{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:22:10Z","timestamp":1760145730500,"version":"build-2065373602"},"reference-count":52,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,18]],"date-time":"2024-08-18T00:00:00Z","timestamp":1723939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Algarve Biomedical Centre\/University of Algarve"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Introduction: Adverse drug reactions are a significant problem in modern society, stemming from the increase in prescribed medications, over-the-counter drugs, and overall polypharmacy. Glomerular disorders are one of the frequently reported renal conditions associated with medication use. VigiBase is a significant tool for evaluating events associated with drug use, and, to the authors\u2019 knowledge, no study has yet assessed this database to identify the primary medications associated with glomerular disorders. Materials and Methods: We collected data from VigiBase for 54 years and evaluated data based on global frequencies, disproportionality (IC025 values), nephrotoxic potential, and physiopathological mechanisms. Results: Over the evaluation period, 33.932.051 spontaneous notifications of adverse drug reactions reported in VigiBase were assessed, from which 106.775 notifications of drug-associated glomerular disorders were extracted. The isolated medications were classified as \u2018potential nephrotoxins\u2019 (47.0%), with 40% of the medications lacking scientific references to report any association with the development of glomerular disorders. Among the evaluated medications, Inotersen (IC025 of 8.3), Penicillamine (IC025 6.8), Bevacizumab (IC025 5.9) and Lenvatinib (IC025 5.4) were identified as having the strongest association with these glomerular disorders. For medications classified as \u2018non-nephrotoxic\u2019, a high disproportionality index was observed, suggesting drugs that might be considered as new potential nephrotoxins. Conclusions: Drug-induced glomerular disorders were significantly associated with medications that had no established nephrotoxic role but demonstrated a high disproportionality index in VigiBase. These newly alleged nephrotoxic drugs warrant further evaluation in dedicated studies to assess their true nephrotoxic potential.<\/jats:p>","DOI":"10.3390\/jcm13164869","type":"journal-article","created":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T06:41:31Z","timestamp":1724049691000},"page":"4869","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Drug-Related Glomerular Phenotypes: A Global Pharmacovigilance Perspective"],"prefix":"10.3390","volume":"13","author":[{"given":"Alexandre","family":"Baptista","sequence":"first","affiliation":[{"name":"School of Medicine and Biomedical Sciences, Algarve University (UAlg), 8005-139 Faro, Portugal"},{"name":"Algarve Biomedical Centre (ABC), 8005-139 Faro, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana M.","family":"Macedo","sequence":"additional","affiliation":[{"name":"School of Medicine and Biomedical Sciences, Algarve University (UAlg), 8005-139 Faro, Portugal"},{"name":"Algarve Biomedical Centre (ABC), 8005-139 Faro, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9410-4772","authenticated-orcid":false,"given":"Ana","family":"Marreiros","sequence":"additional","affiliation":[{"name":"School of Medicine and Biomedical Sciences, Algarve University (UAlg), 8005-139 Faro, Portugal"},{"name":"Algarve Biomedical Centre (ABC), 8005-139 Faro, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1872-8131","authenticated-orcid":false,"given":"Andr\u00e9","family":"Coelho","sequence":"additional","affiliation":[{"name":"Health & Technology Research Center, Escola Superior de Tecnologia da Sa\u00fade de Lisboa, Instituto Polit\u00e9cnico de Lisboa, 1990-096 Lisboa, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6994-2659","authenticated-orcid":false,"given":"Mark A.","family":"Perazella","sequence":"additional","affiliation":[{"name":"School of Medicine, Yale University, New Haven, CT 06520, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Schroll, J.B., Maund, E., and G\u00f8tzsche, P.C. (2012). Challenges in coding adverse events in clinical trials: A systematic review. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0041174"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1038\/ki.2015.115","article-title":"Phenotype standardization for drug-induced kidney disease","volume":"88","author":"Mehta","year":"2015","journal-title":"Kidney Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.therap.2023.10.010","article-title":"Drug-induced glomerular diseases","volume":"79","author":"Garnier","year":"2023","journal-title":"Therapies"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.2215\/CJN.01010115","article-title":"Drug-Induced Glomerular Disease","volume":"10","author":"Radhakrishnan","year":"2015","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.2215\/CJN.00860115","article-title":"Drug-induced glomerular disease: Direct cellular injury","volume":"10","author":"Markowitz","year":"2015","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"290","DOI":"10.4082\/kjfm.21.0193","article-title":"Pharmacovigilance and Its Importance for Primary Health Care Professionals","volume":"43","author":"Hamid","year":"2022","journal-title":"Korean J. Fam. Med."},{"key":"ref_7","unstructured":"Uppsala Monitoring Centre (2024, April 13). Guideline for Using VigiBase Data in Studies. Available online: https:\/\/www.vigiaccess.org."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/s40290-020-00349-6","article-title":"Electronic Reporting Systems in Pharmacovigilance: The Implementation of VigiFlow in Brazil","volume":"34","author":"Vogler","year":"2020","journal-title":"Pharm. Med."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Varallo, F.R., Planeta, C.S., Herdeiro, M.T., and de Mastroianni, P.C. (2017). Imputation of adverse drug reactions: Causality assessment in hospitals. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0171470"},{"key":"ref_10","unstructured":"European Medicines Agency (2024, May 01). European Union. Available online: https:\/\/www.ema.europa.eu\/en\/glossary\/summary-product-characteristics."},{"key":"ref_11","unstructured":"UpToDate (2024, May 01). UpToDate. Available online: https:\/\/www.uptodate.com."},{"key":"ref_12","unstructured":"Drugs.com (2024, May 01). Drugs.com. Available online: https:\/\/www.drugs.com."},{"key":"ref_13","unstructured":"James, E.T., and Douglas, A.M. (2018). Drug-Induced Diseases, American Society of Health-System Pharmacists. [3rd ed.]."},{"key":"ref_14","unstructured":"Ray, S.D. (2016). Side Effects of Drugs Annual 38\u2014A Worldwide Yearly Survey of New Data in Adverse Drug Reactions, Elsevier B.V."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1093\/ndt\/gfx189","article-title":"Glomerular disease frequencies by race, sex and region: Results from the International Kidney Biopsy Survey","volume":"33","author":"Hogan","year":"2018","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1111\/his.13064","article-title":"Drug-induced nephropathies","volume":"70","author":"Paueksakon","year":"2017","journal-title":"Histopathology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.urology.2017.11.023","article-title":"Incidence of Visible Hematuria Among Antithrombotic Agents: A Systematic Review of Over 175,000 Patients","volume":"114","author":"Bhatt","year":"2018","journal-title":"Urology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e3363","DOI":"10.1097\/MD.0000000000003363","article-title":"Association Between the Use of Proton Pump Inhibitors and the Risk of ESRD in Renal Diseases","volume":"95","author":"Peng","year":"2016","journal-title":"Medicine"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Wu, B., Li, D., Xu, T., Luo, M., He, Z., and Li, Y. (2021). Proton pump inhibitors associated acute kidney injury and chronic kidney disease: Data mining of US FDA adverse event reporting system. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-83099-y"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Amin, R., Ahn, S.-Y., and Moudgil, A. (2021). Kidney and urinary tract disorders. Biochemical and Molecular Basis of Pediatric Disease, Academic Press.","DOI":"10.1016\/B978-0-12-817962-8.00010-X"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1053\/j.ackd.2016.08.003","article-title":"Clinical Approach to Diagnosing Acute and Chronic Tubulointerstitial Disease","volume":"24","author":"Perazella","year":"2017","journal-title":"Adv. Chronic Kidney Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1046\/j.1523-1755.2001.060002804.x","article-title":"Drug-induced acute interstitial nephritis","volume":"60","author":"Rossert","year":"2001","journal-title":"Kidney Int."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1097\/QAD.0b013e32835883bf","article-title":"Tenofovir-associated proteinuria","volume":"27","author":"Kelly","year":"2013","journal-title":"AIDS"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1097\/MNH.0000000000000392","article-title":"Potential kidney toxicity from the antiviral drug tenofovir","volume":"27","author":"Chan","year":"2018","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Chadwick, D.R., Sarfo, F.S., Kirk, E.S.M., Owusu, D., Bedu-Addo, G., Parris, V., Owusu, A.L., and Phillips, R. (2015). Tenofovir is associated with increased tubular proteinuria and asymptomatic renal tubular dysfunction in Ghana. BMC Nephrol., 16.","DOI":"10.1186\/s12882-015-0192-4"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Hall, G., and Wyatt, C.M. (2021). Mechanisms of Proteinuria in HIV. Front. Med., 8.","DOI":"10.3389\/fmed.2021.749061"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e226442","DOI":"10.1136\/bcr-2018-226442","article-title":"Adalimumab-induced IgA nephropathy","volume":"12","author":"Singh","year":"2019","journal-title":"BMJ Case Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1159\/000515585","article-title":"IgA Nephropathy in a Patient Treated with Adalimumab","volume":"11","author":"Mertelj","year":"2021","journal-title":"Case Rep. Nephrol. Dial."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1001\/jamainternmed.2013.567","article-title":"No Increase in Risk of Microscopic Hematuria with Aspirin Use by Asymptomatic Healthy People","volume":"173","author":"Jeong","year":"2013","journal-title":"JAMA Intern. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1001\/jama.2017.13890","article-title":"Association Between Use of Antithrombotic Medication and Hematuria-Related Complications","volume":"318","author":"Wallis","year":"2017","journal-title":"JAMA"},{"key":"ref_31","first-page":"278","article-title":"Higher rate of microscopic hematuria in elderly patients who take regular doses of aspirin: Result from AHAP Study","volume":"7","author":"Moudi","year":"2016","journal-title":"Casp. J. Intern. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/S0090-4295(99)00388-X","article-title":"Clinical significance of gross hematuria and its evaluation in patients receiving anticoagulant and aspirin treatment","volume":"55","author":"Avidor","year":"2000","journal-title":"Urology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2473","DOI":"10.1016\/j.juro.2012.09.078","article-title":"Diagnosis, Evaluation and Follow-Up of Asymptomatic Microhematuria in Adults: AUA Guideline","volume":"188","author":"Davis","year":"2012","journal-title":"J. Urol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"100373","DOI":"10.1016\/j.cotox.2022.100373","article-title":"Nephrotoxicity of marketed antisense oligonucleotide drugs","volume":"32","author":"Wu","year":"2022","journal-title":"Curr. Opin. Toxicol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1053\/j.ajkd.2022.08.018","article-title":"Focal Segmental Glomerulosclerosis Complicating Therapy with Inotersen, an Antisense Oligonucleotide Inhibitor: A Case Report","volume":"81","author":"Law","year":"2023","journal-title":"Am. J. Kidney Dis."},{"key":"ref_36","unstructured":"(2024, April 27). Electronic Medicines Compendium. Available online: https:\/\/www.medicines.org.uk\/emc\/files\/pil.2712.pdf."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.ejim.2006.03.001","article-title":"Penicillamine and nephrotic syndrome","volume":"17","author":"Habib","year":"2006","journal-title":"Eur. J. Intern. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1136\/bmj.296.6629.1083","article-title":"Natural Course of Penicillamine Nephropathy: A Long Term Study of 33 Patients","volume":"296","author":"Hall","year":"1988","journal-title":"Br. Med. J."},{"key":"ref_39","first-page":"92","article-title":"Massive proteinuria for minimal change nephropathy secondary to treatment with D-penicillamine in a patient with Wilson\u2019s disease. Case report","volume":"43","year":"2020","journal-title":"Gastroenterol. Y Hepatol."},{"key":"ref_40","first-page":"94","article-title":"D-penicillamine induced membranous glomerulonephritis in a child with Wilson\u2019s disease","volume":"16","author":"Theodoni","year":"2012","journal-title":"Hippokratia"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1038\/s41379-018-0186-4","article-title":"Bevacizumab-associated glomerular microangiopathy","volume":"32","author":"Person","year":"2019","journal-title":"Mod. Pathol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Kiyomi, A., Koizumi, F., Imai, S., Yamana, H., Horiguchi, H., Fushimi, K., and Sugiura, M. (2023). Bevacizumab-induced proteinuria and its association with antihypertensive drugs: A retrospective cohort study using a Japanese administrative database. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0289950"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e23","DOI":"10.1053\/j.ajkd.2006.11.024","article-title":"Nephrotic Syndrome After Bevacizumab: Case Report and Literature Review","volume":"49","author":"George","year":"2007","journal-title":"Am. J. Kidney Dis."},{"key":"ref_44","first-page":"e48787","article-title":"Bevacizumab-Induced Nephropathy Presenting as Crescentic Glomerulopathy","volume":"15","author":"Onteddu","year":"2023","journal-title":"Cureus"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e17870","DOI":"10.1097\/MD.0000000000017870","article-title":"Bevacizumab-induced immunoglobulin A vasculitis with nephritis","volume":"98","author":"Endo","year":"2019","journal-title":"Medicine"},{"key":"ref_46","unstructured":"European Medicines Agency (2023, November 28). Committee for Medicinal Products for Human Use (CHMP) Assessment Report\u2014Lenvatinib. Available online: https:\/\/www.ema.europa.eu\/contact."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Shibutani, Y., Suzuki, S., Sagara, A., Enokida, T., Okano, S., Fujisawa, T., Sato, F., Yumoto, T., Sano, M., and Kawasaki, T. (2023). Impact of lenvatinib-induced proteinuria and renal dysfunction in patients with thyroid cancer. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1154771"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.ejca.2009.11.001","article-title":"VEGF signalling inhibition-induced proteinuria: Mechanisms, significance and management","volume":"46","author":"Izzedine","year":"2010","journal-title":"Eur. J. Cancer"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"319","DOI":"10.5487\/TR.2019.35.4.319","article-title":"Future Directions of Pharmacovigilance Studies Using Electronic Medical Recording and Human Genetic Databases","volume":"35","author":"Choi","year":"2019","journal-title":"Toxicol. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/S0140-6736(22)01841-4","article-title":"A 12-gene pharmacogenetic panel to prevent adverse drug reactions: An open-label, multicentre, controlled, cluster-randomised crossover implementation study","volume":"401","author":"Swen","year":"2023","journal-title":"Lancet"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"100011","DOI":"10.1016\/j.aichem.2023.100011","article-title":"Application of artificial intelligence and machine learning in early detection of adverse drug reactions (ADRs) and drug-induced toxicity","volume":"1","author":"Yang","year":"2023","journal-title":"Artif. Intell. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e137","DOI":"10.1016\/S2589-7500(21)00229-6","article-title":"Key use cases for artificial intelligence to reduce the frequency of adverse drug events: A scoping review","volume":"4","author":"Syrowatka","year":"2022","journal-title":"Lancet Digit. Health"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/16\/4869\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:38:25Z","timestamp":1760110705000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/16\/4869"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,18]]},"references-count":52,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["jcm13164869"],"URL":"https:\/\/doi.org\/10.3390\/jcm13164869","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2024,8,18]]}}}