PRESENTATION

RenAdaptor© is a computerized drug database indexing more than 2,100 molecules (International Nonproprietary Names [INNs]), i.e., more than 95% of the Western systemic pharmacopoeia. Intended to help physicians and clinical pharmacists "at the bedside" of patients with renal failure, RenAdaptor© is intuitive and does not include information not directly useful for the prescription. It can be integrated into most medical and pharmaceutical software as it is written in PHP format.
All pharmacotherapeutic classes are represented. The same active ingredient (INN) might be the subject of several descriptive sheets, depending on the administration mode or the general indication, with sometimes very variable dosages.
A login and a password (Figure 1) are required to access the entire database. Otherwise, only the "demo" version of 26 INNs is accessible. Some integrated versions no longer require these direct access codes.

Figure 1: Login page

The search is done by entering a keyword, either by typing the first letters of the INN and then selecting it from the drop-down list in the first search box, or by typing any keyword in the second search box (INN, brand name, therapeutic class, reference, etc.) (Figure 2). It is also possible to search by brand name, as brand names of the same INN from more than 30 countries are included in the database.

Figure 2: Search box

Once the search is launched, the results are presented as a list, with the possibility of sorting the active ingredients by alphabetical order or therapeutic subclass (Figure 3). A three-color code enables to quickly see whether a dosage must be adapted or whether the molecule is contraindicated. Green means that no dosage adjustment is required. The orange color indicates that an adaptation is necessary at one or more renal failure stages and/or in case of dialysis. Red means that using this drug is contraindicated in one or more renal failure stages and/or in case of dialysis. Sorting the active ingredients according to the color is possible.

Figure 3: Search results in the form of a list

The detailed molecule sheet for a given mode of administration opens when an active ingredient is selected. This sheet is composed of two pages: the first, the main page, contains the essential information to answer the practitioner's concerns (Figure 4). The second, which is the appendix page, provides additional information (Figure 5). The molecule is classified by specialty, according to its pharmacological properties and the ATC classification. Any biological parameters (therapeutic blood monitoring) to be monitored and their reference values are listed. The loading dose, maintenance doses for patients without renal failure, maintenance doses adapted to the five renal failure stages (GFR in ml/min), doses adapted to the various extrarenal purification techniques (intermittent hemodialysis and hemodiafiltration, peritoneal dialysis, continuous renal replacement therapy [CRRT]) as well as doses adapted to severe liver failure (Child-Pugh B and C), with or without renal failure, are then specified. Finally, the detoxification possibilities by an extracorporeal purification technique (hemodialysis, continuous dialysis, hemoperfusion on charcoal, plasmapheresis) are also mentioned.

Figure 4 : Drug page

Maintenance therapy is adjusted by modifying doses and intake intervals, based on pharmacodynamic and pharmacokinetic properties, but also on certain practical modalities, particularly for hemodialysis patients (e.g., intravenous dosage after dialysis). Dosages are proposed as the extreme ranges of dose and administration frequency. It is therefore up to the practitioner to refine the dosage according to the patient's characteristics (age, gender, weight, etc.), as well as the specific medical indication.
The proposed dosages are based on the most recent data available in the pharmaceutical and medical literature. When no data are available, and in the absence of formal contraindication, the proposed dosages as well as the possibilities of extracorporeal detoxification are based on the detailed analysis of the pharmacodynamics and pharmacokinetics and/or on the experience of the authors, which is then specifically indicated by exclamation marks (!!!).
The proposed dosages only apply to adults and can in no way be extrapolated to children. Likewise, the adapted doses are intended for patients with chronic renal failure and do not apply to patients with acute renal failure. Stage 5 dosages as well as those destined for either dialysis technique can only be suggested in the oligo-anuric phase. During acute renal failure recovery phase, no standard recommendations can be made.
On the "List" and "Sheet" pages, a search by therapeutic class can be made by clicking directly on the corresponding box. This function is useful for a quick search for alternatives (e.g., if the active ingredient found in the first search turns out to be contraindicated).
The second page of each sheet (Figure 5) provides additional information: brand names in more than 30 countries, physicochemical, pharmacokinetic, and toxicological properties, as well as an exhaustive list of specific references (more than 20,000 for the entire database).

Figure 5: Appendix page

The software is available in four languages (English, French, German, and Dutch), which can be easily switched between by clicking on the respective flag.
Topical preparations (dermatological, ophthalmological, aerosol, etc.) as well as vaccines are not currently included, as they do not usually require adaptation to renal failure. As a reminder, inactivated vaccines can be given in double doses, whereas attenuated vaccines should be avoided because of the relative immunodeficiency of renal failure patients.
Several specific tabs complete this information: • "Introduction" covers the basics of medication adaptation to CKD. • "Help" gives information on how to use the sheet and its different tabs. • "Who are we?" presents the medical and IT teams that manage the program. • "License and terms of use" explains the limits of use of the presented data. • "Reference" gathers the main medical and pharmacological bibliography, as well as the data from the Internet that have been used. • "Contacts" gives all the information about the authors of the program and gives the possibility to contact them for comments or to ask a direct question.
The content of the database was developed and is updated daily by a team of five nephrologists, two infectious diseases specialists, and a clinical pharmacologist. The computer management is ensured by a team of specialized computer specialists.
A personalized dose, renal function, and liver function calculator is proposed, based on individual biochemical and biometric data, to obtain an accurate categorization of each patient (Figure 6). Thanks to an intelligent algorithm, the personalized CKD stage is automatically determined.

Figure 6: Calculator – "data" page

A simplified version is available on smartphones and tablets. On a mobile device, the user is automatically directed to this version. The user can switch to the basic version at any moment by clicking on the "Exit mobile mode" tab and then return to the mobile version by clicking on the "Mobile mode" tab.
The major assets of RenAdaptor© are its simplicity of use and its accessibility. All our efforts are aimed at providing accurate, up-to-date, and complete information, although no absolute guarantee can be given. This tool has no other claim than to be a simple prescription aid. It does not replace the practitioner's clinical judgment, who remains responsible for his/her decisions.
The brand names are mentioned to facilitate the search. The molecule(s) found by this means is/are contained in the drug's formulation, without considering the presentation, the administration mode, the possible other components, or any other parameter.
The authors of this work cannot be held responsible for therapeutic or other accidents, nor for any possible consequences due to the use or non-use of the software and its contents.

History:

1994-96 : : The "Practical guide to hemodialysis", a syllabus for nephrology assistants at the Liege University Hospital in Belgium, is written by Dr. Luc Radermacher (nephrologist). Chapter 25: "Pharmacological adaptations to renal failure and dialysis"; 400 drugs are processed on an Excel spreadsheet. Creation of the "Pharmacological adaptations to renal failure and extrarenal purification techniques" booklet. Overall, 200 copies based on the Excel file reporting the 400 molecules of the practical guide are published, with the help of the GlaxoWellcome company, and distributed in the hospitals of the Liège region.

2000 : Association with a computer scientist (Mr. Georgios Dracoulis). Creation of the first database on CD-ROM, in FileMaker format, still containing the 400 original molecules updated. Name given: Adaptor.

2006: Expansion of the Adaptor database to 600 molecules and new name: Renadaptor. Medical team expended to four internists (three nephrologists: Dr. Luc Radermacher, Dr. Xavier Warling, and Dr. Martial Moonen; and one infectious diseases specialist: Dr. Eric Firre - CHR de Liège/Citadelle). Translation in four languages (French, English, German, and Dutch).

2009 : Creation of the first internet version of Renadaptor (www.renadaptor.net), still in FileMaker format. "RenAdaptor©" copyright. Expansion of the database to 800 molecules. Several presentations for physicians and clinical pharmacists in Belgian hospitals. Death of Mr. Georgios Dracoulis and IT function taken over by Mr. Ivon Hixon.

2010 : Internet version in PHP format. Expansion of the database to 1,000 molecules. Constitution of the company Medicinformatic sprl and legal framework (DBB association of lawyers - Mons). Poster presented at the nephrology society congress in Brussels.

2012 : Sponsorship by the Groupement de Néphrologues Francophones de Belgique (GNFB). Expansion of the database to 1,300 molecules.

2013 : Expansion of the database to 1,400 molecules.
First "Kidneys & Drugs" symposium in Liege.

2014: Certification of the HONcode ethical label (N°: HONConduct354525). Expansion of the database to 1,500 molecules. Expansion of the IT team to two computer scientists: Mr. Ivon Hixon and Mr. Rachid Bimaghra.
Second symposium "Kidneys & Drugs" on the theme of cardiovascular treatments.

2015 : Creation of a personalized dose calculator, renal function, and hepatic function.
Third "Kidneys & Drugs" symposium on the theme of infectious diseases.

2016 : Creation of a mobile version for smartphones and tablets. Expansion of the database to 1,700 molecules.
Fourth "Kidneys & Drugs" symposium on the theme of pain management.

2017 : ATC encoding. Expansion of the scientific team to five nephrologists (Drs. Luc Radermacher, Xavier Warling, Martial Moonen, Catherine Masset, and Martina Milicevic), two infectious diseases specialists (Drs. Eric Firre and Filip Moerman), and a clinical pharmacist (Mr. Blaise Delhauteur).
Fifth "Kidneys & Drugs" symposium on the theme of new targeted therapies in oncology.

2018 : Development of a second internet version with complete redefinition of graphic outlines. Creation of a medical secretary position for systematic proofreading and sheet syntax standardization, ATC encoding, etc.
Sixth symposium "Kidneys & Drugs" on the theme of fair prescribing in geriatrics.

2019 : The second version of RenAdaptor© becomes active on February 15 at www.renadaptor.org , www.renadaptor.com, www.renadaptor.fr or www.renadaptor.be. Expansion of the database to 1,900 molecules. Creation of a "News" window, divided into four categories: "Company", "Drugs", "Scientists", and "Presentations".
Seventh "Kidneys & Medicines" symposium on gastroenterology treatments.

2020 : : Medicinformatic bvba becomes AGTI SA Dpt NVI. Dr. Filip Moerman, infectious disease specialist, leaves the medical team. Mr. Ivon Hixon leaves the IT team. Expansion of the database to 1,970 molecules.
Eighth "Kidneys & Drugs" symposium, virtually due to the COVID-19 pandemic, on the theme of new antidiabetics in renal failure.

2021 : Created a new "Create List" feature, enabling a created list of drugs to be saved. Created a direct link from references to the PubMed database for abstract reading. Updated the renal function calculator based on the new GFR estimation equations (EKFC and CKD-EPI). Dr. Martina Milicevic, nephrologist, leaves the medical team. Expansion of the database to 2,030 molecules (INN).

2022 : Eighth "Kidneys & Drugs" symposium, in face-to-face mode, on the theme of renal function assessment. Expansion of the database to 2085 molecules (INN).
Signing of a distribution contract with the company Axilios
Dr. Martial Moonen, nephrologist, and Dr. Eric Firre, infectious diseases specialist, leave the medical team.

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