الفهرس 
UREMIC PRURITUSOnly 14 pages are availabe for public view
 |  | from | 32 |  |  |
| | | from | 32 | | |
Abstract
Chronic kidney disease (CKD), also known as chronic renal failure (CRF), is a progressive loss of renal function over a period of months or years. chronic kidney disease is divided into 5 stages of increasing severity. Each stage is a progression through an abnormally decreasing and deteriorating glomerular filtration rate (GFR), which is usually determined indirectly by the serum creatinine level.
End-stage renal disease (ESRD) is a relatively common disease in which nearly all patients have at least one dermatological disorder, Uremic pruritus (UP) remains a frequent and sometimes tormenting problem in patients with end-stage renal failure. Many attempts have been made to relieve patients from this bothersome symptom, with only limited success. Renal itch is a localized or generalized itch, affecting patients with chronic renal failure, where there is no primary skin disease and no systemic or psychological dysfunction that might cause pruritus. Uremic pruritus (UP) is an unpleasant sensation, rarely appearing in earlier stages of chronic kidney disease.
In some patients, UP occurs intermittently and lasts only several minutes, but other patients suffer from prolonged periods of severe pruritus, which can occur throughout the day and night. The occurrence, duration and intensity of UP can change over time and the itching is usually worst at night. The areas most commonly affected by UP are the back, limbs, chest and head, but 20-50% of patients experience generalized pruritus.
The pathophyisiology of uremic pruritus (UP) is not yet fully clarified. Several factors are proposed to play a role in the pathogenesis of UP but a specific general etiology has not been determined. Metabolic abnormalities such as secondary hyperparathyroidism, hyperphosphatemia with increased calcium phosphate deposition in the skin and increased calcium/phosphate product, histamine release by mast cells, alterations in the endogenous opioidergic system with overexpression of opioid μ-receptors and anemia (or possibly some other manifestation of erythropoietin deficiency) have been suggested to contribute to the development of UP; however, not all these findings were confirmed by subsequent studies.
Interactions between dermal mast cells (MC) and afferent C neuron terminals may play an important role in the mediation of pruritus since these structures sit very close together. The skin of chronic renal failure patients with pruritus has a greater number of mast cells. There are various substances released from mast cells including histamine, IL2, TNF-α and proteases such as tryptase.
Mettang et al. (2002) demonstrated no relationship between plasma histamine and pruritus score in patients undergoing dialysis. In addition, antihistamines are relatively ineffective in treating uraemic itch. Therefore, it was hypothesized that probably other mediators released from mast cells are responsible for CKD-associated pruritus; tryptases being one of these mediators.
Tryptase, a major constituent of mast cell secretory granules, has emerged recently as the most specific marker in vivo of mast cell activation in humans. Tryptase is a trypsin like serine protease that hydrolyzes peptide bonds on the C-terminal side of basic amino acids.
Mast cell tryptase activates protease-activated receptors (PAR) on sensory neurons, causing neuronal excitation and release of substance P. Steinhoff et al. (2003) have shown in their experiment that neuronal PAR-2 is involved in pruritus of human skin and that a histamine-independent, protease-dependent, PAR-2-mediated itch pathway may provide a new link to novel therapies for pruritus and cutaneous inflammation.
Certain neurogenic abnormalities have been reported in uremic patients. Abnormal innervation patterns as well as a reduced number and diminished functional activity of cutaneous fibers were shown in these patients. Mast cells in the dermis lie adjacent to afferent C neuron terminals and interactions between these structures may play an important role in UP. Proteases are pruritogenic substances and protease receptors have been described in the distal end of C fibers. The stimulation of these receptors causes a central pruritus sensation and releases substance P that in turn sensitizes mast cells.
In this study we aimed to evaluate the possible role of MCT enzyme in the pathogenesis of uremic pruritus by measuring its level in the serum of chronic hemodialysis patients with pruritus and to correlate its level with the severity of pruritus.
A total of 40 chronic hemodialysis patients 20 of them suffering from pruritus of different degrees (group I); 14 were male and 6 were female with age ranging from 22-72ys. And the other 20 without pruritus (group II); 15were male and 5 were female with age ranging from 20-68ys. And 10 age and sex matched healthy control subjects were included in the study.
Among the 40 chronic hemodialysis patients; the duration of RF ranged from 9 months to 15ys in group I of patients, and ranged from 2ys to 15ys in group II of patients. The cause of renal failure was unknown in 19 patients (47.5%), DM in 9 patients (22.5%), obstructive ”post renal causes” in 5 patients (12.5%), obstetric causes ”e.g. post partum hemorrhage and eclampsia” in 3 patients (7.5%) and hypertention (HTN) in 4 patients (10%).
Among the 20 chronic hemodialysis patients with pruritis (group I); the duration of pruritus ranged from 9 months to 10ys, the pruritus assessment score which evaluate the intensity of pruritus ranged from 3points to 9 points.
By using ELISA the serum level of total MCT enzyme was measured in both groups of patients (group I and II) and the control group.
On comparing both groups of patients and controls in this study there was a significant increase of the mean serum level of total MCT enzyme in chronic hemodialysis patients suffering from pruritus compared with controls, also there was increase of the mean serum level of total MCT enzyme in chronic hemodialysis patients without pruritus compared with controls but this difference was insignificant, on comparing the two groups of patients there was insignificant increase of mean serum level of total MCT enzyme in chronic hemodialysis patients with prurius than those without pruritus, when the three groups (hemodialysis patients with pruritus, hemodialysis patients without pruritus and the controls) were compared for the mean serum level of tryptase the difference was statistically significant .
There was a statistically significant correlation between the intensity of pruritis ”which measured by the ”PAS” and the mean serum level of the tryptase enzyme in the present study, the serum level of MCT enzyme among patients had no correlation with age, sex, duration of RF, cause of RF or duration of pruritus.