Background

Improvement in the quality of life (QOL) of maintenance hemodialysis (MHD) patients is important because poor QOL correlates with mortality and poor adherence to hemodialysis [1,2,3]. In particular, nighttime waking, declining behavioral desire, and mental instability are reported as representative poor QOL in MHD patients [1,2,3]. As a cause of these, uremic toxin such as creatinine, inflammatory substances such as C-reactive protein (CRP) and interleukin-6 (IL-6), anemia, and intact parathyroid hormone (iPTH) have been reported [1,2,3], but the cause is still unknown.

The effects of lower urinary tract symptoms (LUTS), such as nocturia, urinary urgency, frequency, and incontinence, or dysuria attributable to overactive bladder (OAB) and benign prostatic hypertrophy (BPH), can also cause nighttime waking, declining behavioral desire, and mental instability [4, 5]. The symptoms of OAB and BPH are frequently experienced by the elderly [4, 5], and OAB and BPH can be estimated with validated disease-specific questionnaires [6,7,8,9,10]. The effect of LUTS on QOL can also be evaluated by a validated questionnaire [11,12,13]. With aging, and as the duration of their dependence on dialysis becomes longer, MHD patients experience decreased urine volume and lose the need to urinate [14, 15]. There is a possibility that LUTS as QOL disease exists in MHD patients, but there are no reports on LUTS and their effects on QOL in MHD patients. We report an observational study that used validated questionnaires to evaluate LUTS in a group of MHD patients.

Methods

This study was approved by the Ethics Committee of Nankai Medical Center (No. NH-H25-002) and was performed following the ethical guidelines of the Declaration of Helsinki. All patients gave their written informed consent before enrolling in the study. Informed consent has been obtained from the subjects (or their guardians). Eligible patients were ≥ 40 years of age [4, 5], were receiving MHD three times a week at the Nankai Medical Center, were in stable condition, and were able to agree in writing to participate in this study and to complete the questionnaires. Patients with a history of OAB or BPH treatment, kidney transplantation, prostate or bladder cancer, or psychiatric disorder, or a prostate-specific antigen (PSA) level > 4.0 ng/mL, were excluded. Validated Japanese versions of the Overactive Bladder Symptom Score (OABSS) and International Prostate Symptom Score (IPSS) disease-specific, self-administered questionnaires were used to evaluate OAB and BPH [6,7,8,9,10]. The OABSS symptom assessment questionnaire consists of four questions. The possible score ranges from 0 to 15, with higher scores indicating higher symptom severity [6,7,8]. IPSS includes seven questions. The possible score ranges from 0 to 35, with higher scores indicating higher symptom severity [6]. King’s Health Questionnaire (KHQ) is a self-administered questionnaire for evaluating the QOL of LUTS patients and has been validated in Japanese [11]. It measures the impact of urination symptoms on eight domains: general health perceptions, life, role limitations, physical/social limitations, personal relationships, emotions, sleep/energy, and incontinence severity. The responses in each domain are scored from 0 to 100, with higher scores indicating greater impairment of QOL [11,12,13]. An expert nurse and urologist instructed the patients on how to complete the questionnaires. The OABSS, IPSS, and KHQ results and patient clinical data were collected at regularly scheduled clinic visits. Blood samples were collected just before MHD for assays of hemoglobin, albumin, CRP, IL-6, creatinine, and iPTH and PSA in men. Men were evaluated with OABSS, IPSS, and KHQ. Women were evaluated with OABSS and KHQ. Those with urgency scores ≥ 2 and a total OABSS ≥ 3 were considered to have OAB [6,7,8], those with a total IPSS ≥ 8 were considered to have BPH [6], and those with OAB or BPH were included in the LUTS group. The clinical data and KHQ scores of the LUTS and non-LUTS groups were compared.

Statistical analysis

Continuous variables were compared with the Mann–Whitney U test and the Student’s t test. Univariate analysis and multivariate analysis of categorical variables were performed using single regression and stepwise multiple regression analysis. Statistical analysis was performed with EZR(Easy-R) software for medical statistics (Saitama Medical Center, Jichi Medical University), which is a graphical user interface for R commander version 1.6–3 (The R Foundation for Statistical Computing, version 2.13.0) [16]. The level of statistical significance was a p value < 0.05.

Results

This study included 68 men and 63 women with a mean age (standard deviation) of 69.1 (11.3) years and a mean hemodialysis period of 98.1 (95.4) months. Six men and three women had OAB (6.9%), 13 patients (19.1%) had BPH, and two of the six men with OAB also had BPH. There were no significant differences in the age or clinical characteristics of the 20 patients with LUTS (LUTSg) and the 111 without LUTS (non-LUTSg). The HD period was significantly shorter (p < 0.01) in LUTSg than non-LUTSg. The mean KHQ score was significantly higher (p < 0.01) in the LUTSg than in the non-LUTSg. The impact on life (p < 0.01), role limitations (p = 0.01), emotions (p < 0.01), sleep/energy (p < 0.01), and incontinence severity (p = 0.01) domain scores were higher in LUTSg, but the differences in the general health perception, physical limitation, and social limitation domain scores of the two groups were not significant (Table 1). As shown in Table 2, single regression analysis and stepwise multiple regression analysis showed that LUTS was independently associated with the total KHQ score (correlation coefficient 0.292; 95% confidence interval 20.36–89.47; p < 0.01).

Table 1 Characteristics of overall participants and of patients in the two groups being studied
Full size table
Table 2 Univariate and multivariate analysis between the total KHQ score and clinical and laboratory parameters
Full size table

Discussion

The disease-specific questionnaires confirmed that MHD patients experienced LUTS. The KHQ scores confirmed that LUTS impair the QOL in MHD patients and had a negative impact on five domains: life, role limitations, emotions, sleep/energy, and incontinence severity. The correlation coefficient 0.292 is regarded as the weak correlation between LUTS and KHQ score. This seems to be related to the fact that there were no significant differences between the two groups in the other three domains. However, the five domains are closely related to representative factors that impair the QOL of MHD patients, such as nighttime waking, deciding behavioral desire, and mental instability [1,2,3]. Therefore, LUTS should be recognized as an important QOL disease in MHD patients same as the general population.

A recent epidemiological survey found that the percentage of men and women with LUTS increased with age and was 8–12% in the 40s, 50–60% in the 60s, and 80% in the 80s [4, 5]. The frequency of LUTS in this study was approximately 15.3%, which is very low compared to the frequency of the general population. LUTS related to urine storage, such as urgency, frequency, nocturia, and urge incontinence, interfere with daily living and impair QOL [4,5,6,7,8,9,10,11,12,13].

Subjective symptoms and QOL evaluations may be more informative in routine clinical examinations than in objective examinations such as urinary flowmetry, residual urine volume, and cystometric pressure measurement for determining the impact of LUTS [4,5,6,7,8,9,10,11,12,13]. The OABSS and IPSS are determined by the responses to questionnaires validated for OAB and BPH, which are the primary diseases underlying LUTS [4,5,6,7,8,9,10,11,12,13]. KHQ is a validated questionnaire used in clinical practice to evaluate the QOL of patients with LUTS [11,12,13]. The questionnaires easily screen patients for OAB and BPH symptoms and QOL and are tools frequently used in epidemiological studies and assessments of therapeutic effect [4,5,6,7,8,9,10,11,12,13]. However, there have been no previous surveys of the incidence of LUTS in MHD patients.

Residual renal function decreases with the duration of the dialysis requirement, and MHD patients ultimately progress to oliguria, anuria, and loss of urination [15, 16]. Until now, it was not known whether LUTS occurred in MHD patients and whether it impacted QOL. This study confirmed that some MHD patients experience LUTS. Desmopressin has been reported to reduce the urine volume in patients with LUTS who did not respond to anticholinergic drugs, which were the first drug class used in LUTS therapy [17]. It is thus reasonable to assume that the urine volume produced in patients with a short dialysis duration can be linked to the development of LUTS, as seen in this study.

Approximately 45% of MHD patients experience sleep disorders, and 90% of the reported disorders are nighttime waking [1,2,3, 8,9,10,11,12,13,14,15,16,17,18,19,20]. Sleep disorders have been linked to decreased survival, perceived decrease of health-related QOL, and poor adherence to hemodialysis treatment [1,2,3, 8,9,10,11,12,13,14,15,16,17,18,19,20]. The impacts of clinical data including systemic inflammation, dialysis time, and dialysis cycle on QOL and on sleep disorders have been reported [18,19,20]. The clinical characteristics of the LUTS and non-LUTS patients in this study were not significantly different and were in line with those reported in previous studies. However, a specific questionnaire, KHQ, identified sleep disorders associated with LUTS as affecting QOL. It is very important to evaluate LUTS as a cause of sleep disorder in MHD patients and to consider whether their sleep disorders might be improved by urological interventions. QOL improvement would be expected to directly improve both adherence to treatment and the survival of MHD patients [1,2,3, 18,19,20]. MHD patients with perceived problems of daily living may experience feelings of depression, unstable behavior, or insomnia [1,2,3, 18,19,20]. It is important that hemodialysis caregivers understand that LUTS may be involved and may cause a decrease in QOL and that a urological intervention may be effective.

The study limitations included symptom diagnosis by disease-specific questionnaires. The diagnostic accuracy of LUTS would have been increased by objective examinations to estimate prostate weight, measure daily urine volume, and perform urinalysis. Moreover, this was a cross-sectional study including a small number of patients. The clinical value of the OABSS, IPSS, and KHQ assessments can be increased by further evaluation in larger studies including patients with longer dialysis histories. This study found that MHD patients experience LUTS that may impair their QOL. Validated questionnaires are convenient to screen MHD patients who experience LUTS and assess the influence of LUTS on QOL. Urological interventions may contribute to the improvement in the QOL of MHD patients who experience LUTS.

Conclusions

LUTS exists in MHD patients and impairs the QOL of them assessed with validated questionnaires. Urological interventions may contribute to improving the QOL of maintenance hemodialysis patients who experiences LUTS.