Uremic pruritus is caused by a variety of factors, the exact cause of which is not well understood, and therefore treatment options are varied. Except for kidney transplantation, which has a clear therapeutic effect, all other treatments only partially relieve the patient’s symptoms and improve the quality of life.
Physical therapy methods include phototherapy, narrow-spectrum UVB irradiation therapy, etc., which basically have no side effects and can be an option for uremic pruritus, especially for those who are ineffective after drug treatment. Whether subtotal parathyroidectomy can be used as a treatment for pruritus in uremia has been long debated, and although clinical studies have confirmed that subtotal parathyroidectomy significantly improves pruritus in uremic patients, it has not been used as a routine treatment for pruritus due to the lack of evidence of a direct correlation between parathyroid hormone and pruritus. Below we focus on three areas of therapeutic advances.
Improved dialysis techniques
Although some experts believe that a microinflammatory state may contribute to the pathogenesis of pruritus in dialysis patients and that dialysis may exacerbate the microinflammatory state in patients, the incidence of uremic pruritus has gradually decreased over the past decades, which may still be related to the continuous improvement of dialysis technology and the use of biocompatible membranes.
Therefore, the first step to improve pruritus in uremia remains to improve the effectiveness of dialysis treatment, use biocompatible dialysis membranes, and improve the nutritional status of patients. lin et al. demonstrated that dialyzers using polymethylmethacrylate (PMMA) membranes are effective in alleviating the degree of pruritus in uremic patients because the powerful adsorption of PMMA membranes compared to other high-flux dialysis membranes can remove more cytokines.
Topical topical medications
The current topical topical medications for the treatment of pruritus uremicus include skin lubricants, capsaicin cream, tacrolimus ointment, and pramoxine lotion, with skin lubricants being the most commonly used medications. Because of the significant correlation between dry skin and the occurrence of pruritus urealyticus, many studies have concluded that lubricants should be used as first-line agents for the treatment of pruritus urealyticus.
Skin lubricants not only have the effect of rehydrating and preventing water evaporation, but also reduce pruritus symptoms by decreasing the sensitivity of nerve endings within the skin to cold, heat or burning sensations.
Medications
Antihistamines.
Antihistamines are widely used clinically as oral medications for the treatment of pruritus urealyticus, such as paracetamol, ketotifen, and cetirizine, but their antipruritic effects are limited and are not effective in the treatment of intractable pruritus.
Gabapentin.
Gabapentin is a 7-aminobutyric acid analogue with anticonvulsant effects, and it has a proven role in the treatment of neuralgia, especially diabetic neuropathy. Since the neuropathological mechanisms of neuralgia and uremic pruritus are the same, some scholars have used gabapentin in the treatment of intractable uremic pruritus.
The first thing they noticed was that gabapentin was used in the treatment of neuralgia in patients with uremic pruritus, and not only the neuralgia was relieved, but also the pruritus in uremic patients was significantly relieved.
They then conducted a double-blind placebo randomized controlled study, and the results were promising, with significant relief of pruritus in uremic patients treated with gabapentin, and none of the patients dropped out of treatment due to drug side effects. It is important to note that gabapentin is primarily excreted through the kidneys and therefore has a prolonged half-life in uremic dialysis patients and dose adjustment is necessary for its use.
Clinically, patients can take 100-300 mg (starting dose of 100 mg) of gabapentin orally after each dialysis treatment, which can effectively reduce pruritus symptoms. Its adverse effects are mainly in the area of neurotoxicity, including dizziness, drowsiness, and sometimes fatigue and nausea as side effects.
Opioid receptor-targeted therapy.
The use of naltrexone, an opioid receptor antagonist, for the treatment of pruritus in dialysis patients originated from a case report in which Anderson et al. reported the successful treatment of intractable uremic pruritus in a uremic patient with naltrexone, but there have been few reports of naltrexone for the treatment of uremic pruritus since then.
Later, Legroux-Crespel et al. performed a comparative study with naloxone and loratadine, which proved to be poorly treated and tolerated, and they still recommended that naltrexone should only be used as a second-line agent.
However, recently, the use of the opioid K-agonist nalfurafine (nalfurafine) has gained widespread attention. Nalfurafine inhibits the activity of peripheral and central receptors through activation of K-receptors, thereby suppressing pruritus induced by substance P.
A Meta-analysis found encouraging results in 2 randomized placebo-controlled clinical studies in which the application of nafuramorphine significantly reduced pruritus, scratching, and sleep disturbance with a high safety profile. Currently, nafuramorphine can be administered intravenously and used after hemodialysis in patients, but may cause central nervous system adverse effects such as vertigo, insomnia, headache, sleepiness, and nausea.
Niacinamide.
Nicotinamide is one of the components of the vitamin B complex, and Namazi et al. concluded that nicotinamide is effective in the treatment of uremic pruritus and is associated with the following three mechanisms.
(1) suppression of the inflammatory response by inhibiting the expression of MHC-n (major histocompatibility complex-n) and the synthesis of IL-12, Y-interferon, and IL-1.
(2) Inhibition of cAMP (cyclic adenosine monophosphate) phosphodiesterase, which stabilizes mast cells and leukocytes thereby blocking the release of histamine.
(3) Promotes the biosynthesis of ceramide analogues in keratinocytes and relieves dry skin. Therefore, nicotinamide is considered to be the most promising new drug for the treatment of uremic pruritus, but further evidence-based medical evidence is needed to support this.