Validation of the Functional Assessment of Anorexia/Cachexia Therapy Instrument to Assess Quality of Life in Maintenance Hemodialysis-Treated Patients with Cachexia

Background Cachexia is the ultimate state of many maintenance hemodialysis (MHD)-treated patients. Functional Assessment of Anorexia/Cachexia Therapy (FAACT) is a tool used to evaluate the quality of life of patients with cachexia related to various diseases, but its effectiveness in MHD-treated patients has yet to be veried. This study aims to explore the applicability of FAACT in MHD-treated patients. Methods Qualied MHD-treated patients were selected for FAACT and The Kidney Disease Quality of Life Short Form 36 (KDQOL-36) questionnaire survey, and their demographic data and biochemical test results were collected from electronic medical records. Then, data were analyzed using statistical methods. Results This study enrolled 299 effective patients. The reliability of FAACT and its anorexia-cachexia subscale (ACS) were 0.904 and 0.842, respectively, and their retest exceeded 0.85. A reasonable correlation was found between FAACT and its items, and a reasonable calibration validity was identied between FAACT and KDQOL-36 subscale. FAACT and its subscale ACS showed good discriminant validity in the comparison of patients with different cachexia states and inammatory states. Conclusions FAACT and ACS have good reliability and validity in MHD-treated patients and are suitable to measure the quality of life of MHD-treated patients with cachexia.

Cachexia, a complex metabolic syndrome associated with various diseases, is characterized by muscle loss with or without fat loss [1] . However, this syndrome is poorly de ned in patients treated with hemodialysis and in patients with end-stage kidney disease (ESKD) typically present with anorexia, muscular dystrophy, and protein energy waste (PEW) [2,3] . These symptoms are consistent with cachexia observed in other chronic diseases, such as cancer, heart failure, and HIV [3] . Clinically de ned as loss of appetite, anorexia [4] can exacerbate the PEW of hemodialysis-treated patients, resulting in malnutrition and increased mortality [5] . Cachexia is conceptually similar to PEW and is the most severe stage of PEW [3,6] . Up to 75% of patients with ESKD undergoing hemodialysis suffer from wasting/cachexia [3] . Cachexia is generally similar in different diseases. The diagnostic criterion for cancer cachexia is weight loss greater than 5% or weight loss greater than 2% in individuals showing depletion according to current body weight and height (body mass index [BMI] < 20 kg/m²) or skeletal muscle mass (sarcopenia) [7] .
However, a clinical tool to assess cachexia in MHD-treated patients is lacking. FAACT is a tool used to assess the quality of life of patients with cancer, AIDS, and some chronic diseases [8,9] . However, its availability in MHD-treated patients has not been demonstrated. KDQOL-SF, KDQOL-36, and KDQ scales have been used to evaluate the quality of life of hemodialysis-treated patients [10][11][12] , but they have no speci c dimension for cachexia.
Therefore, this study aimed to assess the reliability and validity of the FAACT scale in evaluating the quality of life of MHD-treated patients with cachexia.

Participants and data collection
Patients from three blood puri cation centers were selected as research subjects. The patients must be no less than 18 years old, have regular hemodialysis at least twice a week for 6 more months, and could read and understand our questionnaire. Those patients with non-terminal kidney disease, recent major surgery, or concurrent tumors were excluded. This study was approved by the ethics committee of research institution, and all participants read and signed the informed consent.
The demographic and clinical characteristics of the patients were obtained from electronic medical records. The weight change of the patients over the past 6 months was determined on the basis of their records during each hemodialysis session. Then, patients with cachexia were determined in accordance with the evaluation criteria. The presence of infection was determined on the basis of C-reactive protein (CRP) concentration (CRP>8 mg/L), white blood cell count (WBC>10 10 /L), and physician's most recent diagnosis. The patients completed the FAACT and KDQOL-36 questionnaires under the guidance of a researcher and a nurse. A second survey was conducted using the FAACT questionnaire to assess the test-retest after a week.

Assessment schedule
FAACT is an instrument used to assess the quality of life of patients with anorexia and cachexia. This instrument includes 39 terms in ve dimensions: physical well-being (PWB; 7 items), social well-being (SWB; 7 items), emotional well-being (EWB; 6 items), functional well-being (FWB; 7 items), and anorexiacachexia subscale (ACS; 12 items) [8] . Most of the items (PWB, SWB, EWB, and FWB) were drawn from the general chronic illness questionnaire FACT-G [9,13] . ACS is the core of questionnaire evaluation of cachexia.
All items were rated as a ve-level scoring system: not at all, a little bit, somewhat, quite a bit, and very much. Higher FAACT scores corresponded to better quality of life, and lower ACS scores corresponded to severe cachexia [8] .
KDQOL-36, a simpli ed version of the KDQOL-SF questionnaire, was used to enhance the completion rate of the questionnaire. This scale is widely used to assess the quality of life of hemodialysis-treated patients, and its authority has been recognized by many researchers [14][15][16] . The validity of the Chinese version of KDQOL-36 has also been veri ed [17] . It comprises 36 items, including the generic 12-Item Short-Form Health Survey to provide two summary scores assessing impact on the physical and mental dimensions, and 24 items to provide three disease-speci c subscales: symptom/problem list, effects of kidney disease, and burden of kidney disease [18,19] .

Statistical analysis
Patient characteristics were summarized using conventional descriptive statistical methods. Then, the reliability and validity of FAACT in all patients who completed the questionnaire were evaluated. For reliability evaluation, standardized Cronbach's alpha coe cients were used to assess the internal consistency of FAACT and test-retest. For validity assessment, the divergence and convergence of the questionnaire were evaluated by calculating the Pearson correlation coe cients among FAACT, its dimension scale, and the ve subscales of KDQOL-36, including the correlation coe cients of FAACT and its subscales with each of their own items. The patients were divided into different subgroups (i.e., infection and no infection, cachexia and no cachexia), and their summary scores were compared to analyze the sensitivity of FAACT. Then, independent t test was conducted. Data were analyzed using SPSS 24.0 statistical software, and statistical signi cance was considered at P < 0.05.

Results
Descriptive analysis  As shown in Table 3, the structural validity of FAACT was evaluated by calculating the Pearson correlation coe cients between all subscales and their own items. Except for GP1, GP7, GS7, GF5, and ACT13, the correlation coe cients of FAACT and their dimensions were all less than 0.3, the other 34 items were between 0.3 and 0.7, and the correlation coe cient of ACS exceeded 0.5 for all items except ACT11 and ACT13. The correlation coe cient between FAACT and all its subscales exceeded 0.5, and that between ACS and FAACT was 0.814. All subscales of KDQOL-36 strongly correlated with FAACT, with a correlation coe cient greater than 0.4, and relatively strongly correlated with ACS. The speci c results are listed in Table 4.  Effect size was calculated as (non-cachexia mean-cachexia mean)/SD of the total sample. Italicized numbers denote statistical signi cance at a threshold of P < 0.05  Italicized numbers denote statistical signi cance at a threshold of P < 0.05

Discussion
Cachexia is an important factor affecting the quality of life of patients treated with MHD [20] . Many MHDtreated patients suffer from anorexia, PEW, malnutrition, and eventually cachexia. At present, few studies evaluated the cachexia of patients with ESKD, and a standard evaluation tool for these patients remains lacking. Therefore, exploration of the evaluation tools of cachexia in MHD-treated patients is of high clinical signi cance. FAACT has been veri ed as a tool to measure the quality of life of patients with cachexia related to many diseases [8,9] . This study may serve as a reference for the evaluation of cachexia in MHD-treated patients and for the development of FAACT scale.
This study assessed the reliability and validity of FAACT in MHD-treated patients. In terms of reliability (Table 2), Cronbach's alpha was acceptable, but PWB and FWB were less than 0.7, and FAACT and ACS performed better than other disease detection areas [8,21] . The performance of FAACT test-retest was also outstanding, with the retest coe cients of all dimensions exceeding 0.8. In speci c, the test-retest coe cients of EWB, FACT-G, and FAACT exceeded 0.9. These results proved the reasonable internal consistency of FAACT. Therefore, FAACT and ACS have a stable reliability to measure the quality of life of MHD-treated patients.
In terms of validity, strong correlations were found between the subscales PWB, EWB, SWB, FWB, and ACS and their items, and the items of the subscale itself were more correlated with the subscale than other scales. However, a low relevance was found between individual items, such as ACS and ACT13, in MHD-treated patients with a chronic illness, relatively stable condition, and rare large uctuations in health. In general, the convergence of FAACT is acceptable but worse than that of patients with cancer [21] .
In addition, a correlation was found between PWB, EWB, SWB, FWB, and ACS (0.158-0.526), and the correlation between PWB and ACS was 0.526. Quality of life should be evaluated from various aspects; thus, the presence of correlation is understandable. Cachexia can greatly affect the body function of hemodialysis-treated patients [22,23] . This result explains the relatively large correlation of PWB with ACS. KDQOL-36 is an authoritative scale to measure the quality of life of hemodialysis-treated patients. This scale correlated with FAACT in all dimensions. A large correlation was also found between KDQOL-36 and FAACT in similar dimensions, proving the clinical effectiveness of FAACT.
Comparison of the FAACT scores of MHD-treated patients in different states showed that all dimensions except SWB and EWB were statistically signi cant in different cachexia states (P < 0.05), and ACS and FAACT performed the best (P < 0.001), with effect sizes of 0.60 and 0.54, respectively. FWB also performed excellent, with an effect size even greater than those of ACS and FAACT. This result indicated that cachexia signi cantly affected the physical conditions of MHD-treated patients, which further proves the above conclusion. However, FWB had unsatisfactory internal consistency and poor reliability in the evaluation of patients with cachexia only. In ammation is an important factor causing cachexia. In fact, cachexia is usually accompanied by in ammation [24][25][26] . Therefore, in ammation and severity of patients are important indicators of cachexia. Comparison of the results of in ammatory state in hemodialysis-treated patients revealed that all dimensions except SWB, FWB, FAACT, and KDQOL-36 were statistically signi cant and that ACS and FAACT also performed well (P < 0.001). These data demonstrate that ACS and FAACT have higher sensitivity in patients with anorexia in MHD.
FACT-G and its dimension is a chronic disease common dimension of quality of life. FACT-G, SWB, and EWB in MHD-treated patients show good reliability and verify the validity of some diseases, especially cancer [9,21] . However, their sensitivity was not high as that in the in ammation group (Table 6)  This study has some limitations. First, the international consensus in cancer cachexia was used as a basis because a standard diagnostic criterion for patients with cachexia is unavailable. The patient's skeletal muscle loss was not calculated because of the clinical conditions, which can cause slight deviation. Second, only a cross-sectional survey was performed, and the in uence of changes in the condition of MHD-treated patients on the FAACT score was not analyzed. Finally, only the application of the Chinese version of FAACT in hemodialysis-treated patients was analyzed, which may affect the generalization of the present results.
Prior to the study, this study was approved by the Ethics Committee of the First A liated Hospital of Guangxi Medical University, with the approval number 2019 (KY-E-33). All researchers signed informed consent.