Kidney Function Decline and Serious Adverse Drug Reactions in Patients With CKD
Solène M. Laville, Valérie Gras‐Champel, Aghilès Hamroun, Julien Moragny, Oriane Lambert, Marie Metzger, Christian Jacquelinet, Christian Combe, Denis Fouque, Maurice Laville, Luc Frimat, Bruce Robinson, Brian Bieber, Bénédicte Stengel, Natália Alencar de Pinho, Ziad A. Massy, Sophie Liabeuf, Carole Ayav, Serge Briançon, Dorothée Cannet, Christian Combe, Denis Fouque, Luc Frimat, Yves-Édouard Herpe, Christian Jacquelinet, Maurice Laville, Ziad A. Massy, Christophe Pascal, Bruce Robinson, Bénédicte Stengel, Céline Lange, Karine Legrand, Sophie Liabeuf, Marie Metzger, Élodie Speyer, Thierry Hannedouche, Bruno Moulin, Sébastien Mailliez, Gaëtan Lebrun, Éric Magnant, Gabriel Choukroun, Benjamin Deroure, Adeline Lacraz, G Lambrey, Jean Philippe, Bourdenx, Marie Essig, Thierry Lobbedez, Raymond Azar, Hacène Sekhri, Mustafa Smati, Mohamed Jamali, Alexandre Klein, Michel Delahousse, Christian Combe, Séverine Martin, Isabelle Landru, Éric Thervet, Ziad A. Massy, Philippe Lang, Xavier Belenfant, Pablo Ureña, Carlos Vela, Luc Frimat, Dominique Chauveau, Viktor Panescu, Christian Noël, François Glowacki, Maxime Hoffmann, Maryvonne Hourmant, Dominique Besnier, Angelo Testa, F Kuentz, Philippe Zaoui, Charles Chazot, Laurent Juillard, Stéphane Burtey, Adrien Keller, Nassim Kamar, Denis Fouque, Maurice Laville
Abstract
Rationale & ObjectiveAdverse drug reactions (ADRs) are common in patients with chronic kidney disease (CKD). The impact of kidney function decline on serious ADR risk has been poorly investigated. We comprehensively describe ADRs and assess the relationship between estimated glomerular filtration rate (eGFR) and serious ADR risk.Study DesignProspective cohort study.Setting & Participants3,033 participants in French Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort study, a nationwide sample of nephrology outpatients with moderate to advanced CKD.PredictorsDemographic and biological data (including eGFR), medication prescriptions.OutcomeADRs (preventable or not) were prospectively identified from hospital discharge reports, medical records, and patient interviews. Expert pharmacologists used validated tools to adjudicate ADRs.Analytical ApproachRestricted cubic splines in fully adjusted cause-specific Cox proportional hazard models were used to evaluate the relationship between eGFR and the risk of serious ADRs (overall and by subtype).ResultsDuring a median follow-up period of 4.7 years, 360 patients experienced 488 serious ADRs. Kidney and urinary disorders (n = 170) and hemorrhage (n = 170) accounted for 70% of serious ADRs. The most common medications classes were antithrombotics and renin-angiotensin system inhibitors. The majority of those serious ADRs were associated with hospitalization (n = 467), with 32 directly or indirectly associated with death and 22 associated with a life-threatening event. More than 27% of the 488 serious ADRs were preventable or potentially preventable. The eGFR is a major risk factor for serious ADRs. The risk of acute kidney injury was 2.2% higher and risk of bleeding ADRs was 8% higher for each 1 mL/min/1.73 m2 lower baseline eGFR.LimitationsThe results cannot be extrapolated to patients who are not being treated by a nephrologist.ConclusionsADRs constitute a major cause of hospitalization in CKD patients for whom lower eGFR level is a major risk factor.Plain-Language SummaryPatients with chronic kidney disease (CKD) have complex clinical presentations, take multiple medications, and often receive inappropriate prescriptions. Using data from a large, prospective CKD cohort, we found a high incidence of serious adverse drug reactions (ADRs). The 2 most common serious ADRs were drug-induced acute kidney injury and bleeding. A large proportion of serious ADRs required hospital admission, and 11% led to death or were life threatening. Lower kidney function was a major risk factor for serious ADRs. Many of these serious ADRs were determined to be partly preventable through greater adherence to prescription guidelines. This report enhances our understanding of the potential toxicity of drugs taken by patients with moderate to advanced CKD. It emphasizes the importance of monitoring kidney function when prescribing drugs, particularly for high-risk medications such as antithrombotic agents. Adverse drug reactions (ADRs) are common in patients with chronic kidney disease (CKD). The impact of kidney function decline on serious ADR risk has been poorly investigated. We comprehensively describe ADRs and assess the relationship between estimated glomerular filtration rate (eGFR) and serious ADR risk. Prospective cohort study. 3,033 participants in French Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort study, a nationwide sample of nephrology outpatients with moderate to advanced CKD. Demographic and biological data (including eGFR), medication prescriptions. ADRs (preventable or not) were prospectively identified from hospital discharge reports, medical records, and patient interviews. Expert pharmacologists used validated tools to adjudicate ADRs. Restricted cubic splines in fully adjusted cause-specific Cox proportional hazard models were used to evaluate the relationship between eGFR and the risk of serious ADRs (overall and by subtype). During a median follow-up period of 4.7 years, 360 patients experienced 488 serious ADRs. Kidney and urinary disorders (n = 170) and hemorrhage (n = 170) accounted for 70% of serious ADRs. The most common medications classes were antithrombotics and renin-angiotensin system inhibitors. The majority of those serious ADRs were associated with hospitalization (n = 467), with 32 directly or indirectly associated with death and 22 associated with a life-threatening event. More than 27% of the 488 serious ADRs were preventable or potentially preventable. The eGFR is a major risk factor for serious ADRs. The risk of acute kidney injury was 2.2% higher and risk of bleeding ADRs was 8% higher for each 1 mL/min/1.73 m2 lower baseline eGFR. The results cannot be extrapolated to patients who are not being treated by a nephrologist. ADRs constitute a major cause of hospitalization in CKD patients for whom lower eGFR level is a major risk factor.