Survival outcome in patients undergoing chronic hemodialysis: an Egyptian study at Dakahlia Governorate

Heba Ibrahim A Yousif; Adel A El-Bastawisy; Ahmed A Eldeeb

doi:10.4103/jesnt.jesnt_41_21

ORIGINAL ARTICLE

Year : 2022 | Volume : 22 | Issue : 4 | Page : 224-231

Survival outcome in patients undergoing chronic hemodialysis: an Egyptian study at Dakahlia Governorate

Heba Ibrahim A Yousif¹, Adel A El-Bastawisy², Ahmed A Eldeeb³
¹ Ministry of Health, Department of Internal Medicine and Nephrology, Talkha Hospital, Mansoura, Egypt
² Department of Internal Medicine, Rheumatology and Immunity Unit, Mansoura, Egypt
³ Nephrology Unit, Faculty of Medicine, Mansoura University, Mansoura, Egypt

Date of Submission	07-Dec-2021
Date of Acceptance	28-Mar-2022
Date of Web Publication	22-Sep-2022

Correspondence Address:
Dr. Ahmed A Eldeeb
Department of Internal Medicine, Mansoura Nephrology and Dialysis Unit, Faculty of Medicine, Mansoura University, Elgomhoria Street, Mansoura City 35516
Egypt

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/jesnt.jesnt_41_21

Abstract

Background Several research studies aimed to explain the high mortality among hemodialysis (HD) patients. Our study aimed to describe the mortality in our Governorate (Dakahlia) and to explore its potential risk factors. Patients and methods This prospective (follow-up) study was conducted in four HD units on 120 patients who were followed up over the 12-month period (September 2018–August 2019). At enrollment and every 3 months, all patients were subjected to history taking, physical examination, and laboratory tests for the 12-month period or until the patient died. Results The 120 HD cases were 72 (60%) male patients, and 48 (40%) female patients with a median age of 46.5 years. Over 1-year follow-up, 26 (21.7%) patients died. Survival analysis with the Log-rank test shows no statistically significant difference in survival times based on examined variables (sex, diabetes, hypertension, current smoking, and Subjective Global Assessment). The results of the Cox proportional hazards model [to assess sex, age, diabetes, hypertension, current smoking, HD duration (years), and Subjective Global Assessment as predictors of 1-year mortality in HD patients] show that out of these seven predictor variables, only diabetes was a statistically significant independent predictor. Conclusion HD-related mortality is high in Dakahlia Governorate (21.7%). Diabetes mellitus is an independent risk factor for mortality with a hazard ratio of 2.97.

Keywords: Dakahlia Governorate, diabetes mellitus, hemodialysis, mortality, Subjective Global Assessment, survival

How to cite this article:
Yousif HI, El-Bastawisy AA, Eldeeb AA. Survival outcome in patients undergoing chronic hemodialysis: an Egyptian study at Dakahlia Governorate. J Egypt Soc Nephrol Transplant 2022;22:224-31

How to cite this URL:
Yousif HI, El-Bastawisy AA, Eldeeb AA. Survival outcome in patients undergoing chronic hemodialysis: an Egyptian study at Dakahlia Governorate. J Egypt Soc Nephrol Transplant [serial online] 2022 [cited 2023 Jun 8];22:224-31. Available from: http://www.jesnt.eg.net/text.asp?2022/22/4/224/356689

Introduction

The prevalence of end-stage renal disease (ESRD) in Egypt is 483 patients per million according to the 9th Annual Report of The Egyptian Renal Registry provided by the Egyptian Society of Nephrology and Transplantation [1]. Patients with ESRD on hemodialysis (HD) have markedly elevated mortality rates compared with the general population [2].

To explain these high mortality rates, several research studies explored the risk factors associated with HD-related mortality. A large European study showed an eightfold increase in age-standardized mortality due to cardiovascular and noncardiovascular factors compared with the general population [3]. In a recent systematic review and meta-analysis [4] that described the impact of various characteristics on the risk of mortality in geriatric HD patients, the mortality was high in those who have functional and cognitive impairment and falls. To the best of the authors’ knowledge, exploring this issue is urgently required in our region.

Aim

The aim of this study was to describe the mortality pattern in HD patients over 1 year of follow-up. It also aims to explore the risk factors, which might have an impact on mortality in HD patients.

Patients and methods

This prospective longitudinal observational study was done at four HD units in Dakahlia Governorate (Egypt); the Nephrology and Dialysis Unit of Mansoura University Hospital, Central Talkha Hospital, the Batra Dialysis Unit, and Al Ber Wel-Wafaa Dialysis Unit.

One-hundred-and-twenty chronic HD patients were followed up over 1-year period (September 2018–August 2019).

Inclusion criteria:

(1) Age more than or equal to 18 years.

(2) Both male and female patients.

(3) All eligible patients must have good adherence and stability to dialysis treatment for at least 12 months prior to inclusion.

Exclusion criteria:

(1) Acute renal failure.

(2) Malignant lesions.

(3) Age less than 18 years.

(4) Patient who refused to participate in the study.

Sample size

The sample size was calculated using PASS 15 Power Analysis and Sample Size Software (2017) (NCSS, LLC. Kaysville, Utah, USA, ncss.com/software/pass). The authors of this thesis hypothesized a hazard ratio (HR) for mortality of 1.2 based on previous literature [4]. Cox regression of the log HR on a covariate with a standard deviation of 1.5000 based on a sample of 120 observations achieves 91% power at a 0.05000 significance level to detect a regression coefficient equal to 0.2000.

Methods

At enrollment and every 3 months after the start of the study for 1 year, all patients were subjected to:

(1) Full history taking: onset of chronic kidney disease, etiology of the disease, onset of ESRD and the start of HD, how many sessions per week, length of these sessions, and their efficacy. Associated diseases and complications such as diabetes mellitus, hypertension, anemia, or mineral bone disease. Medications are taken by patients: antihypertensive drugs, antidiabetic medications, iron supplementation, etc. Details regarding the type of vascular access, hepatitis-B vaccination, erythropoietin use, and the complications on HD, including vascular access-related complications.

(2) Physical examination focusing on blood pressure. Nutritional status as assessed by BMI, serum albumin level, and Subjective Global Assessment (SGA). Manifestations of fluid overload. Dialysis adequacy was determined using the single pool Kt/V (sp Kt/V).

(3) Laboratory studies: routine laboratory tests, including serum albumin, calcium, phosphorus, potassium, blood glucose level, complete blood count, serum parathyroid hormone level and serum ferritin level (postdialysis), serum creatinine, and blood urea (predialysis and postdialysis).

Endpoints of the study

Death of the patient or after 1 year from enrollment.

Ethical consideration

Written consent was signed by all participants.

The protocol was approved by the Institutional Research Board (IRB) of the Faculty of Medicine, Mansoura University (Proposal code: MS.19.02.501).

Statistical analysis

Data were entered and analyzed using IBM-SPSS software (IBM Corp. Released 2019. IBM-SPSS Statistics for Windows, Version 26.0.; IBM Corp., Armonk, New York, USA). Incidence rates were calculated by Stata/MP software (version 14 for Windows, StataCorp. 2015. Stata Statistical Software: Release 14. College Station, TX 77845, USA: StataCorp LP (https://www.medcalc.org/)). Qualitative data were presented as absolute frequency (N) and relative frequency (percentage, %). Quantitative data were initially tested for normality using Shapiro–Wilk’s test with data being normally distributed if P value more than 0.050. The presence of significant outliers (extreme values) was tested by inspecting boxplots. Quantitative data were presented as the median and interquartile range. The Kaplan–Meier method was used to estimate the probability of survival past the given time points. The survival distributions of two or more groups of a between-subjects factor were compared for equality using the Log-rank test. The Cox proportional-hazards model is a regression model that was used to investigate the association between the survival time of patients and one or more predictor variables. Every predictor variable was tested in a univariate analysis, then the predictor variables were tested together in a multivariate analysis. For any of the used tests, the results were considered as statistically significant if P value less than or equal to 0.050. Appropriate charts were used to graphically present the results whenever needed using MedCalc Statistical Software (version 18.9.1).

Results

This study involved 120 HD patients. They were 72 (60%) male patients, and 48 (40%) female patients. Their median age was 46.5 years ranging from 20 to 66 years. [Table 1] shows the baseline characteristics of these cases. Over a 1-year follow-up of the 120 HD patients, 26 (21.7%) patients died. Survival analysis was reported in [Table 2][Table 3][Table 4], and [Fig 1][Fig 2][Fig 3][Fig 4][Fig 5]. [Table 2] shows no statistically significant difference in survival times based on examined variables (sex, diabetes, hypertension, current smoking, and SGA). For any of these subgroups as well as the overall number of cases (N=120), no median time of survival was reported (as cumulative survival did not reach 0.5). [Table 3] shows the results of the Cox proportional hazards model, which was run to assess sex, age, diabetes, hypertension, current smoking, HD duration (years), and SGA as predictors of 1-year mortality in HD patients. Of these seven predictor variables, only diabetes was a statistically significant independent predictor. HRs were tested for SGA according to sex. In male participants (N=72), the HR for mortality was 1.3 [95% confidence interval (CI)=0.4–4.1, P=0.672), while in female participants (N=48), the HR for mortality was 0.83 (95% CI=0.25–2.8, P=0.766). The mortality incidence rates and ratios were reported in [Table 4]. The overall incidence rate of 19.7 per 1000 per year (95% CI=13.4–29 per 1000 per year). The incidence rate was statistically significantly higher among diabetic versus nondiabetic patients. It was higher in females versus males, but this difference did not achieve statistical significance. Also, no difference in incidence rates was observed in hypertensive versus normotensives, smokers versus nonsmokers, and in SGA ‘A’ vs. SGA ‘B.’

Table 1: Baseline clinical–laboratory data of the studied cases (N=120)

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Table 2: Log rank (Mantel–Cox) test for comparisons of survival times

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Table 3: Cox proportional-hazards model

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Table 4: Incidence rates and ratios for mortality

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Figure 1: Overall survival in studied cases (N=120).

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Figure 2: Overall survival in male versus female patients (P=0.640).

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Figure 3: Overall survival in current smokers versus nonsmokers (P=0.890).

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Figure 4: Overall survival in diabetic versus nondiabetic patients (P=0.064).

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Figure 5: Overall survival in well-nourished versus mildly to moderately malnourished patients (P=0.871).

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Discussion

Patients with chronic kidney disease on HD have markedly elevated mortality rates compared with the general population [2]. To explain these high mortality rates, several research studies explored the risk factors associated with HD-related mortality [3–7]. In Egypt, a study from Mansoura, Dakahlia; Megahed et al. [8] found that mortality was statistically significantly higher in patients with diabetes, ischemic heart disease, anemia, and low serum albumin. However, the design of their study was cross-sectional with its known limitations regarding risk-factor assessment. Therefore, our study design was prospective with a collection of survival data over 1 year to assess the predictors of 1-year mortality and the related HRs. One-hundred-and twenty HD patients were followed up over the 1-year period (September 2018–August 2019). This sample size was based on a previous study by Song et al. [4]. At enrollment, 60% of our cases were male patients with a median age of 46.5 years. In Megahed et al. [8] study, a rather similar proportion of male sex was reported (57.5%), and slightly older age (mean age of 52 vs. 47 in our study). Diabetes was observed in 18.3% of cases, while hypertension was observed in 60.8%. In Megahed et al. [8] study, a slightly higher proportion of diabetes was reported (19.1%), but a lower proportion of hypertension (46.5 vs. 60.8% in our study). In our study, the results of the Cox proportional-hazards model, which was run to assess sex, age, diabetes, hypertension, current smoking, HD duration (years), and SGA as predictors of 1-year mortality in HD patients. Of these seven predictor variables, only diabetes was a statistically significant independent predictor. Smoking in HD patients is considered a dreadful scenario for the cardiovascular system [9]. In our study, nearly one-fifth of cases were current smokers (19.2%). The HR for 1-year mortality among smokers was 1.2, yet it did not achieve statistical significance. This might be explained by the relatively small sample size and relatively short follow-up period. Compared with our results, a systematic review on smoking hazards in HD patients by Liebman et al. [10], on 6538 patients, found that the pooled HR for all-cause mortality in smokers compared with nonsmokers was 1.65 (P<0.001). According to SGA, around two-thirds of our cases were well-nourished (68.3%) with slightly less than one-third having mild-to-moderate malnourishment (31.7%). This is in accordance with the proportions observed in a study by Ko et al. [11] in which 28.1% of their cases had mild-to-severe malnutrition, while 71.9% had good nutrition. In addition, in Ko et al. [11] study, ‘mild to severe malnutrition’ versus ‘good nutrition’ was more significantly associated with increased mortality in male but not female patients. Accordingly, they concluded that SGA of HD patients can be useful for predicting mortality, especially in male HD patients. In our study, the HRs for mortality among male versus female patients were 1.3 versus 0.83, respectively, which could be like their results. However, in our study, probably due to the small sample size, the results did not achieve statistical significance. The median duration of HD in our cases was 9 years (108 months). This was higher than that reported in Megahed and colleagues study in which the mean dialysis duration was 50.2 months. In our study, Cox proportional-hazards model was run to assess the effects of sex, age, diabetes, hypertension, current smoking, HD duration (years), and SGA as predictors of 1-year mortality in HD patients. Of these seven predictor variables, only diabetes was a statistically significant independent predictor with a HR of 2.97. This contrasts with that observed in a Japanese study by Ajiro et al. [12] in which patients with more than 10 years of HD, high pulse pressure, cerebrovascular disease, low serum creatinine, and low Kt/V values were the mortality-risk predictors, whereas for those with less than 10 years of HD, age and cerebrovascular disease were independent risk predictors for death. Diabetes, coronary artery disease, serum albumin, and C-reactive protein were nonsignificant predictors in those with long-term HD. Also, this contrasts with the results observed in a Moroccan study [13], in which diabetes was not a risk factor for mortality. Also, in contrast with our results, age, undernutrition, and inflammation were statistically significant risk factors for mortality in the Moroccan study. However, like our results, HD duration was not a risk factor to mortality as observed in the Moroccan study. In our study, as shown in [Table 5] and [Fig. 6], diabetes was more frequent in nonsurvivors versus survivors, both in those with more than 10 years of HD, and those with less than or equal to 10 years. However, in both, statistical significance was not achieved probably due to the small sample size. This result is different from that observed in a Japanese study by Ajiro et al. [12] in which diabetes was statistically significantly higher in nonsurvivors versus survivors in those on less than or equal to 10 years of HD (P=0.027) but not in those on more than 10 years of HD (P=0.920). In accordance with our results, a recent study from Japan Moromizato et al. [14] performed a 10-year follow-up, and on univariate and multivariate Cox regression analyses, diabetes mellitus in addition to the history of coronary intervention and hypoalbuminemia were significant risk factors for mortality during the whole follow-up period. In our study, HRs were tested for SGA according to sex. In male participants (N=72), the HR for mortality was 1.3 (95% CI=0.4–4.1, P=0.672), while in female participants (N=48), the HR for mortality was 0.83 (95% CI=0.25–2.8, P=0.766). This contrasts with another Egyptian study by Megahed and colleagues, in which significant male predominance (7.9% in males vs. 5.6% in females, P=0.03) was observed in nonsurvivors.

Table 5: Frequency of diabetes mellitus according to mortality and hemodialysis duration

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Figure 6: Overall survival with 1-year mortality based on HD duration. HD, hemodialysis.

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Finally, despite the major advances in HD modalities, unfortunately, the mortality of patients with ESRD is 10–30 times higher than that of the general population [15]. This mortality is partly explained by the presence of important comorbidities, such as cardiovascular diseases, ischemic heart disease, infections, diabetes, protein-energy malnutrition, and advanced age [16]. In our study, the explanation of the high HD-related mortality (21.7%) at Dakahlia Governorate is first related to uncontrolled diabetic state, second related to inadequate HD as a minority of our cases show adequate HD based on KTV (K; dialyzer clearance - T; duration of dialysis in minutes - V; volume of body water) and urea reduction ratio, which was observed only in 17 (14.2%) cases as our study was conducted in multiple centers including peripheral centers. The third explanation is the anemia that was very frequent (95.8%) among our HD patients.

In conclusion

(1) In our study, HD-related mortality is high in Dakahlia Governorate (21.7%).

(2) We assess which predictor among seven variables [sex, age, diabetes, hypertension, current smoking, HD duration (years), and SGA] is the predictor of 1-year mortality in HD patients, only diabetes was a statistically significant independent risk factor for mortality with a HR of 2.97.

In the end: this study suggests that achieving good control of the diabetic state and providing an adequate dose of HD may further improve survival in patients who are on maintenance HD.

Acknowledgements

Acknowledgement (acknowledgements of scientific help): Professor Monir Bahgat, Professor of Internal Medicine and Gastroenterology, Faculty of Medicine, Mansoura University.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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