Skip Navigation


NDT Advance Access originally published online on February 13, 2007
Nephrology Dialysis Transplantation 2007 22(6):1658-1664; doi:10.1093/ndt/gfm008
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
22/6/1658    most recent
gfm008v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Tanaka, M.
Right arrow Articles by Akizawa, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tanaka, M.
Right arrow Articles by Akizawa, T.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Hypercalcaemia is associated with poor mental health in haemodialysis patients: results from Japan DOPPS

Motoko Tanaka1, Shin Yamazaki2,3, Yasuaki Hayashino2,3, Shunichi Fukuhara2,3, Takashi Akiba4, Akira Saito5, Yasushi Asano6, Friedrich K. Port7, Kiyoshi Kurokawa8 and Tadao Akizawa9

1Department of Nephrology, Akebono clinic, Kumamoto,2Department of Epidemiology and Healthcare Research, Graduate School of Medicine, Kyoto University, Kyoto,3Institute for Health Outcomes and Evaluation Research, Kyoto,4Department of Blood Purification and Internal Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo,5Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine, Kanagawa and6Koga Red Cross Hospital, Ibaraki, Japan,7Arbor Research Collaborative for Health, MI, USA, 8The Research Center for Advanced Science and Technology, University of Tokyo, Tokyo and 9Division of Nephrology, Showa University School of Medicine, Tokyo, Japan

Correspondence and offprint requests to: Motoko Tanaka, MD, PhD, Department of Nephrology, Akebono, Clinic 5-1-1, Shirafuji, Kumamoto 561-4112, Japan. Email: tanaka{at}matusita-kai.or.jp



   Abstract
Top
 Abstract
Background
 Methods
 Results
 Discussion
 Limitation
 Conclusions
 Acknowledgements
 References
 
Background. The Dialysis Outcomes and Practice Patterns Study (DOPPS) reported high incidence of depression in haemodialysis patients. Hypercalcaemia and high parathyroid hormone (PTH) levels are aetiological factors of psychological disorders. We examined the association between mineral metabolism abnormalities and mental health in Japanese-DOPPS patients.

Methods. We used baseline data of Japan-DOPPS, Phase 1 (2755 patients, 1999–2001) and Phase 2 (2286 patients, 2002–03). The outcome variable was mental health using the mental health domain of SF-36. We examined the association between serum corrected calcium, phosphorus, calcium x phosphorus product and intact PTH concentrations, and mental health using analysis of covariance and also the associations between corrected calcium levels and current use of vitamin D and calcium-containing phosphate binder.

Results. There was a significant association between mental health and corrected calcium levels. A significantly lower mental health score was noted in patients with corrected calcium ≥ 11 mg/dl than in <8.4 (P = 0.04), ≥8.4 to <10.2 (P = 0.009) and ≥10.2 to <11 mg/dl (P = 0.003). The association was significant even after adjustment for age, sex and other confounders. However, there was no relationship between intact PTH and mental health. High-corrected calcium levels were significantly associated with the use of intravenous active vitamin D and calcium-containing phosphate binder.

Conclusions. Hypercalcaemia, but not high intact PTH, is associated with poor mental health in dialysis patients. While a cause–effect relationship between hypercalcaemia and deterioration of mental health needs further confirmation by longitudinal and prospective studies, our observational findings suggest the importance of control of serum calcium concentration in dialysis patients.

Keywords: DOPPS; haemodialysis; hypercalcaemia; hyperparathyroidism; mental health



   Background
Top
 Abstract
 Background
Methods
 Results
 Discussion
 Limitation
 Conclusions
 Acknowledgements
 References
 
Poor mental health, which includes depressive symptoms and depression, is a major public health problem and the most frequent group of psychological problems in haemodialysis patients [1–4]. Recent studies reported that among haemodialysis patients, those with depressive symptoms were at higher risk of death, higher risk of hospitalization and had higher rates of dialysis withdrawal than those without depressive symptoms [5,6].

Depression is also a major symptom in patients with primary [7] and secondary [8] hyperparathyroidism. Massry [9] indicated that the parathyroid hormone (PTH) has uraemic effects on multiple organs, which lead to the development of neurotoxicity in the central and peripheral nervous systems, in patients with end-stage renal disease (ESRD) [9]. Driessen et al. [8] reported that patients with secondary hyperparathyroidism and depression have significantly elevated serum PTH levels.

On the other hand, dialysis patients, who are often treated with active vitamin D or calcium preparations, sometimes develop hypercalcaemia [10–13]. Hypercalcaemia per se is known to result in psychoneurological symptoms such as delirium [14–16]. Although hypercalcaemia and high PTH levels are the aetiological factors for psychoneurological symptoms, the exact role of these factors in the pathogenesis of mental disorders in haemodialysis patients is not clear at present.

In the present study, we examined the associations between serum corrected calcium, phosphorus and intact PTH concentrations with mental health status in haemodialysis patients.



   Methods
Top
 Abstract
 Background
 Methods
Results
 Discussion
 Limitation
 Conclusions
 Acknowledgements
 References
 
This cross-sectional research was conducted using baseline data from the Dialysis Outcomes and Practice Patterns Study (DOPPS) [5,17], a multicentre, cohort study conducted in North America, Europe and Japan. Subjects of this study were restricted to those Japanese who lived in Japan (the data from the ‘Japan-DOPPS’). The research protocol was approved by the research committees of institutions participating in Japan-DOPPS. In Japan-DOPPS, Phase 1 was conducted between 1999 and 2001 (2755 patients) and Phase 2 between 2002 and 2003 (2286 patients) as two independent studies.

The methods used for collection of data for DOPPS have been described in detail in previous reports [5,17]. In Japan-DOPPS, dialysis centres in Japan were randomly sampled to represent the entire country and 20–40 patients randomly selected from each centre were registered with the DOPPS and followed-up for up to 3 years (Phase 1) or 2 years (Phase 2). At registration to Phase 1 and Phase 2, the study coordinators extracted the following data from the medical records as baseline characteristics: age, sex, duration of dialysis, medications used, clinical laboratory data [e.g. total calcium (mg/dl), intact PTH (pg/ml), phosphorus (mg/dl), albumin (g/dl), haemoglobin (g/dl)], comorbidity [coronary heart disease, congestive heart failure, hypertension, other cardiovascular diseases, cerebrovascular diseases, diabetes mellitus, cancer, gastrointestinal (GI) bleeding, human immunodeficiency virus (HIV) infection, lung diseases, neurological diseases, peripheral vascular diseases and recurrent cellulites] and history of parathyroidectomy (PTX).

In Phase 2 of DOPPS, to determine the factors that could contribute to hypercalcaemia in haemodialysis patients, the use of medications was investigated by asking the following questions: (i) Has the patient received intravenous vitamin D or vitamin D analogue(s) for the control of serum PTH level within one week before the date of the questionnaire? (ii) Has the patient received a calcium-containing phosphate binder within one week before the date of the questionnaire? (Table 1).


View this table:
[in this window]
[in a new window]

  		Table 1. Percentage of patients using vitamin D or calcium-containing phosphate binder categorized by corrected calcium levels

 
In addition to the medical records, in both phases of the study, the Japanese version of self-report, health-related quality of life (QOL) questionnaire (SF-36 Health Survey, hereafter SF-36) was distributed to patients for response. The SF-36 is a QOL scale that permits quantitative evaluation of subjective health status and its impact on daily function and social function. The SF-36 consists of 36 questions and when all questions are answered, a score ranging from 0 to100 is calculated for each of the eight domains (e.g. physical function, mental health, social function, role-physical, role-emotional, bodily pain, general health and vitality). A low mental health score represents poor mental health. Previous studies showed that the mental health domain of SF-36 could be used as a screening tool for depressive state [18]. Furthermore, the SF-36 has been validated not only for the Japanese general population [19], but also for dialysis patients [20]. Patients who were unable to complete the questionnaire, such as those with ostensible cognitive deficits, were excluded.

Corrected calcium concentration was calculated using the following formula: Corrected calcium = total calcium (mg/dl) + 4 – albumin (g/dl). The outcome of this research was mental health (score 0–100) as a continuous variable. Then, we examined the association between serum corrected calcium, phosphorus, intact PTH concentrations and Ca x P product and SF-36 mental health score.

Statistical methods
Data are expressed as mean ± SD unless otherwise stated. We examined the correlations between serum corrected calcium, phosphorus and intact PTH concentrations, with mental health. In this study, pooled data from Phase 1 and Phase 2 studies from Japan-DOPPS were analysed. Based on the Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines [21], serum corrected calcium, phosphorus and intact PTH concentrations were categorized by the following cut-off concentrations: serum corrected calcium: 8.4, 10.2 and 11.0 mg/dl, phosphorus: 2.5, 3.5 and 5.5 mg/dl, and intact PTH: 150, 300 and 600 pg/ml. Cut-off points of Ca x P product were defined based on 25, 50 and 75 percentiles of Ca x P product levels. First, we examined the correlations between corrected calcium, phosphorus, intact PTH concentrations and Ca x P product levels, with mental health scores from the SF-36 using analysis of variance (crude analysis). Then, analysis of covariance was used to examine the associations with adjustment variables. In this analysis, independent variables in the multivariate model were the following: corrected calcium, phosphorus, intact PTH concentrations, sex, age, duration of dialysis, serum albumin, haemoglobin, use/non-use of vitamin D preparation, use/non-use of calcium-containing phosphate binder, presence/absence of comorbidity (13 variables) and history of PTX. When the association between Ca x P product level and mental health was examined, the independent variables in the multivariate model were Ca x P product level, intact PTH concentrations, sex, age, serum albumin, haemoglobin, use/non-use of vitamin D preparation, use/non-use of calcium-containing phosphate binder, presence/absence of comorbidity (13 variables) and history of PTX. All of these variables were not independent significant factors at various calcium levels. Bonferroni's multiple comparison was performed taking the multiplicity of analysis into consideration. All tests were conducted at two-sided 5% significance level. Statistical analyses were performed using the GLM procedure in the SAS software (release 8.2, SAS Institute Inc., Cary, NC).



   Results
Top
 Abstract
 Background
 Methods
 Results
Discussion
 Limitation
 Conclusions
 Acknowledgements
 References
 
Of 5041 patients with pooled data from Phase 1 and 2 studies, 4115 responded to the mental health questions on the SF-36 and were included in the calculation of mental health scores. The baseline characteristics are listed in Table 2. The mean age of 4115 patients of Phase 1 and 2 studies was 58.2 ± 12.4 and 60.9 ± 12.9 years, respectively, and males formed 63 and 61%, respectively, of the population. The duration of dialysis was less than 6 months in 757 patients. Furthermore, 58% of the patients used vitamin D preparations and 79% used calcium-containing phosphate binders.


View this table:
[in this window]
[in a new window]

  		Table 2. Baseline characteristics

 
Figure 1 shows the results of analysis of variance (crude analysis). As shown in Figure 1A, 64.0% of patients had the target serum calcium levels, 15.4% had less, and 20.6% had more than that. Furthermore, 40.8% of patients had the target serum phosphorus levels, 6.0% had less and 53.2% had more than the target (Figure 1B). As shown in Figure 1C, 26.1% of patients had target serum intact PTH levels, 51.4% had less and 19.5% had more than the target. The mean mental health scores of the group with corrected calcium levels <8.4 mg/dl, ≥8.4 to <10.2 mg/dl, ≥10.2 to <11.0 mg/dl and ≥11.0 mg/dl were 64.1 [95% confidence interval (CI): 62.2–66.1], 64.3 (95%CI: 63.4–65.2), 65.6 (95%CI: 63.6–67.6) and 58.9 (55.9–61.9), respectively. The group with corrected calcium levels ≥11 mg/dl had a significantly lower mental health score than that with <8.4 mg/dl. The difference was 5.2 points (P = 0.04) and its effects size (ES) was 0.22. Similarly, the group with corrected calcium levels ≥11 mg/dl had a significantly lower mental health score than that with levels ≥8.4 to <10.2 mg/dl, and the group with ≥10.2 to <11.0 mg/dl. The differences were 5.4 points (P = 0.009) and 6.7 points (P = 0.003), respectively, and their ESs were 0.25 and 0.31, respectively. Even after adjustment for age, sex, serum albumin concentration, haemoglobin, serum phosphorus concentration, use/non-use of vitamin D preparation, use/non-use of calcium-containing phosphate binder, presence/absence of comorbidity (13 variables) and history of PTX, the differences between the group with corrected calcium levels ≥11.0 mg/dl and groups with ≥8.4 to <10.2 mg/dl and ≥10.2 to <11.0 mg/dl were still significant (Table 3). That is, the mental health score of patients with corrected calcium levels of ≥11.0 mg/dl was 5.0 (95% CI: 0.5–9.6) points lower than that of the group with ≥8.4 to <10.2 mg/dl and 6.6 (95% CI: 1.6–11.8) points lower than the group with ≥10.2 to <11.0 mg/dl. On the other hand, there were no associations between serum phosphorus, intact PTH and Ca x P product and mental health by crude analysis (Figure 1B–D) and multivariate analysis (data not shown).


Figure 1
View larger version (53K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 1. Association between mental health (MH) score of the SF-36 Health Survey and (A) serum corrected calcium, (B) phosphorus, (C) parathyroid hormone (PTH) concentrations and (D) Ca x P product. Data are mean ± SD. P-values represent results of univariate analyses.

 

View this table:
[in this window]
[in a new window]

  		Table 3. Differences in mental health score between serum corrected calcium levels by multiple comparison

 
Table 1 shows the distribution of patients categorized by corrected calcium levels according to the use/non-use of intravenous vitamin D or its analogue for control of PTH and calcium-containing phosphate binder within one week of the investigation date. The percentage of patients receiving intravenous active vitamin D preparations or calcium-containing phosphate binder was significantly higher in dialysis patients with hypercalcaemia than those without (P < 0.0001).



   Discussion
Top
 Abstract
 Background
 Methods
 Results
 Discussion
Limitation
 Conclusions
 Acknowledgements
 References
 
Depressive symptoms and depression are major public health problems and the most frequent psychological problems reported in haemodialysis patients [1–4], probably because these patients perceive having a terminal disease (ESRD) without the possibility of recovery, the need for frequent treatment and presence of serious ESRD-related complications. Our results showed significantly lower mean mental health scores in dialysis patients (range 58–63) compared with the mean value of healthy subjects (71.7 ± 18.8) [18]. This finding suggests that assessment of mental health state and identification of mental health-related factors in dialysis patients are quite important to improve QOL and prognosis.

Previous studies reported that changes in mineral metabolism leading to secondary hyperparathyroidism, hyperphosphataemia and hypercalcaemia were significantly associated with increased risk of mortality in haemodialysis patients [21–23]. Several studies have examined the association between mineral metabolism and renal osteodystrophy and vascular calcifications in haemodialysis patients [21,22], however, there is only little information on the association between mineral metabolism and mental health. Our study importantly reveals a small, but statistically significant association between mineral metabolism and poor mental health in dialysis patients. Dialysis patients are vulnerable to hypercalcaemia because they are often on long-term use of calcium salts for the treatment of hyperphosphataemia or on oral or intravenous active vitamin D preparations for the treatment of secondary hyperparathyroidism [10–13]. In this regard, our results showed that the percentage of patients receiving intravenous active vitamin D preparations or receiving calcium salts for hyperphosphataemia was significantly higher in dialysis patients with hypercalcaemia. Since hypercalcaemia is associated with mental health deterioration, further studies are warranted to confirm the importance of serum calcium control in dialysis patients receiving intravenous active vitamin D preparations or calcium salts.

Massry [9] indicated that PTH has uraemic effects on a variety of organs, which could lead to the development of neurotoxicity in the central and peripheral nervous systems in ESRD patients. Other researchers reported the presence of significantly elevated levels of serum PTH in patients with primary hyperparathyroidism and secondary hyperparathyroidism with depression or neurotoxicity, although these observations were made in a small-study populations [7–9,24–27]. Our study, however, showed no evidence of PTH involvement in mental health deterioration. This might be due to the small population sample (145 patients, 3.5%) of patients with severe secondary hyperparathyroidism (intact-PTH >600 pg/ml) in our study. Further research is required to draw definitive conclusions on the relationship between PTH and mental health in dialysis patients.

The K/DOQI guideline [21], detailing the goals of treatment of abnormal bone mineral metabolism in dialysis patients, was established in 2003. In Japan, only 9% of dialysis patients achieve all the goals for serum calcium, phosphorus and PTH [28]. The percentage of patients achieving the goal for serum corrected calcium is especially low (49%), and 14% of dialysis patients have hypercalcaemia (serum calcium ≥10.2 mg/dl) [28]. In our study, hypercalcaemia (serum calcium ≥10.2 mg/dl) was noted in 677 (16.5%) of the 4115 patients. Of these, 5.0% (204/4115 patients) had severe hypercalcaemia (serum corrected calcium ≥11.0 mg/dl). These findings suggest that many dialysis patients with persistent hypercalcaemia are provided with long-term treatment with active vitamin D preparations or calcium salts to reduce PTH and phosphorus levels in clinical settings. Our finding of the potential negative impact of hypercalcaemia on mental health emphasizes the importance of careful management of serum calcium, phosphorus and PTH concentrations.



   Limitation
Top
 Abstract
 Background
 Methods
 Results
 Discussion
 Limitation
Conclusions
 Acknowledgements
 References
 
This study is cross-sectional research. Our results should be viewed cautiously for three reasons. First, in this study, we used the mental health domain score of the SF-36 as mental health state, but not depressive state. Therefore, if the subjects had a low mental health score, we considered them in poor mental health but not in depression. Second, the SF-36 was developed for comparing the health status of different groups rather than individuals [29]. It is therefore difficult to discuss the impact of low mental health domain score of the SF-36 in each individual. For this reason, the clinical significance of the effect of changes in serum calcium concentration on mental health should be further examined. Third, we analysed the data using a multivariate model that included haemoglobin as a parameter of iron status and albumin as a marker of nutritional status. Previous studies showed the association between haemoglobin and depressive symptoms. Although haemoglobin concentration does not always correlate with iron status, it is one of possible surrogates for iron status. Although albumin is in fact not an appropriate marker for nutritional status, no other appropriate markers of nutritional status were available for analysis. Moreover, three PTH assay methods were available in Japanese haemodialysis centres. Although the normal ranges of serum intact PTH concentrations of these PTH assays are almost the same (10–72 pg/ml), we cannot exclude possible influence of the assay method on the reported results.



   Conclusions
Top
 Abstract
 Background
 Methods
 Results
 Discussion
 Limitation
 Conclusions
Acknowledgements
 References
 
In this study, we found a possible association between hypercalcaemia and poor mental health in dialysis patients. Our study also shows that treatment with intravenous active vitamin D preparations and/or oral calcium salts is responsible for the development of hypercalcaemia in dialysis patients. While a cause–effect relationship between hypercalcaemia and deterioration of mental health needs further confirmation through longitudinal studies as well as prospective randomized studies, our observational findings suggest the importance of control of serum calcium concentration in dialysis patients treated with active vitamin D preparations or calcium salts.



   Acknowledgements
Top
 Abstract
 Background
 Methods
 Results
 Discussion
 Limitation
 Conclusions
 Acknowledgements
References
 
The DOPPS is supported by research grants from Amgen, Inc., and Kirin Brewery Ltd, without restrictions on publications.

Conflict of interest statement. None declared.



   References
Top
 Abstract
 Background
 Methods
 Results
 Discussion
 Limitation
 Conclusions
 Acknowledgements
 References
 

  1. Kessler RC, Berglund P, Demler O, et al. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA (2003) 289:3095–3105.[Abstract/Free Full Text]
  2. Katon W, Schulberg H. Epidemiology of depression in primary care. Gen Hosp Psychiatry (1992) 14:237–247.[CrossRef][Web of Science][Medline]
  3. Finkelstein FO, Finkelstein SH. Depression in chronic dialysis patients: assessment and treatment. Nephrol Dial Transplant (2000) 15:1911–1913.[Free Full Text]
  4. Kimmel PL. Psychosocial factors in dialysis patients. Kidney Int (2001) 59:1599–1613.[CrossRef][Web of Science][Medline]
  5. Lopes AA, Albert JM, Young EW, et al. Screening for depression in hemodialysis patients: associations with diagnosis, treatment, and outcomes in the DOPPS. Kidney Int (2004) 66:2047–2053.[CrossRef][Web of Science][Medline]
  6. Fukuhara S, Green J, Albert J, et al. Symptoms of depression, prescription of benzodiazepins, and the risk of death in hemodialysis patients in Japan. Kidney Int (2006) 70:1866–1872.[CrossRef][Web of Science][Medline]
  7. Wilhelm SM, Lee J, Prinz RA. Major depression due to primary hyperparathyroidism: a frequent and correctable disorder. Am Surg (2004) 70:175–179.[Web of Science][Medline]
  8. Driessen M, Wetterling T, Wedel T, et al. Secondary hyperparathyroidism and depression in chronic renal failure. Nephron (1995) 70:334–339.[Web of Science][Medline]
  9. Massry SG. Parathyroid hormone as a uremic toxin. In: Textbook of Nephrology—Massry SG, Glassock RJ, eds. (2001) 4th. Philadelphia: Lippincott Williams & Wilkins. : 1221–1244.
  10. Gallieni M, Brancaccio D, Padovese P, et al. Low-dose intravenous calcitriol treatment of secondary hyperparathyroidism in hemodialysis patients. Italian Group for the Study of Intravenous Calcitriol. Kidney Int (1992) 42:1191–1198.[Web of Science][Medline]
  11. Dressler R, Laut J, Lynn RI, et al. Long-term high dose intravenous calcitriol therapy in end-stage renal disease patients with severe secondary hyperparathyroidism. Clin Nephrol (1995) 43:324–331.[Web of Science][Medline]
  12. Slatopolsky E, Berkoben M, Kelber J, et al. Effects of calcitriol and non-calcemic vitamin D analogs on secondary hyperparathyroidism. Kidney Int (1992) ([Suppl 38]):S43–S49.
  13. Malberti F, Corradi B, Cosci P, et al. Long-term effects of intravenous calcitriol therapy on the control of secondary hyperparathyroidism. Am J Kidney Dis (1996) 28:704–712.[Web of Science][Medline]
  14. Spivak B, Radvan M, Ohring R, et al. Primary hyperparathyroidism manifestations, diagnosis and management. Psychother Psychosom (1989) 51:38–44.[CrossRef][Web of Science][Medline]
  15. Juvarra G, Bettoni L, Olivieri MF, et al. Hypercalcemic encephalopathy in the course of hyperthyroidism. Eur Neurol (1985) 24:121–127.[Web of Science][Medline]
  16. Petersen P. Psychiatric disorders in primary hyperparathyroidism. J Clin Endocrinol Metab (1968) 28:1491–1495.[Abstract/Free Full Text]
  17. Young EW, Goodkin DA, Mapes DL, et al. The Dialysis Outcomes and Practice Patterns Study (DOPPS): an international hemodialysis study. Kidney Int (2000) 57(Suppl 74):S74–S81.[CrossRef][Web of Science]
  18. Fukuhara S, Bito S, Green J, et al. Translation, adaptation, and validation of the SF-36 Health Survey for use in Japan. J Clin Epidemiol (1998) 51:1037–1044.[CrossRef][Web of Science][Medline]
  19. Fukuhara S, Ware JE, Kosinski M, et al. Psychometric and clinical tests of validity of the Japanese SF-36 Health Survey. J Clin Epidemiol (1998) 51:1045–1053.[CrossRef][Web of Science][Medline]
  20. Green J, Fukuhara S, Shinzato T, et al. Translation, cultural adaptation, and initial reliability and multitrait testing of the Kidney Disease Quality of Life instrument for use in Japan. Qual Life Res (2001) 10:93–100.[CrossRef][Web of Science][Medline]
  21. National Kidney Foundation. K/DOQI Clinical Guideline for Bone Metabolism and Disease in chronic kidney disease. Am J Kidney Dis (2003) 42([Suppl 3]):S1–S202.[Medline]
  22. Block G, Port FK. Calcium phosphate metabolism and cardiovascular disease in patients with chronic kidney disease. Semin Dial (2003) 16:140–147.[CrossRef][Web of Science][Medline]
  23. Young EW, Albert JM, Satayathum S, et al. Predictors and consequences of altered mineral metabolism: the Dialysis Outcomes and Practice Patterns Study. Kidney Int (2005) 67:1179–1187.[CrossRef][Web of Science][Medline]
  24. Cooper JD, Lazarowitz VC, Arieff AI. Neurodiagnostic abnormalities in patients with acute renal failure: Evidence for neurotoxicity of parathyroid hormone. J Clin Invest (1978) 61:1448–1455.[Web of Science][Medline]
  25. Goldstein DA, Feinstein EI, Chui LA, et al. The relationship between the abnormalities in electroencephalogram and blood levels of parathyroid hormone in dialysis patients. J Clin Endocrinol Metab (1980) 51:130–134.[Abstract/Free Full Text]
  26. Guisado R, Arieff AI, Massry SG. Changes in the electroencephalogram in acute uremia. J Clin Invest (1975) 55:738–745.[Web of Science][Medline]
  27. Cogan MG, Covey CM, Arieff AI, et al. Central nervous system manifestations of hyperparathyroidism. Am J Med (1978) 65:963–970.[CrossRef][Web of Science][Medline]
  28. Yokoyama K, Katoh N, Kubo H, et al. Clinical significance of the K/DOQI bone guidelines in Japan. Am J Kidney Dis (2004) 44:383–384.[CrossRef][Web of Science][Medline]
  29. Ware JE, Snow KK, Kosinski M, et al. SF-36 Health Survey manual & interpretation guide (1993) Boston: New England Medical Center.
Received for publication: 25. 8.06
Accepted in revised form: 4. 1.07


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 CJASNHome page
B. M.R. Spiegel, G. Melmed, S. Robbins, and E. Esrailian
Biomarkers and Health-Related Quality of Life in End-Stage Renal Disease: A Systematic Review
Clin. J. Am. Soc. Nephrol., November 1, 2008; 3(6): 1759 - 1768.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
22/6/1658    most recent
gfm008v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Tanaka, M.
Right arrow Articles by Akizawa, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tanaka, M.
Right arrow Articles by Akizawa, T.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?