of all patients in the
DOPPS study reported
of all patients in the
DOPPS study reported
being moderately to
of Medical Directors
included in the DOPPS
study underestimated the
prevalence of pruritus in
*Figure calculated based on total patients reporting being somewhat-extremely bothered by itching.
Watch these videos to hear from leading experts about the prevalence and pathophysiology of CKD-associated Pruritus.
Prof. Maurizio Gallieni
Prof. Maurizio Gallieni is Associate Professor and Director of the School of Nephrology at the University of Milano, Italy. He graduated and trained at the University of Milano and Verona, Italy, and as a Research Fellow at Washington University in Saint Louis, MO, USA.
Prof. Gallieni’s research interests include; clinical nephrology, CKD and dialysis, CKD-mineral and bone disorders, dialysis access, onco-nephrology, glomerular diseases and simulation training in interventional nephrology. He is Coordinating Editor of the Journal of Vascular Access and has authored 285 publications indexed in PubMed (H index: Scopus:33).
Dr Kieran McCafferty
Dr Kieran McCafferty is a Consultant Nephrologist and Renal Clinical Trial Lead at Barts Health NHS Trust and Senior Lecturer at Queen Mary University London. He is also the Deputy UK NIHR nephrology and Renal Network Lead for the North Thames.
Dr McCafferty’s research interests include haemodialysis, diabetic kidney disease and uraemic cardiovascular disease, however his work focuses on the development and delivery of nephrology clinical trials locally and nationally.
An initial theory of CKD-associated Pruritus pathophysiology implicated “uraemic toxins” including vitamin A, aluminium, calcium, phosphorus, and magnesium. This theory was based on several early observations:
- The association of CKD-associated Pruritus with underdialysis and with higher calcium, phosphorus, and parathyroid hormone (PTH) levels
- The improvement in CKD-associated Pruritus prevalence rates over time
- Improvements in pruritus after treatment of high calcium, PTH, and phosphorus levels, including with parathyroidectomy
It is currently thought that underdialysis and toxin deposition may cause CKD-associated Pruritus in a
subset of patients. In these patients, management of CKD-associated Pruritus should focus on
optimisation of haemodialysis in order to achieve Kidney Disease: Improving Global Outcomes (KDIGO)
goals for Kt/V, calcium, phosphorus, and PTH.
The opioid pathway, with receptors located in the brain, peripheral nerves, keratinocytes, melanocytes, hair follicles, and immune cells, has been increasingly recognised as an important modulator of itching. This theory of CKD-associated Pruritus pathophysiology suggests that overstimulation of central mu-opioid receptors, antagonism of peripheral kappa-opioid receptors, or an imbalance of stimulation and antagonism of mu- and kappa-opioid receptors causes itching.
This theory of CKD-associated Pruritus pathophysiology suggests that microinflammation in the skin and possibly systemic inflammation stimulate itching. Higher levels of inflammatory markers are seen in haemodialysis patients, including T-helper 1 cells, C-reactive protein, interleukin-6, and interleukin-2, support this theory. Furthermore, CKD-associated Pruritus is associated with high white blood cell counts, low albumin and high ferritin levels. The allergic response may also be dysregulated in CKD-associated Pruritus. Increased levels of eosinophils, mast cells, in addition to histamine and tryptase, have been found in patients with CKD-associated Pruritus.
Neuropathic itching is thought to result when primary afferent sensory neurons or interneurons are activated out of proportion to or independent of any detectable causative substances (such as toxins). This theory is supported by observation of a high prevalence of peripheral sensorimotor neuropathy and dysautonomia in haemodialysis patients, which may explain their itching. Furthermore, haemodialysis patients with paraesthesia and restless leg syndrome more frequently have CKD-associated Pruritus.
Vitamin A, aluminium,
and kappa-opioid receptor activity
of mu-opioid receptors
Antagonism of kappa-opioid receptors1
Skin microinflammation Allergy: eosinophils, mast cells, histamine
C-reactive protein, interleukin (IL)-6, IL-2, white blood cells, ferretin1
Abnormal skin innervation and nerve conduction1
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