Overview of Polypharmacy and Drug Interactions in Chronic Kidney Disease Patients at Siloam Hospitals Lippo Village

Patients diagnosed with CKD in Indonesia have increased from 2% in 2013 to 3.8% in 2018. Polypharmacy is commonly found in CKD patients, especially in CKD patients with comorbidities. CKD with comorbidities will make the treatment more complex and expensive. This study was conducted to assess the relationship between polypharmacy and drug interactions in CKD patients. Data analysis was carried out descriptively on CKD patients at "X" Hospital in the period October to December 2022 and data were displayed in the form of tables and graphs. The results showed that the majority of patients with chronic kidney disease (CKD) were aged 46-65 years with 42 patients (50.0%). Chronic kidney disease (CKD) patients who get prescriptions for more than 5 drugs are 80 (95.2%) patients. Comorbidities that often occur in chronic kidney disease (CKD) patients are hypertension with 62 (19.62%) patients, diabetes mellitus with 29 (9.18%) patients, and coronary heart disease with 27 (8.54%) patients. From 84 patients, there were 626 potential drug interactions including 152 (24.28%) drug interactions with minor severity, 434 (69.33%) drug interactions with moderate severity, and 40 (6.39%) drug interactions with major severity. CKD patients who have one or more comorbidities will increase the risk of polypharmacy and an increased risk of drug interactions.


INTRODUCTION
Chronic renal failure, also known as chronic kidney disease (CKD), is a disease that affects more than 10% of the world's population, more than 800 million in 2022.Chronic kidney disease (CKD) is one of the non-communicable diseases that shows an increase in mortality rates (Kovesdy, 2022).Based on the evaluation of Riskesdas in 2018, the prevalence of CKD patients diagnosed by doctors in patients aged more than 15 years has increased from 2013 at 2% to 3.8% in 2018 (2018( Riskesdas, 2018)).
CKD accompanied by comorbidities increases the complexity and cost of care due to the many therapies that must be undertaken for life.Common comorbidities are hypertension and diabetes.Comorbidities and polypharmacy are common in chronic kidney disease (CKD) patients, leading to an increased potential for drug interactions (MacRae et al., 2021).According to research conducted by Shahzadi et al (2022), 67 patients out of 96 chronic kidney disease (CKD) patients used more than five kinds of drugs simultaneously (polypharmacy).
Polypharmacy is mostly found in chronic kidney disease (CKD) patients with comorbidities, namely 80.2% of the patient population has hypertension, 25.0% of patients have diabetes mellitus, 17.7% of patients have hypertension and diabetes mellitus, and the remaining 12.5% with other complications (Shahzadi et al., 2022).According to a previous study, out of 209 patients, 46 (22.0%) patients were prescribed <5 drugs and 163 (78.0%) patients were prescribed >5 drugs (Sleem A., Masood I., 2017).
Polypharmacy can have adverse effects on patients such as decreased quality of life, increased risk of death, increased occurrence of adverse drug effects, increased inaccuracy in drug selection, and increased drug incompatibility (Cepeda & Morley, 2012).Factors such as errors in drug selection, taking into account renal function, dosing, selection of route of administration, and how to use the drug can lead to potential unwanted drug interactions.Therefore, drug interactions in chronic kidney disease (CKD) patients are a serious problem and need to be monitored in drug prescribing (Cascorbi, 2012).This study aims to determine This study aims to determine the overview of polypharmacy and drug interactions that occur due to polypharmacy in chronic kidney disease (CKD) patients at "X" Hospital, Tangerang.

METHODS
This study has met the ethical requirements on the date of The Mochtar Riady Institute for Nanotechnology Ethics Committee (MRIN EC) with number 002/MRIN-EC/ECL/II/2023.This study was analysed using descriptive methods on outpatients suffering from chronic kidney disease at Hospital "X" Tangerang retrospectively by analysing prescription data and laboratory results in medical records in the time span of October 1 to December 31, 2022.
The inclusion criteria in this study include patients suffering from chronic kidney disease in the period 1 October to 31 December 2022, chronic kidney disease patients aged> 18 years, patients suffering from chronic kidney disease with category G3a-G5, and having a history of control at least once a month in 3 consecutive months.While the exclusion criteria are patients who have incomplete and illegible medical record data.
Collection of patient demographic data such as gender, age, glomerular filtration rate (GFR) value, number of prescribed drugs, comorbidities, and prescribed drugs will be recorded based on existing data in medical records.Drug interactions will be analysed based on the prescribed drugs using the interaction checker available at www.drugs.comand medscape.Drug interactions that have been analysed using the interaction checker will be checked whether the drug interaction occurred in the patient by adjusting laboratory data such as blood pressure, triglyceride values, and uric acid.The data from the analysis will be displayed in a table.

RESULTS AND DISCUSSION
Based on table 1, there were 84 chronic kidney disease (CKD) patients studied with the majority being male patients with 49 patients (58.3%).The majority of patients with chronic kidney disease (CKD) are aged 46-65 years with 42 patients (50.0%).About 29 (35.4%)chronic kidney disease (CKD) patients were included in category 5. Almost all chronic kidney disease (CKD) patients were prescribed ≥5 drugs, totalling 80 (95.2%) patients.Comorbidities that often occur in chronic kidney disease (CKD) patients are hypertension with 62 (19.62%) patients, diabetes mellitus with 29 (9.18%) patients, and coronary heart disease with 27 (8.54%)patients.One of the potential drug interactions with moderate severity that often appears is sodium bicarbonate with allopurinol, which was found in 34 (19.21%)cases which can be seen in table 4. The interaction that arises is a decrease in the therapeutic effect of allopurinol as an antigout.This can occur because sodium bicarbonate can increase the pH of the stomach so that it inhibits the absorption of allopurinol which causes blood drug levels to decrease.This can be overcome by taking allopurinol 2 hours before or after consuming sodium bicarbonate.In this study, drug interactions that occurred in many patients were interactions between antihypertensive drugs and other drugs such as calcium carbonate which is included in supplements which can be seen in table 5.This is in line with the data in table 2, namely the number of classes of antihypertensive drugs, diuretics, and supplements that are widely prescribed Antihypertensive and antigout drugs are drugs that are often prescribed simultaneously with other drugs in CKD patients.Drug interactions that occur in patients are blood pressure, triglyceride values, and uric acid that do not reach their therapeutic targets.CKD is pathophysiologically related to hypertension so uncontrolled blood pressure is not always due to drug interactions.However, management of drug interactions can help improve blood pressure control.The same applies to triglyceride and uric acid values, diet and physical activity may also affect triglyceride and uric acid values, but this study did not examine these specifically.Drug interaction management can help improve blood pressure, triglyceride and uric acid control in patients.If the potential drug interactions that occur are absorption pharmacokinetics, it can be overcome by giving a 2-hour interval before or after taking other drugs.However, there are also potential drug interactions that cannot be overcome by giving a break in taking the drug, so it is necessary to monitor the side effects and effectiveness of the drug such as the administration of antihypertensive drugs and hydrochlorothiazide recommended in the JNC 8 guideline to achieve therapeutic targets.
. Table 6 shows that the more comorbidities a CKD patient has, the more drugs are prescribed, thus increasing the risk of drug interactions.CKD patients without comorbidities received an average number of drugs of 6 and an average drug interaction of 2. Meanwhile, CKD patients with seven co-morbidities were prescribed an average number of drugs and an average drug interaction of 2. Patients with eight comorbidities had an average number of drugs of 12.28 and an average drug interaction of 14.85.CKD patients with eight co-morbidities had a smaller average number of drugs and drug interactions than those with seven co-morbidities because the number of patients with eight comorbidities was only two patients.

CONCLUSIONS
CKD patients who have one or more comorbidities will increase the risk of polypharmacy because patients are not only given drugs to treat CKD but also to treat comorbidities, especially comorbidities that are directly related to the development of severity in CKD.Polypharmacy also plays a role in increasing the risk of drug interactions because the more drugs administered, the more pharmacokinetic and pharmacodynamic interactions of the prescribed drugs.