Quality of life and mortality from a nephrologist's view: a prospective observational study

"The aging society" is a familiar term as elderly individuals (aged 65 years and older) make up an increasing proportion of the global population [1]. In line with global trends, the proportion of the elderly in Korea is increasing (8.3% in 2003) and is expected to reach 15% in 2019 [2]. This increase may lead to age-associated increases in chronic diseases. Chronic kidney disease (CKD) has been recognized as one of a number of chronic diseases primarily affecting the elderly. Worldwide, the prevalence of CKD in the elderly has increased to nearly half of the population aged 70 years and older [3], and the incidence among the elderly in Korea is similar [4]. Therefore, the problems associated with CKD need to be appropriately managed to reduce the burden of CKD in the aging society.

The ability to predict future morbidity and mortality is a key to reduce the burden of CKD. To this end, monitoring a patient's functional and subjective status of well-being, collectively known as health-related quality of life (HRQOL), is of particular importance in CKD patients [4–7]. Traditional risk factors (e.g., atherosclerosis, smoking, and diabetes mellitus) for mortality had been considered important in the elderly with or without CKD [8, 9]; however, it is currently thought that traditional risk factors do not account for all reported mortality [10]. Recently, HRQOL, comprising physical, mental, and social health, is recognized as an important predictor of mortality in elderly individuals or patients with end-stage renal disease [5, 7, 11, 12]. However, nephrologists have shown little interest in the role that HRQOL plays in mortality in CKD patients [13].

The 36-item Short-Form health survey (SF36) has been validated as a QOL assessment tool for a wide variety of patients, including CKD patients [14–16]. Here, we evaluate HRQOL using the SF36 and assess the impact of HRQOL on mortality in the elderly, who are likely to develop or already have CKD.

Clinicians focus on newer risk factors (e.g., inflammation, oxidative stress, and epigenetic change) as well as traditional risk factors (e.g., atherosclerosis, smoking, and diabetes mellitus) when assessing mortality risk in patients with CKD [21]. It is essential to evaluate non-typical risk factors because the aging society is more heavily confronted with various non-traditional co-morbidities. In the present study, we evaluated the relationship between HRQOL, as measured by the SF36, and all-cause mortality in an elderly population with or without CKD. Both physical and mental components, including each health component, affected all-cause mortality in elderly subjects. This trend was consistent for individuals with CKD. To the best of our knowledge, although HRQOL is known to be related to mortality in patients with end-stage renal disease, no report has been published on the correlation between HRQOL and mortality in patients with CKD. This issue should be kept in mind by nephrologists who may otherwise not be interested in the QOL of CKD patients.

The SF36 is an approved test that is applicable to healthy elderly individuals as well as CKD patients [14–16]. Han et al. also used the SF36 for assessing HRQOL in elderly Koreans (n = 219, aged 73.7 years) [22]. The SF36 scores for each component were similar between Han's cohort and our study cohort, but scores of social functioning, role emotional, and mental health were higher in our cohort. Recently, Mujais et al. reported HRQOL in CKD patients using the Kidney Disease Quality of Life (KDQOL) questionnaire, which combines the generic SF36 instrument with a kidney disease-specific instrument [23]. In their study, the mean physical and mental component scores for stage 3 CKD patients were 40 and 51, respectively. Although comparison between two cohorts is impossible because of different baseline characteristics (low proportion of diabetes mellitus, high serum levels of hemoglobin and albumin in our cohort), we assumed that SF36 scores from the randomly sampled design of our cohort could be representative of HRQOL among the elderly in Seongnam-si.

The association between negative self-assessment of health status and mortality in the elderly has been noted for more than 30 years, since Maddox's report [24]. Bernard et al. evaluated the relationship between self-assessment of health status and the subsequent risk of death among the elderly during a 2.5-year period [12]. When 3,485 elderly subjects were asked, "How would you rate your health at the present time?", the group with an answer of "poor" (the most negative of five possible responses) had an adjusted hazard ratio of 5.5 (4.0-7.5) for mortality compared with those who answered "excellent" (the most positive of five possible responses). Several hypotheses have been proposed to explain the correlation between HRQOL and clinical outcome. For example, a negative self-evaluation of health could stimulate a psychoneuroimmunologic response, reflect the elderly person's accurate self-detection of preclinical changes in body function, or lead to a delay in taking health-protective and maintenance actions [12, 25]. In some reports, HRQOL has been shown to be related to nutritional factors, such as cholesterol and hemoglobin levels [4, 5]. However, it is not fully understood why subjective assessment of health status is strongly correlated with objective clinical outcome after adjustment for chemical markers. Interestingly, the mental component score did not differ between two groups that were divided by an eGFR of 60 ml/min/1.73 m². However, the mental component score in the CKD group was a greater predictor of mortality than in the non-CKD group. The reason for the weak correlation between the mental component score and mortality in the elderly without CKD is not clear. It might be because sample number was modest after classification or that elderly individuals without CKD were more strongly affected by the physical component than by the mental component. On the other hand, some studies have reported that a depressed mental state is common and clearly correlated with mortality in patients with end-stage renal disease, consistent with our results [26, 27].

The importance of HRQOL in patients with end-stage renal disease is well known. DeOreo et al. examined the SF36 score in 1,000 patients who underwent hemodialysis [28]; the median values of the physical and mental component scores were 37 and 47, respectively. It was revealed that a low SF36 score, particularly a low physical component score, was associated with increased hospitalization and mortality rates. Kalantar-Zadeh et al. also measured SF36 scores in 65 end-stage renal disease patients and found a correlation with hospitalization and mortality; the mental component score and total score had the strongest correlations [5]. Furthermore, these researchers revealed that serum albumin and hemoglobin levels were associated with SF36 scores. However, few studies have investigated CKD patients with reduced renal function (GFR less than 60 ml/min/1.73 m²). The present study showed that elderly CKD patients had lower HRQOL scores than subjects without CKD; this reduced HRQOL score was strongly associated with increased all-cause mortality after adjustment for traditional risk factors and chemical markers. Furthermore, as shown in Figure 1 and Figure 2, HRQOL further separated the mortality rate according to the presence of CKD. In this regard, we should treat HRQOL and CKD equally.

Although our results are informative, our study is not without limitations. First, because all participants in our cohort were elderly Asian individuals, our results may not be applicable to other ethnic groups or adults aged <65 years with CKD. Indeed, Lopes et al. have reported differences in HRQOL among various ethnic groups undergoing hemodialysis [29]. Second, the MDRD equation has not yet been investigated in the Korean population and may not be appropriate for the elderly population. Third, HRQOL was measured only once at the start of the present prospective research; therefore, our data do not show changes during the follow-up period. Fourth, HRQOL was higher than expected (mean value: 54.5 in the physical component; 51.7 in the mental component). However, the purpose of our study was not to evaluate the cut-off point of the SF36 score. Rather, we sought to understand an independent correlation between HRQOL and mortality in CKD patients.

The present study demonstrated that HRQOL was a strong predictor of all-cause mortality in an elderly Asian population, including subjects with CKD. Although the present study does not reveal the mechanism by which the subjective HRQOL is correlated with the objective outcome of mortality, it would be reasonable to try to improve HRQOL in the elderly and CKD patients to reduce mortality. This is a responsibility of clinicians that will be more important in the aging society as the prevalence of CKD increases. Further studies are needed to ascertain how interventions to increase HRQOL can reduce mortality rates in CKD patients.