Quantifying the potential contribution of drugs to the occurrence of acute kidney injury in patients with chronic kidney disease
Authors: Laville Solène M , Vendar Janice , Massy Ziad A , Gras-Champel Valérie , Moragny Julien , Frimat Luc , Laville Maurice , Jacquelinet Christian , Pecoits-Filho Roberto , Alencar De Pinho Natalia , Hamroun Aghilès , Liabeuf Sophie ,   the Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) Study Group, de Pinho Natalia Alencar , Combe Christian , Fouque Denis , Frimat Luc , Hamroun Aghilès , Jacquelinet Christian , Lambert Oriane , Lange Céline , Laville Maurice , Liabeuf Sophie , Massy Ziad A , Metzger Marie , Pascal Christophe , Pecoits-Filho Roberto , Stengel Bénédicte , Hannedouche T , Moulin B , Klein A , Combe C , Bourdenx J P , Keller A , Delclaux C , Vendrely B , Deroure B , Lacraz A , Lobbedez T , Landru I , Massy Z , Lang P , Belenfant X , Thervet E , Urena P , Delahousse M , Vela C , Essig M , Clément D , Sekhri H , Smati M , Jamali M , Hacq B , Panescu V , Bellou M , Frimat Luc , Kamar N , Noël C , Glowacki F , Maisonneuve N , Azar R , Hoffmann M , Hourmant M , Testa A , Besnier D , Choukroun G , Lambrey G , Burtey S , Lebrun G , Magnant E , Laville M , Fouque D , Juillard L , Chazot C , Zaoui P , Kuentz F 
Published: November 2024

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 &lt;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.