This is the first population-based analysis of the impact of renal dysfunction on preference-based health utility using a generic preference-based instrument. In this cross-sectional study, we found that moderate renal dysfunction is independently associated with reduced health utility, particularly in the domains of mobility and pain/discomfort.
Until recently, increasing comorbidities, along with the progression of CKD, was thought to play an important role in reduced HRQOL in patients with renal dysfunction [12
]. There are, however, conflicting data on the association between HRQOL and renal function itself, especially among patients with mild-to-moderate renal dysfunction. In the Renal Research Institute-CKD study [25
], eGFR had no linear association with HRQOL, and low eGFR was not an independent determinant of reduced HRQOL. Similarly, Odden et al.
] found that age-adjusted HRQOL is significantly associated with renal dysfunction but that the effect is attenuated by demographic and socioeconomic variables. However, these studies were performed using subjects who had either profound renal dysfunction [25
] or a history of cardiovascular events [9
], both of which are major confounders in a HRQOL analysis. Therefore, these data may not be applicable to population with mild-to-moderate renal dysfunction. On the contrary, Chin et al.
] reported that an eGFR value of 45 mL/min/1.73 m2
or lower is an independent determinant of impaired HRQOL in the elderly Korean population. Similarly, in a population-based study in Australia, Chow et al.
] reported that an eGFR lower than 60 mL/min/1.73 m2
is significantly associated with an impaired HRQOL after adjusting for comorbidities associated with CKD. In accordance with previous population-based studies, we also demonstrated that an eGFR of 30.0-59.9 mL/min/1.73 m2
remains an independent predictor of impaired HRQOL after adjustment for demographic, socioeconomic and psychological factors, and major comorbidities associated with CKD. We hypothesize that the conflicting findings regarding the impact of renal function on preference based health utility are largely due to the differences in study subjects in terms of their renal function and comorbidities. Because the number and severity of comorbidities increase with the progression of CKD, it can be assumed that GFR is a more important determinant of health utility in mild-to-moderate renal dysfunction. Thus, early detection of renal dysfunction and proper therapeutic intervention are important to public health efforts aimed at improving health utility.
In this study, the dimensions of EQ-5D that were particularly affected by moderate renal dysfunction were mobility and pain/discomfort, suggesting that these two components are responsible for the reduction in health utility scores that is associated with declining renal function. Although physical inactivity or functional limitations are frequently observed even in patients with mild-to-moderate renal dysfunction and are also a modifiable risk factor for mortality [26
], there are conflicting data regarding the impact of renal function on physical activity in these patients. Data from a community-based survey of the US adult population showed that impairment in physical function among CKD patients is related to comorbidities and old age rather than to renal function itself [26
]. However, other reports have suggested that renal dysfunction is directly associated with impaired physical function in elderly persons, independent of comorbidities [14
]. Similarly, the prevalence of frailty, of which loss of mobility is a key component, increases with decreasing renal function in elderly cohorts, independent of comorbidities. Although the reasons for the association are unclear, unmeasured confounding variables such as sarcopenia [31
], inflammation [32
], malnutrition, or other co-morbidities may play a role [12
In addition to impaired mobility, we found that more than 70% of the participants with an eGFR of 30.0-59.9 mL/min/1.73 m2
reported that they had some or extreme pain or discomfort, and an eGFR of 30-59.9 mL/min/1.73 m2
remained an independent risk factor for self-reported problems in the pain/discomfort dimension after adjusting for covariates. Similarly, the Renal Research Institute-CKD study showed that the presence of physical pain among patients with CKD stages 3-5 was associated with lower HRQOL [25
]. Unfortunately, chronic pain is often not only unrecognized, but also inadequately treated in the CKD population [33
]. Therefore, regular screening for pain and the development of safe and effective treatments for chronic pain are necessary to improve HRQOL in the CKD population.
The EQ-5D is a useful preference-based measurement of HRQOL that incorporates values or utilities for health status and can be used in health-economic analyses to optimize resource allocation [34
]. In this study, we found that age-adjusted EQ-5D utility scores in participants with moderate renal dysfunction are lower than in patients with diabetes, hypertension, asthma or chronic obstructive pulmonary disease. Despite the substantially lower health utility of these patients and the chronicity of the disease, CKD awareness is extremely low in both high- and low-income countries [36
]. Indeed, the awareness rate of CKD (stage I to III) has been reported to be lower than 10%, whereas the awareness rates of diabetes and hypertension are 55.8% and 51% respectively in Korea [37
]. Moreover, the World Health Organization (WHO) does not yet recognize CKD as a major chronic disease that must be prevented to reduce mortality. Even though it seems apparent that early CKD detection and proper intervention can vastly reduce healthcare expenses for end-stage renal disease, these preventive strategies are implemented less frequently than recommended, even in developed countries. In addition, according to the budget expenditure report of the Centers for Disease Control and Prevention, CKD was allotted the smallest budget considering the burden of the disease [38
]. Taken together, these findings suggest that healthcare resource allocation for CKD is inadequate. Under such circumstances, the results of this study provide evidence that moderate renal dysfunction may be worthy of a proportionate allotment of the available healthcare resources.
This cross-sectional study has several limitations that needed to be addressed. First, the present data showed skewed distributions of gender and eGFR groups. In this study, the proportion of the subjects in the normal renal function (eGFR ≥ 90.0 mL/min/1.73 m2
) group was lower than that of the mildly decreased renal function group (eGFR 60.0-89.9 mL/min/1.73 m2
). In addition, the proportion of women was higher compared with men, especially in the stage III CKD group compared with other population-based studies [39
]. Although these deviant distributions may be partly explained by the inaccuracy of the MDRD equations in Asian populations [40
], and an incorrect coefficient factor for female gender, which underestimates true GFR [41
], the possibility of potential selection bias cannot be ruled out in this study. Second, the possible confounding effect of age which is strongly associated with both CKD and health utility could also affect the results. Furthermore, the associations we observed were only inferred from this analysis, and unmeasured residual confounding should be considered in when interpreting our results. Third, the method for serum creatinine measurement was not calibrated to be traceable to IDMS. Thus, there is the possibility of under-estimating the GFR in participants with GFR over 60 mL/min/1.73 m2
]. Finally, no longitudinal data were available on the associations between health utility and mortality or progression to end stage renal disease among CKD participants. The precise
reason why renal impairment contributes to decreased health utility was not investigated in this cross-sectional analysis, and the interventions that could positively affect CKD patients' health utility remain unknown.