Understanding in one article: Multidisciplinary comprehensive treatment of chronic kidney disease-related pruritus to improve patients' quality of life

World Kidney Day is a global awareness campaign aimed at enhancing people's understanding and attention to kidney health. Chronic kidney disease (CKD)-associated pruritus (CKD-aP) is a common complication in patients with uremia, but its awareness and treatment rates are not satisfactory. On the occasion of the 19th World Kidney Day, Yilu Shenkang will introduce the multidisciplinary comprehensive treatment of CKD-aP in order to improve the understanding of the disease between doctors and patients and provide a reference for optimizing the drug treatment of CKD-aP.

The causes of CKD-aP are very complex, including the accumulation of uremic toxins, dry skin, neuropathy, etc., which seriously reduce the patient's quality of life and lead to problems such as decreased sleep quality, anxiety, and depression. The treatment methods of a single discipline may not be able to fully solve these problems. Nephrologists should collaborate with dermatologists to diagnose and treat CKD-aP. If necessary, the patient should be treated in conjunction with the psychologist and surgeon. For example, patients with psychological problems such as anxiety and depression need psychological treatment; patients with CKD-aP caused by secondary hyperparathyroidism can undergo surgical removal of the parathyroid glands.

Nephrology treatment <br /> In the treatment of CKD-aP, nephrologists help patients control the development of CKD through dialysis, drug therapy, etc., and deal with the effects of CKD-induced metabolic disorders, accumulation of uremic toxins, endogenous opioid disorders, etc. on the skin.

(1) Improve dialysis adequacy

The accumulation of uremic toxins in the body, increased blood calcium and phosphorus levels, and increased parathyroid hormone levels in the blood can all lead to CKD-aP. Generally, uremic patients need hemodialysis to replace kidney function, but hemodialysis can only remove small molecule toxins and a small amount of medium molecule toxins in the blood, and the removal effect on large molecule toxins is not ideal. In this regard, it is possible to consider improving the dialysis treatment method and improving the adequacy of dialysis.

●Increase the amount of dialysate: By increasing the amount of dialysate, the removal efficiency of dialysis can be improved, helping to remove uremic toxins from the body and alleviate symptoms.

●Use high-flux dialyzer: High-flux dialyzer has higher dialysis efficiency, which can remove toxins more effectively and improve the patient's uremia symptoms. High-flux hemodialysis can also remove medium and large molecular toxins and reduce the patient's micro-inflammatory state.

●Hemoperfusion shock therapy: For patients with refractory CKD-aP, hemoperfusion shock therapy can be tried to help remove large molecular toxins from the body, thereby alleviating skin itching.

(2) Drug treatment

● Systemic medication for pruritus mediators: When CKD-aP patients have excessive production of pruritus mediators (histamine, substance P, cytokines, etc.), anti-epileptic, antihistamine or anti-allergic drugs such as gabapentin, tacrolimus, and aprepitant are commonly used in clinical practice. However, there are problems such as ineffective antipruritic effects and intolerance to adverse reactions. Studies have shown that antihistamines are ineffective or less effective for CKD-aP; compared with gabapentin, loratadine is effective and more tolerable [1].

●Opioid receptor agonists and antagonists: Endogenous opioid disorders in CKD patients lead to an increase in the serum β-endorphin/dynorphin ratio, which in turn causes overactivation of the opioid μ receptors in the body's skin cells and immune cells, thereby inducing itching. For refractory uremic itching caused by opioid receptor disorders, opioid receptor agonists and antagonists, such as nalfurafine hydrochloride and naltrexone, can be used. Among them, nalfurafine hydrochloride is a highly selective κ receptor agonist that can significantly reduce the degree of itching in CKD-aP patients, reduce scratching behavior, and improve sleep disorders. This treatment method is based on the mechanism and has a significant effect on the precise treatment of CKD-aP and the relief of itching symptoms.

Dermatological treatment

In order to avoid misdiagnosis, it is best to have a dermatologist perform a preliminary assessment of CKD-aP to rule out other skin diseases that may cause pruritus. [2] Dermatologists also play an important role in the treatment of CKD-aP. They can provide patients with professional skin care advice to relieve pruritus caused by dry skin, thereby alleviating symptoms and improving quality of life; and they can also deal with scratches and infections caused by scratching.

(1) Skin care: Keep the skin clean and moisturized, use mild cleansers and shower gels, and avoid excessive bathing and rubbing of the skin. Choose moisturizing lotions containing ingredients such as aloe vera and vitamin E to help relieve dry skin and itching. About 85% of CKD-aP patients experience dry skin symptoms, which further aggravates the intensity of itching. Moisturizers can usually effectively improve dryness symptoms and relieve itching, and have almost no adverse reactions. Therefore, moisturizers can be used as a first-line treatment for dry skin and itching symptoms [3].

(2) Drug treatment: Topical medications for CKD-aP patients, such as capsaicin cream and tacrolimus ointment, can help reduce inflammation and relieve itching. If a patient scratches the skin and an infection occurs, the affected area needs to be disinfected and antibiotics prescribed for treatment based on the severity of the infection.

(3) Phototherapy: Phototherapy, as a physical therapy method, has been widely used in dermatology to treat various skin diseases, including CKD-aP. The mechanism by which phototherapy relieves skin itching has not yet been clarified. It may be related to the inactivation of itch substances caused by light, the formation of photosynthetic compounds with antipruritic effects, and the production of vitamin D that changes the ion distribution. At present, the commonly used phototherapy methods for the treatment of CKD-aP include ultraviolet A waves, broad-spectrum ultraviolet light, and narrow-spectrum ultraviolet light. Among them, narrow-spectrum ultraviolet light therapy is relatively safe and effective, with fewer erythema complications, and is currently the preferred phototherapy method.

(4) Medicinal bath: CKD-aP patients can use medicinal baths to allow the drug ingredients to penetrate deep into the skin, promote skin sweating, metabolism, and excrete toxins from the body, thereby alleviating itching symptoms and inflammation. In addition, medicinal baths can soothe nerves and relax the body and mind, helping to improve the patient's quality of life.

Surgical treatment

(1) Parathyroidectomy: Hyperparathyroidism can lead to CKD-aP. If dialysis and drug therapy are not effective in improving pruritus, total parathyroidectomy may be considered. This surgery can effectively reduce the level of parathyroid hormone and reduce its adverse effects on the skin, thereby improving pruritus symptoms.

(2) Kidney transplantation: For some patients with refractory moderate to severe CKD-aP, if the itching problem cannot be solved even after a series of conventional treatments, kidney transplantation may be considered. Kidney transplantation can cure CKD-aP from the root, restore normal kidney function, reduce or eliminate the accumulation of uremic toxins, and thus effectively relieve the itching symptoms.

In addition to the above-mentioned disciplines, multidisciplinary collaborative treatment of CKD-aP can also involve doctors from disciplines such as psychology, medical testing, pharmacy, and nursing to jointly participate in the formulation and implementation of treatment plans to meet the treatment needs of patients to the greatest extent. By integrating multidisciplinary expertise and resources, a comprehensive and individualized treatment plan can be provided for CKD-aP patients, which can not only more effectively relieve itching symptoms, but also improve the quality of life of patients, thereby achieving the purpose of improving prognosis and prolonging survival. It is hoped that in future clinical treatments, multidisciplinary treatment will be fully applied to CKD-aP, which will benefit the majority of patients.

References:

[1] Jha CM, Dastoor HD, Gopalakrishnan N, Holt SG. Obstacles to Early Diagnosis and Treatment of Pruritus in Patients with Chronic Kidney Disease: Current Perspectives. Int J Nephrol Renovasc Dis. 2022 Dec 6; 15: 335-352.

［2］Manenti L, Leuci E. Do you feel itchy? A guide towards diagnosis and measurement of chronic kidney disease-associated pruritus in dialysis patients[J]. Clinical Kidney Journal, 2021.

[3] Twycross R, Greaves MW, Handwerker H, et al. Itch: scratching more than the surface. QJM. 2003; 96(1): 7–26.