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Peer-reviewedCC BY 4.0Infection

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

  • Divya Datta1
  • Indu Ramachandra Rao1
  • Raghavendra Shetty2
  • Shankar Prasad Nagaraju1
  • Girish Thunga3
  • Rahul Magazine4
  • Shivashankara Kaniyoor Nagri5
  • Nisha Abdul Khader1
  • Pasumarthi Tejashree3
  • Surulivelrajan Mallayasamy3
  • Praveen Kumar Tirlangi6
  • Dharshan Rangaswamy1
3 more authors
  • Srinivas Vinayak Shenoy1
  • Mohan V. Bhojaraja1
  • Attur Ravindra Prabhu1
6 affiliations
  1. 1Department of Nephrology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, India
  2. 2Navitas Life Sciences Pvt. Ltd, Manipal, 576104 Karnataka India
  3. 3Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, India
  4. 4Department of Respiratory Medicine, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, India
  5. 5Department of Medicine, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, India
  6. 6Department of Infectious Disease, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, India
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Abstract

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.

Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s15010-026-02931-7.

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Cite

BibTeXRIS
BibTeX
@article{datta2026effect,
  title = {{Effect of kidney function on drug concentrations of first-line anti-tubercular treatment}},
  author = {Divya Datta and Indu Ramachandra Rao and Raghavendra Shetty and Shankar Prasad Nagaraju and Girish Thunga and Rahul Magazine and Shivashankara Kaniyoor Nagri and Nisha Abdul Khader and Pasumarthi Tejashree and Surulivelrajan Mallayasamy and Praveen Kumar Tirlangi and Dharshan Rangaswamy and Srinivas Vinayak Shenoy and Mohan V. Bhojaraja and Attur Ravindra Prabhu},
  journal = {Infection},
  year = {2026},
  month = aug,
  doi = {10.1007/s15010-026-02931-7},
  url = {https://doi.org/10.1007/s15010-026-02931-7},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Effect of kidney function on drug concentrations of first-line anti-tubercular treatment
AU  - Divya Datta
AU  - Indu Ramachandra Rao
AU  - Raghavendra Shetty
AU  - Shankar Prasad Nagaraju
AU  - Girish Thunga
AU  - Rahul Magazine
AU  - Shivashankara Kaniyoor Nagri
AU  - Nisha Abdul Khader
AU  - Pasumarthi Tejashree
AU  - Surulivelrajan Mallayasamy
AU  - Praveen Kumar Tirlangi
AU  - Dharshan Rangaswamy
AU  - Srinivas Vinayak Shenoy
AU  - Mohan V. Bhojaraja
AU  - Attur Ravindra Prabhu
PY  - 2026
DA  - 2026/08/31
JO  - Infection
DO  - 10.1007/s15010-026-02931-7
UR  - https://doi.org/10.1007/s15010-026-02931-7
AB  - 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.  Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s15010-026-02931-7.
SN  - 0300-8126
SN  - 1439-0973
ER  -