Unravelling the pathophysiology of chronic kidney disease-associated pruritus

For decades, itch related to chronic kidney disease (CKDaP) has been a clinical problem, but the aetiology and pathophysiology of CKDaP are still not yet fully understood—currently the underlying pathophysiological mechanisms are thought to be multifactorial. As new therapeutic targets have recently been identified and clinical trials have shown promising results, our current understanding of the interrelationships has expanded significantly. Here we review the pathophysiology and recent findings on modulation and sensitization of itch contributing to the development of CKDaP, covering hypothesis regarding immune system dysfunction, metabolic changes, uremic toxin deposition, peripheral neuropathy and imbalances in the endogenous opioid system.