Why does uremia cause pruritus?

From the Guidelines

Uremia causes pruritus primarily due to the accumulation of toxins in the body when the kidneys fail to filter them properly, leading to irritation of nerve endings in the skin and exacerbation by dry skin and inflammation. The pathophysiology of uremic pruritus is complex and multifactorial, involving the accumulation of uremic toxins, secondary hyperparathyroidism, and inflammation 1. These factors contribute to the irritation of nerve endings in the skin, leading to the sensation of itch. Additionally, xerosis (dry skin) is a common condition in uremic patients and can exacerbate the itching sensation.

The symptoms of uremic pruritus can vary from mild intermittent irritation to intractable itch associated with poor sleep and diminished quality of life 1. Treatment approaches include optimizing dialysis to remove toxins, using phosphate binders to control mineral imbalances, moisturizers for dry skin, and antihistamines for symptom relief. Optimizing dialysis to remove toxins, particularly middle molecules like cytokines and β2-microglobulin, is a crucial step in managing uremic pruritus. UV phototherapy, specifically broadband (BB)-UVB phototherapy, has also been shown to be effective in treating moderate-to-severe uraemic pruritus 1.

In terms of specific treatment options, topical capsaicin 0.025% cream applied four times daily for 4 weeks has been shown to be effective in reducing pruritus in patients on haemodialysis 1. Additionally, oral antihistamines such as doxepin 10 mg twice daily have been shown to be effective in reducing pruritus in patients on haemodialysis, although they can cause drowsiness and other side effects 1. Addressing uremic pruritus is important as it significantly impacts quality of life and sleep in patients with advanced kidney disease.

Some key points to consider in the management of uremic pruritus include:

• Optimizing dialysis to remove toxins
• Using phosphate binders to control mineral imbalances
• Moisturizers for dry skin
• Antihistamines for symptom relief
• UV phototherapy for resistant cases
• Topical capsaicin for localized pruritus
• Oral antihistamines such as doxepin for severe pruritus.

From the Research

Pathogenesis of Uremic Pruritus

• Uremic pruritus is a common and distressing symptom in patients with chronic renal failure, with a complex interplay among cutaneous biology and the nervous and immune systems 2, 3.
• Inflammatory processes, such as the release of cytokines during haemodialysis, seem to be important in the pathogenesis of uremic pruritus 2.
• Other factors, including secondary hyperparathyreoidism, mast cell proliferation, and increased calcium phosphate deposition in the skin, may also contribute to the development of uremic pruritus 2, 4.
• Peripheral neuropathy and xerosis are also frequently observed in patients with uremic pruritus 2, 4.

Treatment Options

• Various treatments have been used to manage uremic pruritus, including topical treatments, such as emollients and capsaicin, and systemic treatments, such as gabapentin, antihistamines, and opioid receptor antagonists 2, 3, 5, 6.
• Gabapentin has been shown to be effective in relieving uremic pruritus, with a significant reduction in visual analogue pruritus scores 5, 6.
• Other treatments, such as desloratadine, pregabalin, and anti-histamines, have also been shown to be effective in managing uremic pruritus, with similar efficacy to gabapentin 5, 6.
• Phototherapy, including UVB and UVA, has also been used to treat uremic pruritus, with some studies showing significant improvements in symptoms 2, 3.

Underlying Mechanisms

• The exact mechanisms underlying uremic pruritus are not fully understood, but are thought to involve a complex interplay between inflammatory mediators, neurotransmitters, and opioids 3.
• Advanced glycation end products (AGEs) accumulation in stratum corneum has been proposed as a possible underlying cause of uremic pruritus, with potential implications for treatment with anti-glycation preparations 4.
• High levels of calcium and magnesium in the skin, as well as parathyroid hormone (PTH) and β2-microglobulin, have also been linked to uremic pruritus, highlighting the importance of managing underlying biochemical abnormalities 2, 4.