Solène M Laville1, Valérie Gras-Champel2, Julien Moragny2, Marie Metzger1, Christian Jacquelinet1,3, Christian Combe4,5, Denis Fouque6, Maurice Laville6, Luc Frimat7,8, Bruce M Robinson9, Bénédicte Stengel10, Ziad A Massy1,11, Sophie Liabeuf2,12. 1. Paris-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. 2. Department of Clinical Pharmacology, Amiens University Hospital, Amiens, France. 3. Renal Epidemiology and Information Network Registry, Biomedicine Agency, Saint Denis, France. 4. Department of Nephrology Transplantation Dialysis, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France. 5. Inserm Unit 1026, University of Bordeaux Segalen, Bordeaux, France. 6. Nephrology Department, Centre Hospitalier Lyon Sud, Université de Lyon, Carmen, Pierre-Bénite, France. 7. Nephrology Department, Centre Hospitalier Régional Universitaire de Nancy, Vandoeuvre-lès-Nancy, France. 8. Lorraine University, APEMAC, Vandoeuvre-lès-Nancy, France. 9. Arbor Research Collaborative for Health, Ann Arbor, Michigan. 10. Paris-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 benedicte.stengel@inserm.fr. 11. Division of Nephrology, Ambroise Paré University Hospital, Assistance publique - Hôpitaux de Paris, Boulogne-Billancourt/Paris, France. 12. MP3CV Laboratory, EA7517, University of Picardie Jules Verne, Amiens, France.
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.
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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