What is the first-line treatment for itching in patients with End-Stage Renal Disease (ESRD)?

Treatment of Pruritus in End-Stage Renal Disease (ESRD)

For ESRD patients with itching, start with optimizing dialysis adequacy (target Kt/V ~1.6), normalizing calcium-phosphate balance, controlling parathyroid hormone, correcting anemia with erythropoietin, and applying emollients regularly—then escalate to gabapentin 100-300 mg after each dialysis session (three times weekly) as the most effective first-line medication. 1, 2

Initial Management: Address Underlying Factors

Before initiating pharmacologic therapy, the following foundational steps must be taken:

• Optimize dialysis adequacy 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, since secondary and tertiary hyperparathyroidism frequently accompany ESRD and contribute to pruritus 1, 2
• Correct anemia with erythropoietin if present 1, 2
• Apply emollients liberally (200-400 g per week for full body) to address xerosis, which is the most common cutaneous manifestation in dialysis patients and lowers the threshold for itch 1

First-Line Pharmacologic Treatment

Gabapentin is the most effective medication for uremic pruritus:

• Dose: 100-300 mg administered after each dialysis session (three times weekly for hemodialysis patients) 1, 2
• These doses are substantially lower than those used in non-ESRD populations due to reduced renal clearance 1
• Multicentre, double-blind, placebo-controlled trials demonstrate good response rates with significant reduction in visual analogue ratings 1
• Common side effect: Mild drowsiness 1

Second-Line Topical Treatments

If gabapentin provides insufficient relief or as adjunctive therapy:

• Topical capsaicin 0.025% cream applied to affected areas four times daily shows strong efficacy, with 14 of 17 patients in randomized trials reporting marked relief and 5 achieving complete remission 1, 2
• Capsaicin acts by depleting neuropeptides including substance P in peripheral sensory neurons 1
• Topical calcipotriol can be used for localized areas 1

Third-Line Options

For refractory cases:

• Broad-band UVB (BB-UVB) phototherapy is effective for many patients with uremic pruritus with strong supporting evidence 1, 2
• Doxepin 10 mg twice daily for short-term use, with complete resolution reported in 58% of patients versus 8% on placebo, but caution is advised due to drowsiness 1
• Topical doxepin may be considered for severe localized 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

Critical Pitfalls to Avoid

• Do NOT use cetirizine (10 mg daily) as it has been proven ineffective specifically for uremic pruritus despite efficacy in other pruritic conditions 1, 2
• Avoid long-term sedating antihistamines (diphenhydramine, hydroxyzine) except in palliative care settings, as they may predispose to dementia 1, 2, 3
• Avoid calamine lotion as there is no literature supporting its use for uremic pruritus 1
• Avoid crotamiton cream as it has been shown ineffective compared to vehicle control 1
• Non-sedating antihistamines (fexofenadine 180 mg, loratadine 10 mg) or mildly sedative agents (cetirizine 10 mg) may be tried, but evidence for efficacy specifically in uremic pruritus is limited 1

Definitive Treatment

• Renal transplantation is the only definitive treatment for uremic pruritus but is not always feasible 1, 2

Clinical Characteristics to Monitor

• 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 severely disrupting sleep and quality of life 1
• Symptoms may worsen during summer, at night, or during/soon after dialysis treatment 1