Identifying key prognostic indicators for extended hemodialysis survival: A comprehensive analysis of clinical, laboratory, and demographic factors

INTRODUCTION

Patients undergoing hemodialysis (HD) treatment bear a high burden of disease, particularly cardiovascular comorbidities and frailty, which significantly affect their quality of life and dramatically shorten their life expectancy.^[1] Chronic kidney disease (CKD) ranks among the top 20 causes of disease burden globally.^[2] In 2019, approximately 1.5 million deaths were attributed to CKD, three-quarters of which occurred in low- and middle-income countries. Furthermore, CKD is estimated to affect approximately 15% of the population aged 20 years or older.^[2,3] In Oman, according to this ranking system, CKD was ranked 11^th in 2010, advancing from its previous position of 22^nd in 1990.^[4] Similarly, CKD was ranked 22^nd among the top 25 causes of disability-adjusted life years in the Omani population.^[4]

Historically, inadequate dialysis was considered a partial explanation for poor survival rates in the United States, as substantially higher survival rates have been reported in Europe and Japan, even after adjusting for age, sex, and kidney diagnoses.^[5] Japanese patients, for instance, exhibit far fewer comorbid risk factors than those in the United States.^[6,7] However, it is more likely that factors such as older age, a higher prevalence of diabetes mellitus (DM), more comorbid conditions, and an inability to accurately capture the severity of any noted comorbid diseases contribute to the higher dialysis mortality observed in the United States.^[8] This is particularly relevant given that increasing dialysis doses have been implemented in the United States over time.^[8]

One of the highest survival rates has been reported in Tassin, France, where patients undergo dialysis for 24 h/week, which is significantly longer than the standard 12 h/week observed in almost all other centers.^[9] We conducted a retrospective case–control comparative study. The 10-year cutoff was selected because surviving beyond a decade on maintenance HD is considered a significant clinical milestone in end-stage kidney disease (ESKD) patients.

MATERIAL AND METHODS

It represents a single-center experience. It includes patients aged 18 years and older undergoing regular HD at ASSEEB RDC. The study compares the demographic, laboratory, and clinical data of patients with short-term survival on HD (<10 years) against those with long-term survival (>10 years). Both groups included an equal number of patients (n = 34 each). Our study is based on a retrospective case–control comparative design. The study utilized a convenience sampling method, including all eligible patients during the 3-year period. Patients with incomplete medical records or those who transferred to other centers were excluded.

The Ministry of Health in Oman utilizes an excellent medical record and information technology system, Al Shifaa, which is fully computerized and has received internationally recognized certificates of excellence. All clinical and laboratory data are recorded progressively within this system. Statistical analyses were performed to calculate p-values using Fisher’s exact test for categorical variables to determine significance (p < 0.05).

The following data were collected for each group over a 3-year period (2018, 2019, and 2020):

1. Demographic data: Age in years (categorized as 1 = Children 0–18, 2 = Young adult 19–24, 3 = Middle- aged adult 25–64, 4 = Senior 65 and over), gender, education level, employment status, smoking history, marital status, and family support

2. Clinical data: Comorbidities including hypertension (HTN), DM and its duration in years, ischemic HD (IHD), congestive heart failure, and the type of vascular access

3. Laboratory investigations: Pre- and post-dialysis session urea to calculate dialysis adequacy (urea reduction rate [URR] >65%), serum potassium, bone profile, parathyroid hormone, serum albumin, iron profile (transferrin saturation), hemoglobin (Hgb) level, total white blood cell count (WBCs), and fasting serum glucose levels.

Data were collected by three investigators, while statistical analysis, literature review, and discussion were conducted by two investigators.

RESULTS

Demographic and clinical characteristics

A comparison between the short-term survival (<10 years) and long-term survival (>10 years) groups (n = 34 each) revealed that most patients on HD were middle-aged (24– 64 years), with no significant statistical difference between the two groups (94% vs. 88%, p = 0.672). In the long-term survival group, the gender distribution was equal, whereas males were more prominent in the short-term survival group (67% vs. 32%, p = 0.218).

Diabetic nephropathy was the primary cause of ESKD in our study population (88% in both groups). However, HTN was significantly more prominent in the short-term survival group compared to the long-term survival group (82% vs. 29%, p < 0.001). IHD was also more prevalent in the short-term survival group (23% vs. 6%, p = 0.083). These comorbidity differences are visualized in Figure 1. Regarding vascular access, permanent catheters were more frequently used in the short-term survival group (17% vs. 8%, p = 0.476) [Figure 2].

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Figure 1: Comparison of comorbidities (hypertension, ischemic heart disease, congestive heart failure) between short-term and long-term survival groups.

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Figure 2: Distribution of education levels among patients in the short-term versus long-term survival groups.

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Most patients in the long-term survival group were not working (82%), compared to 64% in the short-term survival group (p = 0.168). The majority of the short-term survival group was married (76%), whereas only 50% of the long-term survival group was married (p = 0.043). A highly significant finding was that 50% of the long-term survival group had higher education or postgraduate degrees, while none in the short-term survival group achieved this level of education (p < 0.001) [Figure 3]. Smoking was more prevalent in the short-term survival group (17.6%) compared to the long- term survival group (5.8%, p = 0.259). These demographic and clinical findings are summarized in Table 1.

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Figure 3: Comparison of key laboratory parameters between short-term and long-term survival groups.

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Table 1: Demographic and clinical data comparison between short-term (<10 years) and long-term (>10 years) survival on HD.

Characteristic	Short-term survival (<10 years)	Long-term survival (>10 years)	p-value
Comorbidities
Diabetes mellitus	30	30	1.000
Hypertension	28	10	<0.001
Ischemic heart disease	8	2	0.083
Congestive heart failure	7	15	0.068
Vascular access
Arteriovenous fistula	25	27	0.776
Arteriovenous graft	3	4	1.000
Permanent catheter	6	3	0.476
Employment status
Working	10	5	0.242
Not working	22	28	0.168
Retired	2	1	1.000
Marital status
Married	26	17	0.043
Not married	2	10	0.023
Divorced	0	5	0.053
Widow	6	2	0.259
Age group
15–24 years	2	0	0.493
24–64 years	32	30	0.672
>64 years	0	4	0.114
Gender
Male	23	17	0.218
Female	11	17	0.218
Education level
Not educated	21	6	<0.001
Primary education	13	11	0.800
Higher education	0	14	<0.001
Postgraduate	0	3	0.239
Smoking status
Smoking	6	2	0.259
Not smoking	28	32	0.259
Family support
Family support present	33	34	1.000
No family support	1	0	1.000
Duration of DM
<5 years	17	0	<0.001
5–10 years	13	0	<0.001
>10 years	0	30	<0.001

Bold values indicates statistical significance, p<0.05. DM: Diabetes mellitus, HD: Heart disease

Laboratory characteristics

Laboratory data revealed that patients with long-term survival on HD exhibited better dialysis adequacy (URR of 70.1%), higher iron levels (transferrin saturation of 38%), higher serum albumin (40 mg/dL), lower fasting blood sugar levels (6.5 mmoL/L), and better Hgb and WBC counts than patients with short-term survival. These results are detailed in Table 2 and visualized in Figure 4.

Table 2: Laboratory characteristics of patients with short-term and long-term survival on hemodialysis.

Laboratory parameter	Short-term survival (<10 years)	Long-term survival (>10 years)
Urea reduction rate (%)	66	70.1
Hemoglobin	10.5 g/dL	10.9 g/dL
White blood cells	7.0	5.4
Transferrin saturation (%)	25.5	38.0
Serum albumin	37.5 mg/dL	40.0 mg/dL
Corrected calcium	2.2 mmoL/L	2.1 mmoL/L
Phosphate (PO4)	1.4 mmoL/L	1.5 mmoL/L
Parathyroid hormone	65 pg/mL	74 pg/mL
Potassium	5.0 mmoL/L	5.2 mmoL/L
Fasting blood sugar	8.8 mmoL/L	6.5 mmoL/L

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Figure 4: Types of vascular access utilized by patients in the short-term and long-term survival groups.

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DISCUSSION

Although maintenance dialysis prevents death from uremia, mortality among patients with ESKD remains high. Patients on dialysis have a substantially higher multivariable-adjusted mortality than patients not on dialysis who have cancer, diabetes, or cardiovascular disease.^[10] However, mortality rates among patients with ESKD have improved over time. According to the United States Renal Data System (USRDS) report in 2022, all-cause mortality in patients with ESKD declined steadily between 2010 and 2019, before sharply increasing in 2020 in association with the COVID-19 pandemic.^[11] Between 2001 and 2016, adjusted relative mortality rates reported by USRDS declined by 29%.^[10] Over this period, the adjusted relative reduction in mortality was 28% among patients on HD and 43% among patients on peritoneal dialysis (PD). HD is the major treatment modality for renal replacement therapy (RRT) worldwide, and it is also the one with the highest mortality rates, followed by kidney transplantation and PD.^[12-14] For these reasons, ESKD requiring RRT remains one of the most concerning outcomes of CKD.

Identifying prognostic factors associated with ESKD can help reduce morbidity and mortality. In the current study, all patients were dialyzed using standard bicarbonate HD, performed 3 times a week with an average duration of 10–12 h/week. Dialysis machines with individual proportioning were used, and water was treated by reverse osmosis. Volumetric ultrafiltration control was available on all machines. The standard dialysate flow rate was 500– 700 mL/min, and blood flow rates were 250–350 mL/min.

A meta-analysis of 30 studies examining sex-stratified data concluded that CKD progression was faster in men compared to women,^[15] although other studies suggest that such differences may be due to nonbiological factors, such as lifestyle, cultural, and socioeconomic elements.^[16] In our study, mortality was higher in males compared to females (67.6% vs. 32.4%) in the short-term survival group, whereas it was equal (50%) in the long-term survival group.

Both groups had the same number of patients with DM (30 out of 34); however, better survival was observed when DM was not accompanied by HTN and IHD. At present, an estimated 425 million people worldwide are diagnosed with DM, and 20–40% of diabetic patients develop CKD.^[17] It is currently the leading cause of ESRD in developed countries.^[18] The presence of diabetic nephropathy as a risk factor for mortality in dialysis patients may be explained by a higher comorbidity index that adds disease burden and higher mortality to patients initiating dialysis.^[19] Emerging treatments, such as pancreas-kidney transplantation, offer promising avenues for diabetic patients with advanced CKD.^[20]

Serum albumin is an independent and powerful prognostic index for HD patients, with evidence indicating that low levels predict poor survival in ESKD.^[12] We found a significant difference in serum albumin values; individuals on HD with serum albumin ≥40 mg/dL had longer survival than those with <40 mg/dL. Many studies have shown that hypoalbuminemia is a strong predictor of mortality. A high risk of mortality in HD patients with serum albumin levels ≤3.8 g/dL. Teixeira et al. (2015)^[21] also found that albumin is related to low survival, while Msaad et al. (2019)^[22] reported that 77.27% of deceased patients had low albumin. Furthermore, Ebrahimi et al. (2019)^[12] demonstrated that for each unit (in g/dL) increase in serum albumin, the survival time for HD patients increased by approximately 23%. A comprehensive study by Kalantar-Zadeh et al. (2003)^[23] indicated. Patients with ESKD experience various hematopoietic abnormalities, most commonly anemia, a multifactorial condition affecting almost all patients undergoing HD and associated with the risk of early death.^[21,24-26] HD patients are predisposed to iron deficiency due to residual blood loss during treatment.^[27,28] In the current study, serum iron and Hgb levels were better in the long-term survival group than in the short-term survival group.

Based on the Kidney Disease Outcomes Quality Initiative 2015 guidelines,^[29] a URR ≥65% is considered the minimum acceptable dialysis dose for a thrice-weekly schedule. Therefore, a URR cutoff point of 65% was used to evaluate dialysis adequacy. In our study, dialysis adequacy was more optimal in the long-term survival group compared to the short-term survival group, though both exceeded the 65% cutoff.

The highest mortality associated with the presence of a central venous catheter (CVC) is infection, as demonstrated by Coentrão et al.^[30] in a study comparing patients starting PD, HD through arteriovenous fistula, and HD through CVC. In our study, the use of CVCs was higher in the short-term survival group (17.6%) compared to the long-term survival group (8.8%). Furthermore, understanding broader risk factors, such as malignancy incidences in renal transplant and ESKD patients, highlights the need for comprehensive long-term care.^[31]

Current evidence suggests that smoking among patients requiring dialysis is associated with accelerated atherosclerosis and increased mortality.^[17] In our study, smoking prevalence was higher in the short-term survival group (17.6%) compared to the long-term survival group (5.8%). Education level has also been associated with better life expectancy and active life expectancy.^[32] In the present study, 50% of the long-term survival group had higher education or postgraduate degrees, whereas 0% in the short- term survival group did [Figure 5].

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Figure 5: Summary of key prognostic factors associated with long-term survival on hemodialysis.

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From the onset of a DM diagnosis, an estimated 4–17% of patients will experience ESRD at 20 years, and 16% will have ESRD at 30 years, making diabetic nephropathy the most common cause and primary etiology of ESRD.^[33,34] In our study, a diabetes duration of <10 years was associated with short-term survival on HD.

One strength of this study is its potential to aid nephrologists in providing patients with well-founded information regarding their prognosis. However, there are several limitations to consider. First, the small sample size (n = 34/group) limits the statistical power of the study and increases the risk of type II errors. Furthermore, due to the small sample size, only Fisher’s exact test was used, precluding multivariate regression analysis to determine independent predictors of survival after adjusting for confounders. Second, the single-center design limits the external validity and generalizability of the findings. Third, the finding that all long-term survival patients had DM for >10 years reflects a survival bias, as their duration of DM is inherently linked to their extended lifespan rather than being a protective factor. Finally, there is missing data for critical variables, such as Kt/V, residual kidney function, inflammatory markers (C-reactive protein), specific causes of mortality, medications used, body weight, and dietary consumption, which may confound the conclusions.

CONCLUSION

The present study identified that elevated values of serum iron, serum albumin, and URR (indicating good dialysis adequacy), along with optimal blood sugar levels, fewer comorbidities (such as HTN and IHD combined with DM), a high level of education, and a lower incidence of smoking, serve as useful prognostic factors for extended survival time in the HD population.