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NDT Advance Access originally published online on May 23, 2006
Nephrology Dialysis Transplantation 2006 21(9):2521-2528; doi:10.1093/ndt/gfl236
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Original Articles: Dialysis and Transplantation

The role of oral dryness in interdialytic weight gain by diabetic and non-diabetic haemodialysis patients

Junne-Ming Sung1, Shih-Chen Kuo3, How-Ran Guo4, Shu-Fen Chuang2, Szu-Yuan Lee5 and Jeng-Jong Huang1

1 Department of Internal Medicine and, 2 Department of Operative Dentistry, National Cheng Kung University Hospital, 3 Institute of Clinical Pharmacy and 4 Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University and 5 Department of Internal Medicine, Kuo's General Hospital, Tainan, Taiwan

Correspondence and offprint requests to: Jeng-Jong Huang, MD, Department of Internal Medicine, National Cheng Kung University Hospital, 138 Sheng-Li Rd, Tainan 70428, Taiwan, R.O.C. Email: jjhuang{at}mail.ncku.edu.tw



   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
Background. Factors influencing the percentage of daily interdialytic weight gain (IDWG%) and their interactions in haemodialysis (HD) patients have not been well-defined, especially in diabetic patients. We analysed contributing factors for the increase of IDWG%, particularly xerostomia (oral dryness), among diabetic and non-diabetic HD patients.

Methods. We collected 3 month prospective data in 184 stable HD patients (116 non-diabetic and 68 diabetic), including assessments of xerostomia by 100 mm visual analog scales (VASs), and the unstimulated whole salivary (UWS) flow rate was measured in 91 patients by a spitting method.

Results. Diabetic patients have higher IDWG% (P = 0.042) and VAS oral dryness score (P = 0.021), whereas, have lower UWS (P = 0.032). In non-diabetic patients, the VAS oral dryness score, age, Kt/V and blood urea nitrogen (BUN) level correlated independently with IDWG%. In diabetic patients, the haemoglobin A1C (HbAIC) correlated significantly with IDWG% after controlling for age, Kt/V and BUN level; however, when VAS oral dryness score was introduced into the regression model, the effect of HbAIC became marginally significant (P = 0.073) while the VAS oral dryness score became significantly correlated with IDWG%. The increases in IDWG% per unit change in VAS oral dryness score did not show significant difference between the non-diabetic and total diabetic patients; however, it was larger in patients with HbAIC ≥9%.

Conclusions. Xerostomia plays a significant role in increasing IDWG% among diabetic and non-diabetic HD patients. In diabetic patients, the increased IDWG% associated with the increasing HbA1C level is largely dependent on the severity of xerostomia, and we speculate that insulin deficiency may operate synergistically with xerostomia in increasing IDWG% in patients with HbA1C ≥9%.

Keywords: diabetes mellitus; haemodialysis; interdialytic weight gain; xerostomia



   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
While excessive percentage of daily interdialytic weight gain (IDWG%) may lead to immediate consequences such as hypertension, lung oedema, post-dialysis fatigue and intradialytic hypotension in haemodialysis (HD) patients, IDWG% has also been characterized as a measure of non-compliance and a deleterious outcome [1,2]. Recent studies have demonstrated that increased IDWG% is independently associated with a higher mortality among diabetic HD patients, but not among non-diabetic patients [2,3]. This may be explained by the fact that diabetic HD patients have a greater prevalence of cardiovascular disease and other comorbidities which may augment the risk of poor prognosis associated with increasing IDWG%. Thus, interventions to reduce IDWG% are important, especially in diabetic patients. The previously reported contributing factors of increasing IDWG% in HD patients include high salt intake, increased blood urea and angiotensin II (Ag II) levels, potassium depletion and psychological factors [4]; however, the effectiveness of interventions based on these findings is generally unsatisfactory. Therefore, it is likely that there are some other unrecognized factors affecting the compliance of fluid restriction.

Although, several studies have demonstrated that diabetic HD patients gain more IDWG% than their non-diabetic counterparts and that the IDWG% is positively correlated with the haemoglobin A1C (HbA1C) level [3,5], the underlying mechanisms are not clear. The hyperglycaemia per se is not a direct stimulus of thirst (the urge to drink) because hypertonic D-glucose infusion does not cause thirst and vasopressin release in humans [6,7]. We recently documented that xerostomia (symptoms of oral dryness) is a contributing factor of excess IDWG% in HD patients and that pharmacological manipulation (by pilocarpine) to increase unstimulated whole salivary flow rate (UWS) is effective in reducing IDWG% [8]. We also noted that diabetic HD patients with high HbA1C levels tend to have more severe xerostomia [9], thus it is conceivable to hypothesize that xerostomia contributes to the larger IDWG% in diabetic HD patients; however, this hypothesis has not been investigated in previous studies.

We conducted this prospective cohort study to determine the contributing factors, including xerostomia, associated with IDWG% and their interactions in diabetic and non-diabetic HD patients, and to delineate the underlying pathophysiological mechanisms.



   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
Patients
The study was approved by the Ethics Committees of the National Cheng Kung University and the Kuo's General Hospital in Tainan, Taiwan, and an informed consent was obtained from each patient. In this prospective study, we collected data from February to April 2005 on 202 participants recruited from a pool of 312 patients who were undergoing HD at the out-patient dialysis unit of the Kuo's General Hospital. Inclusion criteria were: age >18 years, HD three times a week for at least 6 months, daily urine amount <200 ml, stable clinical conditions including stable dry weight and haematocrit for at least 4 months and no change in HbA1C for more than 1% for at least 4 months in diabetic participants (HbA1C was routinely checked in diabetic patients every other month). Exclusion criteria were: haemodynamic instability preventing sufficient ultrafiltration, hospitalization within the preceding 4 months, dementia or terminal diseases, logistical impossibility of investigation, diagnosis of anxiety or depression, inability to stop potentially xerogenic medications (including anticholinergics, antidepressant, antipsychotics, antihistamines, antiparkinsonian agents and diuretics) at least 1 month before entering and throughout the study, and unwillingness to participate. Patients with a diabetic history of <6 months were excluded from this study. These criteria were also applied to the participants during the study period, and participants with changes in target dry weight >0.5 kg or in HbA1C >1% were excluded from the final data analysis.

Age, gender, underlying diseases, HD duration and the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor antagonists (AIIAs) were recorded. Mean values of Kt/V, normalized protein catabolic rate (nPCR), haematocrit and biochemistry data were calculated from monthly pre-dialytic measurements. The serum sodium level in diabetic patients was corrected according to the corresponding blood sugar data. Mean IDWG% was calculated from the data of each dialysis session. Scores of xerostomia, HbA1C values of diabetic participants, values of UWS and plasma levels of AgII and atrial natriuretic peptide (ANP) were determined at the end of the first month and at the end of this study, and the mean values were used for final analysis.

Determination of IDWG%
The body weight was determined using an Electronic Chair Scale (American Scale Co., New York, NY). IDWG% was calculated as the patients’ weight at the beginning (pre-weight) minus the weight after (post-weight) each dialysis session, divided by the dry weight, divided by the interdialytic period in days and expressed as the percentage of change per day (IDWG%). IDWG% was calculated on the basis of the average of all measurements over the 3 month period. All patients were routinely asked to disrobe except their underwear, and put on a clean grown and shoes before entering the dialysis unit. The participant was offered two options: to finish meal before starting dialysis or to eat meal within 1 h after starting dialysis. After choosing an option, the participant stayed with it throughout the study period, and the meal eaten after starting dialysis was weighted to guide the setting of ultrafiltration rate. The target dry weight was determined according to the standard clinical criteria and was reviewed continuously by nephrologists. We set the ultrafiltration rate according to the weight gain and corrected the post-dialysis body weight to the target dry weight in each dialysis session; the post-dialysis body weights of the participants were thus comparable with their target dry weights throughout the study.

Assessment of xerostomia and UWS
The participants were asked to come to the dialysis unit 1 h earlier than their mid-week schedules and they received the assessments. The specific xerostomic conditions were classified into the subjective and the objective measurements. Subjective symptoms of xerostomia investigated included two aspects (five items): one was the global aspect (dryness and discomfort of mouth), and the other was the functional aspect (requirement to sip water when speaking, when chewing and swallowing, and even during sleep time). To assess these subjective items, each participant marked the severity of each symptom on a 100 mm long visual analog scale (VAS) with the negative and the positive on the left and right, respectively (e.g. 100 mm = extremely dry). The items of the VAS scores have been checked for their reliability and validity [10]. These VAS questions for xerostomia were identical to those in many previous multicentre trials for radiation-induced xerostomia and Sjögren syndrome and in our previous study [8]. The objective measurement was to determine UWS before starting HD, and participants were instructed not to eat, drink, chew gum or perform oral hygiene for at least 60 min before the saliva collection. Whole saliva was collected for 10 min using a standard spitting method, and the volume was determined gravimetrically assuming a specific gravity of 1.0.

Statistical analysis
Data are reported as mean ± SD. Since the items of VAS score and UWS were measured twice, the reliability of each item was estimated by correlating corresponding values of each item obtained in the two measurements during the study period, and the validity of each VAS item was estimated by correlating each VAS response with the corresponding UWS [10]. Student's t-test and {chi}2 test were used to evaluate the statistical differences in continuous data and proportions between the two groups. The Spearman correlation coefficient was used to assess associations between the continuous variables. Clinical factors which showed a significance level of 0.15 or smaller in the univariate analyses in relation with IDWG% and the known dipsogenic factors including gender, use of ACEIs or AIIAs, blood urea nitrogen (BUN), sodium, potassium and AgII levels were put into multiple linear regressions with stepwise selections. Comparisons among the three tertiles stratified by the HbA1C level in diabetic HD patients were done by one-way analysis of variance (ANOVA), and Mann–Whitney U test and {chi}2 test were applied to evaluate the differences in continuous variables and proportions, respectively. All statistical analyses were conducted using statistical software SAS® System for Windows release 8.02 (SAS Institute Inc., Cary, NC, USA) at the two-tailed significance level of 0.05.



   Results
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 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
Demographics and patient characteristics
Initially, 202 patients were qualified to be enrolled, but 18 withdrew, including four having been hospitalized, eight having a change of dry weight >0.5 kg and six having HbA1C levels fluctuating for more than 1% during the study period. The clinical characteristics of the 184 patients (116 non-diabetic and 68 diabetic patients) are listed in Table 1. Causes of the end-stage renal disease (ESRD) in non-diabetic HD patients included chronic glomerulonephritis in 54 (46.6%), hypertension in 19 (16.4%), tubulointerstitial nephritis in 12 (10.3%), lupus nephritis in four (3.4%), adult polycystic kidney disease in three (2.6%) and unknown in 24 (20.7%). The mean diabetic history of the diabetic HD patients was 7.8 ± 4.6 years. There was no significant difference in patient demographics and most clinical data between the diabetic and non-diabetic groups (Table 1). Although diabetic HD patients had higher serum triglyceride but lower creatinine values, this is not due to the selection bias since diabetic HD patients tend to have abnormal lipid profiles and an accelerated lean body mass loss. The mean IDWG% in diabetic patients was higher than that in non-diabetic patients (P = 0.042), and the VAS scores of oral dryness, oral comfort and chewing and swallowing were significantly higher in diabetic patients, but those of sleeping and speaking were not significantly different. The measurements of UWS which were appropriate for final analyses were available in 91 participants, and the demographic and clinical data of them did not differ from those of other participants (data not shown). The reasons for the inability to measure UWS in all participants included their unwillingness or failure to come to the dialysis unit 1 h earlier before their mid-week schedules, swallowing the saliva during the measuring period and having only one measurement during the study period. Diabetic HD patients had a significantly lower mean UWS than the non-diabetic counterparts (0.16 ± 0.07 vs 0.20 ± 0.10, P = 0.032). These findings indicate that diabetic HD patients tend to gain more interdialytic weight and have more severe xerostomia (and more severe salivary gland dysfunction) than their non-diabetic counterparts.


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  		Table 1. Demographics and clinical characteristics of the HD patientsa

 
Validation of VAS scores and the relationships among xerostomia, UWS and IDWG%
All five items of the VAS questionnaire demonstrated significant reliability (R = 0.891, 0.834, 0.781, 0.752 and 0.794 for oral dryness, oral comfort, sleep, speech and chewing and swallowing, respectively, and all P ≤ 0.01). About the validity, four of the five VAS items were significantly correlated with the UWS, while the VAS sleep score showed no significant association. These data demonstrated good reliability and validity of the VAS items. Among the five items of xerostomic scores and the total xerostomic score, the VAS score of oral dryness showed the best correlation with IDWG% and objective UWS. While performing a multivariate analysis which included scores of the five VAS items and total score as the independent variables and IDWG% as the dependent variable, we found that only the VAS oral dryness score remained independently associated with IDWG% in the final models (ß = 0.047, 95% confidence intervals [CI]: 0.013–0.072, P ≤ 0.001 in the diabetic group; ß = 0.043, 95% CI: 0.011–0.079, P ≤ 0.001 in the non-diabetic group), suggesting that the VAS oral dryness score convey information beyond other scores and is a good surrogate of xerostomia in relation to IDWG%. The objective UWS was negatively and modestly correlated with IDWG% (R = –0.348, P = 0.041 in non-diabetic patients; R = –0.347, P = 0.035 in diabetic patients).

The role of xerostomia in IDWG% by diabetic and non-diabetic HD patients
In multivariate linear regression analyses of the non-diabetic and diabetic groups that excluded the VAS oral dryness score and HbA1C as predictors (Table 2, models 1 and 3), the age, Kt/V, BUN and sodium level were significantly associated with IDWG%; however, when we introduced the VAS oral dryness score or HbA1C level into the models (Table 2, models 2, 4 and 5), the serum sodium level lost its significance while the VAS oral dryness or HbA1C level became significantly correlated with IDWG%. In the diabetic group, when we further introduced the VAS dryness score into the model 5 (model 6), the HbA1C level turned out to be marginally associated with IDWG% (P = 0.071) while the VAS oral dryness score became significantly associated with the IDWG%. In summary, these results suggest that lower serum sodium, higher HbA1C and higher VAS oral dryness score have overlapping relation with IDWG%. It is reasonable to interpret these findings to mean that the high HbA1C levels and xerostomia caused large fluid intake and thus resulted in low serum sodium levels. Furthermore, high HbA1C levels and xerostomia appeared to share a common pathway leading to large IDWG%, and the positive association between IDWG% and HbA1C levels in diabetic HD patients is attributed to the effect of xerostomia. Noteworthy, the increases in IDWG% in response to per unit increase in the VAS oral dryness score after controlling for age, Kt/V and BUN level were comparable in non-diabetic and diabetic groups (ß = 0.019 vs 0.019, Table 2, models 2 and 4), indicating that although diabetic patients have more severe xerostomia, the response to per unit change of xerostomia in diabetic patients is the same as that in non-diabetic patients disregarding the HbA1C levels.


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  		Table 2. Multivariate linear regression analysis for the daily IDWG% in total population, non-diabetic and diabetic HD patientsa

 
The interaction between xerostomia and HbA1C level on IDWG% in diabetic patients by stratified analyses
We further stratified the diabetic patients into tertiles according to their glycaemic control, namely, those with HbA1C level ≤6% were considered as having good control, those with 6% < HbA1C < 9% as having intermediate control and those with HbA1C ≥ 9% as having poor control. As shown in Table 3, no significant difference was observed in the non-diabetic, total diabetic patients and the three tertiles of increasing HbA1C level in age, Kt/V or serum BUN level, which were identified to be independently correlated with the increased IDWG% in Table 2, while a significant difference was observed for the VAS oral dryness score, UWS, IDWG% and serum sodium level. The ratio of IDWG% to VAS oral dryness score (as the increase of [100 x IDWG%] per 1 mm difference in VAS oral dryness score) showed no significant difference between the non-diabetic and diabetic groups disregarding the HbA1C levels, which once again confirm that larger IDWG% in diabetic patients was generally dependent on the severity of xerostomia. However, this ratio is significantly larger in diabetic patients with poor glycaemic control while it was generally comparable in non-diabetic patients and diabetic patients with good and intermediate glycaemic control (Table 3); this suggested that there are some other factors operated together with xerostomia to cause a large IDWG% in patients with poor glycaemic control. Furthermore, a significant high proportion of patients receiving insulin injection was observed in the tertile of HbA1C ≥9%.


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  		Table 3. The impacts of xerostomia on IDWG% in non-diabetic patients and diabetic patients on HD with different levels of glycaemic controld

 
The clinical variables influencing the xerostomia in HD patients
The increased VAS oral dryness score was associated with younger age and lower serum sodium level in both non-diabetic and diabetic groups (all P < 0.05). In diabetic subjects, VAS score of oral dryness strongly correlated with the HbA1C level (R = 0.668, P ≤ 0.001). There was no other significant association between VAS oral dryness score and other clinical variables. The relationships between objective UWS and clinical variables were generally compatible with those between subjective VAS oral dryness score and clinical variables; however, there was no significant association between the UWS and age.



   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
In this study, xerostomia emerged as an independent factor associated with increased IDWG% in both the diabetic and non-diabetic groups. In addition, we demonstrated that diabetic HD patients tend to have larger IDWG% than their non-diabetic counterparts and that the increased IDWG% was correlated with the increasing HbA1C level, which were largely dependent on the severity of xerostomia. These findings provide new information for delineating the mechanisms and designing therapeutic interventions.

The major mechanism leading to excess IDWG% in HD patients is the osmoregulation pathway [11]. Osmoregulatory thirst was initially envisioned as a single-loop negative feedback system in which dehydration increases plasma osmolality (POsm) and stimulates the osmoreceptors, and thereby provides a stimulus for thirst; in contrast, water intake decreases POsm and removes the excitatory signal for thirst. However, dehydrated animals and humans have been observed to drink water rapidly but to stop after only a few minutes, well before the dilution of POsm becoming evident. This early inhibition occurred even when the ingested water was drained out through a gastric fistula [12,13], indicating a neural mechanism of drinking in which the oropharynx plays an early regulatory role. It is interesting that some studies show that infusion of osmotic active substances such as hypertonic saline, centrally or intravenously, decreases salivary secretion in experimental animals and humans [14], which suggests the presence of central ‘cross-talk’ between the osmoregulatory system and salivary flow. Recently, Brunstrom et al. [15] demonstrated that xerostomia may cause more fluid intake in healthy volunteers. The current study further demonstrated that xerostomia was an independent contributing factor for excess IDWG% in both the non-diabetic and diabetic HD patients, suggesting the involvement of xerostomia in establishing excess IDWG% in both HD patient groups. It is noteworthy that xerostomia may not be a direct dipsogenic factor (stimulus to increase fluid intake) since xerostomia induced by atropine does not usually cause thirst in humans; however, when osmoreceptors are stimulated by high POsm (and thirst is thus induced), it increases the total volume of fluid consumed [15].

We observed an interaction between the corrected serum sodium level and xerostomia in relation to the increased IDWG% (Table 2, models 1–4). Since xerostomia increases fluid intake rather than sodium, it is plausible that xerostomia causes excess fluid intake and the dilution of the serum sodium concentration. Since free water cannot be excreted in anuric HD patients, excess fluid intake causes hypo-osmolality, and the hypo-osmality state will increase salt preference (salt appetite) and sodium intake [16]. Eventually, patients not complying with salt restriction will have large IDWG% without hyponatraemia, whereas patients complying with salt restriction will have large IDWG% with hyponatraemia. This result seems to be comparable with the findings of our previous study [8], which demonstrated that the alleviation of xerostomia by pilocarpine decreases the IDWG% and also tends to increase the serum sodium level.

We also identified age, serum BUN level and HbA1C level as contributing factors of increased IDWG% (Table 2). There is some evidence showing that thirst declines as age increases [16], and this may be associated with the central dopamine level, which is reduced with age, and with the diminished function of central volume receptors [16]. Alternatively, it is possible that the less severe xerostomia in the elderly patients may also contribute to the decreased water intake since there was a significantly negative association between VAS oral dryness score and age in the current study. The association between the serum BUN level and IDWG% is also not unexpected since normal volunteers infused intravenously with a hypertonic urea solution reported thirst and had a rise in plasma vasopressin, although this osmoreceptors-stimulating effect of urea is milder than that caused by a sodium chloride solution [6]. In addition, although Kt/V was also noted to be independently associated with IDWG%, high Kt/V was the result of more intense ultrafiltration during HD sessions.

The mechanism to explain the increased water intake in diabetic HD patients has not been clearly defined before because a high glucose level per se is not an effective stimulus of osmoreceptors [5–7], and uraemia per se does not alter the sensitivity and threshold of osmoreceptors [11]. The current study may be the first to demonstrate the relations between the xerostomia and the HbA1C level in establishing large IDWG% (Table 2), and to suggest that the correlation between the increased IDWG% and elevated HbA1C level in diabetic HD patients is generally caused by their xerostomia. Since diabetes mellitus has emerged to be the leading cause of ESRD and the excess IDWG% independently increases the mortality in diabetic HD patients [2,3], our findings have an important clinical implication for the care of these patients. The stratified analyses (Table 3) showed that the increases in IDWG% associated with per unit change of VAS oral dryness score were significantly larger in diabetic HD patients with poor glycaemic control (HbA1C ≥9%), indicating that the HbA1C in the stratified analyses captured the residual confounding from the multiple linear regression analyses in this patient subgroup. While the actual mechanism is not clear, a possible explanation is the relative deficiency of insulin, because insulin promotes transport of plasma glucose into the osmoreceptor cells and may thus prevent the development of the osmotic gradient of osmoreceptor cells and the development of thirst in diabetic patients [6]. In the absence of appropriate circulating insulin, an osmotic gradient due to the elevated blood glucose concentration then stimulates osmoreceptors and thirst [7]. This interpretation is consistent with our data in Table 3, which show a significantly higher proportion of the poorly controlled diabetic patients who required insulin therapy and a high HbA1C level indicating that they were still in a relatively insulinpenia status. However, we cannot exclude the possibility of the presence of unidentified circulating solutes stimulating osmoreceptors in diabetic HD patients with poor glycaemic control [17].

The causes of xerostomia in HD patients are unknown; however, recent study [18] has demonstrated that uraemic salivary dysfunction is associated with glandular atrophy, fibrosis and accumulation of fibrillar components. The significant correlation of xerostomia and the UWS with the HbA1C level in the current study is consistent with the results of our previous study in diabetic HD patients [9] and other studies in non-dialysis diabetic patients [19,20]. Our study does not provide information on the mechanism of this correlation; however, it has been reported that the structure and function of the salivary glands were affected, and salivary secretion decreased in streptozotocin-diabetic rats [21]. Although Postorino et al. [18] have demonstrated that the impaired salivary function is not associated with autonomic dysfunction in non-diabetic HD patients, the decreased salivary secretion in diabetic humans without renal failure has been reported to be associated with the autonomic neuropathy [20]. It is possible that the salivary glands are more severely damaged by coexisting diabetes and uraemia, but a further comprehensive investigation may provide more information.

A major limitation of the current study is that we did not assess the amount of sodium intake directly, although all patients were instructed to restrict salt intake. In addition, although the measurement of UWS by a spitting method was proved to be a sensitive test for salivary function in relation to the oral dryness complaints in patients with salivary dysfunction [22] and the VAS scores of xerostomia were significantly correlated with the UWS in our patients, we found that some patients with low UWS might report low VAS oral dryness score in our study; in contrast, some patients with high UWS might report high VAS oral dryness score. These discrepancies may be due to the variation of individual perception of oral dryness and, at least in part, the changes in salivary composition [10,22]. It appears that the assessments of UWS and VAS xerostomic scores are most useful for statistical evaluation in a reasonably large sample of patients; for individuals, the greatest value of these measurements will be for repeated, longitudinal determinations [10,22]. Nevertheless, because of the observational nature of our study and the lack of sensitive and objective methods for assessing the xerostomia, further interventional trials, possibly with pilocarpine solutions or tablets, are necessary to confirm the findings of the current study.

In summary, this study demonstrated an important association between xerostomia and IDWG% in both diabetic and non-diabetic HD patients. Diabetic patients tended to have larger IDWG% and the increased IDWG% was associated with the increasing HbA1C, which were largely attributable to the xerostomia. These findings point to a new direction of research for unravelling the mechanism of establishing the large IDWG% and for designing therapeutic interventions.

Conflict of interest statement. None declared.



   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

  1. Leggat JE, Orzol SM, Hulbert-Shearon TE et al. Noncompliance in hemodialysis; predictors and survival analysis. Am J Kidney Dis 1998; 32: 139–145[Web of Science][Medline]
  2. Kimmel PL, Varela MP, Peterson RA et al. Interdialytic weight gain and survival in hemodialysis patients: effects of duration of ESRD and diabetes mellitus. Kidney Int 2000; 57: 1141–1151[CrossRef][Web of Science][Medline]
  3. Szczech LA, Reddan DN, Klassen PS et al. Interactions between dialysis-related volume exposures, nutritional surrogates and mortality among ESRD patients. Nephrol Dial Transplant 2003; 18: 1585–1591[Abstract/Free Full Text]
  4. Giovannetti S, Barsotti G, Cupisti A et al. Dipsogenic factors operating in chronic uremics on maintenance hemodialysis. Nephron 1994; 66: 413–420[Web of Science][Medline]
  5. Ifudu O, Dulin AL, Friedman EA. Interdialytic weight gain correlates with glycosylated hemoglobin in diabetic hemodialysis patients. Am J Kidney Dis 1994; 23: 686–691[Web of Science][Medline]
  6. Zerbe RL, Roberson GI. Osmoregulation of thirst and vasopressin secretion in human subjects: effect of various solutes. Am J Physiol 1983; 244: E607–E614[Medline]
  7. Thompson CJ, Davis SN, Butler PC, Charlton JA, Baylis PH. Osmoregulation of thirst and vasopressin secretion in insulin-dependent diabetes mellitus. Clin Sci 1988; 74: 599–606[Medline]
  8. Sung JM, Kuo SC, Guo HR, Chuang SF, Lee SY, Huang JJ. Decreased salivary flow rate as a dipsogenic factor in hemodialysis patients: evidence from an observational study and a pilocarpine clinical trial. J Am Soc Nephrol 2005; 16: 3418–3429[Abstract/Free Full Text]
  9. Chuang SF, Sung JM, Kuo SC, Huang JJ, Lee SY. Oral and dental manifestations in diabetic and nondiabetic uremic patients receiving hemodialysis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005; 99: 689–695[CrossRef][Web of Science][Medline]
  10. Pai S, Ghezzi EM, Ship JA, Mich AA. Development of a visual analogue scale questionnaire for subjective assessment of salivary dysfunction. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001; 91: 311–316[Web of Science][Medline]
  11. Argent NB, Burrell LM, Goodship TH, Wilkinson R, Baylis PH. Osmoregulation of thirst and vasopressin release in severe chronic renal failure. Kidney Int 1991; 39: 295–300[Web of Science][Medline]
  12. Figaro MK, Mack GW. Regulation of fluid intake in dehydrated humans: role of oropharyngeal stimulation. Am J Physiol 1997; 272: R1740–R1746[Medline]
  13. Appelgren BH, Thrasher TN, Keil LC, Ramsay DJ. Mechanism of drinking-induced inhibition of vasopressin secretion in dehydrated dogs. Am J Physiol 1991; 261: R1226–R1233[Medline]
  14. Holmes JH, Gregersen MI. Relation of the salivary flow to the thirst produced in man by intravenous infection of hypertonic salt solution. Am J Physiol 1947; 151: 252–257[Free Full Text]
  15. Brunstrom JM, Tribbeck PM, MacRae AW. The role of mouth state in the termination of drinking behavior in humans. Physiol Behav 2000; 68: 579–583[Medline]
  16. Stricker EM, Sved AF. Controls of vasopressin secretion and thirst: similarity and dissimilarity in signals. Physiol Behav 2002; 76: 423–429[CrossRef][Medline]
  17. Thompson CJ, Davis SN, Baylis PH. Effect of blood glucose concentration on osmoregulation in diabetes mellitus. Am J Physiol 1989; 256: R597–R604[Medline]
  18. Postorino M, Catalano C, Martorano C et al. Salivary and lacrimal secretion is reduced in patients with ESRD. Am J Kidney Dis 2003; 42: 722–728[CrossRef][Web of Science][Medline]
  19. Dodds MW, Dodds AP. Effects of glycemic control on saliva flow rates and protein composition in non-insulin-dependent diabetes mellitus. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997; 83: 465–470[CrossRef][Web of Science][Medline]
  20. Lamey PJ, Fisher BM, Frier BM. The effects of diabetes and autonomic neuropathy on parotid salivary flow in man. Diabet Med 1986; 3: 537–540[Web of Science][Medline]
  21. Anderson LC, Garrett JR. The effects of streptozotocin-induced diabetes on norepinephrine and cholinergic enzyme activities in rat parotid and submandibular glands. Arch Oral Biol 1994; 39: 91–97[CrossRef][Web of Science][Medline]
  22. Wang SL, Zhao ZT, Lin J, Zhu XZ, Dong H, Zang YG. Investigation of the clinical value of total saliva flow rate. Arch Oral Biol 1998; 43: 39–43[CrossRef][Web of Science][Medline]
Received for publication: 7. 2.06
Accepted in revised form: 3. 4.06


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