Five characteristics of chronic kidney disease-related pruritus

Chronic kidney disease-associated pruritus (CKD-aP) is a common skin symptom in patients with chronic kidney disease (CKD), especially in the late stage of CKD. Up to 70% of dialysis patients are troubled by CKD-aP. CKD-aP has the characteristics of complex pathogenesis, great harm, difficulty in evaluation, diagnosis and treatment, and faces many challenges in clinical diagnosis and treatment.

1. The pathogenesis is complex: not yet fully understood

The pathogenesis of CKD-aP is relatively complex, and many hypotheses have been proposed to explain its pathogenesis, including uremic toxin deposition, peripheral neuropathy, immune system disorders, and endogenous opioid receptor imbalance. However, the etiology and pathophysiological mechanism of CKD-aP have not been fully clarified. In recent years, many advances have been made in the study of CKD-aP caused by endogenous opioid receptor imbalance. Studies have found that refractory CKD-aP is mostly central nervous itch, which is caused by excessive activation of opioid μ receptors. Opioids jointly regulate the occurrence of itch through the interaction of opioid μ and κ receptors on the postsynaptic cell membrane of the spinal dorsal horn. Activation of μ receptors promotes itch formation, while activation of κ receptors inhibits itch. Endogenous opioid disorders in CKD patients and increased serum β-endorphin/dynorphin ratio lead to excessive activation of opioid μ receptors in skin cells and immune cells of the body, resulting in itch. Therefore, the application of opioid μ receptor antagonists or κ receptor agonists can effectively inhibit central nervous itch. This mechanism provides a new target for the treatment of CKD-aP.

2. Serious harm: Significantly reduce the quality of life of patients

CKD-aP has a negative impact on the quality of life of patients. Patients are often unable to concentrate on work, study and daily activities due to the intense itching, which affects their work efficiency and social interaction, directly leading to a decline in the quality of life of patients.

The clinical manifestations of CKD-aP vary from person to person, usually affecting large areas of skin in a discontinuous and symmetrical manner. The face, chest, and limbs are the most common sites for itching. The symptoms are more severe at night. Excessive cooling, overheating, showering, exercise, etc. can induce its onset. Most patients suffer from CKD-aP for months or even years. Over time, long-term itching can cause patients to scratch frequently, leading to secondary skin changes such as epidermal exfoliation or nodular itching, causing skin damage and infection.

In addition, CKD-aP is also associated with poor sleep quality, depression, and increased risk of death. Long-term sleep deprivation, anxiety, and depression in patients will further worsen their physical and mental health. For hemodialysis patients, severe itching may also cause them to withdraw from dialysis treatment.

3. Difficulty in evaluation: Patients are highly subjective and quantification is difficult

Correctly quantifying the severity of CKD-aP is conducive to the accurate diagnosis and treatment of patients. However, CKD-aP is a subjective symptom of a multifactorial nature and is multidimensional. Its diagnosis depends largely on patient-reported outcomes, and it is difficult to objectively and accurately quantify and evaluate it. Moreover, no universally applicable indicators have been found to assess the severity of CKD-aP, and there is no recognized CKD-aP measurement tool in my country or even internationally. Multidimensional measurement tools, such as the 5-D Itch Scale and the 14-item Uremic Skin Itch Scale, are often used in clinical practice to assess CKD-aP. Compared with unidimensional measurement tools such as visual analog scales, digital rating scales, and language rating scales, multidimensional measurement tools can more comprehensively and accurately assess CKD-aP.

4Difficult diagnosis: lack of clear and consistent diagnostic criteria

At present, there are still differences in the definition and description of CKD-aP. Different research and professional organizations use different terms and standards to describe this disease, lacking consistency and uniformity. There are no clear and consistent diagnostic criteria for CKD-aP in China and internationally. The general diagnostic criteria are: (1) Patients in the uremic stage exclude skin itching caused by other diseases. (2) Itching occurs at least 3 days within 2 weeks, and itches several times a day, each time lasting for several minutes, affecting the patient's life. (3) Skin itching occurs in a specific form and lasts for more than 6 months. In my country, most people believe that if skin itching exists in the uremic stage, it can be diagnosed as CKD-aP. As a result, it is difficult to correctly define and diagnose CKD-aP.

In order to solve the problem of inconsistent diagnostic criteria for CKD-aP, further research is needed in the future, and expert consensus and guidelines should be developed to standardize diagnostic criteria. This will help clinicians diagnose and manage CKD-aP patients more accurately and improve their quality of life and prognosis.

5. Difficult to treat: There are many treatments, but the efficacy is poor

CKD-aP is usually a persistent and intractable symptom that is difficult to cure completely. At present, there are many clinical treatment options for CKD-aP. However, most patients have limited or unsatisfactory responses to existing treatments, and there is still a lack of specific and effective treatments in clinical practice. For refractory CKD-aP caused by endogenous opioid receptor imbalance, nalfurafur hydrochloride can be considered. Nalfurafur hydrochloride is a κ opioid receptor agonist that inhibits overactivation of μ receptors by reducing the β-endorphin/dynorphin ratio in the patient's serum, exerts an antipruritic effect, improves the patient's quality of life, and reduces the patient's need for other antipruritic drugs.

Studies have shown that nalfurafur hydrochloride can effectively reduce the itching sensation of CKD-aP and is safe and well tolerated by most patients. Currently, nalfurafur hydrochloride has been approved for the treatment of CKD-aP in countries such as Japan, and has completed Phase III clinical registration, and will soon be approved for marketing in my country.

6. Summary

At present, CKD-aP is still a thorny problem in nephrology. It is seriously underestimated by doctors and patients, and there is a lack of evaluation, diagnosis methods and effective and safe treatment methods. In the future, we should fully understand and recognize the harm of CKD-aP, focus on studying its pathogenesis, find tools to accurately assess the degree of skin itching, and explore more effective therapies such as nalfurafine hydrochloride that treat CKD-aP from a mechanism-based perspective, so as to help patients reduce itching and improve their quality of life.