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Chapter 19: Uremic Pruritus

Teresa Ju BS; Zoe M. Lipman BS; Gil Yosipovitch

UREMIC PRURITUS

Therapeutic Approach

Uremic pruritus, or more accurately termed chronic kidney disease-associated pruritus (CKD-aP), is a chronic pruritus found in greater than 60% patients undergoing dialysis and associated with worsening kidney function, age, and medical comorbidities. While there are currently no FDA-approved treatments for this condition, several treatments including off label treatments have shown anti-pruritic efficacy. Furthermore, new drugs are under clinical trials and show promising results. The first step of management for all patients with uremic pruritus should be dialysis optimized according to Kt/V targets and topical emollients as the uremic skin is xerotic. Topical therapies should be first-line in mild and/or localized uremic pruritus, while systemic should be pursued in generalized, moderate-to-severe, and/or refractory uremic pruritus. Alternative and adjuvant therapy may be considered on a patient-by-patient basis according to accessibility, practicality, financial status, and other comorbidities. See Table 19-1.

Table 19-1Uremic Pruritus Treatment Table
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Table 19-1 Uremic Pruritus Treatment Table
MEDICATION NAME INDICATION MECHANISM OF ACTION DOSING ADVERSE EFFECTS SUGGESTED MONITORING LEVEL OF EVIDENCE (REFERENCE)
Topical Therapy
High-water-content emollients (preferably with glycerol and paraffin) Recommended for all patients Increase skin hydration, protect and restore skin barrier

15% glycerol

10% paraffin

 Pruritic exacerbation, erythema, burning None IB1-3
Gamma-linolenic acid Refractory pruritus Immunomodulation, anti-inflammatory 2.2% Gamma-linolenic acid cream TID Rash, nausea, diarrhea, heated sensation None IB4-5
Pramoxine Mild and/or localized pruritus Blockage of nerve conduction 1% pramoxine BID Erythema, burning, swelling None IB6
Capsaicin Mild and/or localized pruritus Blockage of nerve conduction 0.025% capsaicin cream Burning, stinging, erythema None IB7-10
Cannabinoids Mild and moderate localized pruritus Anti-inflammatory, antinociceptive BID Irritation, rash None IIB11-12
Tacrolimus Treatment-resistant uremic pruritus Immunosuppressive, anti-inflammatory 0.03% or 0.1% tacrolimus ointment BID Increased risk for skin cancer and lymphoma, itch, infection, burning, redness, headache, flu-like symptoms None III13-14
Systemic Therapy
Gabapentin Uremic pruritus Modulation/reduction of sensory transmission and neural sensitization 100-300 mg PO 3 times weekly (after each dialysis session) Somnolence, dizziness, fatigue, nausea, GI upset, tremor, ataxia Mental alertness (upon initiation/dose increase) IB15-23
Pregabalin Uremic pruritus Modulation/reduction of sensory transmission and neural sensitization 25-75 mg PO QD Somnolence, dizziness, ataxia Mental alertness (upon initiation/dose increase) IB15-16,20,23,24
Naloxone Uremic pruritus MOR antagonist 0.8 mg in 1.0 mL saline subcutaneous GI upset, cardiovascular, drowsiness Acute opioid withdrawal III25,26
Naltrexone Uremic pruritus MOR antagonist 25-50 mg PO QD Gastrointestinal symptoms, skin reaction Suicidal thoughts/depression IB15-16,27-29
Difelikefalin Generalized moderate-to-severe pruritus KOR agonist, anti-inflammatory 0.5 μg/kg IV 3 times weekly Abdominal pain, mental status changes, dizziness, somnolence, GI upset, fall None IB61-63
Butorphanol Generalized severe intractable pruritus Mixed MOR antagonist/KOR agonist 1 mg/d intranasal daily Nausea Monitor for abuse III31
Sertraline Comorbid depression Antidepressant with serotonin reuptake inhibition 50 mg PO BID GI upset, may precipitate mania/hypomania, serotonin syndrome, SIADH, sexual ...

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