Drug‐Associated Nephrotic Syndrome: A Global Pharmacovigilance Perspective
DOI:
https://doi.org/10.71749/pkj.42Keywords:
Drug‐Related Side Effects and Adverse Reactions, Nephrotic Syndrome/chemically induced, PharmacovigilanceAbstract
Introduction: Nephrotic syndrome is a rare clinical manifestation, with an estimated incidence of 3 cases per 100 000 population per year, which can be triggered by medications contributing to the development of its histopathological forms. The literature references various drugs such as antibiotics, allopurinol, pamidronate, sirolimus, among others. Pharmacovigilance studies enable the evaluation of the safety of these medications in large populations, identifying drugs most strongly associated with the phenotype under investigation.Methods: This study involved the detection of notifications related to the development of nephrotic syndrome in VigiBase, and assessed the available data based on frequency, disproportionality, and their nephrotoxic role.
Results: During the selected period and among 37 145 123 available notifications, 7211 notifications related to drug‐associated nephrotic syndrome were filtered using the appropriate MedDRA term. These predominantly affected male consumers aged 45‐64 years, with the majority of notifications originating from the USA. Medications classified un‐ der ATC class L‐ antineoplastic and immunomodulating agents, were most frequently involved, and with penicillamine showing the highest association with this phenotype (ROR 231.28), followed by inotersen (ROR 24.49) and sunitinib (ROR 20.31), among others. These notifications had a mortality of 4.2%, with proton pump inhibitors being frequently implicated.
Conclusion: This study assessed VigiBase for the primary medications involved in the development of nephrotic syndrome, both in terms of frequency and associative strength. Clinician involvement is crucial in increasing notifications of adverse drug reactions. Understanding the main agents involved in various renal phenotypes helps improve prescription practices and ensures greater patient safety.
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References
Tapia C, Bashir K. Nephrotic Syndrome. In: StatPearls [Internet]. Trea‐ sure Island: StatPearls Publishing; 2024
Kerlin BA, Ayoob R, Smoyer WE. Epidemiology and pathophysiology of nephrotic syndrome‐associated thromboembolic disease. Clin J Am Soc Nephrol. 2012;7:513‐20. doi: 10.2215/CJN.10131011.
Liu C, Yan S, Wang Y, Wang J, Fu X, Song H, et al. Drug‐Induced Hospital‐ ‐Acquired Acute Kidney Injury in China: A Multicenter Cross‐Sectional Survey. Kidney Dis. 2021;7:143‐55. doi: 10.1159/000510455.
Alkhunaizi AM, Al Shammary M. In‐hospital acute kidney injury. East Mediterr Health J. 2020;26:967‐70. doi: 10.26719/emhj.19.100.
Gowa MA, Yamin R, Murtaza H, Nawaz H, Jamal G, Lohano PD. Fre‐ quency of Drug Induced Acute Kidney Injury in Pediatric Intensive Care Unit. Cureus. 2021;13:e19689. doi: 10.7759/cureus.19689.
Matsubara T, Yokoi H, Yamada H, Yanagita M. Nephrotoxicity as‐ sociated with anticancer agents: perspective on onconephrology from nephrologists. Int J Clin Oncol. 2023;28:625‐36. doi: 10.1007/ s10147‐023‐02307‐z.
Petejova N, Martinek A, Zadrazil J, Teplan V. Acute toxic kidney injury. Ren Fail. 2019;41:576‐94. doi: 10.1080/0886022X.2019.1628780.
Izzedine H, Massard C, Spano JP, Goldwasser F, Khayat D, Soria JC. VEGF signalling inhibition‐induced proteinuria: Mechanisms, sig‐ nificance and management. Eur J Cancer. 2010;46:439‐48. doi: 10.1016/j.ejca.2009.11.001.
Frazier KS, Obert LA. Drug‐induced Glomerulonephritis: The Spec‐ tre of Biotherapeutic and Antisense Oligonucleotide Immune Activation in the Kidney. Toxicol Pathol. 2018;46:904‐17. doi: 10.1177/0192623318789399.
Borrego García E, Hernández García E, Caba Molina M, Navas‐Parejo Casado AM. Massive proteinuria for minimal change nephropathy secondary to treatment with D‐penicillamine in a patient with Wil‐ son’s disease. Case report. Gastroenterol Hepatol. 2020;92–3.
Law S, Arnold J, Rauf MU, Heptinstall L, Gilbertson J, Rowczenio D, et al. Focal Segmental Glomerulosclerosis Complicating Therapy With Inotersen, an Antisense Oligonucleotide Inhibitor: A Case Report. Am J Kidney Dis. 2023;81:606‐10. doi: 10.1053/j.ajkd.2022.08.018.
Izzedine H. Ng JH. Keep in Mind the Spectrum of Drug‐Induced Glo‐ merular Diseases. KidneyNews. 2021;13:27–8
World Health Organization, WHO Collaborating Centre for Inter‐ national Drug Monitoring. The Importance of Pharmacovigilance. Geneve: WHO;2002.
Faillie JL, Montastruc F, Montastruc JL, Pariente A. Pharmacoepide‐ miology and its input to pharmacovigilance. Therapie. 2016;71:211‐ ‐6. doi: 10.1016/j.therap.2016.02.016.
Uppsala Monitoring Centre. VigiBase: WHO’s global database signal‐ ling harm and pointing to safer use. Geneve: WHO; 2002.
MedDRA. MedDRA Hierarchy. [accessed Dec 2023] Available at: https://www.meddra.org/
Lindquist M. VigiBase, the WHO Global ICSR Database System: Basic Facts. Drug Inf J. 2008;42:409–19.
Faillie JL. Case–non‐case studies: Principle, methods, bias and inter‐ pretation. Therapies. 2019; 74:225–32.
European Medicines Agency. [accessed Dec 2023] Available at: https:// www.ema.europa.eu/en/glossary/summary‐product‐characteristics
UpToDate. UpToDate [accessed Dec 2023] Available at: http://www. uptodate.com (2024).
Drugs.com. Drugs.com [accessed Dec 2023] Available at: http:// www.drugs.com (2024).
American Society of Health‐System Pharmacists. Drug‐Induced Dis‐ eases. Bethesda: ASHSP;2018.
Side Effects of Drugs Annual 38‐ A Worldwide Yearly Survey of New Data in Adverse Drug Reactions. Amsterdam: Elsevier; 2016.
Akyol A. Is pantoprazole associated with proteinuria in intensive care patients? J Anesth Crit Care. 2020; 12.
Sanchez‐Alamo B, Cases‐Corona C, Fernandez‐Juarez G. Facing the Challenge of Drug‐Induced Acute Interstitial Nephritis. Nephron. 2023;147:78‐90. doi: 10.1159/000525561.
Kobayashi N, Fujisawa H, Kumagai J, Tanabe M. New‐onset minimal change disease following the Moderna COVID‐19 vaccine. BMJ Case Rep. 2023;16:e255144. doi: 10.1136/bcr‐2023‐255144.
Parikh C, Upadhyay H, Patel S, Sundararajan R, Shah D, Anand A, et al. Nephrotic syndrome following COVID‐19 vaccination: a systematic review. J Nephrol. 2023;36:2431‐40. doi: 10.1007/ s40620‐023‐01710‐z.
Abo Zed SE, Hackl A, Bohl K, Ebert L, Kieckhöfer E, Müller C, et al. My‐ cophenolic acid directly protects podocytes by preserving the actin cytoskeleton and increasing cell survival. Sci Rep. 2023;13:4281. doi: 10.1038/s41598‐023‐31326‐z.
Matsuda S, Aoki K, Kawamata T, Kimotsuki T, Kobayashi T, Kuriki H, et al. Bias in spontaneous reporting of adverse drug reactions in Japan. PLoS One. 2015;10:e0126413. doi: 10.1371/journal.pone.0126413.
O’Connell S, Slattery C, Ryan MP, McMorrow T. Identification of novel indicators of cyclosporine A nephrotoxicity in a CD‐1 mouse model. Toxicol Appl Pharmacol. 2011;252:201‐10. doi: 10.1016/j. taap.2011.02.015.
Fujinaga S, Kaneko K, Muto T, Ohtomo Y, Murakami H, Yamashiro Y. Independent risk factors for chronic cyclosporine induced ne‐ phropathy in children with nephrotic syndrome. Arch Dis Child. 2006;91:666‐70. doi: 10.1136/adc.2005.080960.
Szałach ŁP, Lisowska KA, Cubała WJ, Barbuti M, Perugi G. The im‐ munomodulatory effect of lithium as a mechanism of action in bipolar disorder. Front Neurosci. 2023;17:1213766. doi: 10.3389/fnins.2023.1213766.
Zhang P, Gandhi H, Kassis N. Lithium‐induced nephropathy; One medication with multiple side effects: a case report. BMC Nephrol. 2022;23:309. doi: 10.1186/s12882‐022‐02934‐0.
Łukawska E, Frankiewicz D, Izak M, Woźniak A, Dworacki G, Niemir ZI. Lithium toxicity and the kidney with special focus on nephrotic syndrome associated with the acute kidney injury: A case‐based systematic analysis. J Appl Toxicol. 2021;41:1896‐909. doi: 10.1002/ jat.4167.
Takahashi D, Nagahama K, Tsuura Y, Tanaka H, Tamura T. Sunitinib‐ ‐induced nephrotic syndrome and irreversible renal dysfunction. Clin Exp Nephrol. 2012;16:310‐5. doi: 10.1007/s10157‐011‐0543‐9.
Vigneau C, Lorcy N, Dolley‐Hitze T, Jouan F, Arlot‐Bonnemains Y, Laguerre B, et al. All anti‐vascular endothelial growth factor drugs can induce ‘pre‐eclampsia‐like syndrome’: a RARe study. Nephrol Dial Transplant. 2014;29:325‐32. doi: 10.1093/ndt/gft465.
Saltz LB, Clarke S, Díaz‐Rubio E, Scheithauer W, Figer A, Wong R, et al. Bevacizumab in combination with oxaliplatin‐based chemother‐ apy as first‐line therapy in metastatic colorectal cancer: a Random‐ ized Phase III Study. J Clin Oncol. 2023;41:3663‐9. doi: 10.1200/ JCO.22.02760.
Rini BI, Halabi S, Rosenberg JE, Stadler WM, Vaena DA, Ou SS, et al. Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcino‐ ma: CALGB 90206. J Clin Oncol. 2008;26:5422‐8. doi: 10.1200/ JCO.2008.16.9847.
Sugimoto H, Hamano Y, Charytan D, Cosgrove D, Kieran M, Sudhakar A, et al. Neutralization of circulating vascular endothelial growth factor (VEGF) by anti‐VEGF antibodies and soluble VEGF receptor 1 (sFlt‐1) induces proteinuria. J Biol Chem. 2003;278:12605‐8. doi: 10.1074/jbc.C300012200.
Habib GS, Saliba W, Nashashibi M, Armali Z. Penicillamine and ne‐ phrotic syndrome. Eur J Intern Med. 2006;17:343‐8. doi: 10.1016/j. ejim.2006.03.001.
Theodoni G, Printza N, Karyda S, Pantzaki A, Papachristou F. D‐pen‐ icillamine induced membranous glomerulonephritis in a child with Wilson’s disease. Hippokratia. 2012;16:94.
Fernandes C, Duarte M , Ferreira P, Gonçalves C, Serrão AP, Baptista RB. Penicillamine‐induced membranous nephropathy in an adoles‐ cent with Wilson’s disease. Port J Nephrol Hypert. 2022;63:84‐8. doi 10.32932/pjnh.2022.06.182
Yang Y, George KC, Shang WF, Zeng R, Ge SW, Xu G. Proton‐pump inhibitors use, and risk of acute kidney injury: a meta‐analysis of observational studies. Drug Des Devel Ther. 2017;11:1291‐9. doi: 10.2147/DDDT.S130568.
Athanasopoulou D, Lionaki S, Skalioti C, Liapis G, Vlachoyiannopou‐ los P, Boletis I. Drug‐Induced Podocytopathies: Report of Four Cases and Review of the Literature. Life. 2023;13:1264. doi: 10.3390/ life13061264.
Garnier AS, Laubacher H, Briet M. Drug‐induced glomerular diseases. Therapie. 2024;79:271‐81. doi: 10.1016/j.therap.2023.10.010.
Faillie JL. Case‐non‐case studies: Principle, methods, bias and interpretation. Therapie. 2019;74:225‐32. doi: 10.1016/j. therap.2019.01.006.
National Institutes of Health. PubMed. [accessed Dec 2023] Available at: https://pubmed.ncbi.nlm.nih.gov
Clarivate Analytics. Web of Science. [accessed Dec 2023] Available at: https://access.clarivate.com/login
Google. Google Scholar. [accessed Dec 2023] Available at: https://scholar.google.com
Elsevier. Embase. [accessed Dec 2023] Available at: https://www.embase.com
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Data Availability Statement
The data were obtained through project submission to the Uppsala Monitoring Centre (UMC) with subsequent authorization, so their release will be possible upon request to the UMC. Data is not publicly available.
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Copyright (c) 2024 Alexandre Baptista, Ana M. Macedo, Ana Marreiros, André Coelho (Author)
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