Quantifying the potential contribution of drugs to the occurrence of acute kidney injury in patients with chronic kidney disease

Solène M Laville; Janice Vendar; Ziad A Massy; Valérie Gras-Champel; Julien Moragny; Luc Frimat; Maurice Laville; Christian Jacquelinet; Roberto Pecoits-Filho; Natalia Alencar De Pinho; Aghilès Hamroun; Sophie Liabeuf; Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) Study Group

doi:10.1093/ckj/sfae357

Quantifying the potential contribution of drugs to the occurrence of acute kidney injury in patients with chronic kidney disease

Clin Kidney J. 2024 Nov 18;18(1):sfae357. doi: 10.1093/ckj/sfae357. eCollection 2025 Jan.

Authors

Solène M Laville^{1

2}, Janice Vendar¹, Ziad A Massy^{3

4}, Valérie Gras-Champel⁵, Julien Moragny⁵, Luc Frimat^{6

7}, Maurice Laville⁸, Christian Jacquelinet^{3

9}, Roberto Pecoits-Filho¹⁰, Natalia Alencar De Pinho³, Aghilès Hamroun^{11

12}, Sophie Liabeuf^{1

2}; Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) Study Group

Collaborators

Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) Study Group:
Natalia Alencar de Pinho, Christian Combe, Denis Fouque, Luc Frimat, Aghilès Hamroun, Christian Jacquelinet, Oriane Lambert, Céline Lange, Maurice Laville, Sophie Liabeuf, Ziad A Massy, Marie Metzger, Christophe Pascal, Roberto Pecoits-Filho, Bénédicte Stengel, T Hannedouche, B Moulin, A Klein, C Combe, J P Bourdenx, A Keller, C Delclaux, B Vendrely, B Deroure, A Lacraz, T Lobbedez, I Landru, Z Massy, P Lang, X Belenfant, E Thervet, P Urena, M Delahousse, C Vela, M Essig, D Clément, H Sekhri, M Smati, M Jamali, B Hacq, V Panescu, M Bellou, Luc Frimat, N Kamar, C Noël, F Glowacki, N Maisonneuve, R Azar, M Hoffmann, M Hourmant, A Testa, D Besnier, G Choukroun, G Lambrey, S Burtey, G Lebrun, E Magnant, M Laville, D Fouque, L Juillard, C Chazot, P Zaoui, F Kuentz

Affiliations

¹ Pharmacoepidemiology Unit, Department of Clinical Pharmacology, Amiens-Picardie University Medical Center, Amiens, France.
² MP3CV Laboratory, Jules Verne University of Picardie, Amiens, France.
³ Centre for Research in Epidemiology and Population Health (CESP), INSERM UMRS 1018, Université Paris-Saclay, Université Versailles Saint Quentin, Villejuif, France.
⁴ Department of Nephrology, Ambroise Paré University Hospital, APHP, Boulogne-Billancourt/Paris, France.
⁵ Pharmacovigilance Center, Department of Clinical Pharmacology, Amiens-Picardie University Medical Center, Amiens, France.
⁶ Nephrology Department, Centre Hospitalier Régional Universitaire de Nancy, Vandoeuvre-lès-Nancy, France.
⁷ Lorraine University, APEMAC, Vandoeuvre-lès-Nancy, France.
⁸ Université de Lyon, CarMeN INSERM 1060, Lyon, France.
⁹ Biomedicine Agency, Saint Denis, France.
¹⁰ Arbor Research Collaborative for Health, Ann Arbor, MI, USA.
¹¹ Department of Public Health - Epidemiology, Lille University, Lille Regional University Medical Center, Lille, France.
¹² UMR1167 RID-AGE, INSERM, Institut Pasteur de Lille, Lille University, Lille, France.

Abstract

Background: We sought to comprehensively describe drug-related components associated with acute kidney injury (AKI) in patients with chronic kidney disease (CKD), describing the incidence of drug-related AKI, the proportion of preventable AKI, identified the various drugs potentially associated with it, explored the risk factors, and assessed the 1-year incidences of the recurrence of drug-related AKI, kidney failure, and death.

Methods: CKD-REIN is a French national prospective cohort of 3033 nephrology outpatients with a confirmed diagnosis of CKD (eGFR <60 ml/min/1.73 m²). AKIs and adverse drug reactions (ADRs) were prospectively identified from hospital reports, medical records, and patient interviews. Expert nephrologists used the KDIGO criteria to adjudicate all stages of AKI, and expert pharmacologists used validated tools to adjudicate ADRs (including drug-related AKIs).

Results: Over a median [interquartile range] period of 4.9 [3.4-5.1] years, 832 cases of AKI were reported in 639 (21%) of the 3033 study participants. The drug-related component associated with AKI accounted for 236 cases, and 28% were judged to be preventable or potentially preventable. The three most frequently implicated drug classes were diuretics, renin-angiotensin system inhibitors, and contrast agents. A history of cardiovascular events, diabetes, lower levels of hemoglobin and eGFR, poor medication adherence, and ≥5 drugs taken daily were associated with a greater risk of drug-related AKI. Full recovery was not attained in 64 (27%) of the 236 cases of drug-related AKI. The 1-year cumulative incidences of recurrence of drug-related AKI, kidney replacement therapy, and death were 7%, 15%, and 11%, respectively, after the first drug-related AKI.

Conclusions: Drug-related AKI is prevalent among patients with CKD. Even though a substantial proportion of these events were classified as stage 1, our findings point to a poor prognosis.

Keywords: acute kidney injury; adverse drug reaction; chronic kidney disease; drugs; pharmacoepidemiology.