Uraemic Pruritus

Uraemic pruritus, or chronic kidney disease associated pruritus, is generalised itch attributable to kidney failure that persists for more than 6 weeks. It affects 20 to 40% of patients on dialysis, and a smaller proportion in non-dialysis disease, with moderate to severe itch in up to a third. It impairs sleep, mood and quality of life and independently predicts mortality.

Pathophysiology

• Systemic inflammation and immune dysregulation (raised interleukin-6, C-reactive protein, T helper 1 skew), opioid imbalance (overactive mu opioid receptors and relatively underactive kappa opioid receptors), accumulation of uraemic toxins, xerosis, neuropathic mechanisms, hyperparathyroidism and hyperphosphataemia, mast cell activation, and dialysis related factors (heparin, membrane biocompatibility, inadequate dialysis dose).

• Generalised or localised itch (back, face, arms, scalp, abdomen), worse at night and during or soon after dialysis; often symmetrical.
• Dry skin (xerosis), excoriations, lichenification and prurigo nodularis; no primary rash.
• Sleep disturbance, depression, restless legs, poor concentration, social withdrawal.

Red flags

• Primary rash, burrows, blisters or urticaria: another dermatological diagnosis.
• Jaundice or dark urine (cholestasis), weight loss, night sweats, lymphadenopathy (lymphoma), plethora (polycythaemia).
• Itch with neurological symptoms (notalgia paraesthetica, brachioradial pruritus, cervical spine disease).
• Severe sleep loss with depression or suicidal thoughts.

• Diagnosis of exclusion. Assess intensity with a numerical rating scale (0 to 10; 4 or more is moderate, 7 or more severe) and a multidimensional scale such as the 5-D itch scale.
• Examine the skin for xerosis, scabies, contact dermatitis, eczema, psoriasis; assess scratch marks.
• Blood tests: full blood count and film (iron deficiency, polycythaemia, eosinophilia), ferritin, urea, calcium, phosphate, parathyroid hormone, liver tests with alkaline phosphatase and bilirubin, thyroid function, glucose and HbA1c, hepatitis B and C serology, HIV; Kt/V and urea reduction ratio.
• Review drugs (opioids, aspirin, ACE inhibitors, statins, allopurinol, sevelamer related reactions).

Differential diagnosis

• Xerosis cutis, scabies, atopic dermatitis, drug reactions, cholestatic itch, iron deficiency, hypo- or hyperthyroidism, haematological disease (Hodgkin lymphoma, polycythaemia vera), HIV, diabetic neuropathy, hepatitis C, allergic reactions to dialysis components (ethylene oxide, heparin).

First line: general and dialysis measures

• Emollients (aqueous cream with urea 5 to 10%, or emollient with glycerol) twice daily to wet skin after bathing; lukewarm showers; avoid soap, hot water, wool and alcohol based products; keep nails short.
• Optimise dialysis adequacy (Kt/V of at least 1.2), consider high flux membranes or haemodiafiltration, heparin dose reduction, cool dialysate.
• Control phosphate (1.1 to 1.7 mmol/L), calcium (2.2 to 2.5 mmol/L) and parathyroid hormone (2 to 9 times the upper limit); correct anaemia (haemoglobin 100 to 120 g/L) and iron deficiency. Cinacalcet 30 mg daily or etelcalcetide 5 mg after dialysis reduces itch in hyperparathyroid patients.

Topical therapy (mild to moderate, localised)

• Pramoxine 1% cream, menthol 1% or camphor in emollient two to three times daily; capsaicin 0.025% cream applied up to four times daily to localised areas (initial burning fades); tacrolimus 0.03 to 0.1% ointment twice daily for 2 to 4 weeks.

Systemic therapy (moderate to severe)

• Difelikefalin 0.5 microg/kg intravenously into the venous line at the end of each haemodialysis session (three times weekly); maximum on dry weight; no dose adjustment in dialysis.
• Gabapentin 100 mg orally after each haemodialysis session (or 100 mg at night), increased to a maximum of 300 mg after dialysis; pregabalin 25 mg at night, increased to a maximum of 75 mg daily (dose reduced for kidney failure); monitor for sedation, dizziness, myoclonus and falls.
• Nalfurafine 5 microg orally after the evening meal or intravenously after dialysis (available in some regions). Naltrexone 50 mg daily may be tried when other options fail (watch for opioid withdrawal in patients taking opioids). Sertraline 25 to 50 mg daily has shown benefit in small studies.
• Sedating antihistamines (chlorphenamine 4 mg at night; cetirizine 5 mg at night) help sleep but not itch; use cautiously because of accumulation.

Non-drug therapy

• Narrowband ultraviolet B phototherapy three times weekly for 4 to 8 weeks; acupuncture and cognitive behavioural therapy as adjuncts; kidney transplantation resolves itch in most patients.

Monitoring. Reassess itch score at 4 weeks and after each change; stop agents that fail after 4 to 8 weeks.

Referral and escalation. Dermatology for diagnostic doubt, prurigo nodularis or failure of first line therapy; nephrology for dialysis optimisation; mental health review for severe sleep loss or depression.

Special groups

• Elderly: lower starting doses of gabapentin and pregabalin to reduce falls.
• Children: emollients, optimised dialysis and mineral control; limited drug evidence.
• Pregnancy: emollients, narrowband ultraviolet B and optimised dialysis; avoid systemic agents without specialist advice.