Introduction 

Chronic kidney disease (CKD) is emerging health crisis and leading cause of mortality, morbidity and disease burden globally ^{1, 2}. It’s defined as decrease in glomerular filtration rate of less than 60ml/min/1.73m² for three month or more than three months and abnormality in structure and functioning of kidney ³.  According to Global burden study, disability adjusted life years for CKD has risen to 18^th rank in 2019 from 29^th in 1990⁴. The global prevalence of CKD is estimated to be 13.4% and ranked as 12^th leading cause of mortality ^{5, 6}.  Estimates place the frequency of CKD at 13.4% worldwide. The rising incidence of diabetes mellitus, hypertension, coronary artery disease, infections along with environmental factors are all contributing to the rise in prevalence of renal disease ^{8, 9}.Moreover, diabetes and hypertension accounts for 40-60%of CKD ¹⁰ .The patients with CKD suffer electrolyte imbalance, anemia, cardio vascular complications, CKD induced mineral and bone disorder which leads patients to take multiple medications to assuage the symptoms, progression of disease and comorbidities associated with it ¹¹. Due to alteration in pharmacodynamics and pharmacokinetic parameters and renal insufficiency in patients, the pharmacotherapy regimen should properly selected and monitored to avoid adverse drug reactions, interactions and other complications. For proper selection of medication, drug utilization studies should be done periodically ¹². However, prescribing trend always varying which depends upon chronicity of condition, population, time and physician that makes it important to analyze current prescribing trend in a regular basis ¹². Drug utilization studies are evolving field which significant because which provides baseline data needed in pharmacoepidemiological research and aims to promote rational drug usage ^{13, 14}. Conducting drug utilization studies may drive in to different perspectives such as drug usage, prescribing trend and extent of compliance with guidelines. Prescribing indicators with several dimensions are     used to measure appropriateness of drug use ¹⁵. Hence this study was aimed to evaluate the drug utilisation pattern in patients with chronic kidney disease.

Methods

Study design, setting and study population

A prospective observational study of 120 patients was conducted at Nephrology department of Rajiv Gandhi Cooperative multispecialty hospital, Palakkad for a period of 6 month from July 2022 to January 2023. The subjects were enrolled based on inclusion and exclusion criteria. The chosen patient should be at least 18 years or older and have been diagnosed and treated for CKD, be receiving non dialysis treatment. The exclusion criteria’s are patients with acute renal failure or obstructions, Pregnant lactating women and children, newly diagnosed CKD patients and patients with major chronic diseases like acute stroke or cancer or acute congestive cardiac failure or chronic liver diseases or psychiatric diseases.

Data collection and Assessment

Signed informed consent is acquired from the each participant prior to the study. Demographic details were obtained from patients at the time of consultation and required clinical data’s were extracted from their health records. According to Anatomic Therapeutic Chemical classification (ATC), drugs were categorized in to various classes and medication usages were compared with WHO core prescribing indicators.

Statistical Analysis

The collected cases were entered in MS Excel 2007 for calculating percentage of various parameters.

Result and Discussion

The prevalence of CKD volantly increasing in the world wide due to causative and risk factors which directing the importance optimal usage of medication in the management of patients. Hence this study which documenting the drug utilisation pattern by comparing with prescribing indicators and reporting the poly pharmacy.

The observational study of 120 patients which reveals that more number of the patients were in the age range of 61-70 years with male predominance by 72.5% over female by 27.5% This finding were coincide by previous observational study were reported 75% dominance of male patients over female patients ¹⁶.It may be due to sedentary life style, difference in social habits and hormonal difference.  Table 1 which portrays the socio demographic details of patients. Overall patients, 34 patients (28.3%) had a history of renal disease in their families and, 45 patients (37.5%) of them ascertained to be employed. In the assessment of social habits, 39 patients (32.5%) were either ex or current smokers and 15 patients (12.5%) consuming alcohol in their daily life. Smoking and drinking are two risk factors for developing chronic kidney disease (CKD). Nicotine can produce oxidative stress and alcohol can disrupt the hormonal system, which can damage the kidneys. Of all, 102 patients (85%) were preferred mixed diet over vegetarian diet(15%).The patients were classified basis on BMI and 48patients (40%)of them reported as obese followed by overweight, normal and underweight categories (30.8%),(18.3%),(10.8%) respectively. Due to compensatory hyperfiltration that occurs in obese people to meet metabolic needs, a rise in intraglomerular pressure might harm the kidneys and increase the risk of long-term CKD development. Out of 120 participants, majority of patients belong to stage IV(40%), which is followed by stages V, III, II, and I (18.1%, 37.4%, 3%, and 1%) in stage wise categorization of CKD patients. These results were consistent with earlier cross-sectional research, which led to the conclusion that a greater proportion of patients were in stage IV ^{17, 18}. Figure 1 which represents the five stage classification of CKD and distribution of population in each stage. Table 2. Illustrates the distribution of comorbidities prevailed in the patients. Hypertension (93.3%) was found to be prominent co morbid condition followed by other co morbidities such as diabetes, anaemia, hyperlipidaemia and stroke (85%, 82%, 38% and 10%) among study population. These results were revealed to be identical to a cross sectional study who reported that hypertension was the most prevalent co morbidity reported by 34% of the patients, followed by diabetes and coronary artery disease ¹⁹. Earlier prospective study reported that hypertension was common co morbidity which affected 34% of CKD patients. It possible that hypertension was triggering factor and risk factor for CKD in population ²⁵ .The term Poly pharmacy defined as regular intake 5 or more medications per day. The study revealed a burden of medication, about 86% of patients received poly pharmacy reveals the significant association between comorbidities and number of medications. Earlier prospective study reported that prevalence of poly pharmacy at baseline and FU was 80% ¹¹, which inevitable in management of comorbidities and to control progression of disease with maintaining electrolyte balance. The medication usage pattern was analysed by using WHO prescribing indicators. The total number of drugs encountered in study was 921 drugs. The average of number of drugs prescribed in the study was 7.6%, which was found to be greater than that reported in a cohort study which found that 6.5%, respectively ²⁰. About 11.3% of drugs prescribed by generic name, whereas previous study conducted who showed that 15.7% of drugs prescribed by generic name ²⁴. The wide difference in prescribing pattern of generic drugs and average number of drugs might be due to variation in population, comorbidities and preference of prescriber. The percentage of drugs prescribed from essential medicine list was 49.9% which is smaller than reports of previous observational study conducted and showed as 65% ²². The percentage of patients prescribed with injection was 46%. Similar studies conducted which demonstrate that 66% of patients prescribed with injections ²³. The prescribing injections in CKD patients were normal due to comorbid conditions like anemia and DM where use of erythropoietin and insulin essential for management. The percentage of patients prescribed with antibiotics was 25% which lies between the standard range (20-26%). According to ATC classification established by WHO, Cardiovascular system class of drugs (40.1%) was commonly prescribed followed by drugs for alimentary tract and metabolism (34.8%) and blood and blood forming agents (17.2%). These findings were consistence with previous study conducted who reported that cardio vascular drugs (16.4%) are mostly prescribed followed by gastrointestinal tract drugs (14.4%) and nutritional supplement (10%) ^[21].This is what we expected because of 93.3% of patients were hypertensive and hypertensive management found to be crucial in patients. Among the cardiovascular class of drugs, diuretics (30.1%) were mostly prescribed antihypertensive, followed by calcium channel blocker (19.3%). These results were similar to a previous cross sectional study reported that diuretics were the most often prescribed CVS class of medicines, followed by calcium channel blockers and angiotensin receptor blocker II (8.2%, 6.3%, and 2.8%, respectively) ²². Among the diabetic population, insulin (30.7%) was mostly prescribed drug followed by oral hypoglycemic agents amd lipid lowering therapy initiated by prescribing statin (27%) to patients. These findings were supported by findings of a cohort study conducted which found that statin and insulin were prominently prescribed to patients in their management ^[24].Insulin can be used in hyperkalemia management and statin used as prophylactic agent to patients who attained 50 years of age or greater than 50 years.  In anaemic management, folic acid constituted 61.4% over erythropoietin. This is might due to folic acid are far more affordable and convenient than erythropoietin. In this study, among phosphate binders, 80.9%of selevamer was prescribed to patients while only 19% of calcium acetate was prescribed. These results were similar to study conducted who reported the higher use of selevamer over calcium acetate ^[24]. Selevamer is non calcium based phosphate binder, which do not possess any risk of coronary calcification. In order to control acid-base disorder, 40.2% of the patients prescribed with sodium bicarbonate. Multivitamins are commonly prescribed to patients which constitute 25.1% in total drugs.

Table 1: Baseline characteristics of population

Table 2: Distribution based on Comorbidities and poly pharmacy

Table 3: WHO prescribing indicators

Table 4: Drug classification according to ATC classification

Table 5: Therapeutic class wise drug distribution

Others- Anti thyroid drugs, antacid, lactulose, renal nutrition, antihistamine and analgesics

Figure 1: Distribution of stages of CKD patients   Click here to view figure

Conclusion

Assessment of drug utilization pattern using WHO prescribing indicators in CKD patients aids in reaffirm the existing hospital recommendations for the optimal and effective medication usage. The prevalence of poly pharmacy was high in patients due to increased existence of co morbidities. Drugs from Cardio vascular system were commonly utilized according to ATC Classification and drug utilization pattern studies helps to improve management strategy and facilitate rational drug use. Thereby overall outcome of pharmacotherapy can be improved.

Acknowledgement

The authors are thankful to the principal, Librarian and other faculties in Grace College of Pharmacy for their support and cooperation and thankful to faculties of department of nephrology who supported to conduct the study.

Conflict of Interest

There are no conflict of interest

References

1. ]. Lv JC, Zhang Prevalence and Disease Burden of Chronic Kidney Disease. Adv Exp Med Biol.2019;1165:3-15. DOI: 1007/978-981-13-8871-2_1. PMID: 31399958
2. Nipun Shrestha, Sanju Gautham. Burden of chronic kidney disease in the general population ang high-risk groups in South Asia: A systematic review and meta analysis.Chronic kidney disease in South Asia.2021;22(11):1- DOI: 10.1371/journal.pone.0258494. PMID: 34648578. PMCID: PMC8516300
3. C.H.Moideen KuttyGurukkal, B K Bithun. Co-morbidities and their management in patients with chronic kidney disease in a tertiary hospital of International Journal of Scientific Study.2018;6(1):151-154.
4. Changrong Ke , Juanjuan Liang , Mi Liu , Shiwei Liu. Burden of chronic kidney disease and its risk- attributable burden in 137 low-and middle-income countries, 1990–2019: results from the global burden of disease study BMC Nephrology.2022;23(17):1-12. doi: 10.1186/s12882-021-02597-3.PMID: 34986789
5. Hill NR, Fatoba ST, Oke JL, Hirst JA, O’Callaghan CA, Lasserson Global Prevalence of Chronic Kidney Disease – A Systematic Review and Meta-Analysis.PLOS ONE.2016;11(7):1-18. PMID: 27383068
6. Ellen Carney. The impact of chronic kidney disease on global health. Nature Reviews.2020;16:251
7. Ajay K Singh1 , Youssef MK Farag et al. Epidemiology and risk factors of chronic kidney disease in India – results from the SEEK (Screening and Early Evaluation of Kidney disease) study. BMC Nephrology 2013:14(11):1- doi: 10.1186/1471-2369-14-114.
8. Theo Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017: GBD Chronic Kidney Disease Collaboration. 2020; 395: 709– PMID: 32061315, PMCID: PMC7049905, DOI: 10.1016/S0140-6736(20)30045-3
9. Subeesh VK, Abraham R, Sai MV, Koonisetty KS. Evaluation of prescribing practices and drug-related problems in chronic kidney disease patients: A cross-sectional Perspectives in Clinical Research. 2020;11(2):70-74. DOI: 10.4103/picr.PICR_110_18
10. P P Prevalence of chronic kidney disease in India- Where are we heading? Indian J Nephrol.2015;25(3):133-135
11. Insa M. Schmidt, Silvia Hubner, Jennifer Nadal. Patterns of medication use and the burden of poly pharmacy in patients with chronic kidney disease: the German Chronic Kidney Disease study. Clinical Kidney Journal.2019; 12(5):663–672. PMID: 31584562, PMCID: PMC6768303, DOI: 1093/ckj/sfz046
12. Conrial Marton, Jagadish V Kamath et Assessment of prescribing patterns of drugs in chronic kidney disease patients in a tertiary care. Indian Journal of Pharmacy Practice.2022;15(3):205-209.
13. Santra S, Agrawal D, Kumar S, Mishra A study on the drug utilization pattern in patients with chronic kidney disease with emphasis on antibiotics. Journal of integrative nephrology and andrology. 2015;2(3):85-89.
14. Roja Rani K,Susmitha Bhaskar Yerramasetty.A cross sectional observational study on prescribing patterns of drugs in chronic kidney disease patients in a tertiary care teaching hospital.ACTA scientific pharmaceutical sciences.2020;4(11):30-37
15. Raja smith paul McGrath,Rajaram Abhishek et Evaluation of drug utilisation pattern among geriatrics patients in a district head quarters government hospital using world health organisation indicators.Indian jounal of pharmacy practice.2021;14(1):27-31
16. Stephin V.Mathew, Santhosh Uttangi. Drug utilisation evaluation study and dose adjustment in patients with kidney disease in tertiary care International Journal of Biomedical Engineering and Clinical Sciences.2021;7(3):52-64.
17. Kamath L, Hema NG, Himamani S. A study of drug utilization pattern in patients of chronic kidney disease at a tertiary care hospital.Int J Basic ClinPharmacol 2019;8(2):170-175.
18. Devi DP, George Diabetic nephropathy: prescription trends in tertiary hospital. Indian J Pharm Sci.2015;70(3):374-78.
19. Kanailal Karnakar, Swapan Kumar Mandal etal. A study on evaluating the pattern of medicine use by patients undergoing dialysis in a tertiary care hospital of eastern india. Asian Journal of Medical 2022;13(7):149-153.
20. Ahlawat R, D’cruz S, Tiwari Drug utilization pattern in chronic kidney disease patients at a tertiary care public teaching hospital: Evidence from a cross-sectional study. J Pharm Care Health Syst. 2015;3(1):1-5.
21. Bajait CS, Pimpalkute SA, Sontakke SD, Jaiswal KM, Dawari Prescribing patterns of medicines in chronic kidney disease with emphasis on phosphate binders. Indian J Pharmacol. 2014;46(1):35-39.PMID: 24550582PMCID: PMC3912805 DOI: 4103/0253-7613.125163
22. Shastry CS, Al-Jabri MM, Chand Assessment of drug utilization pattern in chronic kidney disease patients in a tertiary care hospital based on WHO core drug use indicators. J Global PharmaTechnol 2019;11(9):1-9.
23. Shrestha B, Dixit SM. Assessment of drug use pattern using WHO prescribing indicators. J Nepal Health Res Council 2018;16:279-84.
24. Aveli Ali, Pavan kumar. A prospective obsewrvational study on medication usage pattern in patients riskfactors of chronic kidney disease:Asian jounal of pharmaceutical and clinical research.2021:14(12):144-14