Drug-Induced Acute Kidney Injury: a Study from the French Medical Administrative and the French National Pharmacovigilance Databases Using Capture-Recapture Method
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Journal of Clinical Medicine Article Drug-Induced Acute Kidney Injury: A Study from the French Medical Administrative and the French National Pharmacovigilance Databases Using Capture-Recapture Method Anne-Lise Rolland 1 , Anne-Sophie Garnier 2,3, Katy Meunier 1, Guillaume Drablier 4 and Marie Briet 2,4,* 1 Département d’Information Médicale, Centre Hospitalo-Universitaire d’Angers, 49100 Angers, France; [email protected] (A.-L.R.); [email protected] (K.M.) 2 Service de Néphrologie-Dialysis-Transplantation, Centre Hospitalo-Universitaire d’Angers, 49100 Angers, France; [email protected] 3 Laboratoire MitoVasc, INSERM U1083, CNRS UMR 6015, Université d’Angers, 49100 Angers, France 4 Service de Pharmacologie-Toxicologie et Centre Régional de Pharmacovigilance, Centre Hospitalo-Universitaire d’Angers, 49100 Angers, France; [email protected] * Correspondence: [email protected] Abstract: Background: Acute kidney injury (AKI) is a public health concern. Among the pathological situations leading to AKI, drugs are preventable factors but are still under-notified. We aimed to pro- vide an overview of drug-induced AKI (DIAKI) using pharmacovigilance and medical administrative databases Methods: A query of the PMSI database (French Medical Information System Program) of adult inpatient hospital stays between 1 January 2017 and 31 December 2018 was performed using ICD-10 (International Classification of Diseases 10th revision) codes to identify AKI cases which were reviewed by a nephrologist and a pharmacovigilance expert to identify DIAKI cases. In parallel, DIAKIs notified in the French Pharmacovigilance Database (FPVDB) were collected. A capture- Citation: Rolland, A.-L.; Garnier, A.-S.; Meunier, K.; Drablier, G.; Briet, recapture method was performed to estimate the total number of DIAKIs. Results: The estimated M. Drug-Induced Acute Kidney total number of DIAKIs was 521 (95%CI 480; 563), representing 20.0% of all AKIs. The notification Injury: A Study from the French was at a rate of 12.9% (95%CI 10.0; 15.8). According to the KDIGO classification, 50.2% of the DI- Medical Administrative and the AKI cases were stage 1 and 49.8% stage 2 and 3. The mortality rate was 11.1% and 9.6% required French National Pharmacovigilance hemodialysis. Conclusion: This study showed that drugs are involved in a significant proportion of Databases Using Capture-Recapture patients developing AKI during a hospital stay and emphasizes the severity of DIAKI cases. Method. J. Clin. Med. 2021, 10, 168. https://doi.org/10.3390/jcm10020168 Keywords: drug-induced acute kidney injury; capture-recapture method; KDIGO; French pharma- covigilance database; French medical information system program; notification rate Received: 20 November 2020 Accepted: 31 December 2020 Published: 6 January 2021 1. Introduction Publisher’s Note: MDPI stays neu- tral with regard to jurisdictional clai- Acute kidney injury (AKI) is an increasing health burden worldwide in terms of ms in published maps and institutio- morbidity, mortality, and economic impact [1]. The hospital incidence rate for AKI in adults nal affiliations. is 22% and the pooled AKI-associated mortality rates are 24% according to the international meta-analysis performed by Susantitaphong et al. [2]. In addition, AKI is an increasingly recognized risk factor for chronic kidney disease (CKD) and end-stage renal disease [3,4]. Many types of pathological situations may cause AKI including sepsis, critical illness, Copyright: © 2021 by the authors. Li- circulatory shock, radiocontrast agents, and nephrotoxic drugs. Among them, exposure to censee MDPI, Basel, Switzerland. nephrotoxic drugs or radiocontrast agents are preventable factors [5,6]. A deeper under- This article is an open access article standing will allow us to prevent the risk of drug-induced acute kidney injury (DIAKI). distributed under the terms and con- The pharmacovigilance system is based on spontaneous notifications by clinicians. ditions of the Creative Commons At- According to a systematic review of under-reporting of adverse drug reaction (ADRs), tribution (CC BY) license (https:// the median rate of reporting is around 6% [7]. In most cases, the ADRs reported are creativecommons.org/licenses/by/ 4.0/). those that are serious and/or unknown. The current pharmacovigilance system cannot J. Clin. Med. 2021, 10, 168. https://doi.org/10.3390/jcm10020168 https://www.mdpi.com/journal/jcm J. Clin. Med. 2021, 10, 168 2 of 12 therefore provide an exhaustive overview of ADRs occurring in hospitals. In addition to the pharmacovigilance data, epidemiological studies have shown that the French Medical Information System Program (PMSI) is an efficient tool to detect ADRs [8,9]. Using these two databases, the use of the capture-recapture method could provide an estimation of the prevalence of all ADRs of interest such as DIAKIs [10]. The aims of the present study, based on the PMSI and the French Pharmacovigilance Database (FPVDB), is to provide an overview of DIAKI in terms of prevalence, notification, clinical presentation, and involved drugs, and to define the best ICD-10 code association for DIAKI detection. 2. Materials and Methods 2.1. Data Sources This retrospective study was conducted in the University Hospital of Angers (Pays de la Loire, France) with a total number of hospital admissions around 100,000 per year. Two data sources were used: the PMSI database of the Angers University Hospital and the FPVDB. The ethical committee of the Angers University Hospital and the French data protection authority (CNIL) approved the study (decision novar19-0067v0). The French PMSI generates diagnosis-related groups containing administrative data (name, gender, birthdates, dates of hospital admission and discharge), all the diagnoses coded following the International Classification of Diseases 10th revision (ICD-10) and the procedures coded from the Common Classification of Medical Procedures (CCMP), reported by the physicians for each hospital stay. The FPVDB includes all adverse drug reaction (ADR) reports notified to a French regional pharmacovigilance center since 1985 by healthcare professionals and patients. ADR notification by healthcare professionals to the pharmacovigilance system is mandatory by law in France especially for serious and/or unexpected ADR. The registered reports are anonymous. However, the original medical records are archived in the pharmacovigilance center of the university hospital that allows the coupling of the two databases. 2.2. Case Definition We investigated all adult cases of acute kidney injury (AKI) that were managed during a hospital stay with an entry date between 1 January 2017 and 31 December 2018. The definition of the KDIGO (Kidney Disease Improving Global Outcomes) 2012 guidelines were used as diagnostic criteria. To summarize, AKI diagnosis was retained in the presence of one of the following three criteria: i/an increase in serum creatinine greater than 1.5 times the proven or presumed base creatinine in the previous seven days, ii/an increase in serum creatinine greater than or equal to 26.5 µmol/Lin 48 h, or iii/a diuresis of less than 0.5 mL/kg/hour over a minimum period of six h [11]. 2.3. Collection of Drug-Induced Acute Kidney Injury (DIAKIs) Cases The request made from the PMSI of the Angers University Hospital was based on the following criteria: All stays with an entry date between 1 January 2017 and 31 De- cember 2018, adults aged 18 and over, with an ICD-10 code [12] as the main diagnosis or as associated diagnosis recorded: N17.0, N17.1, N17.2, N17.8, N17.9, N99.0, or R39.2 (Table S1). The following variables were automatically extracted: sex, length of stay (days), date of entry, date of discharge, age of the patient at hospital discharge, mode of patient discharge (death, transfer, return home), passage to a medical or surgical resuscitation unit. Recorded codes of renal replacement therapy (RRT) according to the French Com- mon Classification of Medical Procedures (CCMP) were JVJF002 (RRT by intermittent hemodialysis, hemofiltration, or hemodiafiltration for AKI), JVJF005 (RRT by continuous hemodialysis, hemofiltration, or hemodiafiltration for AKI) and JVJB002 (RRT by peritoneal dialysis for AKI) [13]. The following stays were excluded: stays with an act CCMP of renal transplantation, stays where the patient already had end-stage renal disease supple- mented by dialysis, stays with voluntary drug intoxication, and stays with drug overdose. J. Clin. Med. 2021, 10, 168 3 of 12 When several stays referred to the same AKI episode, the first stay or the stay with a notification to the RPVC was selected. All cases were reviewed by a nephrologist and a pharmacovigilance expert to check if the AKI episodes met the definition of the KDIGO. All stays with an episode of AKI not meeting this definition were excluded. All included stays were reviewed by a pharmacovigilance expert and/or a nephrologist to investigate whether a drug-related cause was suspected in the onset of the AKI episode according to observations, reports, and letters related to the stay. For each included stay, the PMSI coding was examined: the AKI ICD-10 codes used (N17, N99, or R39.2) and the presence of the ICD-10 code for adverse drug reaction (ADR) (T88.1, codes Y40, and codes Y50). We extracted all DIAKIs from the FPVDB using the following criteria: notification by a health professional of the Angers University Hospital, ADR occurring between 1 January 2017, and 31 December 2018, adult 18 years of age or older, including the LLT (Lowest Level Term) of the Medical Dictionary for Regulatory Activities (MedDRA): “Creatinine increased”, “Serum creatinine increased”, “Blood creatinine increased”, “Re- nal function aggravated”, “Renal failure”, “Renal insufficiency”, “Acute renal failure”, “Acute renal insufficiency”, “Renal failure aggravated”, “Renal insufficiency aggravated”, “Acute on chronic renal failure”, “Renal failure acute on chronic”, or “Anuric renal fail- ure” [14]. Next, for each selected notification, we verified that the definition of the AKI met the definition provided by the KDIGO guidelines and if there was a hospital stay corresponding to the case recorded in the PMSI by matching.