EVALUATION OF THE DRUG THERAPY MANAGEMENT OF CKD PATIENTS (STAGE 3 5) IN A TERTIARY CARE HOSPITAL

EVALUATION OF THE DRUG THERAPY MANAGEMENT OF CKD

PATIENTS (STAGE 3-5) IN A TERTIARY CARE HOSPITAL

Dr. Parthasaradhi1, Dr. Mehruq Fatima2, Syeda Fareha Fatima*3, Umme Salma4, Nabeela Fathima5

1

Department of Nephrology, Owaisi Hospital and Research Centre, Hyderabad, Telangana,

India.

2

Assisstant Professor, Department of Pharmacy Practice, Deccan School of Pharmacy,

Hyderabad, India.

3,4,5

Doctor of Pharmacy Student, Department of Pharmacy Practice, Deccan School of

Pharmacy, Osmania University, Hyderabad, Telangana, India.

ABSTRACT

Background: Chronic kidney disease population can be distinguished

by its vulnerability as it is associated with multiple concurrent

co-morbidities requiring the use of numerous medications, ensuing

intricate therapeutic regimens, intermittent medication modifications

and restricted lifestyles resulting in a substantial risk for developing

actual and potential drug-related problems (DRPs) which are

associated with significant morbidity, mortality, and cost. Aim: To

evaluate the drug therapy regimens of CKD stage (3-5) patients for

determining the prevalence and identifying the types of DRPs.

Methods: Prospective observational 6-month study was conducted in

CKD (stage3-5) patients who were aged > 18 years and admitted in

owaisi hospital and research centre. Patients' data and drug therapies

were collected through direct patient interview, discussion with

nursing staff, assessment of patients' medication charts and medical records. DRPs were

identified and classified into 6 main categories (according to The PCNE V 5.01). Descriptive

analysis was done for demographic data, comorbidities, drug utilization, and DRPs' profiles

and Pearson's correlation test was used to assess the correlation between drugs and DRPs.

Results: Out of 30 patients in the study, 26 had DRPs. A total of 79 DRPs were identified

with an average of 2.63 + 2.0 DRPs per subject. Of which, 53.16% were actual DRPs and

Volume 8, Issue 13, 711-723. Research Article ISSN 2277– 7105

Article Received on 21 Sept. 2019,

Revised on 11 Oct. 2019, Accepted on 01 Nov. 2019

DOI: 10.20959/wjpr201913-16194

*Corresponding Author

Syeda Fareha Fatima

Doctor of Pharmacy

Student, Department of

pharmacy practice, Deccan

school of pharmacy,

Osmania university,

Hyderabad, Telangana,

46.83% were potential DRPs. Drug interactions (48.10%) and adverse drug reactions

(29.11%) were found to be the major DRPs followed by Drug choice problem (11.39%),

Dosing problem (10.12%), Other DRPs (1.26%) and Drug use problem (0%) respectively.

Conclusion: Our study reveals that DRPs among the CKD (stage3-5) patients were high.

Drug interactions and adverse drug reactions contributed to the majority of DRPs identified.

Timely appropriate monitoring, prevention, identification and resolution of DRPs are crucial

to optimize clinical outcomes in CKD patients.

KEYWORDS: Drug-Related Problems, Chronic Kidney Disease, PCNE, Adverse reactions,

drug interactions, dosing problems.

INTRODUCTION

Chronic kidney disease (CKD) is one of the most prevalent therapeutic problems and the

number of people affected by it is increasing globally each year. In the last decade, the U.S

has witnessed a 30% increase in the prevalence of CKD.[1] According to the World health

organization (WHO), approximately 8,00,000 mortality cases have been reported each year

worldwide.[2] Patients with CKD require early detection and appropriate treatment to prevent

its progression.

CKD is characterized by abnormalities in kidney structure or decline in kidney function, for a

period of 3 months or longer.[3] Frequent complications associated with progression of CKD

include cardiovascular disease, sodium and water imbalance, anemia, metabolic acidosis,

hyperkalemia and renal osteodystrophy and, if left untreated may lead to an extended hospital

stay and increased cost. Moreover, the progression of CKD may lead to an increased number

of drugs to manage its complications and co-morbidities, thereby leading to increased

incidence of drug-related problems (DRPs). The decline in kidney function is associated with

alteration in the pharmacokinetics of the majority of drugs. Pharmacokinetic alteration of

drugs, such as a change in drug bioavailability, protein binding level, drug distribution and

elimination, may worsen the already deteriorating condition of CKD patients and make them

vulnerable to DRPs.[4]

DRP may be defined as an event involving drug therapy that actually or potentially interferes

with desired health outcomes.[5] In this context, a potential problem means a condition that

may cause drug-related morbidity or death if no action is undertaken. An actual problem is

health-related quality of life of patients. Hence, a systematic review of patients' drug use may

help health-care professionals in identifying DRPs, resolving actual DRPs and preventing

potential DRPs for effective drug therapy and better patient health outcomes.[4]

Unfortunately, there are limited prospective studies conducted on evaluating drug therapy

problems in CKD patients in India. Therefore, this study was conducted aiming to identify

and evaluate drug-related problems (DRPs) in patients with stages 3-5 chronic kidney disease

to optimize drug therapy and reduce drug-related morbidity and mortality.

MATERIALS AND METHODS

Study design: A prospective observational 6-month study was conducted in CKD (3-5)

patients who were admitted under the nephrology department of owaisi hospital and research

centre, Hyderabad, Telangana, after obtaining the approval from the institutional review

board of the hospital.

Study participants: The study's inclusion criteria were met by 30 patients, aged 18 years or

older, diagnosed with stages (3-5) of chronic kidney disease who were willing to participate,

expressed a desire to achieve its objectives and gave their written informed consent.

Data collection: Patient's data collection was carried out during hospitalization and at

discharge time. The questionnaire used in this study for data collection included date of

admission/discharge, patients' socio-demographic characteristics (including age, sex, weight,

height, smoking status, alcohol/substance abuse sleep and dietary pattern),

co-morbidities/past medical history, past medication history (including herbal and OTC

medicines), allergy/adverse drug reaction history, current medication profiles (drug name,

indication, dose, frequency and duration), discharge medications, physical and general

examination, clinical information, laboratory investigations and diagnostic examinations. For

the DRP: adverse drug reactions, Indian pharmacopeia commission (IPC) – suspected adverse

drug reaction reporting form was used.

Assessing the Drug-Related Problems: The Investigators identified the DRPs through direct

patient interview, discussion with nursing staff, assessment of patients' medication charts and

medical records with the help of recommendations from IBM Micromedex® Drug Ref and

IBM Micromedex® Drug Interactions software databases. The identified DRPs were

drug-related problems, which categorizes DRPs into six primary domains.[17] Further DRPs

were divided into actual and potential DRPs.

Data Analysis: Descriptive analysis was done for demographic data, drug utilization and

DRPs. The continuous variables were summarized as mean + SD; categorical variables were

summarized as frequencies and percentages. Pearson's correlation was used to assess the

correlation between drugs and DRPs. The statistical test was two-tailed and P<0.05 was used

to indicate statistical significance.

RESULTS

There were 30 patients who met the inclusion criteria for the six-month prospective

observational study and their demographic characteristics are summarised in Table 1. Male

patients (80%) were more than female patients. The mean age of the study population was

51.0 + 14.5 years and a high number of subjects was found in the age range 51-60 years

(36.7%). The data also reveals 27.67% of subjects were smokers or had a history of smoking

and 14% subjects were alcoholics or had a history of drinking. Majority of the patients were

middle class (60%); unemployed or retired (60%) and married (83%).

Table 1: Patients Socio-Demographic Characteristics.

Patient demographics Category No. Of patients n (%)

Age (Mean + SD)

51.0 + 14.5 18-40 41-60 61-80 - 7 (23.3%) 15 (50%) 8 (26.7%) Gender Male Female 24(80%) 06(20%) Addiction Smokers Ex-smokers Non-smokers Alcoholics Ex-alcoholics Non-alcoholics 3 (10%) 5 (17.67%) 22 (73.33%) 2 (7%) 2 (7%) 26 (86%) Educational Status Educated Uneducated 17(57%) 13(43%) Employment Status Employed Unemployed 12(40%) 22(60%) Economic Status Low Middle Upper middle 09(30%) 18(60%) 03(10% Marital Status Married Unmarried

Clinical characteristics

Table 2 outlines clinical characteristics of the study population that depicts the majority of

patients (97%) were diagnosed with CKD stage 3-5 with a mean glomerular filtration rate

(GFR) of 10.56 + 3.64 mL/min. Mean hospital stay of the study population was 8.73 +5.71

days. The average number of co-morbidities per subject was found to be 6.06 + 2.49, the

major co-morbidity being hypertension (97%), Anaemia (90%), coronary artery disease

(57%) followed by Diabetes mellitus (49%).

Table 2: Clinical Characteristics of The Study Population.

Variables Mean + SD

BMI (kg/m2) 22.58 + 6.17

SBP (mm Hg) DBP(mm Hg)

130 + 24.49 79.6 + 11.29

Haemoglobin (g/dL) 7.94 + 1.92

Serum creatinine (mg/dL) 7.76 + 4.43

Glomerular filtration rate (ml/min/1.73m2) 10.56 + 3.64 Serum sodium(mmol/L)

Serum potassium (mmol/L) Serum calcium (mmol/L) Serum phosphorus (mmol/L)

134.04 + 5.02 4.46 + 0.93 7.42 + 1.65 5.17 + 2.24

Blood Urea (mg/dL) 173.8 + 87.89

Serum Uric Acid (mg/dL) 7.95 + 1.46

Mean hospital stay (days) 8.73 +5.71

CKD STAGE n(%)

STAGE 3a STAGE 3b STAGE 4 STAGE 5

0% 0% 1(3%) 29(97%)

Presence of co-morbiditiesn (%)

<5 9 (30%)

5-10 20 (66.7%)

>10 1 (3.33%)

Average no. of co-morbidity per patient (Mean + SD) 6.06 + 2.49

Haemodialysis n (%)

Yes No

Table 3: Co-Morbid Conditions in The Study Population.

Co-morbidities No. Of patients (n=30) Percentage

Hypertension 29 97%

Type 1 diabetes mellitus 1 3%

Type 2 diabetes mellitus 14 46%

Coronary artery disease 17 57%

Pulmonary edema 1 3%

Hypothyroidism 6 20%

Tuberculosis 1 3%

HCV positive 1 3%

Anemia 27 90%

Sepsis 7 23%

Seizure disorder 1 3%

Gastroenteritis 2 6%

COPD 1 3%

Parkinsonism 1 3%

Vitiligo 1 3%

LV dysfunction 9 30%

Hypoglycemia 2 6%

Uremic pericarditis 1 3%

Drug utilization profile and DRPs

Total numbers of medication orders issued to 30 subjects were calculated as 538 with an

average of 16.73 + 6.11 drugs per patient. Half of the study population was prescribed > 16

drugs.

Table 4 depicts commonly used therapeutic class of drugs for the study population, of which

the most common were cardiovascular drugs (18.9%), followed by the class of drugs acting

on blood and blood-forming organs (15.9%). Further, the 10 most prevalent drugs prescribed

were gastrointestinal drugs (15%), other drugs (9.8%), anti-infectives’ (9.6%),vitamins

(9.6%), respiratory drugs (5.3%), analgesics, antipyretics and NSAIDs (4%), CNS agents

(3.1%), hormones and endocrinal agents (3.1%), fluids, electrolytes and parenteral nutrition

Table 4: Therapeutic Classes of Drugs Prescribed for the Study Population.

Therapeutic Classes n (%)

Cardiovascular drugs 102 (18.9%)

Fluids, Electrolytes and Parenteral Nutrition 16 (2.9%)

Gastrointestinal drugs 81 (15%)

Anti-Infectives 52 (9.6%)

Drugs acting on blood or Blood Forming organs 86 (15.9%)

Vitamins and minerals 52 (9.6%)

Hormones and Endocrine drugs 17 (3.1%)

Respiratory drugs 29 (5.3%)

CNS agents 17 (3.1%)

Anti-hyperuricemic agents 11 (2%)

Analgesics, antipyretic and NSAIDs 22 (4%)

Others 53 (9.8%)

Total no. of drugs prescribed during the study 538

Drugs prescribed per patient

≤10 11-15 ≥16 2 13 15

Average no. of drugs prescribed per patient (Mean + SD) 16.73 + 6.11

86.66% of the study population experienced DRPs. On average, DRPs per patient was found

to be 2.25 + 1.42. Drug interactions (48.10%) and adverse drug reactions (29.11%) were

found to be the major drug therapy problems followed by Drug choice problem (11.39%),

Dosing problem (1012%), Other DRPs (1.26%) and Drug use problem (0%) respectively.

Potential DRPs accounted for the majority of the cases as opposed to actual/manifest DRPs.

Table 5 summarizes the DRPs identified in the participants. The study showed that there was

an increase in the number of drug-related problems with an increase in the number of drugs

per prescription and the association was statistically significant (P=0.008).

Table 5: Summary of DRPs Identified in The Study Population.

Identified Drug Therapy Problems Code

Frequency TOTAL (%) Actual DRPs Potential DRPs ADVERSE REACTIONS a) Side effects suffered (allergic) b) Side effects suffered (non-allergic) c) Toxic effects suffered

P1.1 P1.2 P1.3 23 29.11% 29.11%

0 0

23 0

0 0

DRUG CHOICE PROBLEM a) Need for additional drug b) Unnecessary drug

c) Inappropriate drug choice

P2.1 P2.2 P2.3 9 11.39% 8.86% 2.53%

4 3

1 1

0 0

a)Drug dose too low or dosage regime not frequent enough

b) Drug dose too high or dosage regime too frequent (need dosage adjustment according to CKD stage)

c) Duration of treatment too short d) Duration of treatment too long

P3.1

P3.2

P3.3 P3.4

0 2

2.53%

6.32%

1.26%

0 5

0 0

0 1

DRUG USE PROBLEM

a) Drug not taken/administered at all b) Wrong drug taken/administered

P4.1 P4.2

0

0%

0 0

0 0

DRUG INTERACTIONS a) Potential interaction

b) Actual/Manifest interaction

P5.1 P5.2

38 48.10%

31.64% 16.45%

0 25

13 0

OTHER DRPs

a) Patient dissatisfied with therapy despite taking drug(s) correctly

b) Insufficient awareness of health and diseases (possibly leading to future problems)

c) Unclear complaints. Further clarification necessary

d) Therapy failure (reason unknown)

P6.1 P6.2 P6.3 P6.4 1 1.26% 1.26%

0 0

0 0

0 0

1 0

TOTAL =79

DRPs- Drug related problems

Table 6: Drugs V/s Drug Related Problems.

Mean + SD P-Value DRUGS (average no. Of drugs per patient) 17.93 + 6.11

0.008

DRPs (average no. Of DRPs per patient) 2.63 + 2.0

Note: P < 0.05 is statistically significant

DISCUSSION

During the 6 month study, patients diagnosed with chronic kidney disease of stages 3-5

including patients on maintenance hemodialysis of a tertiary care hospital were included to

evaluate their drug therapy to identify the associated drug-related problems.

Several co-morbidities were found among the study population and the major co-morbid

conditions were hypertension (97%), Anaemia (90%), Coronary artery disease (57%) and

Diabetes mellitus (49%). This is concordant to the findings of N.Vanitha Rani et.al.[4] in

diabetes mellitus, and Coronary artery disease. The mean number of comorbidities per patient

was 6.06 + 2.49.

This study has revealed a very high proportion (86.66%) of CKD (stage 3-5) patients with

DRPs. Almost all the patients (97%) in the study were diagnosed with stage 5 CKD and only

3% were diagnosed with stage 4 CKD and no patient had stage 3 CKD.

Total numbers of 538 medication orders were issued to 30 subjects with an average of 16.73

+ 6.11 drugs per patient, which eminently indicates polypharmacy. This is a little high

compared to the studies conducted by Car done et.al.[10] which stated that dialysis patients

were prescribed an average of 12 medications and Rani et al.[4] where the average number of

drugs per prescription was found to be 8.93 + 3.26.

A total of 79 Drug-related problems were identified in 86.66% of the study population while

13.33% had no DRPs, which is similar to the study conducted by Maxwell O Adibeet.al.[25]

where they reported that 70.03% of CKD patients in their study had DRPs. Average no. Of

DRPs per patient was found to be 2.63 + 2.0. When comparing the rate of DRPs experienced

by each patient, Patel HR et.al.[11] reported a mean of 3.2 DRPs per patient.

The drug-related problems (DRPs) identified in the study were as follows:

Adverse Drug Reactions All the ADRs identified were non-allergic, which is in line with the

study conducted by Hesty U. Ramadaniati et.al.[2] where they reported non-allergic adverse

drug events as one of the major DRPs. The most common ADR found in the study population

was nausea (26%). Majority of the ADRs observed were falling under the gastrointestinal

system category (65.2%). On the WHO-UMC scale, the most frequent category was

‘possible’ (79.41%), followed by ‘probable’ (11.76%), ‘unlikely’ (8.82%). 0% ADRs were

assessed as ‘certain’, ‘conditional’ and ‘unclassifiable.

Drug choice problems 9 DRPs (11.39%) were identified as problems of drug choice. 7

problems were found under the sub-category ‘Need for additional drug’, and 2 problems were

found under the category ‘Unnecessary drug’.

Dosing problems 8 DRPs (10.12%) were identified to be problems of drug dosing. 5 dosing

problems were found under the sub-category, ‘Drug dose too high or dosage regime too

frequent’; 2 dosing problems were found under the sub-category, ‘Drug dose too low or

‘Duration of treatment too long’; however no dosing problem was found under the sub- category, ‘Duration of treatment too short’. All the dosing problems identified in this study

are potential DRPs. No Drug use problems (0%) were identified in this study.

Drug interactions The assessment of the drug therapies on the software program

MICROMEDEX revealed a total of 38 (48.10%) drug interactions in the study population

and all of them were found to be drug-drug interactions (DDIs). DDIs is the major DRP

identified in this study which is concordant to the findings of N.vanitha rani et.al.[4] in which

they have reported Drug interactions as the most frequent DRP observed in their study. Out

of the total DDIs identified, 65.78% are potential DRPs and 34.21% are actual DRPs, which

is in line with the study conducted by Alessandra batista marquito[13] where potential drug

interactions were majorly reported. According to the severity classification, the DDIs are

classified as follows in the descending order of their occurrence– 47.36% were major, 45%

were moderate, 7.89% were contraindicated and minor drug interactions are 0%. By using the

Drug interaction probability scale (DIPS)[18] the DDIs are classified as follows: Highly

probable (0%), probable (2.63%), possible (31.57%) and doubtful (66%). Only 1 problem

(1.26%) is identified under the category ‘Other DRP’

Out of the total DRPs identified, 53.16% are actual DRPs and 46.83% are potential DRPs. In

a study conducted by Hesty U. Ramadaniati et.al.[2] potential DRPs accounted for the

majority of the DRPs as opposed to actual/manifest DRPs. The findings of this study conform

to the reports of studies by Rani et al.[4] and St. Peter WL[16] that there is an upward tendency

of incidence of DRP in accordance to the increased number of medications. Drug interactions

(48.10%) and adverse drug reactions (29.11%) were the major sources of DRPs in this study.

These findings were similar with Hesty u. Ramadaniati et.al.[2] where they concluded adverse

drug reactions and sub-optimal effect of treatment as the major DRPs and also with the study

findings of Levey AS et.al.[14] and Sarnak MJ et.al.[15] in which the common DRPs in CKD

are adverse events, drug interactions and improper doses. A study carried out by Grabe D.W

et.al[12] also reported drug interactions as the most common DRP identified.

It has been well defined that reducing the occurrence of DRPs will bring about better

outcomes for patients, and alleviate the financial burden.[6-8] In addition, there may also be

great personal costs to those involved and may result in time away from work, low patient

satisfaction and lessened public trust toward health care.[7-9] Hence, it is significant to

CONCLUSION

Our study reveals that the prevalence of drug-related problems among the CKD (stage3-5)

patients was high. 79 DRPs were identified in thirty study participants. Drug interactions and

adverse drug reactions were the most common DRPs. Actual DRPs accounted for the

majority of the DRPs identified as compared to the potential DRPs. The nature of prospective

observation of our study provides better opportunities to capture actual and potential DRPs.

DRPs have profound ramifications in CKD patients already burdened by multimodal therapy.

It has been well defined that the consequences of DRPs result in extended hospitalization,

readmissions to the hospital, higher cost and premature death. Our study advocates the

importance of timely appropriate monitoring, prevention, identification, intervention and

resolution of Drug-related problems to optimize clinical outcomes and reduce drug-related

morbidity and mortality in CKD patients and implores the need for further studies on a larger

study population.

ACKNOWLEDGEMENT

All authors contributed to the design of the study, interpretation of data and writing of the

manuscript. The authors would like to extend sincere gratitude to their respective family

members for their great support.

Conflict of Interests

The authors have none to declare.

Abbreviations

ADR: Adverse drug reaction; BMI: Body mass index; CCBs: Calcium channel blockers;

CNS: Central nervous system; COPD: Chronic obstructive pulmonary disease; CKD: Chronic

kidney disease; ClCr: creatinine clearance; DBP: Diastolic blood pressure; DRPs: Drug

related problems; DDIs: Drug-drug interactions; DIPS: Drug interaction probability scale;

ESA: Erythropoietin stimulating agent; ESRD: End stage renal stage disease; FDA: Food and

Drug Administration; GI: Gastrointestinal; GFR: Glomerular filteration rate; HD:

Hemodialysis; IPC: Indian pharmacopoeia commission; IV: Intravascular; MBD: Mineral

and Bone Disorder; NSAIDs: Non-steroidal Anti-Inflammatory Drugs; PCNE:

Pharmaceutical care network europe; SBP: Systolic blood pressure; SCr: Serum creatinine;

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