Effect of kidney function on drug concentrations of first-line anti-tubercular treatment.

BACKGROUND: Tuberculosis (TB) and chronic kidney disease (CKD) are interconnected global health concerns. CKD patients have a higher risk of developing TB. Decreased clearance of drugs in kidney disease enhances toxicity risk. Current guidance on medication doses is not based on therapeutic drug monitoring. We measured and compared the concentrations of first-line anti-TB drugs in CKD and those with normal kidney function. METHODS: A prospective observational study was conducted from September 2020 to December 2023. Patients with microbiologically confirmed tuberculosis were included, and drug concentrations were determined by using Liquid Chromatography-Tandem Mass Spectrometer (LC-MS/MS) and compared between CKD and those with normal kidney function. RESULTS: Of 151 participants, 51 had CKD. Higher trough concentrations were found in CKD for isoniazid [697.15 ng/mL (IQR 199.07-3321.68) vs. 187.58 ng/mL (IQR 95.56-323.65), P < 0.0001], rifampicin [141.53 ng/mL (IQR 40.86-730.66) vs. 33.24 ng/mL (IQR 22.49-86.20), P < 0.0001], and ethambutol [635.67 ng/mL (IQR 264.38-1594.12) vs. 230.92 ng/mL (IQR 161.95-417.22), P < 0.0001], while pyrazinamide level [1469.79 ng/mL (IQR 0.00-5160.53) vs. 4273.94 ng/mL (IQR 2151.29-8023.81), P = 0.002] was higher in those with normal kidney function. At 2-hours, a greater number of CKD patients had below the reference threshold for rifampicin [33/51 (64.7%) vs. 48/100 (48%), P = 0.059] and pyrazinamide [39/40 (97.5%) vs. 29/91 (31.8%), P < 0.0001]. CONCLUSION: CKD affects anti-tubercular drug concentrations, highlighting the need for therapeutic drug monitoring. CLINICAL TRIAL REGISTRATION NUMBER: CTRI/2020/09/027951.