. 1 This represents a critical pitfall to avoid.

Steroid Safety in TB Context

While steroids suppress immune function and can reactivate latent TB, the FDA label specifically permits their use in active TB when combined with appropriate anti-TB treatment. 5 Close observation is necessary, but the combination is not contraindicated. 5

Monitoring Requirements

Regular monitoring of kidney function is essential during the entire treatment course. 6, 7 The ADQI consensus recommends that drug selection and monitoring should be guided by the functional phase, trajectory, and stage of AKD. 6

Renal Recovery Outcomes

The prognosis for renal recovery is generally favorable when rifampicin is discontinued and steroids are administered: 1, 2

• 80% of patients achieved normalized renal function 1
• All patients in prospective monitoring achieved renal recovery and completed TB treatment 3
• Complete remission occurred after cessation of the offending drug with steroid therapy 2

The key to successful management is early recognition, immediate discontinuation of rifampicin, steroid administration for AIN, and continuation of TB treatment with a modified regimen using levofloxacin as the rifampicin substitute. 1, 4