Challenges in causality assessment of renal dysfunction during sequential treatment for presumed rifampicin-resistant...

Renal impairment during treatment for rifampicin-resistant tuberculosis (RR-TB) is uncommon but clinically significant, especially in elderly patients with limited physiological reserve. Determining whether renal dysfunction is attributable to anti-tuberculosis drugs or patient-related factors remains a major clinical challenge, particularly following sequential regimen changes.

A 74-year-old man with a low body mass index (17.5 kg/m²) was treated for presumed RR-TB based on a single Xpert MTB/RIF assay showing rifampicin resistance despite persistently negative smear microscopy and mycobacterial culture. Baseline renal function was normal (serum creatinine 89 µmol/L; estimated glomerular filtration rate [eGFR] 73.2 mL/min/1.73 m²). Eighteen days after initiation of a long oral regimen (D2: levofloxacin, clofazimine, linezolid, pyrazinamide, and cycloserine), acute kidney injury developed, with serum creatinine increasing to 140 µmol/L and eGFR declining to 42.34 mL/min/1.73 m². The regimen was switched to BPaLM, during which renal function worsened with marked fluctuations (eGFR 24.65-57.3 mL/min/1.73 m²), requiring supportive care. Renal function partially improved after treatment interruption. Rechallenge with the D2 regimen was associated with relatively less fluctuation in renal function. WHO-UMC causality assessment classified the relationship between anti-tuberculosis treatment and renal dysfunction as "possible."

This case highlights the complexity of evaluating renal dysfunction during sequential treatment for RR-TB. Advanced age, low BMI, frailty, and fluctuating hydration status should be considered when interpreting changes in renal function. Careful interpretation requires integration of the clinical course and available diagnostic information rather than reliance on temporal associations alone.