NDT Advance Access originally published online on June 27, 2007
Nephrology Dialysis Transplantation 2007 22(10):2944-2949; doi:10.1093/ndt/gfm319
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Disturbed mineral metabolism is associated with muscle and skin complaints in a prospective cohort of dialysis patients
1Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Centre, University of Amsterdam, 2Hans Mak Institute, Naarden, 3Department of Internal Medicine, St. Antonius Hospital, Nieuwegein, 4Department of Clinical Epidemiology, Leiden University Medical Centre, Leiden and 5Department of Nephrology, Academic Medical Centre, University of Amsterdam, the Netherlands, 6Apperloo AJ, Bijlsma JA, Boekhout M, Boer WH, Boog PJM van der, Büller HR, Buren M van, Charro FTh de, Doorenbos CJ, Dorpel MA van den, Es A van, Fagel WJ, Feith GW, Fijter CWH de, Frenken LAM, Grave W, Geelen JACA van, Gerlag PGG, Gorgels JPMC, Huisman RM, Jager KJ, Jie K, Koning-Mulder WAH, Koolen MI, Kremer Hovinga TK, Lavrijssen ATJ, Luik AJ, Parlevliet KJ, Raasveld MHM, Sande FM van der, Schonck MJM, Schuurmans MMJ, Siegert CEH, Stegeman CA, Stevens P, Thijssen JGP, Valentijn RM, Vastenburg GH, Verburgh CA, Verstappen VMC, Vincent HH and Vos PF
Correspondence and offprint requests to: Marlies Noordzij, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Centre, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands. Email: m.noordzij{at}amc.uva.nl
 |
Abstract |
|---|
 Top Abstract IntroductionSubjects and methodsResultsDiscussionAcknowledgementsReferences |
|---|
Background. Disturbed mineral metabolism is associated with increased morbidity and mortality, however, its influence on physical symptoms is less clear. We explored the effects of disordered plasma calcium, phosphorus, calcium-phosphorus (Ca x P) product and intact parathyroid hormone (iPTH) concentrations according to the K/DOQI guideline for bone metabolism and disease on the risk of muscle and skin complaints in dialysis patients.
Methods. As part of NECOSAD, a prospective multicentre study in the Netherlands, we included 1469 consecutive patients who started haemodialysis or peritoneal dialysis between 1997 and 2004. Muscle pain, cramps and itching (pruritus) and dry (xerosis) skin were repeatedly measured using the Kidney Disease Quality of Life-Short Form questionnaire. Odds ratios (OR) for the risk of complaints over time were calculated by generalized estimating equations (GEE) models.
Results. Mean age was 59 ± 15 years, 61% of the patients were male and 63% were on haemodialysis. At baseline >65% of the patients had muscle and skin complaints. Compared with patients who met the target, the risk of muscle pain was increased in patients with hyperphosphataemia [OR: 1.2; 95% confidence interval (CI): 1.1–1.5] iPTH concentrations below the target range were associated with lower risk of cramps (OR 0.8, 95%CI: 0.6–0.9). The risk of pruritus was increased in patients with severely elevated plasma calcium (OR 1.4; 95%CI: 1.1–1.7), phosphorus (OR 1.4; 95%CI: 1.1–1.7) and Ca x P product levels (OR 1.6; 95%CI: 1.3–2.0). Finally, increased plasma calcium concentrations were associated with an elevated risk of xerosis (OR 1.4; 95%CI: 1.1–1.9).
Conclusions. Disturbed mineral metabolism according to the K/DOQI guideline is associated with more muscle and skin complaints in dialysis patients. These findings emphasize the importance of keeping mineral metabolism in dialysis patients in tight control.
Keywords: calcium; dialysis; mineral metabolism; muscle complaints; phosphorus; skin complaints
|
Introduction |
|---|
|
TopAbstractIntroductionSubjects and methodsResultsDiscussionAcknowledgementsReferences |
|---|
In the past decade, numerous studies have shown that disturbances in mineral metabolism, such as elevated plasma calcium, phosphorus and intact parathyroid hormone (iPTH) levels increase morbidity and mortality risk in haemodialysis (HD) and peritoneal dialysis (PD) patients [1–3]. For that reason, the National Kidney Foundation-Kidney Disease Outcome Quality Initiative (NKF-K/DOQI) published their guideline for bone metabolism and disease in chronic kidney disease (CKD) in October 2003 [4]. This guideline recommends tight regulation of serum calcium, phosphorus, calcium-phosphorus product (Ca x P product) and iPTH concentrations in patients suffering from end-stage renal disease (ESRD).
In addition to morbidity and mortality, physical well-being, i.e. the presence and severity of symptoms or complaints, is an important outcome measure in the evaluation of dialysis therapy. Dialysis patients suffer from various symptoms, such as fatigue, sore muscles, upset stomach or nausea, skin complaints, sleeping problems and cramps. It has been suggested that hypercalcaemia and hyperphosphataemia could cause complaints such as itching (pruritus) and dryness (xerosis) of the skin [5]. Moreover, derangements in calcium concentration could possibly lead to muscle complaints [6].
Since the 1970s some studies explored the influence of clinical parameters on the occurrence of symptoms, especially pruritus, in dialysis patients [5,7,8]. Recently, a study of 67 prevalent HD patients showed no significant differences in calcium, phosphorus and PTH concentrations between patients with and without pruritus [7]. Also Virga et al. [8] and Dyachenko et al. [9] could not detect any significant differences between HD patients in categories of pruritus frequency and intensity. So, although associations of mineral metabolism with symptoms are described in conventional textbooks, these associations could not be confirmed in all clinical studies and remain inconclusive.
Therefore, the aim of this large prospective, observational, cohort study was to determine whether disturbances in mineral metabolism according to the K/DOQI guideline are associated with the risk of muscle and skin complaints over the first 4 years of dialysis treatment in incident HD and PD patients in the Netherlands.
|
Subjects and methods |
|---|
|
TopAbstractIntroductionSubjects and methodsResultsDiscussionAcknowledgementsReferences |
|---|
Subjects
The Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD) is a large, prospective, multicentre, cohort study in which all new ESRD patients from 38 out of 51 Dutch dialysis centres were consecutively enrolled. To be included in the study, patients had to be 18 years or older and dialysis had to be their first renal replacement therapy. In addition, patients had to have measurements of plasma calcium, phosphorus and iPTH concentrations, and information on symptoms available at 3 months after the start of dialysis (baseline). The patients in the present study started chronic HD or PD treatment in the period between 1997 and 2004. Because the major part of this study period was before publication of the K/DOQI guideline for bone metabolism and disease in CKD in 2003 [4], nephrologists probably did not aim for these targets. The resulting large variation in plasma concentrations enabled us to study the effects of the K/DOQI-targets on muscle and skin complaints over time. Before inclusion, all patients gave informed consent and all medical ethical committees of the participating centres approved of the study. Patients were followed until death, transplantation, or end of follow-up (1 March 2005).
Demographic and clinical data
Data on demography, primary kidney disease and comorbidity were collected 0–4 weeks before initiation of dialysis treatment. Data on residual renal function, biochemistry, dialysis characteristics and symptoms were repeatedly collected at fixed time points 3 and 6 months after the start of dialysis and every 6 months onward.
Comorbidity was scored according to Davies’ comorbidity index and patients were classified as having no, intermediate or severe comorbidity based on the number of comorbid conditions [10]. Primary kidney disease was classified according to the codes of the European Renal Association-Dialysis and Transplantation Association (ERA-EDTA). The nutritional status was scored on the standardized 7-point scale of the Subjective Global Assessment (SGA) which is based on the clinical judgement of the dialysis nurse [11]. We defined malnourishment as a SGA score of 5 or lower. Residual renal function was expressed as residual glomerular filtration rate (rGFR), calculated as the mean of creatinine and urea clearance adjusted for body surface area (ml/min/1.73 m2). Dialysis dose, the Kt/Vurea per week, was calculated as dialysis urea clearance, divided by urea distribution volume (V) according to Watson et al. [(12]). For HD patients, dialysis urea clearance was calculated using a second-generation Daugirdas formula [13] and for PD patients peritoneal Kt/Vurea was calculated from a 24 h dialysate collection.
Laboratory variables were evaluated in reference to the targets advised in the K/DOQI guideline for bone metabolism and disease in CKD [4]. This guideline recommends serum concentrations of corrected calcium in the range from 8.4 to 9.5 mg/dl (2.10–2.37 mmol/l) and phosphorus concentrations between 3.5 and 5.5 mg/dl (1.13 and 1.78 mmol/l). Serum Ca x P product concentration should be <55 mg2/dl2 (<4.4 mmol2/l2) and serum iPTH concentrations should range from 150 to 300 pg/ml (15.8 to 31.6 pmol/l) in patients suffering from CKD stage 5. Plasma calcium concentrations (mg/dl) were corrected for albumin concentration (g/dl) [4]. The Ca x P product in mg2/dl2 was calculated by multiplying the corrected calcium concentration by the phosphorus concentration, both in mg/dl. The iPTH measurements were based on intact molecule assays.
Symptoms
Symptoms were measured at 3 and 6 months after the start of dialysis and subsequently at 6-month intervals, as part of the Kidney Disease Quality of Life Short Form (KDQOL-SF) questionnaire. The KDQOL-SF is a validated health measure for individuals with ESRD [14,15]. This questionnaire includes a generic part which was originally developed for the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) and a disease-specific part which is targeted at quality of life concerns that are specifically relevant for patients receiving dialysis therapy. The KDQOL-SF and its validation are described in more detail in a previous publication [15].
The dimension symptoms/problems is incorporated in the disease-specific part of the KDQOL-SF and comprises soreness in muscles, chest pain, cramps, itchy skin, dry skin, shortness of breath, faintness or dizziness, lack of appetite, feeling washed out and problems with access (HD) or catheter site (PD). The patients were asked at each time point in the study whether they suffered from these complaints in the preceding 4 weeks. We studied the symptoms related to muscle and skin: soreness in muscles, cramps, itchy skin (pruritus) and dry skin (xerosis). The extent of burden for each symptom was scored on a 5-point Likert scale with the values 1 (not at all), 2 (somewhat), 3 (moderately), 4 (very much) and 5 (extremely). We classified a symptom as prevalent when a patient reported a symptom score of 2 or higher. Results from the questionnaire were not reported to the nephrologists who were treating the patients.
Statistical analysis
Plasma concentrations were divided in categories below, on, or above the recommended K/DOQI targets. In addition, we defined categories for extremely elevated plasma calcium (>10.6 mg/dl; >2.65 mmol/l), phosphorus (>7.0 mg/dl; 2.3 mmol/l), Ca x P product (>70 mg2/dl2; >5.6 mmol2/l2) and iPTH (>600 pg/ml; >63.2 pmol/l) concentrations. Patients with plasma concentrations below or above the recommended target were compared with patients who met the target (reference category).
For the longitudinal analyses, we used generalized estimating equations (GEE) analyses to analyse risk of symptoms over the first 4 years after the start of dialysis. This method takes into account the correlation between repeated measurements within the same patient. All available time points in the first 4 years after dialysis initiation, i.e. 3, 6, 12, 18, 24, 30, 36, 42 and 48 months after the start of dialysis, were included in the analyses. Adjustments were made for a number of possible confounding effects selected from the available literature. These included the presence of muscle- or skin complaints, age, Davies’ comorbidity score, primary kidney disease and SGA as recorded at baseline. Moreover, we adjusted for plasma calcium, phosphorus, iPTH, albumin level, Kt/Vurea and haemoglobin level as repeatedly measured variables. In the analyses of Ca x P product, we used a similar model without adjustments for calcium and phosphorus.
All statistical analyses were performed using SAS statistical software, version 9.1 (SAS Institute; Cary, NC, USA).
|
Results |
|---|
|
TopAbstractIntroductionSubjects and methodsResultsDiscussionAcknowledgementsReferences |
|---|
Description
From a total of 1997 patients who started chronic HD or PD treatment in the period between 1997 and 2004, we excluded 210 patients because of missing data on mineral metabolism at 3 months after the start of dialysis (baseline visit). Another 318 patients were excluded because information on symptoms was unavailable at baseline. In most cases, this was due to the refusal of patients to participate in the part of the study regarding Health Related Quality Of Life, in which they had to complete the KDQOL-SF questionnaire. Excluded patients had a statistically significant lower rGFR and glomerulonephritis was less frequently the primary kidney disease compared with included patients. Other baseline characteristics were not different between included and excluded patients.
The total of 1469 patients who were included had a mean age of 59 years, 61% were men and 63% were treated with HD. Baseline characteristics of the patients are listed in Table 1.
|
Symptoms at baseline
At baseline, a vast majority of patients suffered from muscle pain (68%), cramps (67%), pruritus (68%) and xerosis (67%). HD patients had significantly more muscle pain at baseline compared with PD patients (71% vs 64%, P = 0.002). Because there were no significant differences between HD and PD patients concerning the other symptoms of interest, all analyses are presented for HD and PD patients combined.
Symptoms over time
After 4 years of follow-up time 229 HD patients and 124 PD patients were still in the study. During the study, there were 332 deaths among HD patients (n = 930) and 119 deaths among the PD patients (n = 539). Two-year patient survival was 75% in the HD group and 86% in the PD group. When we compared patients who died during follow-up with patients who survived, the prevalence of muscle pain at baseline was significantly higher in patients who died (73% vs 67%, P = 0.03). Also, the baseline prevalence of xerosis was higher in patients who died than in those who survived (71% vs 63%, P = 0.009).
In general, the extent of symptoms remained stable during the study period. Only for muscle pain, we observed that the complaints increased during the first 4 years of dialysis therapy. Three months after the start of dialysis 68% of patients were bothered by muscle pain and this increased to 81% 4 years after the initiation of dialysis treatment.
GEE models were used to calculate odds ratios (ORs) for the risk of having symptoms over time in categories as defined in the K/DOQI guideline for bone metabolism and disease in CKD and in additional categories for extremely elevated plasma concentrations. K/DOQI target ranges were used as reference categories.
In patients with moderately elevated plasma phosphorus levels, we found a 20% increased risk of muscle pain [OR: 1.2; 95% confidence interval (CI): 1.1–1.5] when compared with patients who met the K/DOQI target. Moreover, low calcium concentrations were associated with a lower risk of muscle pain (OR: 0.6; 95% CI 0.3–0.9).
The risk of having cramps was increased with 20% in patients with severely elevated plasma phosphorus concentrations (OR 1.2, 95% CI: 1.0–1.5). A plasma iPTH concentration below the advised target was associated with a lower risk of cramps (OR 0.8, 95% CI: 0.6–0.9).
The risk of pruritus was elevated in patients who had elevated plasma calcium, phosphorus and Ca x P product concentrations compared with patients who met the targets. These risks became higher as the plasma concentrations were higher.
Finally, both moderately and severely elevated plasma calcium concentrations were associated with an increased risk of xerosis (OR 1.3, 95% CI: 1.0–1.6 and OR: 1.4; 95% CI: 1.1–1.9, respectively). Adjusted ORs are listed in Tables 2 and 3. As an example to visualize the changes over time, proportions of patients with muscle pain, cramps and pruritus in categories of time updated phosphorus concentrations are depicted in Figure 1A, B and C.
|
|
|
In an additional analysis, we subsequently studied whether a decrease in plasma calcium and phosphorus concentrations was associated with decreased symptom burden. We selected patients who reported to suffer from muscle pain at baseline, and divided these patients into a subgroup that still had muscle pain 1 year later (n = 903) and a subgroup that did not have muscle pain anymore after 1 year of dialysis therapy (n = 90). We observed that in patients who did not have muscle pain any longer plasma phosphorus levels had significantly declined during the first year of dialysis, when compared with patients who still had muscle pain after one year (–0.47 mg/dl vs + 0.04 mg/dl, P = 0.01). Similarly, plasma phosphorus levels decreased for patients who had cramps (n = 126) or pruritus (n = 108) at baseline but not anymore 1 year later, when compared with patients who still suffered from cramps (n = 898; –0.33 mg/dl vs + 0.04 mg/dl, P = 0.04), or pruritus (n = 916; –0.37 mg/dl vs + 0.04 mg/dl, P = 0.03) 1 year later. Plasma calcium concentrations did not differ between patients with or without an improvement of muscle and skin complaints.
|
Discussion |
|---|
|
TopAbstractIntroductionSubjects and methodsResultsDiscussionAcknowledgementsReferences |
|---|
In the current study, we demonstrated that disturbances in mineral metabolism, according to the K/DOQI guideline for bone metabolism and disease in CKD, are associated with more muscle and skin complaints in dialysis patients. More than 65% of HD and PD patients were bothered by muscle pain, cramps, pruritus and xerosis. We observed that patients with plasma calcium concentrations above the advised target had an elevated risk of pruritus and xerosis, while calcium levels less than the target were associated with a lower risk of muscle pain, when compared with patients who met the target. Hyperphosphataemia was associated with a higher risk of muscle pain, cramps and pruritus. Finally, iPTH concentrations below the target range were associated with a lower risk of cramps.
This study might have some limitations. First, the presence and severity of the symptoms of the patients before they started dialysis treatment was not determined. Consequently, we could not incorporate symptom scores before initiation of dialysis treatment in our analyses and the influence of starting dialysis therapy on symptoms could not be studied. Second, biochemical measurements were not performed in a central lab, but in the participating centres separately. The iPTH measurements were performed by various first generation immunometric iPTH-assays depending on the participating centre. These methods may yield different results which will lead to more variation in the obtained concentration, probably resulting in an underestimation of the true effect. However, since we found effects of plasma iPTH levels which are in accordance with the international literature, we believe that the use of different iPTH-assays had only a minor influence on our findings. Finally, data on the prescribed phosphate-binding medication was incomplete. More than 90% of the patients were administered phosphate binders. However, the type and dosage of prescribed phosphate binders, as well as the prescription of vitamin D analogues, in our study was not known.
The percentages of patients with skin complaints, i.e. pruritus, that we observed (68% at baseline) is consistent with most sources, which report that at least half of patients undergoing dialysis complain of varying degrees of pruritus [7,8,16–18]. Also, the prevalence of cramps (67%) is in line with the literature, which indicates that cramps occur in 35–86% of HD patients (19). We could not detect any previous studies that reported prevalences of muscle pain or xerosis or studies that investigated muscle or skin complaints over time.
Several pathophysiological mechanisms underlying the studied symptoms have been suggested. Excessive dialysis ultrafiltration, intradialytic hypotension, or tissue hypoxia may lead to abnormal muscle energy metabolism. The subsequent lactic acid formation could be the cause of muscle weakness and painful muscular cramping [20]. In addition, it is known that tetany, a condition of mineral imbalance, can occur when the concentration of calcium ions in extra cellular fluids such as plasma falls below normal. Tetany results in muscle cramps [6]. We indeed observed an increased OR of 1.2 (95% CI: 0.9–1.7) for cramps in patients with too-low plasma calcium concentrations, although this association was not statistically significant, partly due to the small number of patients with hypocalcaemia.
Different hypotheses on the pathophysiology of skin complaints have been generated [7,8,21]. Multiple factors may contribute to the rough and scaly skin appearance of xerosis, including skin dehydration, reduced sebum excretion and reduced stratum corneum hydration [22]. Moreover, skin dryness is correlated with the severity of pruritus [16,22]. Many different metabolic disorders, frequently associated with uraemia, have been suggested to play a role in the development of pruritus. PTH initially was implicated as causing pruritus [5], but was subsequently found not to be involved [23,17], which is in agreement with our results. Another possible mechanism underlying skin complaints is the formation of calcium-phosphorus crystals in the skin [21]. Although some other studies could not confirm this theory [7,23], we indeed observed statistically significant associations of hypercalcaemia, hyperphosphataemia and especially elevated Ca x P product with pruritus. Also Narita et al. [18] and Pisoni et al. [24] recently identified hypercalcaemia and hyperphosphataemia as independent risk factors for the development of moderate-to-severe pruritus in HD patients.
Recent studies in dialysis patients have shown that deregulated mineral metabolism increases the risk of morbidity and mortality. In addition, we now demonstrate that plasma calcium, phosphorus and Ca x P product concentrations above the targets recommended in the K/DOQI guideline are associated with an increased risk of muscle and skin complaints. This study, therefore, emphasizes the importance of keeping mineral metabolism of dialysis patients in tight control.
|
Acknowledgements |
|---|
|
TopAbstractIntroductionSubjects and methodsResultsDiscussionAcknowledgementsReferences |
|---|
The authors wish to thank the NECOSAD trial nurses and data managers for data collection and management.
Conflict of interest statement. This study was funded by unrestricted grants from the Dutch Kidney Foundation, Genzyme and Amgen. The sponsors of the study were not involved in study design; in the collection, analysis and interpretation of data. They were also not involved in the writing of the report; and in the decision to submit the report for publication.
|
References |
|---|
|
TopAbstractIntroductionSubjects and methodsResultsDiscussionAcknowledgementsReferences |
|---|
- Block GA, Klassen PS, Lazarus JM, Ofsthun N, Lowrie EG, Chertow GM. Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol (2004) 15:2208–2218.
[Abstract/Free Full Text] - 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]
- Noordzij M, Korevaar JC, Boeschoten EW, Dekker FW, Bos WJ, Krediet RT. The K/DOQI guideline for bone metabolism and disease in CKD: association with mortality in dialysis patients. Am J Kidney Dis (2005) 46:925–932.[CrossRef][Web of Science][Medline]
- National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease. Am J Kidney Dis (2004) 42:S1–S202.
- Massry SG, Popovtzer MM, Coburn JW, Makoff DL, Maxwell MH, Kleeman CR. Intractable pruritus as a manifestation of secondary hyperparathyroidism in uremia. Disappearance of itching after subtotal parathyroidectomy. N Engl J Med (1698) 279:697–700.
- Baker SB, Worthley LI. The essentials of calcium, magnesium and phosphate metabolism: part II. Disorders. Crit Care Resusc (2002) 4:307–315.[Medline]
- Akhyani M, Ganji MR, Samadi N, Khamesan B, Daneshpazhooh M. Pruritus in hemodialysis patients. BMC Dermatol (2005) 5:7.[CrossRef][Medline]
- Virga G, Visentin I, La Milia V, Bonadonna A. Inflammation and pruritus in haemodialysis patients. Nephrol Dial Transplant (2002) 17:2164–2169.
[Abstract/Free Full Text] - Dyachenko P, Shustak A, Rozenman D. Hemodialysis-related pruritus and associated cutaneous manifestations. Int J Dermatol (2006) 45:664–667.[CrossRef][Web of Science][Medline]
- Davies SJ, Russell L, Bryan J, Phillips L, Russell GI. Comorbidity, urea kinetics, and appetite in continuous ambulatory peritoneal dialysis patients: their interrelationship and prediction of survival. Am J Kidney Dis (1995) 26:353–361.[Web of Science][Medline]
- Visser R, Dekker FW, Boeschoten EW, Stevens P, Krediet RT. Reliability of the 7-point subjective global assessment scale in assessing nutritional status of dialysis patients. Adv Perit Dial (1999) 15:222–225.[Medline]
- Watson PE, Watson ID, Batt RD. Total body water volumes for adult males and females estimated from simple anthropometric measurements. Am J Clin Nutr (1980) 33:27–39.
[Abstract/Free Full Text] - Daugirdas JT. Second generation logarithmic estimates of single-pool variable volume Kt/V: an analysis of error. J Am Soc Nephrol (1993) 4:1205–1213.[Abstract]
- Hays RD, Kallich JD, Mapes DL, Coons SJ, Carter WB. Development of the kidney disease quality of life (KDQOL) instrument. Qual Life Res (1994) 3:329–338.[CrossRef][Web of Science][Medline]
- Korevaar JC, Merkus MP, Jansen MA, Dekker FW, Boeschoten EW, Krediet RT. Validation of the KDQOL-SF: a dialysis-targeted health measure. Qual Life Res (2002) 11:437–447.[CrossRef][Web of Science][Medline]
- Zucker I, Yosipovitch G, David M, Gafter U, Boner G. Prevalence and characterization of uremic pruritus in patients undergoing hemodialysis: uremic pruritus is still a major problem for patients with end-stage renal disease. J Am Acad Dermatol (2003) 49:842–846.[CrossRef][Web of Science][Medline]
- Duque MI, Thevarajah S, Chan YH, Tuttle AB, Freedman BI, Yosipovitch G. Uremic pruritus is associated with higher Kt/V and serum calcium concentration. Clin Nephrol (2006) 66:184–191.[Web of Science][Medline]
- Narita I, Alchi B, Omori K, et al. Etiology and prognostic significance of severe uremic pruritus in chronic hemodialysis patients. Kidney Int (2006) 69:1626–1632.[CrossRef][Web of Science][Medline]
- Chang CT, Wu CH, Yang CW, Huang JY, Wu MS. Creatine monohydrate treatment alleviates muscle cramps associated with haemodialysis. Nephrol Dial Transplant (2002) 17:1978–1981.
[Abstract/Free Full Text] - Churchill DN. Sodium and water profiling in chronic uraemia. Nephrol Dial Transplant (1996) 11(Suppl. 8):38–41.
[Abstract/Free Full Text] - Momose A, Kudo S, Sato M, et al. Calcium ions are abnormally distributed in the skin of haemodialysis patients with uraemic pruritus. Nephrol Dial Transplant (2004) 19:2061–2066.
[Abstract/Free Full Text] - Morton CA, Lafferty M, Hau C, Henderson I, Jones M, Lowe JG. Pruritus and skin hydration during dialysis. Nephrol Dial Transplant (1996) 11:2031–2036.
[Abstract/Free Full Text] - Cho YL, Liu HN, Huang TP, Tarng DC. Uremic pruritus: roles of parathyroid hormone and substance P. J Am Acad Dermatol (1997) 36:538–543.[CrossRef][Web of Science][Medline]
- Pisoni RL, Wikstrom B, Elder SJ, et al. Pruritus in haemodialysis patients: International results from the Dialysis Outcomes and Practice Patterns Study (DOPPS). Nephrol Dial Transplant (2006) 21:3495–3505.
[Abstract/Free Full Text]
Accepted in revised form: 2. 5.07
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  E. Golan, I. Haggiag, P. Os, and J. Bernheim Calcium, Parathyroid Hormone, and Vitamin D: Major Determinants of Chronic Pain in Hemodialysis Patients Clin. J. Am. Soc. Nephrol., August 1, 2009; 4(8): 1374 - 1380. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-L. Chiu, H.-Y. Chen, Y.-F. Chuang, S.-P. Hsu, C.-F. Lai, M.-F. Pai, S.-Y. Yang, and Y.-S. Peng Association of uraemic pruritus with inflammation and hepatitis infection in haemodialysis patients Nephrol. Dial. Transplant., November 1, 2008; 23(11): 3685 - 3689. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||