Abstract
Objectives
Chronic kidney disease (CKD) is a common disorder all over the world. Therapeutic goals are early detection of declining renal function and implementation of adequate pharmacological treatments regarding underlying and secondary diseases. As therapy becomes more complex with increasing stages of CKD, a decision-making tool for healthcare professionals could help to ensure safe drug treatment in patients with CKD in the outpatient setting. Therefore, a list of renally relevant drugs as a decision-making tool was developed to improve medicines optimisation for CKD patients in the outpatient setting long term.
Methods
A renally relevant drug list (RRD-list) with renally relevant drugs, based on data from a study on medicines optimisation in patients with CKD from June 2015 to March 2018, was developed at the nephrological outpatient clinic at the Klinikum Fulda, Germany. The whole study is published elsewhere. A clinical pharmacist reviewed the patients’ medications, current drug-related problems and all nephrologists’ recommendations, and categorised all detected drugs into renally relevant and non-renally relevant groups. The 10 most frequently detected renally relevant drug groups were summarised in the RRD-list and extended by treatment alternatives and advice.
Results
The medication of 160 patients, who were receiving overall 1376 drugs, was analysed; 831 drugs were defined as renally relevant. Drug-related problems were caused by 543 renally relevant drugs. The nephrologists made 292 recommendations regarding 28 drug classes. Considering the 10 most frequent drug groups, in total 16 renally relevant drug groups with 36 drug classes were added to the RRD-list.
Conclusions
The RRD-list could be an essential tool for all healthcare professionals in their daily work, such as general practitioners and community pharmacists, for the treatment of patients with renal insufficiency.
Keywords: kidney failure, chronic, pharmacy service, hospital, safety, drug-related side effects and adverse reactions, nephrology
Introduction
Chronic kidney disease (CKD) is a common disorder all over the world.1–4 In Europe there is no updated data system which records newly occurred cases of CKD without renal replacement therapy per year. Data about the prevalence of CKD in Europe can only be estimated.2 5 For example, the prevalence in Germany varies for adults with at least CKD stage 3 or higher from 2.3% up to 25.5%, depending on comorbidities and increased age.2 6 Although the prevalence of CKD varies worldwide, data from high-income countries including Germany and the USA can be compared.7 This includes the assumption of similar values for the largest increase in CKD stage 3.8–10
CKD is frequently a consequence of several underlying diseases and risk factors such as age >60 years, arterial hypertension, diabetes mellitus, hyperlipidaemia, obesity and other cardiovascular diseases.11–13 The combination of several comorbidities can increase CKD progression, especially if they are not adequately controlled. Advanced stages of CKD are often associated with further complications caused by declining renal function and the loss of metabolic and endocrine control.14 15 The occurrence of renal anaemia, metabolic acidosis, and bone and mineral disorders requires further medication. As a result, polymedication and insufficient pharmacological treatment of underlying and CKD-related diseases aggravate the risk for drug-related problems (DRPs) such as inappropriate dose or drug interactions.16 17 DRPs, defined as an event or circumstance involving drug therapy that actually or potentially interferes with desired health outcomes, can lead to ineffective pharmacotherapy and may cause drug-related morbidity and mortality.18 Therefore, adequate medication is important to prevent end-stage renal disease and slow the progression of CKD.
The effect of drugs on renal function can be desirable or undesirable and depends on the pharmacological profile of the substance, including the renal route of elimination. Therefore, drug accumulation in patients with moderate to severe renal impairment may lead to increased systemic adverse drug reactions or nephrotoxicity. This leads to a more complex medication process for patients with CKD.19 20
In order to ensure adequate pharmacological treatment in the outpatient care by general practitioners (GPs) and pharmacists, knowledge of renally relevant drugs, including possible side effects on non-adherence to dose adjustments, disregarding contraindications and selection of suitable alternatives in the case of contraindication, is necessary.21 22
Drugs were defined as renally relevant if they:
(a) are frequently used by the nephrologist in daily practice to maintain renal function and slow the progression of CKD; these drugs may have a desirable or undesirable effect on renal function (eg, renin-angiotensin-aldosterone system (RAAS) inhibitors or diuretics)
b) require dose adjustment for renal function because they may cause systemic risks if they accumulate (eg, antidiabetics)
c) are contraindicated in certain stages of CKD due to ineffectiveness, nephrotoxicity, further deterioration of renal function or accumulation with increase of adverse drug reactions (eg, analgesics)
d) are used for the treatment of CKD-associated sequelae caused by inadequate therapy or long-term progression of renal insufficiency (eg, vitamin D derivatives, antiacidotics).
A substantial assistance for all healthcare professionals in their daily work could be a list of renally relevant drugs, containing the most important medications for therapy of underlying and CKD-related diseases with further treatment recommendations and therapeutic alternatives.
The aim of the study was to develop a renally relevant drug list (RRD-list) with renally relevant drugs as an assistant tool for outpatient healthcare professionals. The RRD-list was supposed to include renally relevant drugs and to contain specific treatment recommendations and practical advisory references for GPs that are a practical supplement to the manufacturers’ drug information and handbooks.
Methods
Study design
The development of the RRD-list with renally relevant drugs was part of a study on medicines optimisation in patients with CKD, where patients were consecutively recruited in a prospective study performed in the nephrological outpatient clinic of the department of nephrology at the Klinikum Fulda, Fulda, Germany, from June 2015 to March 2018. The whole study is published elsewhere.23 The nephrologists in the outpatient unit treat patients after referral from their GP. At the nephrological consultation information on the patient’s current medications is requested. The nephrologist performs further diagnostics to evaluate the CKD stage and the possible progression of declining renal function. Based on the diagnostic results the nephrologist recommends renally relevant drugs for optimising underlying and CKD-related diseases. The recommendation and reasons for the nephrologist’s decision are summarised in a clinic letter for the GP.
For development of the RRD-list a clinical pharmacist records the medication of 160 patients with CKD (estimated glomerular filtration rate (eGFR) (Modification of Diet in Renal disease, MDRD) <60 mL/min)10 and at least one concomitant disease such as arterial hypertension, diabetes mellitus, secondary hyperparathyroidism (sHPT), metabolic acidosis or proteinuria. The medication of patients being on dialysis or after renal transplantation was not reviewed.
The RRD-list is based on the 10 most common drug groups that were (a) detected in the patients’ medication, (b) involved in the patients’ DRPs, and (c) included in the nephrologist’s recommendations. In order to identify these drug groups, the pharmacist provides with medication reconciliation a summarised and accurate list of all medications that were taken, including allergies, history of side effects, individual patient’s non-adherence, and differences to prescribers’ orders. Subsequently, the medications were analysed for DRPs including the evaluation of assessed laboratory parameters, medical history and patients’ individual problems with their medication. Furthermore, all recommendations regarding drugs given by the nephrologist in the clinic letter were analysed.
All detected drugs were evaluated for renal relevance, categorised into different drug groups, classified according to the pharmaceutical agents, and sorted by the frequency of occurrence. The classification of the drug groups and drug classes was based on the ATC (anatomical therapeutic chemical) system. The drug groups refer to the second level, therapeutic subgroup, and the drug classes to the third level, pharmacological subgroup or fourth level chemical subgroup.24
Type of renally relevant drugs in patients’ medication and frequency of occurrence
All prescribed drugs of the patients were analysed with regard to renal relevance and their frequency of occurrence.
Type and frequency of DRPs
We identified all drugs that were involved in any DRP. Furthermore, the number, frequency and type of all DRPs that occurred were analysed and classified by ADKA-DokuPik, a validated tool for recording DRPs by clinical pharmacists in Germany.25
Drug-specific recommendations by the nephrologist
We identified all renally relevant drugs which were involved in any drug-related recommendation by the nephrologist. Furthermore, the number and type of all specific recommendations were analysed and classified. The categories for all evaluated types of recommendations are shown in box 1.
Box 1. Evaluated types of recommendations by the nephrologist.
Type of recommendation
Change of drug
Withdrawal of drug
Introduction of new drug
Dose adjustment to renal insufficiency (DARI)
Dose reduction
Dose increase
Change of administration time
Change of administration interval
Check of appropriate indication
No intake allowed
No change to current dosage
Pause the intake
Use with caution under monitoring
Based on the evaluation of these parameters the RRD-list was created.
In addition to drugs that meet the definition of renally relevant drugs, drug groups for the therapy of cardiovascular diseases were also considered for the compilation of the RRD list. Cardiovascular diseases are not a specific secondary disease of CKD. Nevertheless, the risk for CKD patients is significantly increased. In addition, cardiovascular diseases can worsen CKD in the long term if therapy remains insufficient.
To provide a tool of high practical relevance for GPs, the basic drug-specific parameters in the RRD-list have been extended to include detailed information with recommendations for use in patients with CKD. Therefore, additional information about therapeutic alternatives and pharmaceutical specifics were added to the RRD-list. All advice and references were elaborated by combining the nephrologists’ expert opinions with pharmacological and therapeutic common practice as well as drug prescribing information, the current study evidence and pharmacokinetic considerations.20 26–43 In order to ensure optimal support for GPs in the outpatient setting, the clinical pharmaceutical relevance of all recommendations was evaluated. As a result, GPs can focus on the most important aspects of the therapy of underlying diseases and their sequelae.
Results
The medication data of 160 patients were evaluated. Patients’ characteristics are shown in table 1. Nearly half of all patients (48.7%) had CKD stage 3b. Hypertension was present in all patients and type 2 diabetes in nearly half of them.
Table 1.
Demographic characteristics of study cohort
| Variables | Total | |
| n=160 | % | |
| Age (years) | 74±8 | |
| Gender | ||
| Male | 101 | (63) |
| Female | 59 | (37) |
| CKD staging by KDIGO | ||
| 3a | 27 | (16.9) |
| 3b | 78 | (48.7) |
| 4 | 51 | (31.9) |
| 5, without dialysis | 4 | (2.5) |
| Main risk factors for CKD progression | ||
| Arterial hypertension | 160 | (100) |
| Type 2 diabetes | 75 | (46.9) |
| Hyperlipidaemia | 98 | (61.3) |
KDIGO CKD stages defined as eGFR (mL/min/1.73 m²): 3a = ≥45 to ≤59, 3b = ≥30 to <45, 4 = ≥15 to <30, 5 = <15.
CKD, chronic kideny disease; eGFR, estimated glomerular filtration rate; KDIGO, Kidney Disease: Improving Global Outcomes.
The overall medication of all patients (n=160) consisted of 1376 drugs with an average of 8.6±3.5 drugs per patient. We identified 831 renally relevant drugs. These drugs were categorised into 35 renally relevant drug classes and 17 drug groups.
Type of renally relevant drugs in patients’ medication and frequency of occurrence
The results of all identified renally relevant drug groups and classes of all patients are shown in table 2. The top 10 occurring drug groups of all renally relevant drugs are diuretics, RAAS inhibitors, lipid-lowering drugs, antihypertensives with predominant effects on the vessels, gout therapeutics, antidiabetics (parenteral), antidiabetics (oral), sHPT therapeutics, anticoagulants (oral) and analgesics (non-opioid).
Table 2.
Identified renally relevant drug groups and classes of patients’ medication
| Drug group | Drug class | Total drug classes separated into drug groups |
Total drugs according to drug classes |
||
| n=831 | % | n=831 | % | ||
| Analgesics (non-opioid) | NSAID | 32 | (3.9) | 4 | (0.5) |
| Non-NSAID | 28 | (3.4) | |||
| Analgesics (opioid) | Opioids | 18 | (2.2) | 18 | (2.2) |
| Antianaemics | EPO | 6 | (0.8) | 3 | (0.4) |
| Iron | 3 | (0.4) | |||
| Antiacidotics | Antacids | 7 | (0.8) | 7 | (0.8) |
| Antidiabetics (oral) | Biguanides | 41 | (4.9) | 9 | (1.1) |
| DPP-4 inhibitors |
22 | (2.6) | |||
| Meglitinides | 5 | (0.6) | |||
| Sulfonylurea | 4 | (0.5) | |||
| Glucosidase inhibitors | 1 | (0.1) | |||
| Antidiabetics (parenteral) | Insulin | 46 | (5.5) | 44 | (5.3) |
| Incretin mimetics | 2 | (0.2) | |||
| Antihypertensives with predominant effects on the vessels | Calcium channel blockers | 76 | (9.1) | 76 | (9.1) |
| Anticoagulants (oral) | Vitamin K antagonists |
36 | (4.3) | 23 | (2.8) |
| Factor X inhibitors |
11 | (1.3) | |||
| Thrombin inhibitors | 2 | (0.2) | |||
| Antisympathotonics | α2-agonists | 11 | (1.3) | 11 | (1.3) |
| Bone disease therapeutics | Bisphosphonates | 1 | (0.1) | 1 | (0.1) |
| Diuretics | Thiazides and analogues | 174 | (20.9) | 58 | (7.0) |
| Loop diuretics | 102 | (12.3) | |||
| Potassium-sparing diuretics | 14 | (1.7) | |||
| Electrolyte disorders therapeutics | Potassium | 17 | (2.0) | 11 | (1.3) |
| Potassium binders | 6 | (0.7) | |||
| Gout therapeutics | Uricostatics | 76 | (9.1) | 76 | (9.1) |
| Immunomodulating agents | Immunosuppressives | 7 | (0.7) | 7 | (0.7) |
| Lipid-lowering drugs | Statins | 103 | (12.4) | 95 | (11.4) |
| Other lipid modifying agents | 8 | (1.0) | |||
| RAAS inhibitors | ACE inhibitors | 142 | (17.1) | 73 | (8.8) |
| AT-II receptor antagonists | 67 | (8.1) | |||
| Renin inhibitors | 2 | (0.2) | |||
| sHPT therapeutics | Native vitamin D3 |
38 | (4.5) | 31 | (3.7) |
| Active vitamin D3 and analogues | 2 | (0.2) | |||
| Calcium | 4 | (0.5) | |||
| Antiphosphate | 1 | (0.1) | |||
ACE, angiotensin-converting enzyme; AT-II, angiotensin II; DPP-4, dipetidyl peptidase-4; EPO, erythropoietin; NSAID, non-steroidal anti-inflammatory drug; RAAS, renin-angiotensin-aldosterone system; sHPT, secondary hyperparathyroidism.
Type and frequency of DRPs
In total, 543 renally relevant drugs were involved in DRPs. The type and frequency of the corresponding drug classes are shown in table 3. The top 10 occurring drug classes of all renally relevant drugs were loop diuretics, insulin, uricostatics, thiazides and analogues, opioids, calcium channel blockers, dipetidyl peptidase-4 (DPP4) inhibitors, angiotensin-converting enzyme (ACE) inhibitors, potassium-sparing diuretics, and antisympathotonics.
Table 3.
Identified renally relevant drug classes which are involved in DRPs
| Drug class | Total drugs | |
| n=543 | % | |
| Loop diuretics | 62 | (11.4) |
| Insulin | 59 | (10.9) |
| Uricostatics | 49 | (9.0) |
| Thiazides and analogues | 44 | (8.1) |
| Opioids | 36 | (6.6) |
| Calcium channel blockers | 32 | (5.9) |
| DPP-4 inhibitors | 31 | (5.7) |
| ACE inhibitors | 25 | (4.6) |
| Potassium-sparing diuretics | 23 | (4.2) |
| Antisympathotonics | 21 | (3.9) |
| Statins | 18 | (3.3) |
| NSAID | 15 | (2.8) |
| AT-II receptor antagonists | 14 | (2.6) |
| Biguanides | 14 | (2.6) |
| Factor X inhibitors | 13 | (2.4) |
| Non-NSAID | 13 | (2.4) |
| Sulfonylurea | 13 | (2.4) |
| Incretin mimetics | 12 | (2.2) |
| Antianaemics | 6 | (1.1) |
| Immunosuppressives | 6 | (1.1) |
| Vitamin D3 and analogues | 6 | (1.1) |
| Vitamin K antagonists | 5 | (0.9) |
| Antiacidotics | 4 | (0.7) |
| Meglitinides | 4 | (0.7) |
| Potassium | 4 | (0.7) |
| Potassium binder | 4 | (0.7) |
| Other oral antidiabetics | 3 | (0.6) |
| Calcium | 2 | (0.4) |
| Other lipid modifying agents | 2 | (0.4) |
| Renin inhibitor | 2 | (0.4) |
| Thrombin inhibitors | 1 | (0.2) |
ACE, angiotensin-converting enzyme; AT-II, angiotensin II; DPP-4, dipetidyl peptidase-4; DRPs, drug-related problems; NSAID, non-steroidal anti-inflammatory drug.
All 543 renally relevant drugs provoke 664 DRPs. The classification by ADKA-DokuPik is shown in table 4. The five most common DRP categories are: ‘indication, but no drug prescribed’ (25.6%), ‘prescription/documentation incomplete/incorrect’ (11.6%), ‘contraindication’ (11.1%), ‘inappropriate dose’ (10.8%), and ‘inappropriate administration interval’ (7.5%). All 543 renally relevant drugs provoke 664 DRPs. The classification by ADKA-DokuPik is shown in table 4.
Table 4.
DRP categories renally relevant drugs by ADKA-DokuPik classes
| DRP class | Total | ||
| n=664 | % | ||
| (Clear) indication but no drug prescribed | (DR 2) | 170 | (25.6) |
| Prescription/documentation incomplete/incorrect | (DR 11) | 77 | (11.6) |
| Contraindication | (CI 1) | 74 | (11.1) |
| (Inappropriate) dose | (D 2) | 72 | (10.8) |
| (Inappropriate) administration interval | (D 3) | 50 | (7.5) |
| Failure to adjust dose for organ dysfunction | (D 1) | 46 | (6.9) |
| Interaction | (I 1) | 45 | (6.8) |
| Patient counselling or education | (O 4) | 42 | (6.3) |
| Inappropriate or not most suitable drug in terms of indication | (DR 10) | 24 | (3.6) |
| Adverse drug reaction | (ADR 1) | 21 | (3.2) |
| TDM not performed or not considered | (D 4) | 18 | (2.7) |
| Double prescription | (DR 4) | 13 | (2.0) |
| (Clear) indication not (or no longer) given | (DR 1) | 12 | (1.8) |
ADR, adverse drug reaction; CI, contraindication; D, dosage; DR, drug; DRP, drug-related problem; I, interaction; O, other; TDM, therapeutic drug monitoring.
The DRP class ‘prescription/documentation incomplete/incorrect’ includes all problems regarding application such as splitting a tablet without a break mark, inappropriate dosage form such as sustained release tablets for acute pain treatment, unsuitable duration of therapy and inappropriate administration time.
Drug specific recommendations by the nephrologist
A total of 292 recommendations were made by the nephrologists on renally relevant drugs in 28 drug classes. The results are shown in online supplemental table 6. The 10 most common recommendations affect the following drug classes: non-steroidal anti-inflammatory drugs (NSAIDs), loop diuretics, thiazides and analogues, ACE inhibitors, uricostatics, calcium channel blockers, vitamin D3 and analogues, antianaemics, statins and antiacidotics.
ejhpharm-2020-002571supp001.pdf (111.6KB, pdf)
The most common type of recommendation was ‘introduction of a new drug’ (n=72) with the highest percentage of vitamin D3 and analogues (18.1%), antiacidotics (13.9%), ACE inhibitors (9.7%), calcium channel blockers (9.7%), antianaemics (8.3 %) and statins (6.9%). This was followed by ‘no intake allowed’ (n=46) with mainly NSAIDs (89.1%), ‘dose increase’ (n=41) with largest quantity of loop diuretics (48.8%), and ‘withdrawal of drug’ (n=37) with mainly thiazides and analogues (29.7%).
In conclusion, we identified 14 out of 17 renally relevant drug groups that appeared at least once in the top 10 in either the patients’ medication or in involved DRPs or in drug-specific recommendations by the nephrologist. In total, the 14 groups consist of 35 different drug classes. Pharmacological treatment with parenteral antidiabetics such as insulin or incretin mimetics requires individual dosages that are tailored to the special needs of each patient. Therefore, no standardised dose recommendation can be given regarding the level of CKD. Hence, we did not include parenteral antidiabetics in the RRD-list and rather used 13 drug groups with 33 drug classes from the combination of all results, for developing the RRD-list.
Due to the clinical complexity of the pharmacological treatment of diseases, which concern calcium homeostasis, not all therapeutic options could be grouped under drugs for sHPT. So, we added three additional drug groups with three drug classes: drugs for hypercalcaemia, drugs for hyperphosphataemia, and drugs for bone diseases.
Finally, there are 16 renally relevant drug groups with 36 drug classes which are presented in the RRD-list. The high amount of DRPs in the section ‘prescription/documentation incomplete/incorrect’ indicates that, in addition to knowledge about the right dose and dose interval in different CKD stages, further information such as special application advice, treatment recommendations and therapy options are necessary to enable a sufficient and safe medication process. This is affirmed by the increased percentage of nephrologists’ recommendations about introduction of a new drug, no intake allowed and withdrawal of a drug. Special information such as avoidance of NSAIDs, correct intake of antiacidotics to reduce side effects, or monitoring of electrolytes and patient’s glomerular filtration rate during increased diuretic dosage could be helpful to enable a successful CKD treatment.
An extract of the list can be seen in figure 1. For detailed information, please refer to online supplemental table 7.
Figure 1.
Extract from the RRD-list by the example of oral antidiabetics. **Only in combination with other antidiabetics. AKI, acute kidney disease; CI, contraindication; CKD, chronic kidney disease; DARI, dose adjustment in renal insufficiency; DDmax, maximum daily dose; DPP-4, dipetidyl peptidase-4; eGFR, estimated glomerular filtration rate; GIT, gastrointestinal tract; Hb, haemoglobin; NT, nephrotoxicity; RRD, renally relevent drugs; SGLT-2, sodium-glucose co-transporter-2; SH, sulfonylurea; SR, systemic risks.
ejhpharm-2020-002571supp002.pdf (1.4MB, pdf)
Discussion
The developed RRD-list with practical and clinically relevant aspects illustrates with realistic reference to nephrological practice the most common renally relevant drugs, which are used in patients with CKD to treat underlying and secondary diseases. The list gives a review of the standard dosages, contraindications, and dose adjustments to declined renal function including the reason, as well as therapeutic alternatives and special recommendations for administration. Currently there is no comparable list available for healthcare professionals nationwide.
Our data of occurring renally relevant drug groups and drugs that cause DRPs align with results of other researchers. Dorks et al 44 assessed the frequency of inappropriate drug prescription in non-hospitalised patients with CKD. They found drugs acting on the RAAS, oral antidiabetics, and uric acid lowering agents were the most inappropriately prescribed drug classes.44 Mahner et al 45 evaluated the medication of patients with CKD stage ≥3 in primary care to assess the number of inappropriately prescribed drugs regarding contraindication and overdosing. They observed that 25% of all patients had one inappropriate prescription. Most of them concerned ACE inhibitors, oral antidiabetics and diuretics.45 Both research studies focused on drugs for treatment of underlying CKD diseases and did not include drugs for treatment of CKD-related diseases such as anaemics, antiacidotics and sHPT therapeutics.
Drug lists that can be found in the literature are mostly based on guidelines for the evaluation and management of CKD20 or on studies in the range of medicines optimisation. These studies have examined the medication of patients with CKD for occurring DRPs. Many researchers only focus on the adaption of drug dosing to the current renal filtration rate or potential contraindications, mostly in an inpatient setting. The resulting drug lists are primarily based on the type and frequency of drugs analysed in those study populations and cannot be generalised to patients in an outpatient setting. When recommendations for dose adjustment or withdrawal have been made, those are often only assessed from one source such as the manufacturer’s drug information, drug handbooks or guidelines or pharmacokinetic studies.16 44 46–52 Holm et al 51 mentioned that the inconsistency from different sources complicates the process of therapeutic decision making.
Our data show that pharmacotherapy of patients with CKD in regard to dose adjustments and contraindications cannot only be related to the manufacturers’ drug information. The current literature must also be considered as well as the clinical relevance and pharmacokinetic and pharmacodynamic parameters of the drugs. For example, according to the manufacturer’s drug information, lercanidipine should not be used in patients with CKD stage 3 or higher. However, current studies show that there are no increased side effects in patients with CKD stage 3 and 4 compared with patients without renal impairment. This implied a possible safe use at CKD stage 3 or higher.39 Mahner et al 45 point out that for better monitoring of the prescription quality of drugs in CKD, a consensus is needed based on manufacturers’ drug information, recommendations of professional societies and clinical relevance. Particularly at risk are patients with CKD stages ≥3b and polypharmacy. Combining different sources and linking them to a practical level for all GPs is the advantage of our RRD-list.
Blix et al 16 and other researchers refer to the inclusion of clinical relevance in pharmacological therapy decisions to ensure practicality.16 51 52 Many drug groups and drug classes which are used in patients with CKD are blamed for DRPs, but they are often essential in therapy because of their renoprotective effect such as RAAS inhibitors. Therefore our findings are not surprising as most nephrological recommendations, which refer to ‘introduction of a new drug’, concern ACE inhibitors. The situation is similar with diuretics. Loop diuretics were often recommended to ‘dose increase’ to minimise the harm of comorbidities. A temporary decline in renal function may be the result. But this can be accepted in favour of an overall reduced progression of CKD.16 51 52 In order to assess the value of these drugs and to avoid over-cautiousness in prescribing, GPs need to know the reason for sufficient therapeutic monitoring as well as the correct dosage range to enable safe use. This information is presented in our RRD-list.
In general practice our RRD-list can be beneficial for all healthcare professionals in every part of the decision-making process for choosing suitable therapeutic options, especially in the outpatient setting with regard to its practical orientation. Problems of non-detection, wrong dose adjustments or selecting inappropriate alternatives are often based on large numbers of various recommendations and the lack of consistency in different resources.53
Limitations
Our study has some limitations. First, due to our ambulatory setting we were assigned to the patients’ correct statements regarding drugs taken and answers to the question of administration and DRPs. Second, we developed the list by analysing the medication of 160 patients in the outpatient setting. Further studies with larger patient collectives might be beneficial to reinforce our results. Thirdly, our developed RRD-list includes only the most common drug groups and classes that occur specifically at the nephrology clinic in our study population. Therefore, the RRD-list is not an all inclusive list of medications with considerations for patients with CKD. There might be more renally relevant drug groups for the outpatient and inpatient setting which are not considered by our developed list, for example, antibiotics.
In conclusion, the RRD-list can be a valuable tool for the treatment of patients with renal insufficiency. The data show that pharmacotherapy in patients with CKD is complex. Considerations of dose adjustments and contraindications are as relevant as specific treatment recommendations and advisory references. The list could be an essential tool for all healthcare professionals in their daily work, such as GPs and community pharmacists.
What is this paper adds.
What is already known on this subject?
Pharmacotherapy in patients with chronic kidney disease is complex
Adequate pharmacological treatment in patients with chronic kidney disease requires knowledge of renally relevant drugs (RRDs), including possible side effects, dose adjustments, contraindications and selection of suitable alternatives in the case of a contraindication.
What this study adds
An RRD-list could be an essential tool for all healthcare professionals for the treatment of patients with renal insufficiency.
Acknowledgments
We would like to thank the participating patients and physicians who supported our study.
Footnotes
Contributors: All authors certify that they have participated sufficiently in the work to take public responsibility for the entire content of the manuscript and that they adhere to the ICMJE definition of authorship and state that they had complete access to the study data that support the publication.
Funding: The study was supported by the Dr August and Dr Anni Lesmüller Stiftung, Munich, Germany.
Competing interests: None declared.
Provenance and peer review: Not commissioned; externally peer reviewed.
Supplemental material: This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.
Data availability statement
The data are de-identified participant data. Data are available upon reasonable request from the corresponding author. Re-use is not permitted.
Ethics statements
Patient consent for publication
Not required.
Ethics approval
All procedures performed in this study were in accordance with the ethical standards of the ethics committee Philipps-University Marburg, department of human medicine, Germany and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
ejhpharm-2020-002571supp001.pdf (111.6KB, pdf)
ejhpharm-2020-002571supp002.pdf (1.4MB, pdf)
Data Availability Statement
The data are de-identified participant data. Data are available upon reasonable request from the corresponding author. Re-use is not permitted.