End-Stage Renal Disease in the Gaza Strip and Its Relationship to Risk Factors

: End Stage Renal Disease (ESRD) is an important cause of morbidity and mortality globally. Understanding the risk factors of ESRD can help identify preventive strategies. This study aimed to determine the risk factors of ESRD among patients undergoing hemodialysis in the governmental hospitals in Gaza Strip. Retrospective-hospital based-case control study was conducted on patients with ESRD, at Ministry of Health Hospitals at the time of study in 2014 ( N = 264), proportional stratified random sample used for sample selection ( n = 132) cases matched with sex, age, and locality to 132 control were chosen. Data was collected using a questionnaire including socio-demographic, medical history, and life style and additional data were obtained from medical record. The results showed that the most common risk factors associated with ESRD were hypertension (42.4% versus 20.5%) and diabetes mellitus (28% versus 16.7%). Kidney stone (21.2% versus 4.5%), urinary tract infection (65.9% versus 27.3%) and glomerulonephritis (19.7% versus 6.1%) follow it. For medications analgesic drug formed among cases and controls (22% versus 9.1%). For smoking it was (47.7% versus 23.5%), obesity (41.7% versus 34.1%), anxiety (17.4% versus 6.1%). For low activity (48.5% versus 28%), primary educational level (95.1% versus 39.4%), low household income (76.5% versus 59.1%), family history (70.5% versus 47.7%). A multiple logistic regression controlling for age, gender, and location showed that significant predictors of ESRD were hypertension, glomerulonephritis, and obesity. In conclusion, the study suggests that most of the identified risk factors are preventable by easy ways as screening of highly risk people and encourage health life style.


Introduction 
End Stage Renal Disease (ESRD) is one of the serious kidney diseases that affect the body system [1]. It is a major health burden because not only it is progressive and irreversible, but also the patient with ESRD is increasing dramatically in the past few decades [2,3], in addition to diabetes mellitus and hypertension which consider as major risk factors to develop the disease [4]. The increasing of ESRD can lead to premature morbidity, mortality and lower quality of life.
ESRD occurs when both kidneys are no longer capable of working at the level of what is needed till it reaches the point where renal function fewer than 10% of standard [5]. It is a long-term problem caused by damage of both kidneys. The damage is usually irreversible and can lead to ill health [6]. It is a fatal condition unless supported by some form of dialysis, or kidney transplantation [7].
The situation is particularly serious in developing countries where smoking and other cardiovascular risk factors are increasing clearly [8,9] and health information and health resource are limited. Palestine one of these countries will face the complications of this problem in the future, where the burden of this disease expected to exhaust its medical and financial system. The awareness of the risk factors of ESRD helps in developing programs and plan preventive measure for the community [10].

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The current study aimed to characterize ESRD population in the Gaza strip and identify socio-demographic (e.g. age, sex), life style (e.g. smoking, physical activity) or comorbid disease (e.g. hypertension, diabetes) risk factors relevant to this population, in order to inform suggestions for strategies to reduce morbidity and mortality of patients.

Design and Setting
This was a retrospective hospital based case-control study that was conducted on ESRD patients treated at hospitals in the Gaza Strip. We collected data on eligible patients (n = 132) who were on hemodialysis at the time of study in 4-dialysis centers. Data collection was carried out between July 2014 and September 2014. Three months were spent at each of the 4-dialysis centers. Each patient was personally interviewed in the dialysis center using a structured questionnaire prepared by the researcher. The questionnaire collected comprehensive data related to ESRD patients. Relevant data for the present study included variables such as age and gender, living area, marital status, monthly income, diabetes mellitus, cardiovascular disease, family history of chronic disease and kidney stone, in addition to date of life style history as smoking, water, obesity and physical activity pattern.

Sample
The researcher used Epidemiological Information Program to calculate the sample size at 95% CI with power 80% and based on-one-to one case to control ratio. The total number of proportional stratified random samples is composed of 196 subjects. To overcome non-respondents, the researcher decided to take 264 persons, divided into 132 cases and 132 controls. A total of 264 cases and controls agreed to participate in this study.

Data Collection
The patients were interviewed by researcher to

Data Management and Statistical Analysis
The quantitative data were analyzed using Statistical Package for Social Sciences (SPSS) program version 19.0. The analyses of data to be conducted were reviewing the filled questionnaire, coding the questions, data entry, defining and coding the variables, and data cleaning. Frequency tables of all the variables and cross tabulation of the results were done. Differences between means were analyzed using independent sample t-test, Odds ratio, 95% confidence interval, and chi-square test is statistical tool of measurement of association. A P-value ≤ 0.05 is considered statistically significant. Logistic regression used to control for a confounder.

Ethical and Administrative Considerations
An academic Approval was obtained from School of Public Health at Al-Quds University, and an ethical End-Stage Renal Disease in the Gaza Strip and Its Relationship to Risk Factors 26 approval was obtained from Helsinki Committee in Gaza to carry out the study. An administrative approval was obtained from Ministry of Health-Gaza to conduct the study at four hospitals. Every participant was provided with a full explanatory form attached to questionnaire included the purpose of the study, assurance about the confidentiality of the information, the instructions how to respond to the questionnaire, and a statement indicating that the participation is voluntary. Honesty was maintained during reporting and analysis of the data with respect to confidentiality and respecting of results Table 1 shows that the prevalence of males among the cases was 56.8% and 38.6% of them were in the age range 45-60 years. The highest prevalence was found in Gaza city (28.6%) and the lowest percentage was in Mid-zone (15.2%). This distribution is corresponding to the population differences in the Governorates, where one-third of the population is living in Gaza city.

Socio-demographic Characteristics
The prevalence of ESRD was higher in low educational level with 59.1% among cases and only  Table 2 shows that the prevalence of Cardiovascular Disease (CVD) and diabetes mellitus among end-stage renal disease was higher (51.5%, 28.0% respectively) than among controls and the association reaches statistically significant level (OR = 4.13 versus 1.94). Hypertension represents the most CVD (42.4%) compared to controls (20.5%). This association reaches statistically significant level (OR = 0.67). Type II diabetes was the prominent among cases than type I (26.5%) and (18.9%) treated with insulin for more than ten years.

Medical History
The prevalence of lung diseases among end-stage renal disease was higher (13.6%, 2.3% respectively) than among controls and the association reach statistically significant level (OR = 6.78). Most of them suffer from bronchitis (9.1%). For kidney diseases, end-stage renal disease was significantly higher in subjects with kidney stones (OR = 5.65), urinary tract infection (OR = 5.15), and glomerulonephritis (OR = 3.80). Regarding analgesic drug, the prevalence among cases was higher than controls (22.0 versus 9.1%). and the association reach statistically significant level (OR = 2.18). The prevalence of positive family history among end-stage renal disease was higher (70.5%, 47.7% respectively) than among controls and the association reach statistically significant level (OR = 2.52), most of them have family history to DM (25%), followed by HTN (14.3%), end-stage renal disease (6.1%).

Life Style Factors
ESRD was significantly higher in subjects who were smoking, former smoking, obese, exposed to psychological troubles and physically inactive persons. Low activity is much higher among cases (48.5%) compared to controls (28%). This association reached statistically significant level. End-stage renal disease is positively associated with the current smoking status where the prevalence of current smoking among cases (17.5%) was higher compared to controls (8.4%). ESRD patients who former smoking was much two time among cases than controls (30.3%, 15.1% respectively) and reach positively significant level (OR = 2.43). There was negative association between exposed to other form of smoking and end-stage renal disease occurrence, which the prevalence among controls was higher than cases (67.5% versus 52.2%). Concerning body mass index, the prevalence was significantly higher in cases than controls (OR = 1.60), and with psychological troubles (OR = 4.03). Table 4 demonstrates logistic regression analysis for the ESRD risk factors. Significant ESRD predictors as revealed by multivariate logistic regression analysis included CVD, glomerulonephritis, and high BMI remained associated with ESRD, and reached statistically significant level. The association between ESRD and physical inactivity, smoking group, past  occupations, and educational group did not reach statistically significant level.

Discussion
The study result revealed that the prevalence of ESRD was higher in men than women, this result matched with national and international studies showed that men had significantly higher rate of end-stage renal disease compared with women [11][12][13][14][15]. In contrast to this, women seem to develop end-stage renal disease most often than men [16]. It also revealed that age group between 45-60 years is a higher risk for developing end-stage renal disease; this finding coincident with other studies showed that the prevalence of chronic renal disease increases with age [13,[17][18][19]. Most of end-stage renal disease patient is refugees and settle in Gaza city, this settle is corresponding to the population differences in the Governorates, where Gaza city is the highest population density with average 13.2% of the total population [20] and 67% of them are refugees [21]. The researchers concluded that being refugees could be increased the risk of end-stage renal disease. This may be due to siege; bad socioeconomic, epidemiological transitions in Palestine, as well as transitions in food consumption patterns and lifestyle have aggravated the burden of poverty-related diseases, as people are suffering from emerging epidemics of NCDs. The prevalence of end-stage renal disease was higher in low educational level; this result corresponded with other studies showed low educational level considered a risk for chronic kidney diseases [22,23]. The present study showed highest risk of ESRD among subjects who lived under poverty line with significant relationship between renal disease and subject's monthly income; these results reflect a poor economic situation was higher among cases, this significant may related to other factors affect it, for example, Palestine is usually unstable because of policies of closure and siege and shelling and destruction perpetrated by Israel. Unstable economic situation, limited income, and lack of unemployment opportunities, all of these reasons lead to drop in standard living and increased poverty, which has a negative effect on health [24]. This statement agrees with study result that confirms low household income is a risk factor for developing ESRD. Another study agrees this statement, for example, Ward, performed studies to examine the association between socioeconomic status with increased risk of ESRD due to diabetes and access to care in California, reported that there is a strong association between the incidence of ESRD related to diabetes and access to care [25]. Other studies confirm that positive relation between living in low socioeconomic status and severity of chronic renal disease [17,26]. This study found statistical significant association between occupation, primary educational level, low income, and citizenship subjects tended to have significantly higher end-stage renal disease prevalence.
This study also revealed that, 68% of ESRD patients have history of CVD; Hypertension considered the main risk factor that represents 42.4% of the cases. Average duration of CVD in years among cases was higher than among controls (13.7-8.4 respectively); this means that uncontrolled blood pressure seriously increased the risk of developing end-stage renal disease. The study results agreed with previous studies that hypertension considered a risk factor leads to end-stage renal disease. Abumwais revealed that the three most common causes of chronic kidney disease were diabetes, hypertension and glomerulonephritis (33.32%, 16.7% and 13.1%) respectively [27]. Basheer demonstrated that diabetes, hypertension, cardiovascular disease, recurrent taken analgesic drug and urinary tract infection are major risk factors that significantly associated with the onset of the ESRD [28]. Additionally, Elsharif, M. and Elsharif, E, reported that hypertension and obstructive nephropathy are the leading causes of end-stage renal disease in Gazira state [12]. Moreover, Sweileh et al. conducted study in A-Watani governmental medical center; show that hypertension and diabetes were the most common causes of the end-stage renal disease [29]. Although, Domrongkitchaiporn et al. shows that HTN was the most important independent risk factor for future development of kidney disease [30]. Similarly, Hsu et al. concluded that the risk of end-stage renal disease is increased even with relative modest elevations of blood pressure [31]. Finally, many studies informed that hypertension is a risk factor for chronic kidney disease [32][33][34][35]. In contrast to that, Fesler et al. informed association between hypertension and chronic kidney disease did not reach statistical significance [36] and Bakris and Ritz, indicated that hypertension is the second most common cause of end-stage renal disease [37]. The study also, identified common risk factors in this study was diabetes mellitus with prevalence was 28% among cases. This funding agreed with the results that diabetes mellitus is a risk factor. Abumwais, revealed that the three most common causes of Chronic Renal Failure (CRF) were diabetes mellitus, hypertension and glomerulonephritis (33.32%, 16.7% and 13.1%) respectively [27]. Although, a retrospective cohort study conducted in A-Watani governmental medical center in Palestine; show that hypertension and diabetes mellitus were the most common causes of the ESRD [29]. Additionally, Shaheen and Al-Khader, detailed that diabetes mellitus is still the most common cause of ESRD in Egypt, Kuwait, Lebanon and Saudi Arabia [38]. Similarly, Malekmakan et al. stated that the risk factors of chronic renal disease according to the age, hypertension (30.5%) and diabetes mellitus (30.1%) were the most common causes of end-stage renal disease [4]. Another study agrees with this result, conducted at a Mostafa Khomini hospital in Iran, showed that the prevalence of chronic renal disease is higher in Iran and the most common risk factor is diabetes mellitus 26.85% [13]. In Jordan, a study conducted by Abdullah et al. confirms that diabetes mellitus was the major leading cause of end-stage renal disease 29.2% of cases [39]. In contrast to study positive association, Chadban et al. conducted a large cross-sectional Australian cohort study, stated that there is no association between diabetes mellitus and the presence of chronic kidney diseases [35]. This study identified another risk factor was lung diseases with a positive history of lung disease among ESRD. It is congruent with Daggett who found abnormalities of glomerular filtration rate among chronic bronchitis patients [40]. Moreover, it indicates that kidney stone is considered as another risk factor for developing ESRD. This result agreed with international studies that found that nephrolithiasis is still another risk factor that develop end-stage renal disease [41,42].
There is positive association between subject's history of glomerulonephritis and the occurrence of end-stage renal disease. This finding is in agreement with other national and international studies, that found urinary tract infection and glomerulonephritis are major risk factors that significantly associated with the onset of ESRD [4,11,12,27,28,32,39].
Family history is considered as another risk factor for developing ESRD in this study. This funding agreed with the results that family history is a risk factor. McClellan, et al. showed that the firstor second-degree family members of patients with end-stage renal disease have two to three times as likely to have incident end-stage renal disease [43]. Additionally, as a population-based telephone survey conducted in the southeastern state of 402 residents showed that a family history of ESRD was reported by 3.7% of respondents and that black residents were six times more likely to develop family history end-stage renal disease compared with white individuals [44]. The prevalence of taking an analgesic drug 20.5% among cases take diclofen while 1.5% takes Trufen was higher and association reaches significant level. This result is consistent with literature. Perneger et al. confirmed that frequently taken analgesic drugs (acetaminophen or none steroidal Anti-inflammatory Drugs) have an increased risk of ESRD, aspirin is excluded from this study [45].
Active smoking is divided into two categories as shows above, 30.3% former smoker while 17.4% smoker. The average of cigarette smoking per day among cases was higher than among controls (1.26-1.18 respectively) and the association does not reach statistically significance (P value 0.39). In addition, the average duration of smoking per years among cases was higher than controls (1.18-1.09 respectively) and the association does not reach statistically significance (P value 0.23). This is consistent with the studies revealed that cigarette smoking is considered as a risk factor for developing and progressing of chronic kidney disease in the community [46,47]. Moreover, Yacoub et al. concluded that the risk of chronic renal disease increased significantly with smoking when comparing to non-smoker, and there is no statistically significant difference between former smoker and chronic renal disease and this study found that heavy smoking more than 30 packs per year is an important risk factor for developing chronic renal disease [48]. Moreover, Chadban et al. confirm the association between smoking and renal damage [35]. On the other hand, population base case control study showed that there was strong association between heavy smoking and chronic renal disease [49]. Concerning obesity as a risk factor, the study showed that 41.7% of end-stage renal disease was obese, while 34.1% among controls were obese. This reflected the increase of obesity in the Palestinian population as a result of lifestyle shifting toward physical inactivity and increased food consumption. We noted that there was strong association between ESRD and obesity (P value 0.000) indicating that obesity is a risk factor of ESRD. These results agree with international studies that conducted in Japan, California, and Singapore which showed that there are strong positive association between body mass index and the risk of developing ESRD [17,[50][51][52], but inconsistent with Pinto-Sietsma et al. who reported body mass index had no effect on the prevalence of chronic kidney disease [53].
The study also identified psychological troubles as risk factors with prevalence (34.1%) among cases. Among them, 17.4% facing anxiety followed by depression 14.4%. This funding agreed with the results that psychological trouble is a risk factor. DiMatteo et al. identified that the two common psychiatric symptoms in medical patients are depression and anxiety; and it is also associated with deteriorated health status and increased health care utilization [54]. Moreover, Lew and Patel found that in ESRD population, women are more common and at a higher level than men for expressing psychological problem such as depression, anxiety and personality disorder [55]. Similarly, Kimmel stated that the most prevalent psychiatric problem among patients undergoing hemodialysis is depression [56,57].

Conclusion
ESRD is one of the serious kidney diseases of chronic renal disease that affect the body system. Identification of risk factors for end stage renal disease supports intervention policies to minimize the disease morbidity and mortality. This disease is serious in Palestine, mostly GS and it is apparent as chronic disease, dangerous and leading to death. Chronic diseases are responsible for 81% of the total deaths in Palestine. The general objective of this study is to identify the main risk factors that contribute to the ESRD among hemodialysis patients in GS. This study gets its importance because there is no study examines the risk factors associated with end-stage renal disease in GS. This study might enhance national effort to modify and control of those factors and help in developing preventive promotional and educational health programs. Also it help for developing screening programs of people at high risk of renal disease, and all patients with diabetes or and have hypertension. Moreover, preventive strategies to integrate health life style into the community approach to primary prevention should start early to change bad habits to good behaviour as encourage walking, playing and bicycling, improve physical activity level, and put strict laws by the relevant ministries to prevent smoking in public places and then private places, especially at home. Additionally, this study might increase awareness about renal disease among the clients with the identified risk factors in order to decrease morbidity and mortality from this disease.