Assessment of medication-related liver and kidney impairment in admitted patients in Depok, Indonesia: an observational study employing the Naranjo algorithm
DOI:
https://doi.org/10.12928/pharmaciana.v15i1.29012Keywords:
medication-related liver impairment, medication-related renal impairment, Naranjo algorithmAbstract
Liver and kidney impairment caused by medications represents serious side effects that may extend hospital stays and increase the risk of patient death. Implementing strategies to recognize, document, and analyze cases of patient harm related to drug use is crucial for medicines optimization. This study aimed to evaluate the prevalence of medication-related liver and kidney impairment among hospitalized patients, while also identifying the specific medication categories implicated. A retrospective review of patient records was conducted at Universitas Indonesia Hospital (Depok, Indonesia), focusing on adult patients diagnosed with liver or kidney impairment during their 2021 hospital admission. The Naranjo algorithm was applied to assess the likelihood that these injuries were caused by medications. Among the 4,273 admitted patients, it was found that 1.01% experienced medication-related liver impairment (MRLI), while 0.77% experienced medication-related kidney impairment (MRKI). The most common medications associated with liver impairment were antibiotics (31.58%), cardiovascular medications (24.21%), pain relievers (14.74%), anti-ulcer medications (11.58%), antiviral medications (8.42%), antiemetics (8.42%), and antidiabetic medications (1.05%). In contrast, kidney disease was primarily linked to diuretics (29.76%), antibiotics (21.43%), ACE inhibitors/ARBs (21.43%), antiviral medications (9.52%), and NSAIDs (7.14%). Importantly, there was no statistically significant correlation between the occurrence of MRLI or MRKI and factors such as gender, age, body mass index (BMI), or the presence of other health conditions (p > 0.05). These findings underscore the need for heightened awareness regarding the potential for medication-related impairments in hospitalized patients and suggest that careful monitoring of medication use is essential to mitigate these risks.
References
Alkhunaizi, A. M., & Al Shammary, M. (2020). In-hospital acute kidney injury. Eastern Mediterranean Health Journal, 28(8), 967–970. https://doi.org/10.26719/emhj.19.100
Amacher, D. E. (2014). Female gender as a susceptibility factor for drug-induced liver injury. Human & Experimental Toxicology, 33(9), 928–939. https://doi.org/10.1177/0960327113512860
Andrade, R. J., Chalasani, N., Björnsson, E. S., Suzuki, A., Kullak-Ublick, G. A., Watkins, P. B., Devarbhavi, H., Merz, M., Lucena, M. I., Kaplowitz, N., & Aithal, G. P. (2019). Drug-induced liver injury. Nature Reviews Disease Primers, 5(1), 58. https://doi.org/10.1038/s41572-019-0105-0
Arrang, S. T., & Widyati, W. (2018). The Incidence and risk factor analysis of drug induced liver injury (Dili) in a Surabaya Hospital. Jurnal Farmasi Galenika (Galenika Journal of Pharmacy) (e-Journal), 4(2), 79–86. https://doi.org/10.22487/j24428744.2018.v4.i2.10459
Awdishu, L., & Mehta, R. L. (2017). The 6R’s of drug induced nephrotoxicity. BMC Nephrology, 18(1), 124. https://doi.org/10.1186/s12882-017-0536-3
BPOM. (2020). Modul Farmakovigilans Dasar. Badan Pengawasan Obat dan Makanan. https://e-meso.pom.go.id/web/useruploads/files/reference/5eaa2698c3abc_Modul Farmakovigilans Dasar.pdf
Caparrotta, T. M., Antoine, D. J., & Dear, J. W. (2018). Are some people at increased risk of paracetamol-induced liver injury? A critical review of the literature. European Journal of Clinical Pharmacology, 74(2), 147–160. https://doi.org/10.1007/s00228-017-2356-6
Cheng, X., Wu, B., Liu, Y., Mao, H., & Xing, C. (2017). Incidence and diagnosis of Acute kidney injury in hospitalized adult patients: a retrospective observational study in a tertiary teaching Hospital in Southeast China. BMC Nephrology, 18(1), 203. https://doi.org/10.1186/s12882-017-0622-6
Choong, C. L., Lee, F. Y., Wong, H. S., Mohamed Ali, N., & Tay, J. F. (2017). 154 Drug-induced acute kidney injury in Malaysia. Kidney International Reports, 2(4), S23–S24. https://doi.org/10.1016/j.ekir.2017.06.081
Chouchana, L., Preta, L.-H., Tisseyre, M., Terrier, B., Treluyer, J.-M., & Montastruc, F. (2021). Kidney disorders as serious adverse drug reactions of remdesivir in coronavirus disease 2019: a retrospective case–noncase study. Kidney International, 99(5), 1235–1236. https://doi.org/10.1016/j.kint.2021.02.015
CIOMS. (2020). Drug-Induced Liver Injury (DILI): Current status and future directions for drug development and the post-market setting. https://doi.org/10.56759/ojsg8296
Couse, M., & Syed, S. (2020). A rise in aspartate transaminase and alanine transaminase associated with ondansetron administration in a pregnant female. Cureus. 12(11), e11540 https://doi.org/10.7759/cureus.11540
Cui, Y., Yang, Y., Lei, W., Lang, X., & Chen, J. (2021). The clinicopathological features of drug-induced acute kidney injury—a single-center retrospective analysis. Annals of Translational Medicine, 9(5), 400–400. https://doi.org/10.21037/atm-20-3826
Farooqi, S., & Dickhout, J. G. (2016). Major comorbid disease processes associated with increased incidence of acute kidney injury. World Journal of Nephrology, 5(2), 139. https://doi.org/10.5527/wjn.v5.i2.139
Fontana, R. J., Hayashi, P. H., Gu, J., Reddy, K. R., Barnhart, H., Watkins, P. B., Serrano, J., Lee, W. M., Chalasani, N., Stolz, A., Davern, T., & Talwakar, J. A. (2014). Idiosyncratic drug-induced liver injury is associated with substantial morbidity and mortality within 6 months from onset. Gastroenterology, 147(1), 96-108.e4. https://doi.org/10.1053/j.gastro.2014.03.045
Ghabril, M., Gu, J., Yoder, L., Corbito, L., Ringel, A., Beyer, C. D., Vuppalanchi, R., Barnhart, H., Hayashi, P. H., & Chalasani, N. (2019). Development and validation of a model consisting of comorbidity burden to calculate risk of death within 6 months for patients with suspected drug-induced liver injury. Gastroenterology, 157(5), 1245-1252.e3. https://doi.org/10.1053/j.gastro.2019.07.006
Hosack, T., Damry, D., & Biswas, S. (2023). Drug-induced liver injury: a comprehensive review. Therapeutic Advances in Gastroenterology, 16. https://doi.org/10.1177/17562848231163410
Jiang, F., Yan, H., Liang, L., Du, J., Jin, S., Yang, S., Wang, H., Hu, T., Zhu, Y., Wang, G., Hu, Y., Cai, T., & Aithal, G. P. (2021). Incidence and risk factors of anti‐tuberculosis drug induced liver injury (DILI): Large cohort study involving 4652 Chinese adult tuberculosis patients. Liver International, 41(7), 1565–1575. https://doi.org/10.1111/liv.14896
Jonny, J., Hasyim, M., Angelia, V., Jahya, A. N., Hilman, L. P., Kusumaningrum, V. F., & Srisawat, N. (2020). Incidence of acute kidney injury and use of renal replacement therapy in intensive care unit patients in Indonesia. BMC Nephrology, 21(1), 191. https://doi.org/10.1186/s12882-020-01849-y
Kang, H., & Hong, S. H. (2019). Risk of kidney dysfunction from polypharmacy among older patients: a nested case-control study of the south Korean senior cohort. Scientific Reports, 9(1), 10440. https://doi.org/10.1038/s41598-019-46849-7
Khan, S., Loi, V., & Rosner, M. H. (2017). Drug-induced kidney injury in the elderly. Drugs & Aging, 34(10), 729–741. https://doi.org/10.1007/s40266-017-0484-4
Ko, D. H., Kim, T. H., Kim, J. W., Gu, J. J., Yoon, B. H., Oh, J. H., & Hong, S. G. (2017). Tranexamic acid-induced acute renal cortical necrosis in post-endoscopic Papillectomy Bleeding. Clinical Endoscopy, 50(6), 609–613. https://doi.org/10.5946/ce.2017.021
Kong, X., Guo, D., Liu, S., Zhu, Y., & Yu, C. (2021). Incidence, characteristics and risk factors for drug‐induced liver injury in hospitalized patients: A matched case‐control study. British Journal of Clinical Pharmacology, 87(11), 4304–4312. https://doi.org/10.1111/bcp.14847
Kulkarni, A. V., Kumar, P., Tevethia, H. V., Premkumar, M., Arab, J. P., Candia, R., Talukdar, R., Sharma, M., Qi, X., Rao, P. N., & Reddy, D. N. (2020). Systematic review with meta‐analysis: liver manifestations and outcomes in COVID‐19. Alimentary Pharmacology & Therapeutics, 52(4), 584–599. https://doi.org/10.1111/apt.15916
Kumar, B., Prabhakar, R., & Thangavelu, S. (2020). Tenofovir-induced delayed nephro-osteo toxicity. Journal of the Royal College of Physicians of Edinburgh, 50(3), 291–294. https://doi.org/10.4997/jrcpe.2020.316
Leite, T. T., Macedo, E., Martins, I. da S., Neves, F. M. de O., & Libório, A. B. (2015). Renal outcomes in critically ill patients receiving propofol or midazolam. Clinical Journal of the American Society of Nephrology, 10(11), 1937–1945. https://doi.org/10.2215/CJN.02330315
Lescot, T., Karvellas, C., Beaussier, M., Magder, S., & Riou, B. (2012). Acquired liver injury in the intensive care unit. Anesthesiology, 117(4), 898–904. https://doi.org/10.1097/ALN.0b013e318266c6df
Lewandowski, M. J., & Chapman, S. A. (2008). Ondansetron‐induced aminotransferase level elevation: case report and review of the literature. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 28(12), 1542–1546. https://doi.org/10.1592/phco.28.12.1542
Lexicomp. (2022). Lexicomp (version 7.4.1) [mobile application software].
Li, X., Tang, J., & Mao, Y. (2022). Incidence and risk factors of drug‐induced liver injury. Liver International, 42(9), 1999–2014. https://doi.org/10.1111/liv.15262
Liss, G., & Lewis, J. H. (2009). Drug-induced liver injury: what was new in 2008? Expert Opinion on Drug Metabolism & Toxicology, 5(8), 843–860. https://doi.org/10.1517/17425250903018904
Liu, C., Yan, S., Wang, Y., Wang, J., Fu, X., Song, H., Tong, R., Dong, M., Ge, W., Wang, J., Yang, H., Wang, C., Xia, P., Zhao, L., Shen, S., Xie, J., Xu, Y., Ma, P., Li, H., … Yang, L. (2021). Drug-induced hospital-acquired acute kidney injury in China: a multicenter cross-sectional survey. Kidney Diseases, 7(2), 143–155. https://doi.org/10.1159/000510455
Liu, Y., Zhan, S., Song, L., Chen, Y., Jia, Y., Liu, F., Sun, F., Wang, Q., & Xia, P. (2020). Drug-induced liver injury: Clinical and etiologic features at a large tertiary teaching hospital in China. Medical Science Monitor, 26, e919435. https://doi.org/10.12659/MSM.919435
LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Heparin. [Updated 2017 Nov 13]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK548126/
Low, E. X. S., Zheng, Q., Chan, E., & Lim, S. G. (2020). Drug induced liver injury: East versus West – a systematic review and meta-analysis. Clinical and Molecular Hepatology, 26(2), 142–154. https://doi.org/10.3350/cmh.2019.1003
Lucena, M. I., Sanabria, J., García-Cortes, M., Stephens, C., & Andrade, R. J. (2020). Drug-induced liver injury in older people. The Lancet Gastroenterology & Hepatology, 5(9), 862–874. https://doi.org/10.1016/S2468-1253(20)30006-6
Mohamed, M., Al-Hillan, A., Flores, M., Kaunzinger, C., Mushtaq, A., Asif, A., & Hossain, M. (2020). Concomitant acute hepatic failure and renal failure induced by intravenous amiodarone: a case report and literature review. Gastroenterology Research, 13(1), 40–43. https://doi.org/10.14740/gr1254
Murayama, H., Sakuma, M., Takahashi, Y., & Morimoto, T. (2018). Improving the assessment of adverse drug reactions using the Naranjo Algorithm in daily practice: The Japan Adverse Drug Events Study. Pharmacology Research & Perspectives, 6(1), e00373.. https://doi.org/10.1002/prp2.373
Naranjo, C. A., Busto, U., Sellers, E. M., Sandor, P., Ruiz, I., Roberts, E. A., Janecek, E., Domecq, C., & Greenblatt, D. J. (1981). A method for estimating the probability of adverse drug reactions. Clinical Pharmacology and Therapeutics, 30(2), 239–245. https://doi.org/10.1038/clpt.1981.154
National Institut for Health and Care Excellence. (2015). Medicines optimisation: the safe and effective use of medicines to enable the best possible outcomes NICE guideline. www.nice.org.uk/guidance/ng5
Nurulmaya. (2016). Analysis of adverse drug reactions related to drug-induced renal injury based on spontaneous adverse drug reactions reporting in Malaysia 2016. Universiti Teknologi Mara.
Paudel, R., Dogra, P., Suman, S., Acharya, S., & Matta, J. (2016). Acute liver and renal failure: a rare adverse effect exclusive to intravenous form of amiodarone. Case Reports in Critical Care, 2016, 1–4. https://doi.org/10.1155/2016/5232804
Perazella, M. A., & Rosner, M. H. (2022). Drug-induced acute kidney injury. Clinical Journal of the American Society of Nephrology, 17(8), 1220–1233. https://doi.org/10.2215/CJN.11290821
Pierson‐Marchandise, M., Gras, V., Moragny, J., Micallef, J., Gaboriau, L., Picard, S., Choukroun, G., Masmoudi, K., & Liabeuf, S. (2017). The drugs that mostly frequently induce acute kidney injury: a case − noncase study of a pharmacovigilance database. British Journal of Clinical Pharmacology, 83(6), 1341–1349. https://doi.org/10.1111/bcp.13216
Riskesdas. (2018). Laporan Nasional Riskesda 2018. https://repository.badankebijakan.kemkes.go.id/id/eprint/3514/1/Laporan Riskesdas 2018 Nasional.pdf
Rolland, A.-L., Garnier, A.-S., Meunier, K., Drablier, G., & Briet, M. (2021). Drug-induced acute kidney injury: a study from the french medical administrative and the french national pharmacovigilance databases using capture-recapture method. Journal of Clinical Medicine, 10(2), 168. https://doi.org/10.3390/jcm10020168
Rotundo, L., & Pyrsopoulos, N. (2020). Liver injury induced by paracetamol and challenges associated with intentional and unintentional use. World Journal of Hepatology, 12(4), 125–136. https://doi.org/10.4254/wjh.v12.i4.125
Sabatino, D., Tillman, M., Pawasauskas, J., & Brothers, T. (2020). Nonsteroidal anti-inflammatory drug induced acute kidney injury; A review and case study. Journal of Renal Injury Prevention, 9(4), e30–e30. https://doi.org/10.34172/jrip.2020.30
Sales, G. T. M., & Foresto, R. D. (2020). Drug-induced nephrotoxicity. Revista Da Associação Médica Brasileira, 66(suppl 1), s82–s90. https://doi.org/10.1590/1806-9282.66.s1.82
Sattar, S., Hasan, M. J., Ray, N. C., & Quddus, A. R. (2018). Non-steroidal anti-inflammatory drugs induced acute kidney injury: incidence, clinical presentation, management and outcomes of patients at Tertiary Hospital based longitudinal study in Mymensingh, Bangladesh. Community Based Medical Journal, 7(2), 9–16. https://doi.org/10.3329/cbmj.v7i2.55450
Shen, T., Liu, Y., Shang, J., Xie, Q., Li, J., Yan, M., Xu, J., Niu, J., Liu, J., Watkins, P. B., Aithal, G. P., Andrade, R. J., Dou, X., Yao, L., Lv, F., Wang, Q., Li, Y., Zhou, X., Zhang, Y., … Chen, C. (2019). Incidence and etiology of drug-induced liver injury in Mainland China. Gastroenterology, 156(8), 2230-2241.e11. https://doi.org/10.1053/j.gastro.2019.02.002
Shirali, A., & Pazhayattil, G. S. (2014). Drug-induced impairment of renal function. International Journal of Nephrology and Renovascular Disease, 457. https://doi.org/10.2147/IJNRD.S39747
Stephens, C., Robles-Diaz, M., Medina-Caliz, I., Garcia-Cortes, M., Ortega-Alonso, A., Sanabria-Cabrera, J., Gonzalez-Jimenez, A., Alvarez-Alvarez, I., Slim, M., Jimenez-Perez, M., Gonzalez-Grande, R., Fernández, M. C., Casado, M., Soriano, G., Román, E., Hallal, H., Romero-Gomez, M., Castiella, A., Conde, I., … Lara, C. (2021). Comprehensive analysis and insights gained from long-term experience of the Spanish DILI Registry. Journal of Hepatology, 75(1), 86–97. https://doi.org/10.1016/j.jhep.2021.01.029
Susantitaphong, P., Cruz, D. N., Cerda, J., Abulfaraj, M., Alqahtani, F., Koulouridis, I., & Jaber, B. L. (2013). World incidence of AKI. Clinical Journal of the American Society of Nephrology, 8(9), 1482–1493. https://doi.org/10.2215/CJN.00710113
Welch, H. K., Kellum, J. A., & Kane‐Gill, S. L. (2018). Drug‐associated acute kidney injury identified in the united states food and drug administration adverse event reporting system satabase. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 38(8), 785–793. https://doi.org/10.1002/phar.2152
Wikman, P., Safont, P., Palacio, M. Del, Moreno, A., Moreno, S., & Casado, J. L. (2013). The significance of antiretroviral-associated acute kidney injury in a cohort of ambulatory human immunodeficiency virus-infected patients. Nephrology Dialysis Transplantation, 28(8), 2073–2081. https://doi.org/10.1093/ndt/gft210
Worland, T., Chin, K. L., Rodrigues, B., & Nicoll, A. (2020). A retrospective case-controlled cohort study of inpatient drug induced liver injury: the RIDDLE study. Translational Gastroenterology and Hepatology, 5, 33–33. https://doi.org/10.21037/tgh.2019.10.15
Wu, B., Luo, M., Wu, F., He, Z., Li, Y., & Xu, T. (2022). Acute kidney injury associated with remdesivir: a comprehensive pharmacovigilance analysis of COVID-19 reports in FAERS. Frontiers in Pharmacology, 13692828. https://doi.org/10.3389/fphar.2022.692828
Wu, J., Liu, J., Zhao, X., Liu, C., Wang, W., Wang, D., Xu, W., Zhang, C., Yu, J., Jiang, B., Cao, H., & Li, L. (2020). Clinical characteristics of imported cases of Coronavirus Disease 2019 (COVID-19) in Jiangsu Province: a multicenter descriptive study. Clinical Infectious Diseases, 71(15), 706–712. https://doi.org/10.1093/cid/ciaa199
Xu, L., Liu, J., Lu, M., Yang, D., & Zheng, X. (2020). Liver injury during highly pathogenic human coronavirus infections. In Liver International, 40(5),998–1004. Blackwell Publishing Ltd. https://doi.org/10.1111/liv.14435
Yu, C., Guo, D., Yao, C., Yang, H., Liu, S., Zhu, Y., & Kong, X. (2020). Clinical characteristics of hospitalized patients with drug‐induced acute kidney injury and associated risk factors: a case‐control study. BioMed Research International, 2020(9742754), 1-8. https://doi.org/10.1155/2020/9742754
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Nadia Farhanah Syafhan, Ghea Shafa Aldora, Shinta Kamila

This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with Pharmaciana agree to the following terms:
- Authors retain copyright and grant the journal the right of first publication with the work simultaneously licensed under a Creative Commons Attribution License (CC BY-SA 4.0) that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.