Epidemiology of End-Stage Renal Disease in Fayoum governorate (Egypt)

Introduction: Chronic kidney disease represents a common health burden in Egypt and worldwide. Hemodialysis remains the main renal replacement modality in spite of the advent of kidney transplantation. Identification of the risk factors is the first line to control disease spread and decrease its prevalence. Aim of the work: To evaluate the main causes and risk factors for end-stage renal disease (ESRD) among the Egyptian population Subjects and Methods: This cross-sectional study was


Introduction
End-Stage Renal Disease (ESRD) is an increasingly major health problem worldwide.It is associated with considerable co-morbidity and mortality.Despite the widespread use of peritoneal dialysis and renal transplantation, hemodialysis (HD) remains the main renal replacement therapy in most countries worldwide.Chronic kidney disease (CKD) is one of the primary causes of premature death and economic cost to both the public and private sectors [1].
Chronic kidney disease is devastating due to poverty and lack of awareness among individuals with a family history of diabetes mellitus (DM), hypertension (HTN), or kidney disease [2].
Identified risk factors for CKD are HTN, DM, cardiovascular diseases (CVDs), chronic glomerulonephritis (GN), smoking, autoimmune disease, family history of kidney disease, nephrotoxic drugs, poor education level, and infectious disease next to poor sanitation, poor clean and safe water supply [3].
CKD is associated with age-related renal function decline accelerated in HTN, DM, obesity, and primary renal disorders.However, CKD of unknown etiology (CKDu) is also prevalent and rapidly progressing in some regions of the world notably in Africa, Central America, and Asia [4].
In spite of the presence of various epidemiological studies evaluating the risk factors for chronic kidney diseases, this type of study is still deficient in Egypt.With the advent of renal biopsy, identification of original kidney disease became more feasible, while better results from epidemiological studies might be obtained.
The current study aimed to evaluate the main causes and risk factors for ESRD among the Egyptian population in the Fayoum governorate.

Subjects
The material of the current Crosssectional study included 1000 HD patients who were recruited from Fayoum governmental hospitals and Fayoum university hospital, Egypt.
The sample size was calculated using the G-power program with α.Error = 0.05 and power 80% depending on the prevalence of HD in Egypt in previous studies and it was equal to a minimum of 1000 patients.
Informed consent was obtained from all participants and approval was obtained from institutional review board (IRB) No. M341 in Faculty of Medicine, Fayoum University, Fayoum, Egypt.

Inclusion criteria
The patients who fulfilled the following criteria were included in the study: maintained on HD; age range from 18 to 60 years; Fayoum governorate resident.

Exclusion criteria
Any patients who had one or more of the following criteria were excluded from the study: age below 18 or above 60 years; resident outside Fayoum governorate.

Statistical analysis
All data were tabulated in SPSS sheet V. 21.Categorical data were expressed in number and percent and were tested using a Chi-square test while continuous data were expressed as mean and standard deviation and were tested using student t-test when comparing between 2 groups or Kruskal Wallis test when comparing more than two groups.

Results
The study included 1000 patients with a mean age of 49±10.1 years and male predominance (68.5%).The mean body weight was 72.8±13.9Kg and the mean body mass index (BMI) was 27.2±4.8Kg/m 2 .Most of the included patients were non-smokers (68.8%).About 42.3% were not working while the remaining patients were working (worker (47.7%); employers (8.4%); professionals (1.6%)).They had different distribution over Fayoum governorate and most of them were Fayoum city dwellers (33.6%) while 16.2% were from Senoris, 11.3% were from Yousif Elsedik, 8.8% were from Ibsheway, 13.8% were from Etsa, and 16.3% from Tamiyya.Only 1.7% of the included patients had a positive family history of renal disease.The included patients have maintained on dialysis for 7.1±3.8years and about 35.2% of them were positive for hepatitis C serology (Table 1).  2 showed that 46.1% of cases had end renal disease caused by HTN, followed by 25.4% because of Kidney stones, and 10.3% of them because of unknown causes, and 6.8% driven by a combination of HTN and DM, and the lowest percentage was for uric acid and nonsteroidal anti-inflammatory drugs (NSAIDs) 0.1%.The distribution of different diseases of the highest frequency was shown in Figure 1.    5 and 6 for occupation and residences parameters, respectively.It worths mentioning that the higher percentage of HTN, and UTI, and /NSAIDS were reported in Tamiyya, while other ESRD were reported in Fayoum cities (Figure 2).

Discussion
Chronic kidney disease (CKD) arises from many heterogeneous disease pathways that alter the function and structure of the kidney irreversibly over months or years.The diagnosis of CKD rests on establishing a chronic reduction in kidney function and structural kidney damage [5].
Most cases of CKD result from kidney damage or other health problems, which might be caused by GN, DM, HTN, autoimmune, or genetic diseases [6].Effective identification and management are necessary to prevent CKD progression and cardiovascular events, reduce the risks associated with acute kidney injury (AKI), and improve patient safety and medication management [7].
The current study aimed to detect the principal causes and risk factors of ESRD patients in the Fayoum governorate, Egypt.One thousand patients on regular HD were included in that cross-retrospective real-life study in Fayoum governmental and Fayoum university hospitals, Egypt.Data were collected from the patients, their relatives, and from their medical records and with age groups between 18-60 years.We excluded patients who did not live in Fayoum governorate, had congenital anomalies, or were aged behind the range of 18-60 years.
The mean age was 49±10.1 years for all participants.A similar age range was reported by El-Ballat et al., 2019, equal to 52.80±13.82years [8].Also, Mukakarangwa et al., 2018, reported the mean age was 52.27 ± 12.91 years [9].Also, Ragab et al., 2021, reported that the mean age in Egypt increased from 45.6 years in 1996 to 49.8 years in 2008, which supported the current findings [10].
Most patients in the current study were males (68.5%).Similarly, Yu et al., 2010, reported that males develop ESRD more than females [11].The results of Mukakarangwa et al., 2018, showed that the prevalence of treated ESRD in males was almost twice that of females (60.7% versus 39.3%), which matched our study results [9].Yet for the study conducted by Duong et al., 2015, the males represented 47% [12].
The mean body weight of the included patients was 72.8±13.9Kg, and the mean BMI was 27.2±4.8Kg/m2.Baramania et al., 2021, reported similar body weight and BMI [13].Also, Megahed et al., 2020, reported the mean body weight for HD patients as 72.3581± 7.035 KG [14].Lower body weight and BMI were reported in another study by Megahed et al., 2021, who reported a mean weight of 59.81±12.8Kg [15].Another previous study reported the average BMI was lower (22.4 ± 3.7 kg/m2) for HD patients [16].
Most patients in the current study were non-smokers, where 24.8% were smokers.Megahed et al., 2021, reported smoking in only 2% of the included patients; however, it was conducted on a smaller sample size [15].A prospective study by Xia et al., 2017, reported that smoking is positively associated with the progression of CKD, which also supported our study results [17].Yacoub et al., 2010, in their study, concluded that smoking, or particularly heavy smoking (> 30 packs/year), was a massive risk factor for the development of CKD [18].
In the current study, workers and unemployed patients had almost equal percentages.Contrary to the current study, Bramania et al., 2021, reported that only 15% of patients were still workers, while the remaining were retired or stopped working due to HD [13].Anees et al., 2014, reported that 34% of patients were workers [19].
About 35.5% of the included patients were positive for HCV serology, while Megahed et al., 2021, reported that over 70% of ESRD patients were HCV positive [15].The study conducted by Bramani et al., 2021, reported that 10% of ESRD patients had positive HCV serology [13].Jin et al., 2018, reported HCV antibody positivity was 4% among HD patients [16].The high prevalence of HCV in Fayoum governorate might be attributed to the high prevalence of HCV in the general population and the high rate of blood transfusion in dialysis units to treat anemia instead of provision of iron therapy and erythropoietin, which is expensive; thus, there is a need to increase the provision of iron therapy and erythropoietin among dialysis patients instead of blood transfusion.
Positive family history of ESRD was reported in only 1.7% of patients.Ghonemy et al., 2016, reported that 1.1% of patients had a history of ESRD in their family members, which matched our study results [20].
In contrast to our results, the epidemiology of ESKD in countries of the Gulf Cooperation Council found that the leading cause of ESRD was diabetic nephropathy (17%), followed by GN (13%), and hypertensive nephropathy (8%), with a significant increase in the prevalence of diabetic nephropathy (DN) [24].
In China, Yao et al., 2009, reported that the incidence of DN increased from 9.9% in 2000 to 17.2% in 2005 and counts as the second cause of ESRD after GN [25].In Japan, DN (37.1%) was the most common primary disease among ESRD patients, followed by chronic GN (33.6%) and nephrosclerosis (8.3%) [26].
Regarding age differences between different CKDs, only bladder cancer patients had older ages than other causes, which were comparable regarding age.That came in handy with the fact that bladder cancer affected mainly the elderly.Saginala et al., 2020, reported that the age range for bladder cancer was 65-73 years [29].Similar results were reported in another study [30].
There were statistically significant differences between males and females regarding the frequency of some CKDs.HTN was more frequent among males than females.Similarly, Ramirez et al., 2018, reported that HTN was more frequent among males than females of different ages [31].On the other hand, Hughson et al., 2014, reported that females were more prone to hypertensive nephrosclerosis than males because females had lower nephron mass than males [32].Kidney stones disease was also more prevalent among males in the current study.In concordance with the current study, Gillams et al., 2021, reported a higher incidence of stone kidney disease among males [33].Unlikely, Zahng et al., 2021, reported that Kidney stones appeared in females three times more than in males [34].Daudon et al., 2018, proved the same results [35].
In the current study, diabetic nephropathy was higher among males than females.Following the current study, Maric et al., 2020, reported that men are at higher risk for diabetic nephropathy than women [36].Also, Thomas et al., 2019, reported that women were more protected from diabetic nephropathy due to hormonal causes [37].
In that study, females were more prone to NSAID-induced renal failure than males.Likely, in a previous Egyptian study, females had more NSAID-induced nephropathy than males [38].On the contrary, Swathi et al., 2021, reported that males had a higher risk for NSAID-induced renal failure [39].
Other causes of original kidney diseases had much lower incidence rates, which could affect the analysis of gender differences.
In the current study, there were no statistically significant effects of working on the frequency of different original kidney diseases.However, it was reported in previous studies that the nature of work could affect the cause of ESRD, such as exposure to certain toxins could cause ESRD [40].Hasson et al., 2020, reported increased incidence among miners and heatrelated jobs [41].Sanoff et al., 2010, reported a Positive association of renal insufficiency with agriculture employment and unregulated alcohol consumption [42].
There is a statistical significance difference with P<0.001 as regards residence in different ESRD, with a higher percentage of HTN and UTI/NSAIDs among cases in Tamiyya, while most of the other causes were reported in Fayoum city.The difference in distribution between different cities might be due to the differences in air pollens percentage, water purity, and the presence of genetic or inherited diseases, which run in families.

Conclusion
The most common cause of ESRD among Fayoum governorate residents was HTN, kidney stones, unknown ESRD causes, and DM.Age-related effect on the original kidney disease was reported with bladder cancer only.There were male-to-female differences in the frequency of some CKDs, such as HTN, kidney stones, and DM, which were more frequent among males.NSAID-induced renal disease was more frequent among females.Future epidemiological studies should be conducted to investigate the unknown causes of ESRD.

Figure 1 :
Figure 1: Distribution of different kidney diseases of the highest frequencies in the study populations.

Figure 2 :
Figure 2: Distribution of Different ESRD causes of the highest frequencies among different cities of the Fayoum Governorate.

Table 1 :
Demographics and baseline characteristics of the study participants.

Table 2 :
Frequency of different causes of ESRD in the total cohort.

Table 3 :
Comparison of mean ages in relation to different causes of ESRD.

Table 4 :
Comparison of gender in relation to different causes of ESRD.

Table 5 :
Comparison of occupation in relation to different causes of ESRD.

Table 6 :
Comparison of residence location in relation to different causes of ESRD.