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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
RENAL DATA FROM THE ARAB WORLD  
Year : 2021  |  Volume : 32  |  Issue : 5  |  Page : 1407-1417
End-stage renal disease at dialysis initiation: Epidemiology and mortality risks during the first year of hemodialysis


1 Department of Nephrology, Charles Nicolle Hospital, Tunis, Tunisia
2 Department of Nephrology, La Rabta Hospital, Tunis, Tunisia
3 Department of Nephrology, Mahmoud El Matri Hospital, Ariana, Tunisia
4 Department of Research Laboratory of Kidney Diseases (LR00SP01), Charles Nicolle Hospital, Tunis, Tunisia

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Date of Web Publication4-May-2022
 

   Abstract 


Chronic kidney disease (CKD) treated by hemodialysis (HD) is a worldwide major public health problem. Its incidence is getting higher and higher, leading to an alarming social and economic impact. The survival of these patients is significantly low, especially during the first year of treatment. The purpose of our study was to identify the epidemiological and clinico-biological characteristics of patients at the HD initiation and to reveal the predictive factors of mortality at three months and one year of HD. This is a prospective, analytical, and descriptive study dealing with 229 patients with an end-stage renal disease (ESRD), followed up in the Nephrology Department of Charles Nicolle Hospital and La Rabta Hospital in Tunisia, that was started HD between January and June 2017. A multivariate logistic regression analysis allowed us to identify the independent predictors of mortality at three months and one year. The average age was 60.2 ± 15.3 years, with a gender ratio of 1.41. Seventy-eight percent of patients had more than two comorbidities, 59% had diabetes, and 88% had hypertension. Diabetic nephropathy was the leading etiology of kidney disease (48.9%), while 11% of nephropathies were of unknown etiology. Only 58% were early referred to a nephrologist. The average glomerular filtration rate at HD initiation was 6.06 ± 2.33 mL/min/1.73 m2. Hypocalcemia and hyperphosphatemia were noted, respectively, in 60.8% and 84.9% of cases. Anemia was objectified in 98.6% of cases. HD was started in an emergency in 56.8% of cases. One of the most urgent indications was acute pulmonary edema (APE) for 43.8% of patients. Only 10.5% of patients had functional arteriovenous fistula at the dialysis initiation. Patients were hemodialyzed one, two, or three sessions per week, respectively, in 23.2%, 26.6%, and 50.2% of cases. The crude mortality rate was 25% and 13% in, respectively, one year and three months of HD. On multivariate analysis, we identified heart failure and insufficient dialysis dose per week as predictive factors of mortality at the 1st year of HD. C-reactive protein more than 21 mg/L, insufficient dialysis per week, modified Charlson Comorbidity Index less than 6, and APE at the dialysis initiation were identified as predictive factors of three-month mortality. Despite the short period of study, this work revealed the alarming conditions of patients at HD initiation. This critical situation is due to the delay in CKD diagnosis, the late nephrologist referral, and the lack of preparation before HD initiation.

How to cite this article:
Mesbahi T, Barbouch S, Najjar M, Fattoum S, Jebali H, Trabelsi R, Bacha MM, Smaoui W, Karoui C, Hamida FB, Hedri H, Rais L, Ounissi M, Zouaghi MK, Abdallah TB. End-stage renal disease at dialysis initiation: Epidemiology and mortality risks during the first year of hemodialysis. Saudi J Kidney Dis Transpl 2021;32:1407-17

How to cite this URL:
Mesbahi T, Barbouch S, Najjar M, Fattoum S, Jebali H, Trabelsi R, Bacha MM, Smaoui W, Karoui C, Hamida FB, Hedri H, Rais L, Ounissi M, Zouaghi MK, Abdallah TB. End-stage renal disease at dialysis initiation: Epidemiology and mortality risks during the first year of hemodialysis. Saudi J Kidney Dis Transpl [serial online] 2021 [cited 2022 May 25];32:1407-17. Available from: https://www.sjkdt.org/text.asp?2021/32/5/1407/344761



   Introduction Top


Chronic kidney disease (CKD) is a major public health problem. It affects about 10% of the adult population in the world.[1] The prevalence of end-stage renal disease (ESRD) is steadily increasing worldwide. In the United States, it was estimated at 650,000 patients in 2010, and it is expected to reach two million patients in 2030.[2] It has an alarming socioeconomic impact. In France, the cost of care was estimated at 3.1 billion euros in 2013, which corresponds to 3% of the total amount of health insurance cost.[3] Several comorbidities are associated with CKD and responsible for an altered clinical state, especially at the initiation of treatment.[4] These patients are often referred late to nephrologists which is a source of complications approved by several studies in the world.[1],[5],[6]

The 1st year of hemodialysis (HD) treatment represents a vulnerable period when multiple physical and psychological changes occur. It is characterized by an increased risk of mortality, compared to the general population, especially during the first three months.[7],[8] The identification of death risk factors during this period allows the assessment of patients’ care pathways, which contributes to the planning of an appropriate management strategy to reduce the mortality rate as well as the care cost.

Many authors worldwide have considered the epidemiological and clinico-biological characteristics of patients at HD initiation and identified the predictors of early mortality, especially during the 1st year of HD. It was based on the use of CKD registers in several countries around the world.[9],[10],[11],[12],[13] However, these factors cannot be standardized because of specificities of epidemiological characteristics, habits, and management strategies of each population.

The aim of this study was to analyze the epidemiological and clinico-biological characteristics at dialysis initiation to identify the outcomes and mortality risk factors during the 1st year of the therapy.


   Methods Top


Study population

It was a prospective, descriptive, and analytic study, carried out in two nephrology departments, during a period of six months. Included patients were over than 18 years old, with an ESRD, and they initiated HD treatment between January and June 2017. Excluded were patients on temporary HD, those who reached CKD Stage 5 but did not initiate HD during our study period, and patients who joined HD after a technical failure in peritoneal dialysis or after a graft rejection.

Data selection

The data were collected from medical files of the included patients at the dialysis initiation then transcribed on a form previously established.

We started with the period preceding dialysis treatment; we identify demographic characteristics, comorbidities, CKD history, predialysis nephrological care, and the stage of the CKD at the beginning of nephrological follow up. The comorbidity index for each subject was calculated based on modified Charlson Comorbidity Index (CCIm). Four grades of increasing comorbidity were established according to the level of the score:

  1. Grade 1: Low comorbidity ≤3
  2. Grade 2: Moderate comorbidity: 4–5
  3. Grade 3: High comorbidity: 6–7
  4. Grade 4: Very high comorbidity ≥8.


The nephrology referral was defined as the time period between the first nephrology evaluation and initiation of dialysis. Early referral (ER) was more than six months, whereas late referral (LR) was <6 months prior to starting dialysis.

Then, we analyzed the circumstances of dialysis initiation as well as clinical and biological parameters at that moment. Biological parameters were estimated glomerular filtration rate (eGFR) using the MDRD equation, hemoglobin, serum calcium, serum phosphate, parathyroid (PTH), serum albumin, C-reactive protein (CRP), and serum uric acid.

Outcomes

Patients were followed up for a total period of 12 months after HD initiation. The primary outcomes in this analysis were all-cause and specific-cause mortality. Causes of death were grouped as follows: cardiovascular, infection, neoplasia, hyperkalemia, hemorrhagic shock, or unknown cause. Early mortality is defined as a death within the first three months.

Ethics

This was a noninterventional descriptive study based on analysis of HD patient files without treatment modification. Patient identification information was kept confidential.


   Statistical Analysis Top


All statistical analyses were carried out using Statistical Package for the Social Sciences for Windows version 19.0 (SPSS Inc., Chicago, Ill., USA). All continuous variables were expressed either as means and standard deviation or medians for variables that are not normally distributed. All categorical variables were described in terms of percentage of the total study population. Mortality was studied using either the Student’s t-test or the Mann–Whitney U-test for the continuous variables depending on the normality of the distribution and the Chi-square test for the categorical variables. Analysis of the mortality over the follow-up period was by the Kaplan–Meier method. P <0.05 was considered statistically significant. A multivariate logistic regression analysis allowed us to identify the independent predictors of mortality at three and 12 months.


   Results Top


During the period of study, 229 patients have initiated HD therapy. Characteristics of these patients are summarized in [Table 1]. The average age was 60.2 ± 15.1 years, with a slight men predominance in a ratio of 1.41. Our population was relatively old. In fact, 42.8% were over the age of 65 years. Women were significantly older than men (62 ± 1.6 years vs. 59 ± 1.2 years P = 0.03). Common comorbidities included diabetes (49.9%), hypertension (88%), previous myocardial infarction (26.2%), congestive heart failure (19.7%), and peripheral vascular disease (26.2%). The median CCIm score at dialysis initiation was 4 (extremes: 0–16), and 4% of patients had no comorbidity associated to the CKD. The most prevalent causes of ESRD were diabetes (48.9%) and hypertension (16.6%), while 11% of etiologies still unknown. CKD was discovered at Stages 4 or 5 in 64% of cases. Only 58% were early referred to a nephrologist.
Table 1: Baseline characteristics of HD incident patients.

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ER was significantly associated with the presence of hypertension (P = 0.004) and number of comorbidities per patient. In fact, patients in the ER group had at least two comorbidities in 82.5% of cases compared to 71% of patients in the LR group (P = 0.037).

Laboratory analyses were summarized in [Table 2]. Mean eGFR was 6.06 ± 2.33 mL/min/ 1.73 m2. It was more than 10 mL/min/1.73 m2 in 11 cases (5%) and less than 6 mL/min/1.73 m2 in 58.7% of cases. Older age, male sex, and diabetes were statistically associated with early HD initiation.
Table 2: Biological parameters at dialysis initiation.

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Hypocalcemia, hypercalcemia, and hyperphosphatemia were noted in, respectively, 138 (60.8%), 13 (5.7%), and 185 (84.9%) patients. PTH level exceeding nine times the upper normal limit was found in 134 cases (72%). Anemia was noted in 226 cases (98.6%).

Overall, 130 patients (56.8%) underwent unplanned dialysis. The delay more than two months of the last nephrology consultation (P ≤0.001), low Hb rate (P = 0.024), and LR (P ≤0.001) was statistically associated with emergency start-up of HD. Reasons for initiating unplanned dialysis are summarized in [Table 3]. Acute pulmonary edema (APE) and uremia complications were more likely to have contributed to urgent dialysis starts. Only 10.5% of patients had functional arteriovenous fistula (AVF) at the dialysis initiation. Hospitalization was necessary to initiate dialysis in 47.2% of cases. It was indicated for patients with lower hemoglobin rate (P ≤0.001), lower eGFR (P = 0.011), higher CRP (P ≤0.001), and LR (P ≤0.001). We had not found any statistic association between hospitalization and age or sex.
Table 3: Reasons for urgent dialysis.

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Patients were hemodialyzed one, two, or three sessions per week, respectively, in 23.2%, 26.6%, and 50.2% of cases.

During the period of follow-up, 19 patients have disappeared. There were 27 deaths (13%) during the first three months and 53 (25.2%) during the 1st year of HD [Figure 1]. Over 51% of all deaths during the first year occurred in the first three months. [Figure 2] shows the causes of death within three and 12 months.
Figure 1: Kaplan-Meier cumulative survival at 1 year's follow-up.

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Figure 2: Causes of death at 3 and 12 months.

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A cardiovascular cause accounted for death in 33.4% and 30% of patients at three and 12 months, respectively. Infectious cause represented 29.6% and 34% of causes of death at, respectively three and 12 months.

On multivariate analysis, we identified congestive heart failure and dialysis less than three sessions per week as predictive factors of mortality at the 1st year of HD [Table 4]. CRP more than 21 mg/L, dialysis less than three sessions per week, CCIm more than 6, and APE at the dialysis initiation were identified as predictive factors of three-month mortality [Table 4].
Table 4: Risk factors for mortality during the first 3 and 12 months of hemodialysis.

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   Discussion Top


This was a prospective study evaluating the demographic and clinico-biological profile of our incident HD population. Even in a short period of time, we succeeded to collect a large representative number of patients from two different services to update our national data.

The mean age at HD initiation in our study was 60.2 ± 15.3 years, whereas it was 51.4 ± 16.1 years in the study conducted in the same department in 2001. We have noted an aging of the incident population. These results could be explained by:

- The less strict strategy of patient selection at dialysis initiation. In fact, age is no longer a limit for chronic HD

- The better chances of patient’s survival before dialysis initiation thanks to the improvement of nephrological care during the predialysis period.

However, our population remains younger than developed countries and older than other countries in Africa.[14],[15] According to the REIN registry, in 2016, the median age of the patients commencing HD was 70.7 years and it was 63.1 years according to the EDTA registry.[16] The advanced age (65 to 70 years) in developed countries reflects the population aging.[7],[17],[18] In return, young age in African studies reflects the youth of the population as well as the frequency of specific nephropathies such as those related to infectious diseases. Several scores were used to assess the impact of comorbidities on the prognosis of patients with ESRD. These scores have been tested for dialysis patients and their prognostic value remains controversial.[4],[19],[20] In our study, we opted for the CCIm calculated at the dialysis initiation. We found that 31% of our patients had a high to very high level of CCIm. These results are consistent with those found in the literature.[21]

In our study, 59% of patients had diabetes at dialysis initiation. This frequency was different between series with a rate varying from 12% in Brazil to 50.7% in Japan and 54.6% in the French departments of America.[17],[22],[23],[24]

Hypertension was the most frequent comorbidity at dialysis initiation. As in our study, it has been reported to occur in 85% to 95% of patients with ESRD.[18],[23],[24],[25] In fact, CKD can be a consequence of hypertension and most of the CKDs of any etiology are associated with hypertension. Moreover, CKD is an independent risk factor for cardiovascular diseases. The prevalence of cardiovascular events increases as eGFR decreases.[26] he cardiovascular diseases in dialysis patients are substantially higher than in the general population.[26]

Worldwide, diabetes and hypertension were the leading causes of dialysis. According to the REIN registry 2016, hypertension (24.3%) was the first cause of CKD followed by diabetes (22.8%),[18] unlike other global and national reviews where diabetes was always the leading cause of CKD.[17],[22],[23],[24] Despite the development of exploration techniques, especially renal biopsy and immunological investigations, causal nephropathy remains undetermined in 11% of cases in our study and over 20% of cases in the literature.[18],[27],[28] In fact, the LR contributes to delay the nephrological care, which could justify the frequency of unknown nephropathy. Indeed, CKD is a silent disease, occurring even in young subjects free from any comorbidity that is why CKD is always diagnosed at an advanced stage.

According to literature, 25%–50% of the population with CKD is late referred to a nephrologist.[19] In our series, LR accounted for 42.4% of cases. These results are higher than those in published European and American series.[6],[29],[30]

In our study, HD was started in an emergency in 130 cases (56.8%). According to the Ben Hamida series[10] and REIN 2016 registry,[31] the first HD session was held in an emergency in 46.3% and 32.4% of cases, respectively.

Urgent start HD is more common in case of LR according to the literature[19] as well as to our series. However, ER cannot avoid completely the urgent start of HD.[31] In fact, according to Hoffmann et al, a quarter of patients referred early and followed regularly did not have a planned first HD session.

In our population, temporary catheters were required in 89.5% of cases, in the range of other national series[32],[33] but higher than those of the data of the literature.[18],[34],[35],[36] According to the REIN 2016 registry, the first vascular access was a central venous catheter in 57% of patients. Dialysis Outcomes and Practice Patterns Study (DOPPS) in the United States found that central venous catheters accounted for 68% of vascular access in incident patients.[34]

The main finding of this study is that mortality during the 1st year of HD remains high, representing 25.2% of incident patients, and 51% of them died during the first three months. Our results showed a lower survival rate in comparison to the patients in developed countries.[37]

The high mortality rate during the first HD year has been described since the 1970s.[37],[38] However, the increased risk of death during the first three months is described more recently.[37],[39] This can be explained by the exclusion of patients who have not completed three months in HD.[40]

In several countries, the DOPPS consistently observed the highest mortality rate during the first three to four months of dialysis.[37]

A study elaborated by Foley et al[41] focuses on the weekly evolution of the mortality rate during the first dialysis year in incident patients in the United States using the USRDS registry. According to this study, the crude death rate in the 1st year was 23.4%, with a peak at the 6th week.[41] Our results are consistent with those published by the EDTA, CORR, and USRDS registries.[16],[41]

The most common causes of death during the 1st year of dialysis, after reviewing the literature, are cardiovascular causes followed by infectious causes.[42] In our study, infection prior to cardiovascular diseases during the 1st year of dialysis. This result can be explained by the frequent use of intravenous catheters at the beginning of dialysis (89.5% of cases) in addition to the prolonged delays of AVF confection which expose to infectious affections due to catheters, especially in our predominantly diabetic population.

Predictors of death in patients with ESRD during their 1st year of dialysis have been evaluated in several studies.[9],[36],[39],[40],[41],[42],[43],[44]

Advanced age was the most frequent predictor factor in the literature.[36],[39],[40],[41],[43] However, in our study, age was not found as a risk factor of death.

As it was noted in literature, the timing of dialysis initiation does not influence mortality during the 1st year. IDEAL study confirmed our findings and has mentioned that early or late dialysis initiation was not associated with an incrementally increased risk of all-cause mortality.[45] In fact, there was no difference in mortality rate between those how initiated dialysis with an eGFR more or less than 10 mL/min/1.73 m2.

Elevated CRP has been identified as a mortality risk factor in our study. CRP is a biological marker of inflammation. It has also been shown to be an independent risk factor for cardiovascular complications and atherosclerosis.[46] Several studies have shown a strong correlation between CRP levels and the risk of cardiovascular events.[47],[48] It is associated with an increase in not only cardiovascular mortality but also all-cause mortality.[49],[50]

Despite the availability of several comorbidity scores specific to hemodialyzed patients, CCIm has demonstrated its reliability in several publications in risk staging and predicting one-year and even 24 and 36-month HD mortality.[19],[20],[44],[51]

The relationship between dialysis dose per week and mortality remains a controversial issue[52] and has attracted the attention of several authors.

The quality of dialysis delivered influences the outcome of patients in short and long terms. This finding was confirmed by the DOPPS study, which found a positive correlation between dialysis dose and short- and long-term patient outcomes in Europe and the United States.[37]

According to Hanson et al,[53] in a study conducted in the United States, the risk of death decreases by 21% for new dialysis patients receiving two sessions per week compared to those receiving three sessions, but this difference was not statistically significant (OR = 0.79, P = 0.06).[53] However, other studies in developing countries have shown that the reduced number of HD sessions per week is associated with an increased risk of death.[54] Indeed, in Lithuania, Stankuviene et al showed that dialysis patients receiving one or two sessions per week had a twice higher mortality risk than dialysis patients receiving three times per week.[55] In addition, in another study in Sudan, Elamin et al demonstrated that one-year survival is estimated at 89% versus 85%, respectively, in groups of three and two sessions per week but without significant association.[56]

In our study, as well as in other national studies,[9],[10] the reduced number of HD sessions per week has been considered as an independent predictor of mortality at three months and at one year. This can be explained by the low residual renal function of our patients at the dialysis initiation, the non-compliance with such hygiene and dietary rules, and malnutrition often associated and aggravated by the limited number of HD sessions per week.

APE is a significant risk factor for hypertension, left ventricular hypertrophy, and mortality in ESRD patients.[57] Several studies have shown that APE is an independent predictor of HD mortality.[58]


   Conclusion Top


CKD is a major health problem. This study illustrated the alarming clinico-biological situation of patients at dialysis initiation. The LR to a nephrologist, the lack of preparation before HD, and the coexistence of serious comorbidities at the initiation of HD resulted in a high rate of early death. There must be more serious focus on early, preventive, multi-disciplinary care, and management of the CKD patients. Such an approach will certainly help to reduce both mortality rate and health-care costs.

Conflict of interest: None declared.



 
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Correspondence Address:
Tasnim Mesbahi
Department of Nephrology, Charles Nicolle Hospital, Tunis
Tunisia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1319-2442.344761

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