Expression of Nerve Growth Factor (NGF) and its receptor (TrK A) in chronic renal failure patients with pruritus

Background: Chronic renal failure or chronic renal disease (CRD) is a progressive loss in renal function over a period of months or years. It is differentiated from acute kidney disease in that the reduction in kidney function must be present for over 3 months.
Uremic pruritus is the most common cutaneous abnormality in patients with CRF.  Uraemicpruritus is unrelated to sex, age, duration, cause of dialysis, a list of unproven suggestions for pruritis include : dry skin; mast cell proliferation; Th1 cytokines; secondary hyperparathyroidism; disturbed balance between μ-opioid and κ-opioid receptors; substance P; increased skin ions Ca, Mg, PO; abnormal transmission via the spine .
Nerve growth factor is a neurotropic polypeptide necessary for the survival and growth of some central neurons, as well as sensory afferent and sympathetic neurons.
It has been found that in AD patients increased levels of NGF in keratinocytes and infiltrating leukocytes which were related to disease severity . Skin from patients with prurtigo nodularis also have increased presence of NGF which is primarily found in infiltrating leukocytes.
Method: The present case-control study was carried out on 30 patients with CRF and uraemic pruritus on hemodialysis who were treated at Sohag Educational Hospital and 20 healthy control subjects. Patients with CRF and uremic pruritus on hemodialysis of both sex, any age and not received any systemic treatment for pruritus for at least 3 weeks prior to the study were included in this study.
 Severity of itching was measured by the 5-D itch score.  5-D is (duration – degree – direction –disability and distribution). Maximum score is 25 and indicate severe itching while the minimum score is 5 and indicate no itching. Skin punch biopsies (3 mm) were taken from them for immunohistochemical studies.  
Results: The present study found that in the skin of the healthy control participants the expressions of NGF were seen in the epidermal basal layer, but there was no expression in upper and mid epidermal cell layers while in dermis about 75% of them showed mild expression and 25% showed moderate expression.
In patients with chronic CRF with pruritus on dialysis the expressions of NGF were strong in epidermal basal layers, upper and mid epidermal layers. There was a strong expression of NGF in dermis with some spindle like infiltrating cells especially in dermal papillae.
 The present study found that in the skin of the healthy control participants the expression of TrKA were seen in the epidermal basal layer, but there was no expression in upper and mid epidermal cell layers while in dermis 75% of them showed mild expression while 25% showed moderate expression.
In patients with chronic CRF with pruritus on dialysis the expressions of TrKA were strong in epidermal basal layers, mid and upper epidermal layers. In dermis especially upper dermis larger number of cells demonstrated strong TrkA immunoreactivity.
This study found that there was a significant correlation between the 5-D itch score and age of the patients. There was a significant correlation between the 5-D itch score and degree of expression of both NGF and TrKA.
Conclusion: A significant increase in the expressions of NGF and TrKA in CRF patients with pruritus on hemodialysis compared to the healthy control participants and also there was significant correlation between degree of expressions of NGF and TrKA and 5-D itching score could be the cause of initiation and maintenance of pruritus in CRF patients with pruritus on dialysis.