Management of DR-TB ADR: Nephrotoxicity [Renal Toxicity]

Adverse Drug Reactions (ADRs), such as renal toxicity, may occur from the Drug-resistant TB (DR-TB) treatment regimen.

Suspected agent(s): Amikacin (Am)

• Prior to starting the treatment, all patients will have their renal function evaluated.
• During the treatment of DR-TB, if the patient presents with symptoms and/or signs of renal impairment (oliguria, anuria, puffiness of face, pedal oedema), all the drugs should be withheld; renal function tests should be done and, if required, the opinion of a nephrologist should be sought.
• The re-introduction of drugs will be undertaken by the DR-TB centre committee in consultation with a nephrologist, along with frequent monitoring of renal parameters.

Suggested Management Strategies

• Discontinue the suspected agent.
• Consider using Capreomycin (Cm) if Aminoglycoside was the prior injectable drug in the regimen. 
• Consider other contributing etiologies (non-steroidal anti-inflammatory drugs, diabetes, other medications, dehydration, congestive heart failure, urinary obstruction, etc.) and address as indicated.
• Follow creatinine (and electrolyte) levels closely, every 1–2 weeks. 
• Consider dosing the injectable agent 2-3 times a week if the drug is essential to the regimen and the patient can tolerate it (close monitoring of creatinine). 
• If creatinine continues to rise despite twice/ thrice a week dosing, suspend the injectable agent.
• Adjust all TB medication according to creatinine clearance in consultation with a nephrologist. 
• Also, note that renal impairment may be permanent.

Points to Note

• During treatment, blood urea and serum creatinine should be done every month for the first three months after treatment initiation and then every three months thereafter whilst injection Am is being administered. Salient renal toxicity may be picked up by these routine follow-up biochemical examinations.
• If at any time, the blood urea or serum creatinine becomes abnormal, treatment should be withheld and further management is decided upon in consultation with the DR-TB centre committee. 
• History of diabetes or renal disease is not a contraindication to the use of agents listed here, although patients with these comorbidities may be at an increased risk for developing acute kidney injury.

Resources

• Guidelines for Programmatic Management of Drug-resistant Tuberculosis in India, March 2021.
• Ready Reckoner for Medical Officer - Adverse Drug Reactions Associated with Anti-TB Drugs Identification and Management, 2019.
• Technical and Operational Guidelines for TB in India, 2016.

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