An Integrated Approach for Representing Knowledge on the Potential of Drugs to Cause Acute Kidney Injury

Daniel Fernández-Llaneza; Romy M. P. Vos; Joris E. Lieverse; Helen R. Gosselt; Sandra L. Kane-Gill; Teun van Gelder; Joanna E. Klopotowska; the LEAPfROG Consortium; Ameen Abu-Hanna; Annemiek Dorgelo; Annette ten Teije; Birgit A. Damoiseaux; Cornelis Boersma; Dave A. Dongelmans; David H. de Koning; Erol S. Hofmans; Evelien Tiggelaar; Frank van Harmelen; Giovanni Cinà; Gerty Holla; Hilda J. de Jong; Iacopo Vagliano; Jan Pander; Jasper M. Boomker; Jurjen van der Schans; Kitty J. Jager; Linda Dusseljee-Peute; Luuk B. Hilbrands; Marianne le Comte; Marieke A. R. Bak; Mariette van den Hoven; Martijn G. Kersloot; Menno Maris; Nicolette F. de Keizer; Otto R. Maarsingh; Paul Blank; Piet Heingraaf; Ron Herings; Ron J. Keizer; Ronald Cornet; Ruben Boyd; Sebastiaan L. Knijnenburg; Sipke Visser; Stephanie Medlock; Tjerk S. Heijmens Visser; Vianda S. Stel; Wanda Konijn

doi:10.1007/s40264-024-01474-w

An Integrated Approach for Representing Knowledge on the Potential of Drugs to Cause Acute Kidney Injury

Daniel Fernández-Llaneza, Romy M. P. Vos, Joris E. Lieverse, Helen R. Gosselt, Sandra L. Kane-Gill, Teun van Gelder, Joanna E. Klopotowska, the LEAPfROG Consortium, Ameen Abu-Hanna, Annemiek Dorgelo, Annette ten Teije, Birgit A. Damoiseaux, Cornelis Boersma, Dave A. Dongelmans, David H. de Koning, Erol S. Hofmans, Evelien Tiggelaar, Frank van Harmelen, Giovanni Cinà, Gerty HollaHilda J. de Jong, Iacopo Vagliano, Jan Pander, Jasper M. Boomker, Jurjen van der Schans, Kitty J. Jager, Linda Dusseljee-Peute, Luuk B. Hilbrands, Marianne le Comte, Marieke A. R. Bak, Mariette van den Hoven, Martijn G. Kersloot, Menno Maris, Nicolette F. de Keizer, Otto R. Maarsingh, Paul Blank, Piet Heingraaf, Ron Herings, Ron J. Keizer, Ronald Cornet, Ruben Boyd, Sebastiaan L. Knijnenburg, Sipke Visser, Stephanie Medlock, Tjerk S. Heijmens Visser, Vianda S. Stel, Wanda Konijn

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

Introduction and Objective
The recent rise in acute kidney injury (AKI) incidence, with approximately 30% attributed to potentially preventable adverse drug events (ADEs), poses challenges in evaluating drug-induced AKI due to polypharmacy and other risk factors. This study seeks to consolidate knowledge on the drugs with AKI potential from four distinct sources: (i) bio(medical) peer-reviewed journals; (ii) spontaneous reporting systems (SRS); (iii) drug information databases (DIDs); and (iv) NephroTox website. By harnessing the potential of these underutilised sources, our objective is to bridge gaps and enhance the understanding of drug-induced AKI.

Methods
By searching Medline, studies with lists of drugs with AKI potential established through consensus amongst medical experts were selected. A final list of 63 drugs was generated aggregating the original studies. For these 63 drugs, the AKI reporting odds ratios (RORs) using three SRS databases, the average frequency of ADEs from four different DIDs and the number of published studies identified via NephroTox was reported.

Results
Drugs belonging to the antivirals, antibacterials, and non-steroidal anti-inflammatory pharmacological classes exhibit substantial consensus on AKI potential, which was also reflected in strong ROR signals, frequent to very frequent AKI-related ADEs and a high number of published studies reporting adverse kidney events as identified via NephroTox. Renin-angiotensin aldosterone system inhibitors and diuretics also display comparable signal strengths, but this can be attributed to expected haemodynamic changes. More variability is noted for proton-pump inhibitors.

Conclusions
By integrating four disjointed sources of knowledge, we have created a novel, comprehensive resource on drugs with AKI potential, contributing to kidney safety improvement efforts.

Original language	English
Article number	e2019209
Pages (from-to)	43-58
Number of pages	16
Journal	Drug Safety
Volume	48
Issue number	1
Early online date	26 Sept 2024
DOIs	https://doi.org/10.1007/s40264-024-01474-w
Publication status	Published - Jan 2025

Funding

This study is part of a larger project called LEveraging real-world dAta to optimize PharmacotheRapy outcomes in multimOrbid patients by using machine learning and knowledGe representation methods (LEAPfROG project) funded by the Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO; Dutch Research Council) under grant agreement KICH1.ST01.20.011 and co-funded in-cash by Dutch Kidney Foundation and National Intensive Care Evaluation (NICE) foundation, and in-kind by PHARMO Institute for Drug Outcomes Research, Castor, InsightRX, Z-Index, Digital Health Link. The funders had no role in the design of the study, the collection, analysis and interpretation of the data, or in writing the manuscript. Daniel Fern\u00E1ndez-Llaneza is a former employee of AstraZeneca and terminated his contract in February 2023. In the last 3 years, Dr. T.vG. has received lecture fees and consulting fees from Roche Diagnostics, Thermo Fisher, Vitaeris, Otsuka, CSL Behring, Astellas and Aurinia Pharma. In all cases money has been transferred to hospital accounts, and none has been paid to his personal bank accounts. Dr. T.vG. does not have employment or stock ownership at any of these companies, and neither does he have patents or patent applications. Dr. S.L.K-G. receives grant funding from the National Institute of Diabetes and Digestive and Kidney Diseases R01DK121730 and U01DK130010, the National Center for Complementary and Integrative Health U54AT008909 and the Jewish Healthcare Foundation. All other authors declared no competing interests for this work.

Funders	Funder number
National Intensive Care Evaluation
Jewish Healthcare Foundation
Nierstichting
Dutch Research Council	KICH1.ST01.20.011
National Institute of Diabetes and Digestive and Kidney Diseases	R01DK121730, U01DK130010
National Center for Complementary and Integrative Health	U54AT008909

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Fernández-Llaneza, D., Vos, R. M. P., Lieverse, J. E., Gosselt, H. R., Kane-Gill, S. L., van Gelder, T., Klopotowska, J. E., Consortium, T. LEAPOG., Abu-Hanna, A., Dorgelo, A., Teije, A. T., Damoiseaux, B. A., Boersma, C., Dongelmans, D. A., de Koning, D. H., Hofmans, E. S., Tiggelaar, E., van Harmelen, F., Cinà, G., ... Konijn, W. (2025). An Integrated Approach for Representing Knowledge on the Potential of Drugs to Cause Acute Kidney Injury. Drug Safety, 48(1), 43-58. Article e2019209. https://doi.org/10.1007/s40264-024-01474-w

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title = "An Integrated Approach for Representing Knowledge on the Potential of Drugs to Cause Acute Kidney Injury",

abstract = "Introduction and Objective The recent rise in acute kidney injury (AKI) incidence, with approximately 30\% attributed to potentially preventable adverse drug events (ADEs), poses challenges in evaluating drug-induced AKI due to polypharmacy and other risk factors. This study seeks to consolidate knowledge on the drugs with AKI potential from four distinct sources: (i) bio(medical) peer-reviewed journals; (ii) spontaneous reporting systems (SRS); (iii) drug information databases (DIDs); and (iv) NephroTox website. By harnessing the potential of these underutilised sources, our objective is to bridge gaps and enhance the understanding of drug-induced AKI. Methods By searching Medline, studies with lists of drugs with AKI potential established through consensus amongst medical experts were selected. A final list of 63 drugs was generated aggregating the original studies. For these 63 drugs, the AKI reporting odds ratios (RORs) using three SRS databases, the average frequency of ADEs from four different DIDs and the number of published studies identified via NephroTox was reported. Results Drugs belonging to the antivirals, antibacterials, and non-steroidal anti-inflammatory pharmacological classes exhibit substantial consensus on AKI potential, which was also reflected in strong ROR signals, frequent to very frequent AKI-related ADEs and a high number of published studies reporting adverse kidney events as identified via NephroTox. Renin-angiotensin aldosterone system inhibitors and diuretics also display comparable signal strengths, but this can be attributed to expected haemodynamic changes. More variability is noted for proton-pump inhibitors. Conclusions By integrating four disjointed sources of knowledge, we have created a novel, comprehensive resource on drugs with AKI potential, contributing to kidney safety improvement efforts.",

author = "Daniel Fern{\'a}ndez-Llaneza and Vos, \{Romy M. P.\} and Lieverse, \{Joris E.\} and Gosselt, \{Helen R.\} and Kane-Gill, \{Sandra L.\} and \{van Gelder\}, Teun and Klopotowska, \{Joanna E.\} and Consortium, \{the LEAPfROG\} and Ameen Abu-Hanna and Annemiek Dorgelo and Teije, \{Annette ten\} and Damoiseaux, \{Birgit A.\} and Cornelis Boersma and Dongelmans, \{Dave A.\} and \{de Koning\}, \{David H.\} and Hofmans, \{Erol S.\} and Evelien Tiggelaar and \{van Harmelen\}, Frank and Giovanni Cin{\`a} and Gerty Holla and \{de Jong\}, \{Hilda J.\} and Iacopo Vagliano and Jan Pander and Boomker, \{Jasper M.\} and \{van der Schans\}, Jurjen and Jager, \{Kitty J.\} and Linda Dusseljee-Peute and Hilbrands, \{Luuk B.\} and Comte, \{Marianne le\} and Bak, \{Marieke A. R.\} and \{van den Hoven\}, Mariette and Kersloot, \{Martijn G.\} and Menno Maris and \{de Keizer\}, \{Nicolette F.\} and Maarsingh, \{Otto R.\} and Paul Blank and Piet Heingraaf and Ron Herings and Keizer, \{Ron J.\} and Ronald Cornet and Ruben Boyd and Knijnenburg, \{Sebastiaan L.\} and Sipke Visser and Stephanie Medlock and Visser, \{Tjerk S. Heijmens\} and Stel, \{Vianda S.\} and Wanda Konijn",

year = "2025",

month = jan,

doi = "10.1007/s40264-024-01474-w",

language = "English",

volume = "48",

pages = "43--58",

journal = "Drug Safety",

issn = "0114-5916",

publisher = "Adis",

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Fernández-Llaneza, D, Vos, RMP, Lieverse, JE, Gosselt, HR, Kane-Gill, SL, van Gelder, T, Klopotowska, JE, Consortium, TLEAPOG, Abu-Hanna, A, Dorgelo, A, Teije, AT, Damoiseaux, BA, Boersma, C, Dongelmans, DA, de Koning, DH, Hofmans, ES, Tiggelaar, E, van Harmelen, F, Cinà, G, Holla, G, de Jong, HJ, Vagliano, I, Pander, J, Boomker, JM, van der Schans, J, Jager, KJ, Dusseljee-Peute, L, Hilbrands, LB, Comte, ML, Bak, MAR, van den Hoven, M, Kersloot, MG, Maris, M, de Keizer, NF, Maarsingh, OR, Blank, P, Heingraaf, P, Herings, R, Keizer, RJ, Cornet, R, Boyd, R, Knijnenburg, SL, Visser, S, Medlock, S, Visser, TSH, Stel, VS & Konijn, W 2025, 'An Integrated Approach for Representing Knowledge on the Potential of Drugs to Cause Acute Kidney Injury', Drug Safety, vol. 48, no. 1, e2019209, pp. 43-58. https://doi.org/10.1007/s40264-024-01474-w

TY - JOUR

T1 - An Integrated Approach for Representing Knowledge on the Potential of Drugs to Cause Acute Kidney Injury

AU - Fernández-Llaneza, Daniel

AU - Vos, Romy M. P.

AU - Lieverse, Joris E.

AU - Gosselt, Helen R.

AU - Kane-Gill, Sandra L.

AU - van Gelder, Teun

AU - Klopotowska, Joanna E.

AU - Consortium, the LEAPfROG

AU - Abu-Hanna, Ameen

AU - Dorgelo, Annemiek

AU - Teije, Annette ten

AU - Damoiseaux, Birgit A.

AU - Boersma, Cornelis

AU - Dongelmans, Dave A.

AU - de Koning, David H.

AU - Hofmans, Erol S.

AU - Tiggelaar, Evelien

AU - van Harmelen, Frank

AU - Cinà, Giovanni

AU - Holla, Gerty

AU - de Jong, Hilda J.

AU - Vagliano, Iacopo

AU - Pander, Jan

AU - Boomker, Jasper M.

AU - van der Schans, Jurjen

AU - Jager, Kitty J.

AU - Dusseljee-Peute, Linda

AU - Hilbrands, Luuk B.

AU - Comte, Marianne le

AU - Bak, Marieke A. R.

AU - van den Hoven, Mariette

AU - Kersloot, Martijn G.

AU - Maris, Menno

AU - de Keizer, Nicolette F.

AU - Maarsingh, Otto R.

AU - Blank, Paul

AU - Heingraaf, Piet

AU - Herings, Ron

AU - Keizer, Ron J.

AU - Cornet, Ronald

AU - Boyd, Ruben

AU - Knijnenburg, Sebastiaan L.

AU - Visser, Sipke

AU - Medlock, Stephanie

AU - Visser, Tjerk S. Heijmens

AU - Stel, Vianda S.

AU - Konijn, Wanda

PY - 2025/1

Y1 - 2025/1

N2 - Introduction and Objective The recent rise in acute kidney injury (AKI) incidence, with approximately 30% attributed to potentially preventable adverse drug events (ADEs), poses challenges in evaluating drug-induced AKI due to polypharmacy and other risk factors. This study seeks to consolidate knowledge on the drugs with AKI potential from four distinct sources: (i) bio(medical) peer-reviewed journals; (ii) spontaneous reporting systems (SRS); (iii) drug information databases (DIDs); and (iv) NephroTox website. By harnessing the potential of these underutilised sources, our objective is to bridge gaps and enhance the understanding of drug-induced AKI. Methods By searching Medline, studies with lists of drugs with AKI potential established through consensus amongst medical experts were selected. A final list of 63 drugs was generated aggregating the original studies. For these 63 drugs, the AKI reporting odds ratios (RORs) using three SRS databases, the average frequency of ADEs from four different DIDs and the number of published studies identified via NephroTox was reported. Results Drugs belonging to the antivirals, antibacterials, and non-steroidal anti-inflammatory pharmacological classes exhibit substantial consensus on AKI potential, which was also reflected in strong ROR signals, frequent to very frequent AKI-related ADEs and a high number of published studies reporting adverse kidney events as identified via NephroTox. Renin-angiotensin aldosterone system inhibitors and diuretics also display comparable signal strengths, but this can be attributed to expected haemodynamic changes. More variability is noted for proton-pump inhibitors. Conclusions By integrating four disjointed sources of knowledge, we have created a novel, comprehensive resource on drugs with AKI potential, contributing to kidney safety improvement efforts.

AB - Introduction and Objective The recent rise in acute kidney injury (AKI) incidence, with approximately 30% attributed to potentially preventable adverse drug events (ADEs), poses challenges in evaluating drug-induced AKI due to polypharmacy and other risk factors. This study seeks to consolidate knowledge on the drugs with AKI potential from four distinct sources: (i) bio(medical) peer-reviewed journals; (ii) spontaneous reporting systems (SRS); (iii) drug information databases (DIDs); and (iv) NephroTox website. By harnessing the potential of these underutilised sources, our objective is to bridge gaps and enhance the understanding of drug-induced AKI. Methods By searching Medline, studies with lists of drugs with AKI potential established through consensus amongst medical experts were selected. A final list of 63 drugs was generated aggregating the original studies. For these 63 drugs, the AKI reporting odds ratios (RORs) using three SRS databases, the average frequency of ADEs from four different DIDs and the number of published studies identified via NephroTox was reported. Results Drugs belonging to the antivirals, antibacterials, and non-steroidal anti-inflammatory pharmacological classes exhibit substantial consensus on AKI potential, which was also reflected in strong ROR signals, frequent to very frequent AKI-related ADEs and a high number of published studies reporting adverse kidney events as identified via NephroTox. Renin-angiotensin aldosterone system inhibitors and diuretics also display comparable signal strengths, but this can be attributed to expected haemodynamic changes. More variability is noted for proton-pump inhibitors. Conclusions By integrating four disjointed sources of knowledge, we have created a novel, comprehensive resource on drugs with AKI potential, contributing to kidney safety improvement efforts.

UR - https://www.scopus.com/pages/publications/85205077791

UR - https://www.scopus.com/inward/citedby.url?scp=85205077791&partnerID=8YFLogxK

U2 - 10.1007/s40264-024-01474-w

DO - 10.1007/s40264-024-01474-w

M3 - Article

SN - 0114-5916

VL - 48

SP - 43

EP - 58

JO - Drug Safety

JF - Drug Safety

IS - 1

M1 - e2019209

ER -

An Integrated Approach for Representing Knowledge on the Potential of Drugs to Cause Acute Kidney Injury

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