Year : 2008 | Volume
: 19 | Issue : 1 | Page : 62--66
Inflammation and Pruritus in Hemodialysis Patients
E Razeghi, S Tavakolizadeh, F Ahmadi
Department of Internal Medicine and Nephrology, Sina Hospital, Medical Sciences/University of Tehran, Tehran, Iran
Department of Internal Medicine and Nephrology, Sina Hospital, Imam Khomeini St., Tehran
Pruritus is a common problem in dialysis patients. The aim of this study was to determine the cause(s) of pruritus and its relationship with inflammatory proteins. In a cross sectional study, all patients on hemodialysis at the Emam Khomaine and Sina Hospital, Tehran, Iran who did not have any pruritus-producing skin lesions were studied. They were questioned about the occurrence of pruritus during the preceding two weeks. Variables including inflammatory proteins (C-reactive protein, albumin, ferritin, transferrin, fibrinogen), hemoglobin, red blood cell indices, iron, iron binding capacity, transferring saturation, urea, creatinine, calcium, phosphorus, calcium x phosphorus product, alkaline phosphatase and parathormone were determined. Data were analyzed using Anova or Chi-square tests for evaluation of difference between variables. Of the 164 patients studied, 80 (49%) had pruritus. Of these, 45 subjects (23.8%) had severe and 35 (21.3%) mild to moderate pruritus. There were no significant differences between groups with or without pruritus for age, sex, duration on dialysis, dialysis adequacy, cause of renal failure and erythropoetin usage. Mean CRP was 16.6 mg/L; 58.5% of the patients had CRP > 10 mg/L. There was no significant correlation between CRP levels and presence or severity of pruritus. Also, none of the other inflammatory proteins revealed any significant differences. Among the other parameters, only the mean MCV levels were significantly different between the three groups (P < 0.05). Our study suggests that inflammatory proteins do not play any part in hemodialysis associated pruritus.
|How to cite this article:|
Razeghi E, Tavakolizadeh S, Ahmadi F. Inflammation and Pruritus in Hemodialysis Patients.Saudi J Kidney Dis Transpl 2008;19:62-66
|How to cite this URL:|
Razeghi E, Tavakolizadeh S, Ahmadi F. Inflammation and Pruritus in Hemodialysis Patients. Saudi J Kidney Dis Transpl [serial online] 2008 [cited 2019 Aug 25 ];19:62-66
Available from: http://www.sjkdt.org/text.asp?2008/19/1/62/37435
Uremic pruritus is a common disabling problem in patients on hemodialysis (HD), and its prevalence has been reported to be between 30 and 90% in different studies. It is often disseminated and could be disabling and persistent. Although a variety of factors have been suggested for its etiology and pathogenesis, including hyperparathyroidism,  hyperphosphatemia and increased accumulation of calcium and phosphates in skin,  elevated serum level of histamine and skin mast cells  and elevated opioid receptors,  none of the studies have confirmed the role of these factors as major and universal causes of pruritus in these patients. ,,
The recent increasing evidence on the role of inflammation and pro-inflammatory factors in the occurrence of pruritus, indicate that uremic pruritus may be a systemic phenomenon due to dysfunctional regulation of immunologic parameters. ,,, Between 30 and 60% of patients with end-stage renal disease (ESRD) have inflammatory status of varied etiology, and the C-reactive protein (CRP) is used as the best marker to indicate the presence of inflammation. 
In the context of relation between pruritus and inflammatory proteins, few studies have been performed.  The objective of this study was to evaluate the prevalence of pruritus and its association with acute phase proteins, especially CRP, in patients on HD.
Materials and Methods
This cross sectional study was conducted on 164 patients with chronic renal failure undergoing regular HD three times a week in the HD units at the Imam Khomeini and Sina hospitals, Tehran, Iran. Patients with skin lesions known to cause pruritus (e.g., eczema and psoriasis) as well as elderly patients (> 70 years) were excluded from the study. The questionnaire, which was designed by the physician, was completed through interview with the patients before the mid-week HD session. Patients were considered to have pruritus if they had at least three episodes of itching, lasting several minutes, severe enough to catch the patients' attention. The intensity of pruritus was ranked based on the response to the following questions: (a) intensity (mild, moderate, severe); (b) episodes of itching (rarely, sometimes, often or always); (c) sleep disturbance or dysfunction of activity (itching without sleep disturbance and dysfunction of activity, itching with sleep disturbance and dysfunction of activity); (d) taking antipruritus medication (itching without requirement for antipruritus medication and/or taking medication sometimes, itching present despite taking regular medication). Patients were classified into three overall categories based on above grading (patients without pruritus, those with mild to moderate pruritus, and patients with severe pruritus). Patients were considered as having severe pruritus if their itching was disseminated and they had one the following characteristics: (a) severe intensity; (b) almost always present; (c) associated with sleep disturbance or dysfunction of activity; (d) taking antipruritus medication regularly. Demographic characteristics of the patients, such as age and sex were evaluated. Clinical parameters including type of renal disease and use of erythropoietin, laboratory parameters including inflammatory proteins (CRP, ferritin, albumin, transferrin), and hematological parameters (hemoglobin, iron, total iron binding capacity (TIBC), percent of transferrin saturation and erythrocyte indices) parathyroid hormone (iPTH), calcium, phosphate, calcium and phosphate product (Ca × P), alkaline phosphatase, and creatinine before the HD session were examined as well. The quality of dialysis was assessed during the study period by calculating Kt/V for all the patients. The high sensitive enzyme-linked immunosorbent assay (ELISA) was used to measure CRP and its normal limit was considered less than 10 mg/L.
The analysis of data was preformed using SPSS for windows 11.5 version; the parametric variables were compared by mean values + standard deviations (SDs) and median. For the analysis of parametric and categorical variables, we used the one- way analysis of variance (ANOVA) following post Hoc Scheffe test, and Chi square test, respectively. For comparing the parametric variables with and without normal distribution, the mean and median were used, respectively.
Of the 164 patients, 80 patients (49%) had pruritus of whom, 45 (27.6%) had severe pruritus and 35 (21.3%) had mild to moderate pruritus. The remaining 84 cases (51%) had never suffered from pruritus. The characteristics of the study patients are shown in [Table 1].
The average CRP of all patients was 16.6 + 20 mg/L and overall, 41.5% of the patients had CRP > 10 mg/L. The average CRP in the group with severe pruritus was 23.4 + 18.5 mg/L and in the group with mild to moderate pruritus was 21.2 + 17.8 mg/L. In patients without pruritus the mean CRP was 18.1 + 15 mg/L. However, there was no significant difference between the groups at the level of 95% confidence interval (p = 0.6). Comparing the mean of other inflammatory proteins (ferritin, fibrinogen, transferrin and albumin), no significant differences were observed between the categories [Table 2]. There was no correlation between the intensity of pruritus and non-inflammatory laboratory parameters (PTH, calcium, phosphate, calcium × phosphate, alkaline phosphatase, iron, TIBC, percent of transferring saturation, MCH, MCHC and creatinine).
However, the average MCV was significantly different between the three groups; the values were 86.9 + 8.4, 88.4 + 7.60 and 90.4 + 6.3 among patients with severe pruritus, mild to moderate pruritus and lack of pruritus, respectively (p = 0.037) at the level of 95% CI The underlying variables (e.g., age, sex, cause of renal failure, duration on HD, Kt/V and use of erythropoietin) had no significant difference between the three groups. Separately, all the inflammatory and non-inflammatory parameters were compared between categories of pruritus based on (a) intensity, (b) frequency of pruritus, (c) sleep disturbance and dysfunction of activity, and (d) use of antipruritus agents. Only the average MCV and regular usage of antipruritus medication was significantly differrent in patients with pruritus in comparison to those without pruritus (P = 0.011 and P = 0.05, respectively).
Our study on 164 HD patients showed that almost half of the patients (49%) had pruritus, and its prevalence was lower than the rate reported in studies published over the last three decades; however, it was higher than the rate of 22% reported in a recent study in Germany.  We found no correlation between pruritus and underlying variables such as age, sex, duration on HD and type of renal disease, similar to the findings of other authors. In our patients, 41.5% had CRP > 10 mg/L, which is considered to be within the inflammatory range. In previous studies, its frequency was between 30 and 60%.  There was no statistically significant correlation between the three major categories and the mean and median of CRP, fibrinogen, transferrin, ferritin and albumin, although in a recent study, the patients with more intense pruritus had higher mean of ferritin and lesser mean of albumin and transferrin.  However, the CRP levels were not significantly different between groups with or without pruritus. Since CRP shows more specific and early reaction in comparison with other inflammatory proteins, it seems that the findings of this study were due to non-inflammatory causes.
In the current study, we did not notice any statistically significant relationship between pruritus and non-inflammatory laboratory parameters, such as iPTH, calcium, phosphate, calcium ×phosphate, hemoglobin, serum iron, TIBC, percent of transferrin saturation, consistent with other studies. ,,,
Of the hematologic parameters, only MCV levels were lower in patients with pruritus. Interpretation of iron status is a difficult issue in HD patients. Some patients have functional deficiency of iron and diagnosis of this condition is impossible using above parameters. , Also, the difference in MCV was not statistically significant within groups (results of post Hoc test). It is deemed that this is an accidental finding, because MCV can be influenced by other factors. However, to our knowledge, the role of functional deficiency of iron in uremic pruritus has not been studied and hence, further investigations are required.  We also studied the reported effect of erythropoietin on uremic pruritus and found no significant difference between use of erythropoietin and three categories.
In conclusion, our study indicates that there is no statistically significant correlation between pruritus and CRP or other inflammatory serum proteins, and CRP cannot be applied as a reliable and good indicator to classify the uremic pruritus patients and improve their management. Since CRP is a nonspecific and universal marker for systemic inflammation,  it is suggested that other specific marker(s) involved in inflammatory processes of uremic pruritus, should be used to assess the role of inflammation in uremic pruritus.
The authors wish to convey their thanks to Dr. Shekarpour, Dr. Heydari and Dr. Emamzadeh as well as the staff of the hemodialysis units of the Sina and Imam Khomeini Hospitals.
|1||Mettang T, Pauli Magnus C, Alsher DM. Uraemic pruritus: New perspectives and insights from recent trials. Nephrol Dial Transplant 2002;17(9):1558-63.|
|2||Hampers CL, Katz AI, Wilson RE, Merrill JP. Disappearance of Uremic Pruritus After subtotal parathyroidectomy. N Engl J Med 1968;279(13):695-7.|
|3||Blachley JD, Blankenship DM, Menter A, Parker TF 3rd, Knochel JP. Uremic Puritus, skin divalent ion content & response to UVB phototherapy. Am J Kidney Dis 1985;5(5):237-41.|
|4||Mettang T, Fritz P, Weber J. Uremic pruritus in patient on hemodialysis or CAPD, The role of plasma histamine and skin mast cell. Clin Nephrol 1990;34 (3):136-41.|
|5||Peer G, Kivity S, Agami O, et al. Randomised crossover trial of naltrexone in uraemic pruritus. Lancet 1996;348 (9041):1552-4|
|6||Pauli-Magnus C, Mikus G, Alscher DM, et al. Naltroxon dose not relieve uremic pruritus result of a randomized plalebocontrolled cross over study. J Am SOC Nephrol 2000;11(3):514-9.|
|7||Cho YL, Liu HN, Huang TP, Tarng DC. Uremic pruritus: Roles of parathyroid hormone and substance P. J Am Acad Dermatol 1997;36(4):538-43.|
|8||Francos GC, Kanh YC, Gitten SD, et al. Elevated histamine in chronic uremia. Int J Dermatol 1991;30(12):884-9.|
|9||Virga G, Visentin I, La Milia V, Bonadonna A. Inflammation and pruritus in hemodialysis patient. Nephrol Dial Transplant 2002;17(12):2164-9.|
|10||Kimmel M, Alsher DM, Dunst R, et al. The role of micro-inflammation on the pathogenesis of uremic pruritus in hemodialysis patient. Nephrol Dial Transplant 2006;21(3):749-55.|
|11||Garssen J, Vandebriel RJ, De Gruijl FR, et al. UVB exposure induced systemic modulation of TH1 and TH2 mediated immune responses. Immunology 1999;97 (3):506-14.|
|12||Amore A, Coppo R. Immunological basis of inflammation in dialysis. Nephrol Dial Transplant 2002;17(Suppl 8):16-24.|
|13||Eschbach JW, Cook JD, Scribner BH, Finch CA. Iron Balance in hemodialysis patient. Ann Intern Med 1977;87(6):710-3.|
|14||Macdougall IC. What is the most appropriate strategy to monitor functional iron deficiency in the dialyzed patient on rhEPO therapy? Nephrol Dial Transplant 1998;13(4):847-9.|