Topical treatment of chronic kidney disease-related pruritus

Chronic kidney disease-associated pruritus (CKD-aP) refers to skin itching symptoms caused by chronic kidney disease (CKD). For nephrologists and dermatologists, the diagnosis and treatment of CKD-aP is a difficult problem. Currently, there are no standardized diagnostic criteria and effective treatment methods.

Itch is a common problem for CKD patients, and the incidence is particularly high in patients with advanced CKD. CKD-aP seriously affects the quality of life of patients and is associated with sleep disorders, anxiety and depression, and also significantly increases the mortality rate of patients. Although systemic treatment is currently the preferred method for managing CKD-aP, as a skin disease, local treatment of CKD-aP can also play a role in relieving itching symptoms. Today we will introduce the local treatment of CKD-aP.

01Moisturizer

The clinical manifestations of CKD-aP vary, and dryness is a common skin manifestation, and the degree of dryness is related to the intensity of CKD-aP. The main function of the stratum corneum is to form a permeable barrier and regulate water loss and hydration in the epidermis. The destruction of the water content in the stratum corneum will interfere with the function of proteases, which manifests as dry skin, leading to dull, rough skin, scaling, and even peeling, erythema, cracking, and itching.

The lipid composition of the stratum corneum of hemodialysis patients changes. This change leads to increased transepidermal water loss and causes symptoms of dry skin in hemodialysis patients [1]. Studies have shown that the stratum corneum hydration level of hemodialysis patients with CKD-aP is significantly lower than that of patients without itching.

After understanding the mechanism of dry skin in CKD-aP patients, appropriate local treatment to correct dry skin can reduce the patient's itching level and thus improve the patient's quality of life.

Improving stratum corneum hydration is the cornerstone of CKD-aP treatment. Topical treatments can immediately improve the skin area affected by pruritus and minimize the risk of systemic effects. They can also improve the integrity of the stratum corneum barrier, thereby correcting dry skin and reducing the severity of itching. The European S2k chronic pruritus guidelines recommend that CKD-aP patients use a moisturizer every day, especially after bathing, to improve the skin barrier and reduce the severity of itching.

Currently, moisturizers have been widely recommended for the treatment of CKD-aP. In addition, moisturizers such as glycerin, 10% salicylic acid ointment, vaseline, and vitamin E can be applied to keep the skin moist and relieve itching symptoms.

02Capsaicin cream

Capsaicin is an alkaloid extracted from plants of the genus Capsicum that can reduce the accumulation of substance P associated with pruritus and effectively relieve itching. [2] Studies have found that 0.025% to 0.030% capsaicin ointment is effective for CKD-aP. Apart from causing burning pain, it has no other serious adverse reactions and can be used for patients with local itching. [3]

03Local anesthetics

Local anesthetics such as pramoxine, lidocaine, and procaine can relieve pruritus by numbing the nerve endings in the skin. Studies have shown that using 1% pramoxine lotion twice a day can relieve pruritus in CKD-aP patients after four weeks [3].

04Tacrolimus Cream

Tacrolimus is a calcineurin inhibitor that inhibits the production of interleukin-2 and is mainly used to treat pruritus and rash caused by atopic dermatitis. A prospective study showed that 25 hemodialysis patients with CKD-aP had significantly improved pruritus symptoms after six weeks of treatment with tacrolimus ointment [4].

However, considering that tacrolimus ointment increases the risk of skin cancer and lymphoma, it is only recommended for the treatment of patients with refractory CKD-aP, and the maximum usage duration should not exceed 6 weeks. It should be used with caution, especially in patients who are about to undergo a kidney transplant, because kidney transplant patients have a higher risk of skin cancer.

05γ-linolenic acid cream

GLA has anti-inflammatory effects. Studies have shown that applying 2.2% GLA cream to itchy areas three times a day for two weeks can relieve CKD-aP.［5］

06 Chinese medicine bath

Wrap the medicine that can induce sweating and eliminate turbidity in a cloth bag and put it in a steam generator or bathtub. The patient sits in the treatment device or bathtub for fumigation or heated bathing to promote sweating of the skin to excrete toxins in the body, which can play an antipruritic effect.

07 Summary

The relief of CKD-aP by topical treatment may be temporary, and the effects vary from patient to patient. For some patients, topical treatment can provide lasting relief of itching symptoms. For other patients, long-term or regular use of topical treatment may be required to maintain the effect. It should be noted that CKD-aP is a complex problem with diverse causes, and treatment also requires comprehensive consideration of physical factors. If the above topical treatments are not effective, systemic treatment should be considered. For systemic or severe itching, local treatment + systemic treatment should be selected [6].

Systemic treatment of pruritus should be targeted at its pathogenesis. At present, commonly used systemic treatment drugs include antihistamines, antiepileptic drugs, antidepressants, opioid receptor antagonists/agonists, etc. However, most therapies are off-label treatments, which can only relieve the patient's itching symptoms to a certain extent, and cannot achieve the effect of curing CKD-aP. The root cause of this problem is that there are no clear guidelines or consensus in China to provide standardized treatments for CKD-aP, nor are there any approved treatment plans.

For the treatment of CKD-aP, it is worth clinically referring to the 2020 edition of the "Japanese Guidelines for the Diagnosis and Treatment of Pruritus" which recommends the use of a highly selective κ receptor agonist, nalfurafur hydrochloride. For CKD-aP caused by opioid disorders, nalfurafur hydrochloride can inhibit the overactivation of μ receptors by reducing the β-endorphin/dynorphin ratio in the serum of patients with uremic syndrome, thereby alleviating pruritus from the mechanism of action. Moreover, my country recently completed a phase III multicenter bridging study on nalfurafur hydrochloride. The results showed that nalfurafur hydrochloride was effective for refractory CKD-aP in hemodialysis patients who met the predefined criteria in my country, and its safety was consistent with that observed in previous studies, with no new safety issues found [7]. Nalfurafur hydrochloride has been approved for marketing this month, and we look forward to its performance in the treatment of CKD-aP patients in my country.