Rifampin-induced Acute Kidney Injury Is Associated With Hemolysis and Drug Re-exposure

Rationale & objective Acute kidney injury and hemolysis are rare side effects of rifampin that are sometimes linked with drug re-exposure. We studied this association in a contemporary patient cohort to comprehensively correlate the clinical, laboratory, and biopsy findings. Study design Adult patients who underwent kidney biopsy for acute kidney injury while on rifampin during an 11-year period (2012-2023) were identified. Electronic medical records and biopsy pathology were correlated. Setting & participants Eighteen patients (50% men, ages 43-81) were prescribed rifampin for active pulmonary tuberculosis (7), latent tuberculosis (3), Mycobacterium avium complex infection (4), septic arthritis (3), and Bartonella endocarditis (1). Nine patients had prior rifampin exposure. Results Patients most commonly presented with gastrointestinal and 'flu-like' symptoms, 1 day to 1 month after rifampin (re-)exposure. Creatinine at biopsy was 2.2-26.1 mg/dL. Importantly, 15 patients had evidence of hemolysis. All biopsies demonstrated acute tubular injury, yet inflammation (acute interstitial nephritis) was variable. Eleven had pigmented casts, 9 with hemoglobin and 2 with myoglobin. Thus, we highlight acute tubular necrosis with hemoglobin casts as a major finding in rifampin kidney injury. Management included supportive care, steroids, and discontinuation of rifampin. Eleven patients required hemodialysis. Fifteen patients had complete renal remission. Limitations Retrospective case series without uniformly available clinical and laboratory data. Conclusions Hemolytic anemia, hemoglobin cast nephropathy, and acute kidney injury are rare but serious complications of rifampin. Clinicians and patients should be aware of this side effect, and interrupted use of rifampin therapy should be avoided.