Causes of Pruritus in Hemodialysis Patients
Pruritus in end-stage renal disease patients on hemodialysis is multifactorial, with xerosis (dry skin), inadequate dialysis, secondary/tertiary hyperparathyroidism, calcium-phosphate imbalance, anemia, and impaired skin barrier function being the primary contributors. 1, 2
Primary Pathophysiologic Mechanisms
Xerosis and Skin Barrier Dysfunction
- Xerosis affects 54-69% of hemodialysis patients and is the most common cutaneous finding, markedly lowering the threshold for itch 1
- Reduced stratum corneum hydration and increased transepidermal water loss correlate significantly with pruritus severity (r=0.191 and r=0.162 respectively) 3
- Impaired skin barrier function creates a vicious cycle where dry skin triggers and perpetuates itching 3
Inadequate Dialysis
- Pruritus is more common in underdialyzed patients, with higher dialysis efficacy (Kt/V approximately 1.6) reducing the prevalence of itching 1, 2, 4
- However, no consistent correlation exists between pruritus and standard dialysis adequacy markers across all studies 5, 4
- The relationship suggests that uremic toxin accumulation plays a role, though specific pruritogenic substances remain unidentified 6
Metabolic and Endocrine Abnormalities
- Secondary and tertiary hyperparathyroidism contribute to cutaneous manifestations in end-stage renal disease 1, 2
- Calcium-phosphate imbalance is a recognized contributor, though blood levels of calcium, phosphorus, and parathyroid hormone do not consistently differentiate between patients with and without pruritus 4, 6
- The mechanism likely involves tissue deposition and metabolic effects rather than simple serum concentration 6
Anemia
- Anemia is a contributing factor that should be corrected with erythropoietin as part of the initial management strategy 2, 6
- Iron-deficiency anemia has been specifically hypothesized as a mechanism 6
Clinical Characteristics and Exacerbating Factors
Prevalence and Pattern
- Pruritus affects 32-74% of hemodialysis patients, with approximately 66-70% experiencing it at some point and 42-48% actively affected at any given time 1, 7, 5, 4, 3
- The distribution is generalized in approximately 50-65.7% of cases, or localized to areas such as the back, legs, face, or arteriovenous fistula arm 2, 7, 4
Temporal and Environmental Triggers
- Major exacerbating factors include rest, heat, dry skin, and sweating 5
- Some patients experience worsening during or immediately after dialysis sessions 2, 7
- Pruritus may intensify during summer months or at night, severely disrupting sleep and quality of life 2, 5
Additional Contributing Mechanisms
Neuropathic Components
- Neuropathy and neurological changes have been hypothesized as contributing mechanisms 6
- The efficacy of gabapentin (a neuropathic pain medication) supports a neurogenic component 8, 2
Histamine and Mast Cell Involvement
- Histamine release and proliferation of skin mast cells have been proposed, though the limited efficacy of antihistamines suggests this is not the primary mechanism 6
- Cetirizine is specifically ineffective for uremic pruritus 8, 2
Medication-Related Causes
- Drug-induced eruptions from medications used in dialysis patients should be considered as an alternative or contributing diagnosis 1, 9
- Angiotensin inhibitors appear more commonly used among patients with pruritus (P=0.02), while furosemide is more common in those without itching (P=0.002) 5
Important Clinical Pitfalls
- No single laboratory parameter reliably predicts or correlates with pruritus presence or severity 7, 5, 4
- Hemoglobin, creatinine, urea, phosphorus, calcium, albumin, parathyroid hormone, and alkaline phosphatase levels show no statistically relevant differences between pruritus groups 4
- Duration of hemodialysis does not correlate with pruritus occurrence 5, 4
- Renal transplantation remains the only definitive cure, though it is not always feasible 8, 2, 9