Original Articles: Chronic Kidney Disease

Adverse Drug Reactions in Patients with CKD

Laville, Solène M.; Gras-Champel, Valérie; Moragny, Julien; Metzger, Marie; Jacquelinet, Christian; Combe, Christian; Fouque, Denis; Laville, Maurice; Frimat, Luc; Robinson, Bruce M.; Stengel, Bénédicte; Massy, Ziad A.; Liabeuf, Sophie; on behalf of the Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) Study Group

Author Information

¹Paris-Saclay University, Versailles Saint-Quentin-en-Yvelines University, National Institute of Health and Medical Research, Center for research in Epidemiology and Population Health (CESP), Clinical Epidemiology Team, Villejuif, France

²Department of Clinical Pharmacology, Amiens University Hospital, Amiens, France

³Renal Epidemiology and Information Network Registry, Biomedicine Agency, Saint Denis, France

⁴Department of Nephrology Transplantation Dialysis, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France

⁵Inserm Unit 1026, University of Bordeaux Segalen, Bordeaux, France

⁶Nephrology Department, Centre Hospitalier Lyon Sud, Université de Lyon, Carmen, Pierre-Bénite, France

⁷Nephrology Department, Centre Hospitalier Régional Universitaire de Nancy, Vandoeuvre-lès-Nancy, France

⁸Lorraine University, APEMAC, Vandoeuvre-lès-Nancy, France

⁹Arbor Research Collaborative for Health, Ann Arbor, Michigan

¹⁰Division of Nephrology, Ambroise Paré University Hospital, Assistance publique – Hôpitaux de Paris, Boulogne-Billancourt/Paris, France

¹¹MP3CV Laboratory, EA7517, University of Picardie Jules Verne, Amiens, France

Correspondence: Dr. Bénédicte Stengel, Équipe Épidémiologie Clinique, Centre for Epidemiology and Population Health (CESP) — Inserm U1018, 16 Avenue P. Vaillant Couturier, Villejuif Cedex, France. Email: [email protected]

^*The CKD-REIN Study Group steering committee and coordinators are as follows: Natalia Alencar De Pinho, Carole Ayav, Serge Briançon, Dorothée Cannet, C.C., D.F., L.F., Yves-Edouard Herpe, C.J., M.L., Z.A.M., Christophe Pascal, B.M.R., B.S., Céline Lange, Karine Legrand, S.L., M.M., and Elodie Speyer. The CKD-REIN investigators/collaborators are as follows: Thierry Hannedouche, Bruno Moulin, Sébastien Mailliez, Gaétan Lebrun, Eric Magnant, Gabriel Choukroun, Benjamin Deroure, Adeline Lacraz, Guy Lambrey, Jean Philippe Bourdenx, Marie Essig, Thierry Lobbedez, Raymond Azar, Hacène Sekhri, Mustafa Smati, Mohamed Jamali, Alexandre Klein, Michel Delahousse, C.C., Séverine Martin, Isabelle Landru, Eric Thervet, Z.A.M., Philippe Lang, Xavier Belenfant, Pablo Urena, Carlos Vela, L.F., Dominique Chauveau, Viktor Panescu, Christian Noel, François Glowacki, Maxime Hoffmann, Maryvonne Hourmant, Dominique Besnier, Angelo Testa, François Kuentz, Philippe Zaoui, Charles Chazot, Laurent Juillard, Stéphane Burtey, Adrien Keller, Nassim Kamar, D.F., and M.L.

CJASN 15(8):p 1090-1102, August 2020. | DOI: 10.2215/CJN.01030120

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Abstract

Background and objectives

Little is known about the burden of adverse drug reactions in CKD. We estimated the incidence of overall and serious adverse drug reactions and assessed the probability of causation, preventability, and factors associated with adverse drug reactions in patients seen by nephrologists.

Design, setting, participants, & measurements

The Chronic Kidney Disease-Renal Epidemiology and Information Network cohort included 3033 outpatients (65% men) with CKD and eGFR<60 ml/min per 1.73 m², with follow-up for 2 years. Adverse drug reactions were identified from hospitalization reports, medical records, and participant interviews and finally assessed for causality, preventability, and immediate therapeutic management by experts in pharmacology.

Results

Median (interquartile range) age was 69 (60–76) years old; 55% had eGFR≥30 ml/min per 1.73 m², and 45% had eGFR<30 ml/min per 1.73 m². Participants were prescribed a median (range) of eight (five to ten) drugs. Over 2 years, 536 patients had 751 adverse drug reactions, 150 (in 125 participants) classified as serious, for rates of 14.4 (95% confidence interval, 12.6 to 16.5) and 2.7 (95% confidence interval, 1.7 to 4.3) per 100 person-years, respectively. Among the serious adverse drug reactions, 32% were considered preventable or potentially preventable; 16 caused death, directly or indirectly. Renin-angiotensin system inhibitors (15%), antithrombotic agents (14%), and diuretics (10%) were the drugs to which the most adverse drug reactions were imputed, but antithrombotic agents caused 34% of serious adverse drug reactions. The drug was discontinued in 71% of cases, at least temporarily. Adjusted hazard ratios for serious adverse drug reaction were significantly higher in patients with eGFR<30 versus ≥30 ml/min per 1.73 m² (1.8; 95% confidence interval, 1.3 to 2.6), in those prescribed more than ten versus less than five medications (2.4; 95% confidence interval, 1.1 to 5.2), or in those with poor versus good adherence (1.6; 95% confidence interval, 1.4 to 2.4).

Conclusions

Adverse drug reactions are common and sometimes serious in patients with CKD. Many serious adverse drug reactions may be preventable. Some specific pharmacologic classes, particularly antithrombotic agents, are at risk of serious adverse drug reactions.

Clinical Trial registry name and registration number

Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN), NCT03381950

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Article Keywords

Keywords
chronic kidney disease, pharmacoepidemiology, antithrombotic agents, adverse drug reactions, risk factors, diuretics, Renin-Angiotensin System, glomerular filtration rate, Cohort Studies, Renal Insufficiency, Chronic, Drug-Related Side Effects and Adverse Reactions, hospitalization, Medical Records

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Adverse Drug Reactions in Patients with CKD