الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Chronic kidney disease patients are particularly vulnerable to drug-related problems and ADEs because they have impaired renal function and altered drug clearance, along with multiple comorbidities and frequent hospitalizations. The convergence of these factors increases CKD patients’ susceptibility to adverse safety events.
Non-steroidal anti-inflammatory drugs are the most common therapeutic products used for the management of inflammation and pain. However, NSAIDs have several adverse effects including nephrotoxicity, resulting in changes in the haemodynamics of the kidney. This could lead to renal impairment and worsen the degree of renal dysfunction in CKD patients and consequently lead to the development of ESRD.
The aim of the present study was to investigate the use of NSAIDs among CKD patients diagnosed in pre-ESRD (i.e. before dialysis or transplantations) and with the following specific objectives:
1. To estimate the prevalence of NSAIDs use among the study pre-ESRD patients.
2. To identify the pattern of NSAIDs use among pre-ESRD patients.
3. To assess the knowledge of pre-ESRD patients about the adverse effects of NSAIDs.
A cross sectional study was conducted among adult CKD patients (18 years and above) diagnosed in pre-ESRD. The study included 350 pre-ESRD patients attending the outpatient and the inpatient wards of Internal Medicine Department of Alexandria Main University Hospital.
Data collection was done using a predesigned interview questionnaire including personal data, history of comorbid diseases, history of selected drugs interacting with NSAIDs, NSAIDs use (prevalence, type, purpose, pattern, source of advice, and adverse effects of NSAIDs), and data about the knowledge of adverse effects of NSAIDs. Measurements (blood pressure, weight, and height) and laboratory investigations (standardized serum creatinine from patients’ data with calculation of the eGFR) were done.
Data entry and statistical analysis were done using the software Statistical Package for Social Science (SPSS) version 23. Statistical analysis was performed in both descriptive and inferential forms.
The study revealed the following main results:
A. Characteristics of CKD patients:
The age of patients ranged between 18 and 93 years with a mean age of 55±13 years.
The percentage of males was slightly higher than females (51.4 % versus 48.6%, respectively).
Almost three quarters (74.5%) of the study patients were married, while only 4.9% were single. Widowed patients constituted 16.3% of the study patients.
More than one third (38.6%) of the patients were illiterate. More than one fourth of the patients were either with preparatory education or read and write (25.4% and 25.1%, respectively). Only 3.2% of the participants were university graduates.
More than two fifths (43.1%) of the study patients were housewives, 20.9% were retired, 15.7% were non-working and only 8.3% were employees.
More than the half (59.2%) of study patients were non-smokers and about one fifth (19.1%) were currently smoking.
The percentage of overweight and obese patients were nearly equal (42.6% and 42%, respectively).
More than the half of study patients were hypertensive, 46% were diabetics, 28% were suffering from osteoarthritis, and 18.3% had CVDs.
The median (Inter-quartile range) eGFR was 27(18-37) ml/min/1.73m2 among the study patients. More than half (56%) of study patients were in stage 4 while 40.3% were in stage 3 (12.6% in stage 3a and 27.7% in stage 3b). Only 3.7% were in stage 2. None of the patients were in stage 1.
The percentage of patients who gave history of using RAAS inhibitors (ACEI/ARBs) and diuretics were 20% and 9.7% respectively. Only 6.3% of patients gave history of using both.
B. The prevalence of NSAIDs use among the pre-ESRD patients was 65.7%.
C. NSAIDs use among CKD patients:
Ketoprofen was the most commonly used NSAID (50.3%), followed by diclofenac (33.7%), ibuprofen (23.1%), ketorolac (2.6%) and meloxicam (2.3%).
More than two thirds (68.7%) of CKD patients mentioned headache as the main reason for NSAIDs use, followed by generalized pain (49.6%) and joint pain (43.9%).
Two fifths of CKD patients took NSAIDs twice a week, while more than one fifth took them every day or three times a week (22.2% and 20.4% respectively) within the last month.
More than two fifths (46.1%) of study CKD patients used NSAIDs for a period exceeding three years, 41.7% for 1-3 years and 12.2% less than one year.
More than three quarters (82.6%) of study patients gave history of regular use in the form of at least twice a week for more than two months.
The percentage of patients using one type of NSAIDs was 44.8%. Those using two and three types constituted 40% and 13.5% respectively during the last month.
About three quarters (74.3%) of the patients used NSAIDs by oral route while almost one fourth (24.8%) used both oral and injection route.
About one third (31.3%) of CKD patients with a history of NSAIDs use mentioned having adverse effects and 90.3% of them reported GIT effects, while 20.8% reported kidney problems.
The majority of patients (76.5%) used NSAIDs by self-decision, while 25.2% used them after the advice of physicians. Those who mentioned relatives and friends constituted 13.5%. Pharmacists and previous prescription constituted 10.4% and 9.1% respectively.
There was a significant inverse/negative correlation between the eGFR and the duration of NSAIDs use (r = -0.25, p< 0.001).
D. Factors associated with NSAIDs use among CKD patients:
In univariate analysis: gender, occupation, smoking status, hypertension, osteoarthritis, hepatitis C, and eGFR were significantly associated with NSAIDs use.
In logistic regression analysis: age, occupation, hypertension, osteoarthritis, hepatitis C, and eGFR were significantly associated with NSAIDs use.
E. Knowledge of CKD patients about the adverse effect of NSAIDs:
More than the half (53.2%) of the patients did not know whether NSAIDs have adverse effects or not. Those who mentioned that NSAIDs have adverse effects constituted 37.1%, and only 9.7% said that NSAIDs have no adverse effects.
Among CKD patients who mentioned that NSAIDs have adverse effects, 55.4% of them thought that NSAIDs cause kidney problems. The percentage of patients who thought that NSAIDs lead to gastrointestinal tract, liver and heart problems were 45.4%, 19.2% and 2.3%, respectively.
Based on the results of the current study, the following can be concluded:
• The use of NSAIDs is widely prevalent among pre-ESRD patients. About two thirds (65.7%) of the patients enrolled in this study were NSAIDs users.
• The NSAIDs use was associated with a decline of eGFR in CKD patients in a time-dependent manner.
• The use of NSAIDs is related to certain comorbid diseases as osteoarthritis and hypertension.
• Improper use of NSAIDs with interacting drugs as RAAS inhibitors (ACEI/ARBS) and/ or diuretics at the same time was reported by more than one third (37.4%) of the study patients.
• The majority NSAIDs users were using them by self-decision.
• Age, occupation, hypertension, osteoarthritis, hepatitis C, and eGFR were significantly associated with NSAIDs use.
• More than the half (53.2%) of study patients did not know whether NSAIDs have adverse effects or not.
The main recommendations of the study are:
A. Recommendations to the Ministry of Health and Population:
• Implementing the pharmacovigilance system and helping health care professionals (HCPs) managing patients with CKD to understand the role of pharmacovigilance in ensuring patient safety through continuous health education and clinical training in pharmacovigilance.
• Communicating the effects of NSAIDs use especially their nephrotoxicity and potential interactions with RAAS inhibitors and diuretics to physicians, other prescribers of medication and the community through training courses and workshops.
• Educating pharmacists about the basic principles of rational use of NSAIDs, with special stress on adverse effects and possible drug-drug interactions.
• Improving patient understanding and awareness of CKD and risks of use NSAIDs to prevent further kidney damage and progression of the disease through the mass media and public health programs.
• Banning self-medication with NSAIDs through enforcing strict regulations.
B. Recommendations to physicians:
• Considering doing renal function tests to all patients when prescribing NSAIDs and doing a risk benefits analysis for NSAIDs use.
• Prescribing the lowest effective NSAID, for the shortest possible time, and discouraging its chronic use.
C. Recommendations to pharmacists:
• Pharmacists should spend more time with NSAIDs purchasers explaining the rational use, the adverse effects of NSAIDs and their interactions with other drugs such as RAAS inhibitors and diuretics.
D. Recommendations to researchers:
• Further researches are required to detect the effect of continuous use of NSAIDs on the renal function in order to create more awareness among the prescribers.
• Additional studies are required to estimate the burden of other nephrotoxic drugs in patients with CKD, with the aim of reducing the poor outcomes of CKD including progression to ESRD.