What is the optimal management of pruritus in patients undergoing dialysis due to impaired renal function?

Management of Pruritus in Dialysis Patients

For dialysis patients with pruritus, start with optimizing dialysis adequacy (target Kt/V ≥1.5-1.6), normalizing calcium-phosphate balance, controlling parathyroid hormone, correcting anemia with erythropoietin, and applying emollients, then add gabapentin 100-300 mg after each dialysis session (three times weekly) as first-line medication, with topical capsaicin 0.025% cream four times daily or broad-band UVB phototherapy as effective alternatives. 1

Stepwise Treatment Algorithm

Step 1: Optimize Dialysis Parameters and Basic Management

Before initiating any pharmacologic therapy, address these fundamental factors:

• Ensure adequate dialysis: Target Kt/V of 1.5-1.6, as pruritus is significantly more common in underdialyzed patients 1, 2. Research demonstrates that Kt/V ≥1.5 is the optimal threshold for reducing pruritus intensity, and use of high-flux dialyzers may provide additional benefit 2.

• Normalize metabolic parameters: Control calcium-phosphate balance and parathyroid hormone levels to accepted ranges, as secondary and tertiary hyperparathyroidism commonly accompany end-stage renal disease and contribute to pruritus 1.

• Correct anemia: Use erythropoietin if anemia is present 1.

• Apply emollients regularly: Address xerosis (dry skin), which is the most common cutaneous finding in dialysis patients and lowers the threshold for itch 1.

Step 2: First-Line Pharmacologic Treatment

Gabapentin is the most effective first-line medication:

• Dosing: 100-300 mg administered after each dialysis session (three times weekly) 1. These doses are substantially lower than those used in non-ESRD populations due to reduced renal clearance 1.

• Efficacy: Multicentre, double-blind, placebo-controlled trials demonstrate good response rates with significant reduction in visual analogue scale ratings 1.

• Side effects: Mild drowsiness is common 1. If beta-blocker therapy for heart failure is present, monitor carefully as sedation risk may be compounded 3.

• Important caveat: One smaller study suggested marginal efficacy with gabapentin compared to desloratadine, with excessive sedation being problematic 4. However, the guideline evidence from larger trials supports gabapentin as first-line 1.

Step 3: Alternative or Adjunctive Topical Treatments

Topical capsaicin 0.025% cream:

• Application: Apply to affected areas four times daily 1.

• Efficacy: Strong evidence from randomized trials shows 14 out of 17 patients reported marked relief, with 5 achieving complete remission 1.

• Mechanism: Works by depleting neuropeptides including substance P in peripheral sensory neurons 1.

Broad-band UVB (BB-UVB) phototherapy:

• Effective treatment for many patients with uremic pruritus, with strong supporting evidence 1.

• Consider as an alternative to gabapentin or when gabapentin causes intolerable side effects 1.

Step 4: Additional Options for Severe or Refractory Cases

Topical doxepin:

• Can 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.

• Oral doxepin 10 mg twice daily showed complete resolution in 58% of patients versus 8% on placebo, but caution is needed due to potential drowsiness 1.

Topical calcipotriol:

• Can be used for localized areas 1.

Critical Pitfalls to Avoid

Do NOT use these medications for uremic pruritus:

• Cetirizine: Specifically ineffective for uremic pruritus despite efficacy in other pruritic conditions 1, 3. Additionally contraindicated in severe renal impairment (CrCl <10 mL/min) 3.

• Calamine lotion: No literature supports its use for uremic pruritus 1.

• Crotamiton cream: Shown to be ineffective compared to vehicle control 1.

• Long-term sedating antihistamines (diphenhydramine, hydroxyzine): Should be avoided except in palliative care settings, as they may predispose to dementia 1, 3.

Non-sedative antihistamines have limited efficacy:

• Fexofenadine 180 mg, loratadine 10 mg, or cetirizine 10 mg may be tried, but evidence for their efficacy specifically in uremic pruritus is limited 1.

• If antihistamines are used for true urticaria (not uremic pruritus), fexofenadine 180 mg daily is preferred as it requires no dose adjustment in renal impairment 3.

Special Considerations

Localized versus generalized pruritus:

• Pruritus can be generalized (approximately 50% of cases) or localized, commonly affecting the back, face, or arteriovenous fistula arm 1, 5.

• For localized itching, start with topical capsaicin 0.025% cream four times daily while optimizing dialysis parameters 5.

• If localized itching spreads to become generalized, this indicates broader uremic pruritus requiring systemic therapy with gabapentin 5.

Timing considerations:

• Pruritus may worsen during summer or at night, and some patients experience itch during or soon after dialysis treatment 1.

• Administer medications after hemodialysis sessions to avoid premature drug removal and facilitate adherence 3.

Dialysis modality:

• Peritoneal dialysis patients may experience lower severity of uremic pruritus compared to hemodialysis patients 6.

Definitive treatment:

• Renal transplantation is the only definitive treatment for uremic pruritus but is not always feasible 1. In desperate cases with refractory pruritus, patients suitable for transplantation might be considered for high-urgency status 7.