Anorexia Assessed by Simplified Nutritional Appetite Questionnaire and Association with Medication in Older Patients Undergoing Hemodialysis

Abstract

Anorexia is a common symptom in older patients undergoing hemodialysis (HD) and has become a serious problem in dialysis facilities with the aging of patients. Polypharmacy, defined as the prescription of several medications, is known to cause drug-induced anorexia. Although polypharmacy is also common in older patients undergoing HD, only a few studies have examined the association between anorexia and polypharmacy. This study used the Simplified Nutritional Appetite Questionnaire for Japanese Elderly (SNAQ-JE) to evaluate patients’ appetite, and examined its association with medications. This cross-sectional study included 233 patients (aged ≥65 years) who underwent HD in October 2021. Among the 233 patients (median age, 73.0 [interquartile range (IQR), 69.0–80.5] years; men, 57.3%; median dialysis vintage, 62.0 [IQR, 30.0–122.0] months), 116 and 117 were classified into the poor (SNAQ-JE total score ≤14) and good (>14) appetite groups, respectively. Although the total number of medications prescribed was not significantly different between the two groups (p = 0.12), the number of antihypertensive drugs was significantly lower (p = 0.03), and that of sleeping medications was significantly higher (p = 0.002) in the poor appetite group. Multivariable logistic regression analysis showed that the number of sleeping medications was associated with poor appetite (odds ratio, 2.08; 95% confidence interval, 1.32–3.27; p < 0.001). The findings suggest that the number of sleeping medications is an important contributing factor to poor appetite in older patients undergoing HD. A proper and regular review of prescriptions may be necessary to improve anorexia.

INTRODUCTION

Anorexia generally occurs in older adults,¹⁾ and pathological factors such as depression, dementia, and anxiety commonly observed in older adults could account for age-related anorexia.²⁾ Anorexia is also prevalent in patients undergoing hemodialysis (HD),³⁾ and it has been shown that approximately one-third of HD patients have anorexia.⁴⁾ With the aging of patients,⁵⁾ diminished appetite has become a serious problem in dialysis facilities.⁶⁾ The causes of anorexia in patients have not been fully elucidated; however, possible factors include uremic toxins, altered amino-acid patterns, hormones (i.e., leptin and ghrelin), and inflammation.⁷⁾ Additionally, polypharmacy, which is also common among patients undergoing HD,^8–10) can be the reason for anorexia.¹¹⁾ Polypharmacy, the prescription of several medicines to patients, is known to cause drug–drug interactions, leading to adverse effects in patients.¹²⁾ There is a concern that poor appetite in older adults leads to inadequate dietary intake, and malnutrition, subsequently resulting in poor mortality.³⁾

An accurate assessment of appetite is important to improve anorexia; however, food records and diet recall are difficult to implement in older patients with cognitive impairment. Recently, the Simplified Nutritional Appetite Questionnaire (SNAQ) was developed to identify poor appetite in older adults,¹³⁾ and the reliability, validity, and reproducibility of the revised version of the Japanese Elderly Questionnaire (SNAQ-JE) were demonstrated in previous studies.¹⁴⁾ Notably, SNAQ-JE has been proven to be effective for older adults with cognitive impairment,¹⁴⁾ as well as for malnutrition screening.¹⁵⁾ However, no studies have evaluated the appetite of older Japanese patients undergoing HD using the SNAQ-JE or examined the association between appetite and medication.

We hypothesized that anorexia assessed using the SNAQ-JE in older patients undergoing HD is related to the number of medicines prescribed. This study aimed to (i) evaluate the appetite of older patients undergoing HD using the SNAQ-JE and (ii) examine the association between medication and appetite.

MATERIALS AND METHODS

Patients

This cross-sectional study included patients who underwent HD at the Nagasaki Renal Center in October 2021. The inclusion criteria were age ≥65 years and dialysis duration ≥3 months. Patients who were unable to undergo the SNAQ-JE interviews were excluded.

Appetite Assessment with SNAQ-JE

The SNAQ-JE consists of four domains: appetite, feeling of fullness, taste, and mental state.^14,15) The score for each subitem ranged from 1 (very poor) to 5 (very good), and the total score ranged from 4 to 20 points.^14,15) A total score of ≤14 points was considered a risk factor for poor appetite.^14,15) In addition to the four SNAQ-JE questions, we asked about the number of meals per day to obtain details about the patients’ feeding patterns.

Data Collection

Patient characteristics, including age, sex, dialysis vintage, body mass index (BMI), blood examinations, complications, and prescribed medicines, were obtained from medical records. The geriatric nutritional risk index (GNRI) was used to evaluate the nutritional status of patients.¹⁶⁾ The GNRI was calculated based on the serum albumin level and body weight using a modified formula proposed by Yamada et al.¹⁶⁾:

GNRI = (14.89 × albumin [g/dL]) + (41.7 × [body weight/ideal body weight]; for BMI ≥22, body weight/ideal body weight = 1).

Patients on oral medicines prescribed regularly were classified into the medicinal group. The dose and number of medications were not considered.

Statistical Analyses

Categorical values are shown as numbers (%), and continuous variables are shown as mean ± standard deviation or median values with interquartile ranges. Wilcoxon rank-sum test and chi-square test were used to compare the two groups. Spearman’s rank correlation coefficient (ρ) was used to examine the association between the number of medications and the SNAQ-JE subitems. Logistic regression analysis was conducted to elucidate the association of a poor appetite with patients’ background factors, and medications. As our study aimed to identify medications affecting appetite, we excluded medications prescribed for improving or compensating for anorexia, such as gastrointestinal medicines, potassium aspartate, and vitamins. Moreover, medications prescribed for an extremely small number of patients (less than 3% in total) were also excluded. A multivariable logistic regression analysis was conducted using the parameters with p < 0.05 in the unavailable logistic regression analysis. The Steel–Dwass test was used to determine the difference in the SNAQ-JE total score among the three groups classified according to the number of sleeping medications. Statistical significance was set at p < 0.05. All statistical analyses were performed using JMP 15 software (SAS Institute Inc., Cary, NC, U.S.A.).

Ethic

This study was approved by the Institutional Review Board of the Nagasaki Renal Center (Nagasaki, Japan) (21012 and 22015) and was conducted in accordance with the 1964 Declaration of Helsinki and its subsequent amendments. SNAQ-JE was obtained after the verbal consent of each participant.

RESULTS

Patient Background

As at this study time, 371 patients underwent HD at the Nagasaki Renal Center. After excluding 138 patients, 233 patients (median age, 73.0 [69.0–80.5] years; male, 57.3%) were included in the analysis. The patient selection flow chart is shown in Fig. 1.

Fig. 1. Patients’ Flow Chart

Appetite Assessment and Medication

The average SNAQ-JE total score was 13.9 ± 2.0. Of the 233 patients, 116 and 117 were classified into the poor (SNAQ-JE total score ≤14) and good (>14) appetite groups, respectively. The nursing home residents accounted for 9.4% of the participants, with no significant difference between the two groups. However, there were significant differences in sex, dialysis vintage, C-reactive protein (CRP), intact parathyroid hormone, Kt/V, GNRI, BMI, and the number of meals per day between the two groups (Table 1).

Table 1. Summary of Patients’ Background

	Total (n = 233)	SNAQ-JE total score (≤14) (n = 116)	SNAQ-JE total score (>14) (n = 117)	p
Age (years)	73.0 (69.0–80.5)	72.0 (69.0–79.8)	73.0 (69.0–82.0)	0.36
Sex, n (%)
Male	133 (57.3)	57 (49.1)	76 (65.0)	0.01
Female	100 (42.7)	59 (50.9)	41 (35.0)
Dialysis vintage (months)	62.0 (30.0–122.0)	72.0 (33.3–145.8)	49.0 (24.0–104.0)	0.01
Dialysis time (h)	4.0 (3.5–4.0)	4.0 (3.5–4.0)	4.0 (3.5–4.0)	0.07
Nursing home residents (%)	22 (9.4)	11 (9.5)	11 (9.4)	0.98
DM history (%)	64 (27.5)	29 (25.0)	35 (29.9)	0.40
CVD history (%)	95 (40.8)	49 (42.2)	46 (17.1)	0.74
Stroke history (%)	38 (16.3)	18 (15.5)	20 (16.6)	0.88
Dementia (%)	22 (9.4)	11 (9.5)	11 (9.4)	0.98
Total protein (g/dL)	6.3 ± 0.5	6.3 ± 0.5	6.4 ± 0.5	0.41
Ch E	192 (159–231)	186 (158–231)	194 (165–234)	0.43
AST (U/L)	14 (11–17)	15 (11–19)	13 (11–16)	0.07
ALT (U/L)	9 (7–12)	9 (7–13)	9 (7–12)	0.89
Total cholesterol (mg/dL)	152.2 ± 38.2	151.1 ± 40.2	153.4 ± 36.2	0.33
Triglycerides (mg/dL)	83.0 (60.0–121.5)	76.0 (59.0–115.0)	89.0 (60.0–134.5)	0.19
cCa (mg/dL)	8.6 ± 0.7	8.7 ± 0.7	8.6 ± 0.6	0.11
BUN (mg/dL)	54.3 (45.2–65.6)	53.7 (44.1–65.0)	55.9 (46.0–66.0)	0.23
Cr (mg/dL)	8.71 ± 2.29	8.42 ± 2.17	9.00 ± 2.37	0.18
Phosphate (mg/dL)	5.1 ± 1.2	5.1 ± 1.3	5.2 ± 1.1	0.63
Potassium (mEq/L)	4.5 ± 0.7	4.3 ± 0.6	4.6 ± 0.7	0.06
CRP (mg/dL)	0.2 (0.07–0.5)	0.25 (0.08–0.71)	0.17 (0.05–0.40)	0.03
Hemoglobin (g/dL)	11.1 (10.4–11.9)	10.9 (10.2–11.9)	11.2 (10.5–12.0)	0.08
Intact-PTH (pg/mL)	74 (34–121)	62 (30–112)	80 (42–126)	0.03
nPCR (g/kg/d)	0.78 (0.68–0.91)	0.76 (0.67–0.91)	0.78 (0.69–0.91)	0.38
KT/V	1.5 (1.3–1.7)	1.5 (1.3–1.8)	1.4 (1.3–1.6)	0.046
Alb (g/dL)	3.5 (3.3–3.7)	3.5 (3.2–3.7)	3.5 (3.3–3.7)	0.53
GNRI	90.8 (86.6–95.3)	90.0 (85.4–93.8)	91.8 (87.6–96.4)	0.01
Body mass index (kg/m2)	21.0 (18.8–23.1)	20.4 (17.8–22.5)	21.4 (19.5–23.7)	0.002
SNAQ-JE total score	13.9 ± 2.0	12.5 ± 1.8	15.4 ± 0.6	<0.001
No. of meals per day	3 (3–3)	3 (2–3)	3 (3–3)	<0.001

Values are expressed as mean ± standard deviation, median (interquartile range), or number of patients (percentage). Wilcoxon rank-sum test and chi-square test were used for analysis. DM, diabetes mellitus; CVD, cardiovascular disease; ChE, cholinesterase; AST, aspartate aminotransferase; ALT, alanine aminotransferase; cCa, corrected calcium; BUN, blood urea nitrogen; Cr, creatinine; CRP, C-reactive protein; PTH, parathyroid hormone; nPCR, normalized protein catabolism rate; Alb, albumin; GNRI, geriatric nutritional risk index; SNAQ-JE, Simplified Nutritional Appetite Questionnaire for Japanese Elderly.

The average number of medications prescribed regularly was 10.0 ± 3.6. There was no significant difference in the total number of medications between the two groups (p = 0.12). However, there were significant differences in the number of the following specific medications used: antibiotics (p = 0.04), antihypertensive drugs (p = 0.03), sleeping medications (p = 0.002), and potassium aspartate (p = 0.037). There were no significant differences in the number of laxatives (p = 0.06) or vitamins (p = 0.06) between the two groups (Table 2).

Table 2. Comparison of the Number of Major Drugs between the Two Groups Classified Using the Simplified Nutritional Appetite Questionnaire for Japanese Elderly

	Total (n = 233)	SNAQ-JE total score (≤14) (n = 116)	SNAQ-JE total score (>14) (n = 117)	p
No. of total dugs	10.0 ± 3.6	10.3 ± 3.4	9.6 ± 3.6	0.12
Analgesic	0.1 ± 0.5	0.2 ± 0.6	0.1 ± 0.3	0.17
Antiarrhythmic drug	0.1 ± 0.3	0.1 ± 0.3	0.1 ± 0.3	0.97
Antibiotics	0.02 ± 0.13	0.03 ± 0.18	0	0.04
Antidiabetics drugs	0.3 ± 0.7	0.4 ± 0.7	0.3 ± 0.6	0.81
Anti-epileptic, parkinsonism, and depression medicine	0.2 ± 0.6	0.3 ± 0.6	0.2 ± 0.6	0.63
Antihypertensive drugs	1.9 ± 1.4	1.7 ± 1.4	2.1 ± 1.4	0.03
Antihyperlipidemic drugs	0.4 ± 0.5	0.4 ± 0.6	0.4 ± 0.5	0.60
Antiplatelets	0.5 ± 0.6	0.4 ± 0.6	0.5 ± 0.6	0.30
Calcimimetics	0.2 ± 0.4	0.2 ± 0.4	0.2 ± 0.4	0.23
Corticosteroid	0.1 ± 0.2	0.1 ± 0.3	0.1 ± 0.2	0.41
Gastrointestinal medicines (antiulcer,gastrointestinal prokinetic, H2 blocker, and PPI)	1.3 ± 0.9	1.3 ± 0.8	1.2 ± 0.9	0.17
H1 blocker	0.2 ± 0.5	0.2 ± 0.5	0.2 ± 0.5	0.75
Laxatives	0.9 ± 1.0	1.0 ± 1.0	0.7 ± 0.9	0.06
Potassium binder	0.1 ± 0.4	0.2 ± 0.4	0.1 ± 0.3	0.81
Phosphate binder	0.9 ± 0.8	0.9 ± 0.8	0.9 ± 0.9	0.96
Sleeping medications	0.4 ± 0.7	0.5 ± 0.8	0.3 ± 0.5	0.002
Vasopressors	0.3 ± 0.7	0.3 ± 0.7	0.3 ± 0.7	0.96
HIF-PHIs	0.3 ± 0.5	0.3 ± 0.5	0.3 ± 0.4	0.28
Iron drug	0.02 ± 0.15	0.02 ± 0.13	0.03 ± 0.16	0.67
Potassium Aspartate	0.07 ± 0.25	0.10 ± 0.31	0.03 ± 0.18	0.037
Vitamins	0.1 ± 0.3	0.1 ± 0.4	0.1 ± 0.2	0.06
Vitamin D	0.3 ± 0.5	0.3 ± 0.4	0.4 ± 0.5	0.08

Values are expressed as mean ± standard deviation. Wilcoxon rank-sum test was used for analysis. SNAQ-JE, Simplified Nutritional Appetite Questionnaire for Japanese Elderly; PPI, proton pump inhibitor; HIF-PHIs, hypoxia-inducible factor proly-4-hydroxylase inhibitors.

Particularly, there was a large difference in the number of sleeping medications between the two groups. According to Spearman’s rank correlation coefficients, the number of sleeping medications was correlated with SNAQ-JE subitems as follows: “total score,” ρ=−0.231, p < 0.001; “appetite,” ρ=−0.203, p = 0.002; “feeling of fullness,” ρ=−0.096, p = 0.14; “taste,” ρ=−0.226, p = 0.001; and “mental state,” ρ=−0.147, p = 0.03. Moreover, patients without sleeping medications had significantly higher SNAQ-JE total scores than those with more than two sleeping medications (p = 0.01) (Fig. 2).

Fig. 2. The Simplified Nutritional Appetite Questionnaire for Japanese Elderly (SNAQ-JE) Total Score Classified by the Number of Sleeping Medications

The Steel–Dwass test was used to compare the SNAQ-JE total score among the the three groups.

Univariate logistic regression analysis for poor appetite (≤14) was conducted based on patient characteristics, such as age, sex, dialysis conditions (vintage, time, and Kt/V), CRP, and the number of drugs prescribed. As mentioned in Materials and Methods, we excluded medications prescribed for improving or compensating for anorexia, such as gastrointestinal medicines, potassium asparate, and vitamins, in the logistic regression analysis. In addition, we excluded antibiotics because they were prescribed for only four patients (1.7% of total patients) in the poor appetite group. Finally, we included the numbers of total drugs, antihypertensive drugs, laxatives, and sleeping medications as the logistic regression variables. Univariate logistic regression analysis revealed that sex, dialysis vintage, CRP level, and the number of antihypertensive and sleeping medications were significantly associated with poor appetite. Next, a multivariable logistic regression analysis was conducted with the parameters that were significantly associated with poor appetite in the univariate regression analysis. We found that poor appetite was associated with sex (odds ratio (OR), 0.56; 95% confidence interval (CI), 0.32–0.98; p = 0.04), CRP (OR, 1.38; 95% CI, 0.96–1.99; p = 0.04), and the number of sleeping medications (OR, 2.08; 95% CI, 1.32–3.27; p < 0.001) (Table 3).

Table 3. Logistic Regression Models for Lower Simplified Nutritional Appetite Questionnaire for Japanese Elderly Total Scores (≤14)

	Univariable				Multivariable
	OR	95% CI		p	OR	95% CI		p
		Lower	Upper			Lower	Upper
Age per year	0.98	0.95	1.02	0.29
Male vs. female	0.52	0.31	0.88	0.021	0.56	0.32	0.98	0.04
Dialysis vintage per 1 month	1.04	1.01	1.08	0.01	1.03	0.99	1.06	0.10
Dialysis time per 1 h	1.46	0.88	2.42	0.48
Kt/V	1.70	0.79	3.66	0.17
CRP	1.38	1.02	2.10	0.04	1.38	0.96	1.99	0.04
No. of total drugs	1.06	0.98	1.14	0.14
Antihypertensive drugs	0.81	0.66	0.97	0.02	0.87	0.71	1.06	0.16
Laxatives	1.31	1.00	1.74	0.053
Sleeping medications	2.05	1.33	3.18	<0.001	2.08	1.32	3.27	<0.001

OR, odds ratio; CI, confidence interval; CRP, C-reactive protein.

DISCUSSION

This study assessed the appetite of older patients undergoing HD using the SNAQ-JE and elucidated the association of poor appetite with medication use. Among the older participantsin in this study, almost half (116 out of 233) were classified as having a poor appetite, as assessed by the SNAQ-JE (≤14); the percentage of anorexia among those over 65 years was higher in this study than in a previous study.⁴⁾ In addition, The number of some particular medications was suggested to be related to poor appetite.

Previous studies have demonstrated a strong association between high levels of inflammatory markers and anorexia.⁴⁾ Cytokines associated with inflammation are also known to inhibit appetite by affecting meal frequency.¹⁷⁾ In this study, the level of CRP, which is an inflammatory marker, was higher, and the number of meals was lower in the poor appetite group; in addition, dialysis vintage was significantly longer in the poor appetite group. These results indicate that inflammation, which is more likely to occur in patients with a longer dialysis duration, has a negative effect on appetite as shown in the literature.⁷⁾ Indeed, nutrition-related indicators, such as GNRI and BMI, were significantly lower in the poor appetite group; the finding is similar to that of a previous study.¹⁵⁾

Although the definition of polypharmacy remains unclear, it generally refers to taking 5 or more medications.¹²⁾ However, more medications are usually prescribed in patients undergoing HD; thus, 10 or more medications were defined as excessive polypharmacy in the patients undergoing HD in previous studies.^18,19) In older patients in this study, 94.0% of the patients took 5 or more drugs, and 55.8% of patients took 10 or more drugs; the average number of prescribed medications was approximately 10. This finding suggests that polypharmacy is common in older patients undergoing HD.

In this study, we examined the association between poor appetite and medication. Regarding antihypertensive drugs, unlike other medications, the number of prescriptions was higher in the group with a good appetite. As patients undergoing HD require fluid removal during dialysis, the management of blood pressure is crucial.²⁰⁾ As hypertension can cause various cardiovascular diseases, a diet therapy tool for antihypertensive has been proposed.²¹⁾ However, the concomitant use of antihypertensive drugs and diet and exercise therapy is still recommended.²²⁾ In other words, antihypertensive drugs are essential medications for comorbidities in patients undergoing HD.²³⁾ Indeed, our previous study showed that antihypertensive drugs improved the prognosis of patients on HD.²³⁾ Additionally, antihypertensive drugs can have favorable effects not only by lowering blood pressure but also by protecting the cardiovascular system, leading to prognostic benefits.^24,25) Although some antihypertensive drugs show side effects, such as dizziness and fatigue, which can lead to anorexia,²⁶⁾ our patients were taking several types of antihypertensive drugs in combination, which might have led to the suppression of side effects.²⁷⁾ Appropriate prescription of antihypertensive drugs may improve pathological conditions and appetite.

Constipation is common in the older population,²⁸⁾ and poor digestive symptoms associated with constipation can produce the feeling of fullness, thereby leading to anorexia.²⁾ There is also a concern that a vicious cycle of decreased food intake and further constipation may occur.²⁹⁾ In this study, the number of laxatives prescribed was higher in the poor appetite group. To improve constipation, methods other than laxatives, such as diet and exercise therapy, may be considered.^28,30)

As for sleeping medications, more prescriptions for sleeping medications had negative effects on appetite, taste, and mental state. Side effects of sleeping medications, such as fatigue and dry mouth, may cause a decrease in the sense of taste.³¹⁾ In addition, patients prescribed sleeping medications may be in a poor mental state and less motivated to eat. The findings suggest that sleeping medications negatively affect appetite in many ways.

Antihistamines, which are frequently prescribed to patients undergoing HD,³²⁾ have been reported to affect anorexia.³³⁾ However, in our study, there was no significant difference between the two groups, and medications that can affect appetite were suggested to be commonly prescribed medications for the elderly. The findings suggest that the aging of patients undergoing HD negatively affects drug-induced anorexia.

Multivariable logistic regression models showed that the number of sleeping medications was an important contributing factor to poor appetite. We further compared appetite among the three groups classified according to the number of sleeping medications and found that the higher the number of medications, the lower the SNAQ-JE total score. As mentioned above, this finding is because sleeping medications affect multiple factors related to eating, resulting in a decrease in the amount of food intake. Notably, insomnia is a common symptom in older patients undergoing HD³⁴⁾; therefore, the administration of several sleeping medications for the elderly requires careful consideration.³¹⁾ Particularly, unjustified prescriptions of sleeping medications should be avoided.

Based on the results of this study, the following strategies may be necessary for improving drug-induced anorexia. First, the essential drugs should be identified. Although polypharmacy is generally defined by the total number of medications taken,¹²⁾ proper prescribing for a better prognosis needs to be maintained. Instead of reducing all drugs in the same manner, screening for essential drugs may be important. Second, there is a need for improvement in lifestyle at home. As most of the participants in this study were community dwellers, not institutionalized residents, lifestyle at home can be key to managing medications. According to previous studies, increased mobility and social interaction can improve sleep disturbances.^35,36) Third, the prescriptions should be regularly evaluated. Drug-induced anorexia may be improved by withdrawal of the causative drug.³⁷⁾ Identifying unnecessary medications would also result in a reduction in medical expenditure.^10,38)

This study had several limitations. First, causal relationships could not be clarified because this was a cross-sectional study. For example, an increase in the number of antihypertensive drugs could have resulted from an increased appetite, and a larger number of laxatives could be prescribed because of a smaller amount of food intake. Second, we only investigated oral medicines prescribed regularly, and the dose and number of medications were not considered. Thus, the impact of medication on appetite might have been underestimated. Third, we could not evaluate drug–drug interactions with the multivariate logistic regression analysis.

CONCLUSION

Among older patients undergoing HD in this study, almost half had poor appetite, and more than half experienced polypharmacy. Antihypertensive drugs were suggested to positively affect appetite. Although the total number of medications was not significantly associated with poor appetite, the number of sleeping medications was a significant factor associated with poor appetite. To improve appetite and maintain the nutritional status of older patients undergoing HD, proper prescription of medications and regular review of prescriptions may be necessary.

Acknowledgments

This study was supported by the Yuumi Memorial Foundation for Home Health Care.

Conflict of Interest

The authors declare no conflict of interest.

REFERENCES

• 1) Donini LM, Poggiogalle E, Piredda M, Pinto A, Barbagallo M, Cucinotta D, Sergi G. Anorexia and eating patterns in the elderly. PLOS ONE, 8, e63539 (2013).
• 2) Wysokiński A, Sobów T, Kłoszewska I, Kostka T. Mechanisms of the anorexia of aging—a review. Age (Dordr.), 37, 81 (2015).
• 3) Bossola M, Tazza L, Giungi S, Luciani G. Anorexia in hemodialysis patients: an update. Kidney Int., 70, 417–422 (2006).
• 4) Kalantar-Zadeh K, Block G, McAllister CJ, Humphreys MH, Kopple JD. Appetite and inflammation, nutrition, anemia, and clinical outcome in hemodialysis patients. Am. J. Clin. Nutr., 80, 299–307 (2004).
• 5) Matsuzawa R, Roshanravan B. Management of physical frailty in patients requiring hemodialysis therapy. Contrib. Nephrol., 196, 101–109 (2018).
• 6) Hara H, Nakamura Y, Hatano M, Iwashita T, Shimizu T, Ogawa T, Kanozawa K, Hasegawa H. Protein energy wasting and sarcopenia in dialysis patients. Contrib. Nephrol., 196, 243–249 (2018).
• 7) Bergström J. Mechanisms of uremic suppression of appetite. J. Ren. Nutr., 9, 129–132 (1999).
• 8) Toida T, Toida R, Takahashi R, Uezono S, Komatsu H, Sato Y, Fujimoto S. Impact of polypharmacy on all-cause mortality and hospitalization in incident hemodialysis patients: a cohort study. Clin. Exp. Nephrol., 25, 1215–1223 (2021).
• 9) Battistella M, Ng P. Addressing polypharmacy in outpatient dialysis units. Clin. J. Am. Soc. Nephrol., 16, 144–146 (2021).
• 10) McIntyre C, McQuillan R, Bell C, Battistella M. Targeted deprescribing in an outpatient hemodialysis unit: a quality improvement study to decrease polypharmacy. Am. J. Kidney Dis., 70, 611–618 (2017).
• 11) Malafarina V, Uriz-Otano F, Gil-Guerrero L, Iniesta R. The anorexia of ageing: physiopathology, prevalence, associated comorbidity and mortality. A systematic review. Maturitas, 74, 293–302 (2013).
• 12) Masnoon N, Shakib S, Kalisch-Ellett L, Caughey GE. What is polypharmacy? A systematic review of definitions. BMC Geriatr., 17, 230 (2017).
• 13) Wilson MM, Thomas DR, Rubenstein LZ, Chibnall JT, Anderson S, Baxi A, Diebold MR, Morley JE. Appetite assessment: simple appetite questionnaire predicts weight loss in community-dwelling adults and nursing home residents. Am. J. Clin. Nutr., 82, 1074–1081 (2005).
• 14) Tokudome Y, Okumura K, Kumagai Y, Hirano H, Kim H, Morishita S, Watanabe Y. Development of the Japanese version of the Council on Nutrition Appetite Questionnaire and its simplified versions, and evaluation of their reliability, validity, and reproducibility. J. Epidemiol., 27, 524–530 (2017).
• 15) Shimizu A, Fujishima I, Maeda K, Murotani K, Inoue T, Ohno T, Nomoto A, Ueshima J, Ishida Y, Nagano A, Kayashita J, Mori N. Accuracy of the simplified nutritional appetite questionnaire for malnutrition and sarcopenia screening among older patients requiring rehabilitation. Nutrients, 13, 2738 (2021).
• 16) Yamada K, Furuya R, Takita T, Maruyama Y, Yamaguchi Y, Ohkawa S, Kumagai H. Simplified nutritional screening tools for patients on maintenance hemodialysis. Am. J. Clin. Nutr., 87, 106–113 (2008).
• 17) Plata-Salamán CR. Cytokines and feeding. Int. J. Obes. Relat. Metab. Disord., 25 (Suppl. 5), S48–S52 (2001).
• 18) van Oosten MJM, Logtenberg SJJ, Hemmelder MH, Leegte MJH, Bilo HJG, Jager KJ, Stel VS. Polypharmacy and medication use in patients with chronic kidney disease with and without kidney replacement therapy compared to matched controls. Clin. Kidney J., 14, 2497–2523 (2021).
• 19) St. Peter WL. Management of polypharmacy in dialysis patients. Semin. Dial., 28, 427–432 (2015).
• 20) Charra B, Laurent G, Chazot C, Calemard E, Terrat JC, Vanel T, Jean G, Ruffet M. Clinical assessment of dry weight. Nephrol. Dial. Transplant., 11 (Suppl. 2), 16–19 (1996).
• 21) Yasutake K, Sawano K, Yamaguchi S, Sakai H, Amadera H, Tsuchihashi T. Self-monitoring urinary salt excretion in adults: a novel education program for restricting dietary salt intake. Exp. Ther. Med, 2, 615–618 (2011).
• 22) Unger T, Borghi C, Charchar F, Khan NA, Poulter NR, Prabhakaran D, Ramirez A, Schlaich M, Stergiou GS, Tomaszewski M, Wainford RD, Williams B, Schutte AE. 2020 International Society of Hypertension global hypertension practice guidelines. Hypertension, 75, 1334–1357 (2020).
• 23) Kitamura M, Yamaguchi K, Ota Y, Notomi S, Komine M, Etoh R, Harada T, Funakoshi S, Mukae H, Nishino T. Prognostic impact of polypharmacy by drug essentiality in patients on hemodialysis. Sci. Rep., 11, 24238 (2021).
• 24) Tepel M, Hopfenmueller W, Scholze A, Maier A, Zidek W. Effect of amlodipine on cardiovascular events in hypertensive haemodialysis patients. Nephrol. Dial. Transplant., 23, 3605–3612 (2008).
• 25) Sarafidis PA, Persu A, Agarwal R, et al. Hypertension in dialysis patients: a consensus document by the European Renal and cardiovascular Medicine (EURECA-m) working group of the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) and the hypertension and the kidney working group of the European Society of Hypertension (ESH). Nephrol. Dial. Transplant., 32, 620–640 (2017).
• 26) Cheung BMY, Wong YL, Lau CP. Queen Mary Utilization of Antihypertensive Drugs Study: side-effects of antihypertensive drugs. J. Clin. Pharm. Ther., 30, 391–399 (2005).
• 27) Guerrero-García C, Rubio-Guerra AF. Combination therapy in the treatment of hypertension. Drugs Context, 7, 212531 (2018).
• 28) De Giorgio R, Ruggeri E, Stanghellini V, Eusebi LH, Bazzoli F, Chiarioni G. Chronic constipation in the elderly: a primer for the gastroenterologist. BMC Gastroenterol., 15, 130 (2015).
• 29) Jeong E, Kim JA, Kim BS, Lee CK, Kim M, Won CW. Functional constipation and anorexia in community-dwelling older adults: Korean frailty and aging cohort study (KFACS). Int. J. Environ. Res. Public Health, 18, 5754 (2021).
• 30) Menees SB, Guentner A, Chey SW, Saad R, Chey WD. How do U.S. gastroenterologists use over-the-counter and prescription medications in patients with gastroesophageal reflux and chronic constipation? Am. J. Gastroenterol., 110, 1516–1525 (2015).
• 31) Atkin T, Comai S, Gobbi G. Drugs for insomnia beyond benzodiazepines: pharmacology, clinical applications, and discovery. Pharmacol. Rev., 70, 197–245 (2018).
• 32) Omae K, Yoshikawa M, Sakura H, Nitta K, Ogawa T. Efficacy of antihistamines on mortality in patients receiving maintenance hemodialysis: an observational study using propensity score matching. Heart Vessels, 32, 1195–1201 (2017).
• 33) Doty RL, Shah M, Bromley SM. Drug-induced taste disorders. Drug Saf., 31, 199–215 (2008).
• 34) Cukor D, Unruh M, Mc Curry SM, Mehrotra R. The challenge of insomnia for patients on haemodialysis. Nat. Rev. Nephrol., 17, 147–148 (2021).
• 35) Benloucif S, Orbeta L, Ortiz R, Janssen I, Finkel SI, Bleiberg J, Zee PC. Morning or evening activity improves neuropsychological performance and subjective sleep quality in older adults. Sleep, 27, 1542–1551 (2004).
• 36) Naylor E, Penev PD, Orbeta L, Janssen I, Ortiz R, Colecchia EF, Keng M, Finkel S, Zee PC. Daily social and physical activity increases slow-wave sleep and daytime neuropsychological performance in the elderly. Sleep, 23, 1–9 (2000).
• 37) Suri RS, Nesrallah GE, Mainra R, Garg AC, Lindsay RM, Greene T, Daugirdas JT. Daily hemodialysis: a systematic review. Clin. J. Am. Soc. Nephrol., 1, 33–42 (2006).
• 38) Hatano M, Mizuno T, Arakawa Y, Inagaki R, Kato A, Matsuzaki H, Mizokami F, Koseki T, Yamada S. Efficacy of a pharmacist team clinical medication review in older adults: a prospective and retrospective observational study. Biol. Pharm. Bull., 45, 1166–1171 (2022).