Research suggests the pathophysiology of CKD-aP is multifactorial1
Several causes of the disease have been implicated, including:
Opioid dysregulation
  • An imbalance of activation and antagonism between central mu- and peripheral kappa-opioid receptors (MORs and KORs, respectively) in patients with CKD-aP is believed to cause itching
Immune system dysfunction
  • Patients with CKD-aP have high levels of pro-inflammatory cytokines that stimulate itching, including IL-6, IL-2, and CRP
  • The cytokines activate receptors on peripheral sensory neurons, leading to increased pruritic signaling
Toxin deposition
  • Uremic toxins such as vitamin A, aluminum, calcium, phosphorus, and magnesium are thought to contribute to CKD-aP
Peripheral neuropathy
  • Sensory neurons in patients with CKD-aP are often activated out of proportion to or independently of any causative substances, and this is thought to cause itching

A multifactorial mechanism of disease may
lead to under-recognition of CKD-aP1,2

CKD-aP=chronic kidney disease–associated pruritus; IL=interleukin; CRP=C-reactive protein.

Hear from an expert

Watch Dr. Shirazian explain the unique and multifactorial pathophysiology of CKD-aP.

This is an actual treating physician who was compensated for his time and consents to this use. Nothing in this video or website constitutes medical advice or treatment guidance.

More information about the expert

Shayan Shirazian, MD

Nephrologist, New York, NY
Member, ASN, ISN

  1. Verduzco HA, Shirazian S. CKD-associated pruritus: new insights into diagnosis, pathogenesis, and management. Kidney Int Rep. 2020;5(9):1387–1402. doi:10.1016/j.ekir.2020.04.027
  2. Sukul N, Karaboyas A, Csomor PA, et al. Self-reported pruritus and clinical, dialysis-related, and patient-reported outcomes in hemodialysis patients. Kidney Med. 2020;3(1):42–53. doi:10.1016/j.xkme.2020.08.011
  3. Millington GWM, Collins A, Lovell CR, et al. British Association of Dermatologists’ guidelines for the investigation and management of generalized pruritus in adults without an underlying dermatosis, 2018. Br J Dermatol. 2018;178(1):34–60. doi:10.1111/bjd.16117