What causes raised Renal Function Tests (RFT) in patients undergoing Anti-Tuberculosis Treatment (ATT)?

Causes of Raised Renal Function Tests in Anti-Tuberculosis Treatment

Nephrotoxicity from anti-tuberculosis drugs is a significant cause of raised renal function tests (RFT) in patients undergoing anti-tuberculosis treatment (ATT), with aminoglycosides like streptomycin, amikacin, and kanamycin being the primary culprits. 1

Primary Causes of Renal Impairment During ATT

1. Drug-Induced Nephrotoxicity

Aminoglycoside Antibiotics

• Streptomycin: Causes nephrotoxicity in about 2% of patients requiring discontinuation 1
• Amikacin/Kanamycin: More nephrotoxic than streptomycin, with renal impairment occurring in 3.4-8.7% of patients 1, 2
• Capreomycin: Significant nephrotoxicity in 20-25% of patients, manifesting as:
  • Reduced creatinine clearance
  • Potassium and magnesium depletion
  • Proteinuria 1

Risk Factors for Aminoglycoside Nephrotoxicity

• Pre-existing renal impairment
• Advanced age (>59 years)
• Larger cumulative doses
• Concurrent use of other nephrotoxic agents
• Dehydration 1, 2

2. Acute Interstitial Nephritis (AIN)

• Rifampicin: Leading cause of AKI during ATT, primarily through acute interstitial nephritis 3
• Typically occurs after 21-54 days of treatment (median 45 days) 3
• Can cause significant elevation in serum creatinine (median peak of 4.0 mg/dL) 3

3. Hyperuricemia-Related Renal Dysfunction

• Pyrazinamide and Ethambutol: Cause hyperuricemia by decreasing uric acid clearance 4
• This effect is typically reversible and peaks around 2 weeks after starting treatment
• Serum uric acid levels can increase significantly (from baseline 4.44 mg/dL to 9.78 mg/dL) 4
• Usually resolves after discontinuation of pyrazinamide 1, 4

4. Tuberculosis-Related Renal Involvement

• Miliary tuberculosis can directly affect kidney function 5
• Renal tuberculosis can cause impaired renal function that may improve with appropriate ATT 5

Monitoring and Management

Baseline Assessment

• Perform baseline renal function tests before starting ATT
• Assess for pre-existing risk factors:
  • Age >59 years
  • Diabetes mellitus
  • Hypertension
  • Pre-existing renal disease 1, 6

Ongoing Monitoring

• Monthly assessment of renal function for all patients on ATT 1, 2
• More frequent monitoring (every 1-2 weeks) for high-risk patients:
  • Those receiving aminoglycosides
  • Patients with baseline renal impairment
  • Elderly patients 1, 2

Management of ATT-Induced Renal Impairment

1. For Aminoglycoside-Induced Nephrotoxicity:

   • Dose adjustment based on creatinine clearance
   • For patients with renal insufficiency, maintain dose at 12-15 mg/kg but extend interval to 2-3 times weekly 1, 2
   • Consider drug level monitoring to avoid toxicity 1
   • Administer after dialysis in patients on hemodialysis 1, 2

2. For Rifampicin-Induced AIN:

   • Temporary discontinuation of all ATT drugs
   • Consider short-term steroid administration
   • Restart ATT without rifampicin; levofloxacin may be an alternative 3

3. For Pyrazinamide/Ethambutol-Induced Hyperuricemia:

   • Usually self-limiting and resolves after discontinuation
   • Rarely requires specific treatment for arthralgia 4

Special Considerations

Renal Transplant Patients

• Avoid rifampicin-containing regimens in post-renal transplant patients due to interaction with cyclosporin 6
• Higher risk of ATT toxicity and mortality in transplant patients 7

Patients with Pre-existing Renal Disease

• Dosages must be adjusted according to creatinine clearance, especially for:
  • Streptomycin
  • Ethambutol
  • Isoniazid 6
• In acute renal failure, ethambutol should be given 8 hours before hemodialysis 6

Hepatorenal Syndrome

• Patients with severe hepatic disease may be at greater risk for nephrotoxicity from aminoglycosides due to predisposition to hepato-renal syndrome 1
• Require close monitoring of renal function

By understanding these mechanisms and implementing appropriate monitoring and management strategies, clinicians can minimize the risk of renal impairment during anti-tuberculosis treatment and optimize outcomes for patients.