What are the treatment options for uremic pruritus in patients with End-Stage Renal Disease (ESRD)?

Treatment of Uremic Pruritus in ESRD Patients

Gabapentin 100-300 mg administered after each dialysis session (three times weekly) is the most effective first-line medication for uremic pruritus in hemodialysis patients, combined with optimization of dialysis adequacy (target Kt/V ~1.6) and regular emollient use. 1

Stepwise Treatment Algorithm

Step 1: Optimize Dialysis and Metabolic Parameters (Foundation)

Before initiating pharmacologic therapy, address these fundamental factors:

• Ensure adequate dialysis with a target Kt/V of approximately 1.6, as pruritus is significantly more common in underdialyzed patients 1, 2
• Normalize calcium-phosphate balance and control parathyroid hormone levels to accepted ranges, as secondary and tertiary hyperparathyroidism frequently accompany ESRD and contribute to pruritus 1, 2
• Correct anemia with erythropoietin if present 1, 2
• Apply emollients regularly as supportive care to address xerosis (dry skin), which is the most common cutaneous manifestation in dialysis patients and lowers the threshold for itch 1, 2

Step 2: First-Line Pharmacologic Treatment

• Gabapentin 100-300 mg after each dialysis session (three times weekly) demonstrates the strongest evidence from multicentre, double-blind, placebo-controlled trials with good response rates and significant reduction in visual analogue ratings 1
• These doses are substantially lower than those used in non-ESRD populations due to reduced renal clearance 1
• Common side effect is mild drowsiness, which is generally well-tolerated 1

Step 3: Topical Adjunctive Therapy

• Capsaicin 0.025% cream applied four times daily to affected areas has shown significant efficacy, with 14 of 17 patients reporting marked relief and 5 achieving complete remission in randomized trials 1
• Capsaicin works by depleting neuropeptides including substance P in peripheral sensory neurons 1
• Topical calcipotriol can be used for localized areas 1

Step 4: Phototherapy for Refractory Cases

• Broad-band UVB (BB-UVB) phototherapy is effective for many patients with uremic pruritus who have insufficient relief after 2-4 weeks of consistent topical and systemic treatment 1

Step 5: Alternative Systemic Options

• Doxepin 10 mg twice daily for short-term treatment showed complete resolution in 58% of patients versus 8% on placebo, but use caution due to potential drowsiness 1
• Topical doxepin may be considered for severe cases, but treatment must be strictly limited to 8 days, 10% of body surface area, and maximum 12 g daily 1
• Ketotifen 1 mg daily may be as effective as gabapentin but has less supporting evidence overall 1

Emerging Evidence: Sertraline

• Sertraline 50 mg oral daily showed significant antipruritic effects in clinical trials, with 50% of patients with severe pruritus experiencing weak pruritus and 40% experiencing moderate pruritus after treatment 3, 4
• Sertraline appears to work by reducing inflammatory cytokines, as inflammation plays a significant role in uremic itching 4
• Sertraline requires no dose adjustment in ESRD patients, making it a practical option 4

Critical Pitfalls to Avoid

• Do NOT use cetirizine for uremic pruritus—it has been specifically shown to be ineffective for this condition despite efficacy in other pruritic conditions 1, 2
• Avoid long-term sedative antihistamines (diphenhydramine, hydroxyzine) except in palliative care settings, as they may predispose to dementia 1, 2
• Do NOT use calamine lotion—there is no literature supporting its use for uremic pruritus 1
• Avoid crotamiton cream—it has been shown to be ineffective compared to vehicle control 1
• Non-sedative antihistamines (fexofenadine 180 mg, loratadine 10 mg) or mildly sedative agents (cetirizine 10 mg) have limited evidence for efficacy specifically in uremic pruritus 1

Clinical Presentation Patterns

• Pruritus can be generalized (approximately 50% of cases) or localized (commonly affecting the back, face, or arteriovenous fistula arm) 1
• Intensity ranges from mild intermittent irritation to intractable itch that severely disrupts sleep and quality of life 1
• Symptoms may worsen during summer or at night, and some patients experience itch during or soon after dialysis treatment 1

Definitive Treatment

• Renal transplantation remains the only definitive cure for uremic pruritus but is not always feasible 1