INTRODUCTION:

Chronic kidney disease is characterized by the presence of irreversible kidney injury and the level of renal dysfunction which can be assessed according to the glomerular filtration rate¹.It is a major health issue worldwide and has high morbidity and mortality rates².

According to WHO reports, this disease accounts for almost 8,500,000 deaths per year [3]. It is the 12^th cause of death and 17^th cause of disability worldwide¹. Chronic kidney disease is defined as either kidney damage or GFR <60ml/min/1.73m² for ≥ 3months. Kidney damage can be defined as the pathologic abnormalities or markers of damage including abnormalities in blood or urine or in imaging studies⁴.Glomerular filtration rate can be considered as the best measure of overall kidney function⁵.Chronic kidney disease is usually associated with increasing age, diabetes, hypertension and cardiovascular diseases, obesity, smoking, excessive salt intake and lack of physical exercise. As the kidney function deteriorates, patients develop complications like anemia, increased incidence of cardiovascular diseases, hyperlipidemia and metabolic bone disorders⁶. Patients with CKD having comorbidities have a greater chance of disease progression and have higher risk of developing complications⁷. They should be assessed for the presence of complications and receive optimal treatment to improve their quality of life⁸.

The treatment given will be according to the various stages of the disease⁹.Chronic kidney disease is most often asymptomatic and therefore is usually detected at advanced stage⁸. Renal transplantation and dialysis are the general approaches for the advanced stage. Initiation of the dialysis will be dependent on the patient’s disease status. Symptoms that could indicate its need include persistent weight loss, nausea, vomiting, declining nutritional status and serum albumin levels, uncontrolled hypertension, electrolyte abnormalities and volume overload¹⁰.

Dialysis is a process of removing waste and excess water from the blood. Hemodialysis which is also called an artificial kidney is a lifesaving therapy in cases of CKD ⁹. Its main aim is to restore the intracellular and extracellular fluid movement, i.e., characteristic of normal kidney function¹¹.The principle of hemodialysis is based on the diffusion of the solutes through a semi permeable membrane¹².This process allows the removal of several substances from the bloodstream like water, urea, creatinine, uremic toxins and drugs¹⁰. The hemodialysis procedure is performed at least 2 to 3 times a week for minimum 4 hours. The time taken for dialysis may vary due to various factors like kidney function, level of salts, amount of waste in the body and the patient’s body weight⁸.

Patients undergoing hemodialysis may often have complications like muscle cramps, itching, hypotensive episodes, irregular heart rate and fatigue during a session. There is also a risk of developing infection and bacteraemia due to disease associated immunosuppression and various interventions¹³.Out of these, the most common complication seen is hypotension and occurs in at least 10% of all hemodialysis procedures¹⁴.Symptoms like nausea and cramps are usually present during hypotensive episodes. Muscle cramps usually complicate at least 5 to 20% of all hemodialysis procedures⁸.Infections are a major cause of morbidity and mortality in patients undergoing hemodialysis. With this background, the aim of the study is to assess the drug use pattern in chronic kidney disease patients undergoing maintenance hemodialysis which is the most preferred treatment for patients having end stage renal disease. These patients have multiple comorbid conditions and complications. The inference that can be made from this is that they have a need for these medications as it includes those that might alter the rate of progression of decline in kidney function and those used to treat comorbidities.

Drug use pattern studies can help in understanding how drugs are being used as well as help estimate the number of patients exposed to specific drugs within a given time period¹⁵.This study also assesses the management of complications that arise during the hemodialysis.

METHODS:

Design:

The prospective observational study was done from October 2017 to March 2018 in the dialysis unit of the Nephrology department, Justice K S Hegde Charitable hospital, Mangaluru.

Participants:

A total of 80 patients were recruited for the study. All the out-patients diagnosed with CKD aged above 18 years undergoing maintenance hemodialysis were included in this study. Pregnant and lactating women as well as the patients who were not willing to give consent were excluded. All the relevant information pertaining to the study was collected and entered into a specially designed data collection form.

Data collection:

The data of the patients who have met the inclusion criteria was collected. Relevant details of outpatients undergoing hemodialysis was noted. From the patient's record, the relevant data on drug prescription for each patient was collected. The demographic data (age, sex), diagnosis by the nephrologist was obtained by the patient case record of each patient. In addition, the associated co-morbid conditions, risk factors identified for developing chronic kidney disease and the complications that arose during the hemodialysis along with the management given were also taken from the medical records.

Statistical Analysis:

Descriptive statistics of qualitative characteristics are documented by using Frequency and percentage. Quantitative variables of clinical profiles of patients are presented using mean and standard deviation.

Ethical Considerations:

This research was approved by the Institutional Ethics Committee (NGSM/IEC/22/2017-18), K S Hegde Medical Academy, Mangaluru.

RESULTS:

During the study period, a total number of 80 patients were included and assessed for evaluating the prescribing trends shown in CKD patients that underwent maintenance hemodialysis. Among the 80 patients evaluated, it was observed that, 62 (77.5%) were males and 18 (22.5%) were females. Majority of the patients were in the age group of 54-62 years with a mean age of 51.21 ± 13.47 years as shown in Table 1.

Table 1. Distribution of Patients according to their age group

Table1.Age distribution (in years)	Frequency (n)
Table1.Age distribution (in years)	Male	Female
18-26	5	1
27-35	3	3
36-44	9	3
45-53	11	2
54-62	28	4
63-71	5	4
72-80	1	1

The most common co-morbid conditions were Hypertension (93.75%), followed by anemia (87.5%), Type 2 DM (41.45%), IHD (10%) as depicted in Table 2.

Table 2. Incidence Comorbidities among patients

Comorbidities	Frequency	Percentage %
Hypertension	75	93.75
Anemia	70	87.5
Type 2 Diabetes Mellitus	33	41.45
IHD	8	10
Thyroid	6	7.5
Obstructive uropathy	5	6.25

In this study it was found that antihypertensive agents were prescribed most frequently (30.1%). Following which hematopoietic agents (23.6%), phosphate binders (13.1%) were given. Least prescribed drugs were hormone preparations (1.1%) as depicted in Table 3.

Table 3. Categories of drug prescribed to the patients

Drug Classes		Frequency (n) Percentage %
Antihypertensive agents	CCB	68	13
	Alpha 2 Agonist	33	6.2
	Vasodilators	16	3
	Alpha blockers	17	3.2
	Beta blockers	15	2.9
	ACE inhibitors	3	0.5
	ARB	7	1.3
Gastro Intestinal Tract Agents		52	10
Antiplatelet agents		30	6
Diuretics		36	6.9
Antibiotics		15	2.9
Anti-diabetic agents		34	6.5
Phosphate binders		69	13.1
Hormone preparations		6	1.1
Hematopoietic agents		124	23.6
Total		525	100

In the study 23.6% of hematopoetic agents were given. 13% of calcium channel blockers like amlodipine (5.3), nifedipine (4.5), cilndipine (3%) were given. Gastro intestinal drugs are given in 10% in the study population. Diuretics like torsemide (5%) and furosemide (2), Alpha 2 agonist like clonidine (6.2%) were also significantly used in this population as shown in Table 4.

Table 4. Overall drug utilization pattern in CKD patients

Drug Classes	Drugs	Frequency (n)	Percentage %
CCB	Amlodipine	28	5.3
	Nifedipine	24	4.5
	Cilnidipine	16	3
Alpha 2 Agonist	Clonidine	33	6.2
Vasodilators	Dihydralazine	16	3
Alpha blockers	Prazosin	16	3
Alpha blockers	Tamsulosin	1	0.2
Beta blockers	Carvedilol	10	2
	Atenolol	3	0.5
	Metoprolol	2	0.3
ACE inhibitors	Ramipril	3	0.5
ARB	Losartan	3	0.5
ARB	Olmisartan	4	0.8
Gastro Intestinal Tract Agents	Pantoprazole	39	7.4
Gastro Intestinal Tract Agents	Ranitidine	13	2.4
Antiplatelet agents	Aspirin	22	4.1
Antiplatelet agents	Clopidogrel	8	1.5
Diuretics	Torsemide	26	5
Diuretics	Furosemide	10	2
Antibiotics	Piperacilin+ tazobactum	3	0.5
	Levofloxacin	2	0.3
	Amoxicillin + clavulanic acid	4	0.8
	Cefixime	3	0.5
	Nitrofurantoin	1	0.1
	Feropenem	2	0.3
Anti-diabetic agents	OHA	5	2
Anti-diabetic agents	Insulin	29	5.5
Phosphate binders	With calcium	55	10.5
Phosphate binders	Without calcium	14	2.7
Hormone preparations	Thyroxine	6	1.1
Hematopoietic agents	Erythropoietin	69	13.1
Hematopoietic agents	Iron sucrose	55	10.4
Total		525	100

From the study population, a total number of 21 patients were found to have developed complications during the dialysis sessions. The most frequently occurring complications were observed to be Hypotension (18%) and Vomiting (18%) followed by Hypertension (14%), Cramps (13%) and Chills (11%), infection (8%). The complications are managed as hypotension with Normal saline, vomiting with ondansetron, cramps with dextrose, and chills are treated with antihistamines, infection with vancomycin or with amikacin or both depending on the patient. Complications are represented in the following table 5

Table 5. Complications that occurred during hemodialysis

Complications	Frequency (n)	(%)	Managed by
Hypotension	22	18	250ml saline
Cramps	16	13	25% dextrose
Chills	13	11	Antihistamines
Hypertension	17	14	Antihypertensives
Hypoglycemia	4	4	25% dextrose
Weakness	8	7	Carnitin 20mg
Vomiting	22	18	Ondansetron 4mg
Headache	8	7	Acetaminophen 650mg
Infection	10	8	Vancomycin 1g
Total	120	100

DISCUSSION:

In the present study on CKD patients undergoing maintenance hemodialysis, 77.5% were males and 22.5% were females. This was analogous to a study done by Chacko et al., where out of 150 patients, 77.1 % were males and 23.1% were females. The results show that males are more likely to have CKD and receive proper treatment than females¹⁵.

In the current study, the average age group of patients having CKD was observed to be in the range of 51±13 years which was similar to the study conducted by Shishiru et al., where the age of the majority of patients were 58±15 years. The current study is in correspondence with the previous studies that were conducted. The results show that as age increases, the chances of developing CKD also increase and that CKD is more prevalent in mid to elderly age groups. But in a study done by Ahmad et al., the mean age was 33± 10.5 which is contrary to the present study¹⁶.

In the present study, the most frequent risks and comorbidities were found to be hypertension (93.75%), followed by anemia (87.5%), type 2 DM (41.45 %), smoking (3.75%), alcohol (17.5%), IHD (10%) and thyroid disorders (7.5%) A study done by Santra et al., stated that the most common comorbidities found were hypertension (95%), diabetes (87%) and anemia (86%) [3]. In another study, done by Narayana et al., it showed that hypertension (88.46%) was the most common, followed by smoking (75.5%), alcohol (53.84%), Diabetes (36.53%), anemia (36.53%). These results were similar to the present study which shows that hypertension, anemia, smoking, type 2 DM and alcohol are the most common risks and comorbidities for CKD [10]. However, in a study done by Eghan et al., showed that chronic glomerulonephritis was the leading comorbidity with 35.9% and hypertension was 19.1%¹⁷. In the present study, cardiovascular drugs were the most frequently prescribed drugs (30.1%). After which, were hematopoeitics (23.6%), drugs acting on GIT (10%), antidiabetic agents (6.6%), phosphate binders (13.1%) and 1.1% for hormone preparations. A study done by Kantanavar et al., showed that drugs most commonly given were for the cardiovascular system (31.1%). Subsequently nutritional supplements (15.3%), haematinics (10.7%) and drugs acting on gastrointestinal system (10.3%), antidiabetic drugs (4.7%) and phosphate binders (9%). The results are concomitant with the current study which shows that CKD patients who undergo hemodialysis are very frequently prescribed with antihypertensives, hematopoietics, antidiabetics, phosphate binders and drugs that act on GIT¹⁸.

In the current study, Anemia was the second most common comorbidity and hence erythropoietin was given frequently (86.25%) along with multivitamins (13%). Hypertension, being the most common co morbid condition in the study population was treated frequently with antihypertensives like clonidine (41.25%), amlodipine (35%), torsemide (32.5%) and nifedipine (30%). Pantoprazole (48.8%) was also given which could be for preventing stress ulcers. Rajeshwari et al., conducted a study where, the most repeatedly prescribed were anticoagulants (100%), followed by antihypertensives (94%), calcium salt, erythropoietin ulcer protectives, antiplatelet and multivitamins. This was analogous to the present study¹⁹.

In a study done by Ahmad et al., it was shown that the most common complications that arise during hemodialysis was chills, vomiting, cramps, headache, hypertension This was found relevant to the present study where, chills, vomiting, hypotension cramps, hypertension, headache and weakness were the main complications that arose during hemodialysis²⁰.

LIMITATION:

The Short term duration (6 months) and also its narrow sample size were the limitations of this study. Future studies that will address all these limitations are needed.

CONCLUSION:

In this study, the prescribing trends in managing CKD patients who were on maintenance hemodialysis was evaluated. It was found that males were more prone to CKD than females. The most common comorbidities seen in the study population were hypertension, anemia, Type 2 DM. Although hemodialysis has been proven to be a lifesaving therapy for end stage CKD patients, it was observed that complications like hypertension, vomiting, hypotension, cramps and chills can arise during the dialysis session. During the study period, out of the 80 patients, 73 patients had survived and 7 had expired. Drug utilization studies are effective in showing the trend in prescribing according to various physician.

ABBREVIATIONS:

CKD: Chronic kidney disease, WHO: World health organisation, GFR: Glomerular filtration rate, DM: Diabetes mellitus, IHD: Ischemic heart disease, ACE: Angiotensin converting enzyme, ARB: Angiotensin receptor blockers.

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Received on 31.05.2019 Modified on 20.06.2019

Research J. Pharm. and Tech. 2019; 12(10):5024-5028.

DOI: 10.5958/0974-360X.2019.00872.2