CKD-Associated Pruritus: New Insights Into Diagnosis, Pathogenesis, and Management

Abstract

Chronic kidney disease-associated pruritus (CKD-aP) is a common, troubling and in some cases debilitating problem for patients with CKD and end-stage renal disease. Despite a prevalence rate of approximately 20% in CKD and 40% in end-stage renal disease, and a clear association with poorer psychosocial and medical outcomes, this condition is often underreported by patients and overlooked by health care providers. This is likely due, in part, to uncertainty regarding its pathogenesis and treatment. Most commonly, CKD-aP is attributed to toxin build-up, peripheral neuropathy, immune system dysregulation, or opioid dysregulation. Prior treatment studies of CKD-aP have targeted these potential etiologies but have been limited by noncontrolled design, small sample size, and non-uniform definitions of CKD-aP. Recently, several large, randomized controlled trials targeting opioid dysregulation have yielded promising results. These trials have spurred new hope for understanding and treating this condition.

Keywords: chronic kidney disease; depression; end-stage renal disease; itching; pruritus; uremia.

Figure 1

Chronic kidney disease–associated pruritus with xerosis and superimposed complications of itching including crust, erosions, and papules.

Figure 2

Pathophysiology of chronic pruritus. (a) Histamine, prostaglandins (PGs), cytokines, neuropeptides, and proteases in the skin activate primary afferent sensory neurons with cell bodies in the dorsal root ganglia (DRG) and trigeminal ganglia through G protein–coupled, Toll-like, or interleukin receptors. These sensory neurons then activate secondary neurons in the dorsal horn of the spinal cord through itch-specific neurotransmitters and ultimately activate projection neurons that transmit the itch signal up the spinothalamic tract to the brain. (b) Multifactorial pathophysiology of chronic kidney disease–associated pruritus. Al, aluminum; Ca, calcium; CRP, C-reactive protein; Eos, eosinophils; IL, interleukin; Mg, magnesium; NPPB, natriuretic polypeptide B; P, phosphorus; TLR, Toll-like receptor; WBC, white blood cell.