Uremic pruritus is a common problem for patients with kidney disease that significantly impacts quality of life. The document discusses the prevalence, diagnosis, management, and pathophysiology of uremic pruritus based on evidence from multiple studies. Control of calcium, phosphorus and PTH levels can help reduce pruritus. Pregabalin is often used as first-line treatment, with other options including topical moisturizers, UVB phototherapy, pentoxifylline, and drugs targeting opioid and calcium channels if initial treatments are ineffective. Further research is still needed due to limitations and inconsistencies in current studies.

1. Uremic Pruritus
A Life Annoying Problem
Mohammed Abdel Gawad
Nephrology Specialist
Kidney & Urology Center (KUC)
Alexandria – EGY
drgawad@gmail.com

2. Talk Outline
• Prevalence
• Itching scales
• Effect on Sleep & QOL
• Diagnosis: Is it uremic pruritus?
• Management approach
• Basic science & evidence of some lines
• Terminology

3. Talk Outline
• Prevalence
• Itching scales
• Effect on Sleep & QOL
• Diagnosis: Is it uremic pruritus?
• Management approach
• Basic science & evidence of some lines
• Terminology

4. Perit Dial Int. 1993;13 Suppl 2:S527-32

5. Nephrol Dial Transplant. 2006 Dec;21(12):3495-505
Pruritus data were collected from 18801
HD patients (1996–2004)

6. Clin J Am Soc Nephrol. 2017 Sep 18

8. Talk Outline
• Prevalence
• Itching scales
• Effect on Sleep & QOL
• Diagnosis: Is it uremic pruritus?
• Management approach
• Basic science & evidence of some lines
• Terminology

9. Talk Outline
• Prevalence
• Itching scales
• Effect on Sleep & QOL
• Diagnosis: Is it uremic pruritus?
• Management approach
• Basic science & evidence of some lines
• Terminology

10. Semin Nephrol. 2015 Jul; 35(4): 383–391

11. Allergol Int. 2017 Jan;66(1):3-7

12. Talk Outline
• Prevalence
• Itching scales
• Effect on Sleep & QOL
• Diagnosis: Is it uremic pruritus?
• Management approach
• Basic science & evidence of some lines
• Terminology

13. Talk Outline
• Prevalence
• Itching scales
• Effect on Sleep & QOL
• Diagnosis: Is it uremic pruritus?
• Management approach
• Basic science & evidence of some lines
• Terminology

14. Nephrol Dial Transplant. 2006 Dec;21(12):3495-505
P<0.0001

15. Kidney Int. 2006 May;69(9):1626-32

16. Nephrol Dial Transplant. 2006 Dec;21(12):3495-505
Pruritus is
associated with
a 17% higher
mortality risk

17. WHOQOL-BREF questionnaire
J Clin Diagn Res. 2016 Mar; 10(3): WC01–WC05

18. Qual Life Res. 2012 May;21(4):603-12
Center for Epidemiological Studies Depression

19. Nephrol Dial Transplant. 2006 Dec;21(12):3495-505
Pruritus data were collected from 18801
HD patients (1996–2004)

20. Factors associated with odds of developing severe pruritus
Br J Dermatol. 2009 Aug;161(2):384-9

21. Talk Outline
• Prevalence
• Itching scales
• Effect on Sleep & QOL
• Diagnosis: Is it uremic pruritus?
• Management approach
• Basic science & evidence of some lines
• Terminology

22. Talk Outline
• Prevalence
• Itching scales
• Effect on Sleep & QOL
• Diagnosis: Is it uremic pruritus?
• Management approach
• Basic science & evidence of some lines
• Terminology

23. Is it uremic pruritus?
• Site: most commonly localized to the back, followed by the
forearm with an AVF, abdomen, or head.
• Symptoms tend to be worse at night
• increased pruritus with heat (especially with excessive
perspiration) and stress
• Decreased pruritus with physical activity, cooler
temperatures, and with either hot or cold showers
• Most cases presents dry and scaly.
Thomas Mettang. Kidney International (2015) 87, 685–691.
Am J Kidney Dis. 2007;50(1):11
01

24. Is it uremic pruritus?
Thomas Mettang. Kidney International (2015) 87, 685–691.
• Suspect other etiology if:
–More generalized.
–Primary specific skin lesions.
–Resistant pruritus.
Acta Derm Venereol 2012; 92: 563–581
01

25. Talk Outline
• Prevalence
• Itching scales
• Effect on Sleep & QOL
• Diagnosis: Is it uremic pruritus?
• Management approach
• Basic science & evidence of some lines
• Terminology

26. Talk Outline
• Prevalence
• Itching scales
• Effect on Sleep & QOL
• Diagnosis: Is it uremic pruritus?
• Management approach
• Basic science & evidence of some lines
• Terminology

27. Control Ca, Phosphrous, PTH
03
Thomas Mettang. Kidney International (2015) 87, 685–691.

28. Thomas Mettang. Kidney International (2015) 87, 685–691.
Modification: M.Gawad www.NephroTubeCNE.com
Control Ca, Phosphrous, PTH
Pregabalin
(25mg after HD
to 75 mg daily)
if not well
tolerated or
no response
(50 mg daily) !!! Skin cancer
02
After each
HD session

29. Control Ca, Phosphrous, PTH
Pregabalin
(25mg after HD
to 75 mg daily)
if not well
tolerated or
no response
(50 mg daily) !!! Skin cancer
Exclusion of
other
causes
including
drugs if
resistant
0
After each
HD session
Thomas Mettang. Kidney International (2015) 87, 685–691.
Modification: M.Gawad www.NephroTubeCNE.com

30. But remains substantially
higher than in the
general population and
impacts upon quality of
life in these patients
Clin Transplant. 2017 Mar;31(3)

31. Talk Outline
• Prevalence
• Itching scales
• Effect on Sleep & QOL
• Diagnosis: Is it uremic pruritus?
• Management approach
• Basic science & evidence of some lines
• Terminology

32. Talk Outline
• Prevalence
• Itching scales
• Effect on Sleep & QOL
• Diagnosis: Is it uremic pruritus?
• Management approach
• Basic science & evidence of some lines
• Terminology

33. Weak Soft Evidence
• Small number of patients were tested by different
studies.
• Conflicting and contradictory results
• Short time of follow up
• Lack of head-to-head comparisons among different
agents
• Different scoring systems for the intensity of pruritus
19

34. Risk-of-bias assessment for all
included studies
19
Am J Kidney Dis. 2017;70(5):638-655

35. Thomas Mettang. Kidney International (2015) 87, 685–691.
Modification: M.Gawad www.NephroTubeCNE.com
Control Ca, Phosphrous, PTH
Pregabalin
(25mg after HD
to 75 mg daily)
if not well
tolerated or
no response
(50 mg daily) !!! Skin cancer
Exclusion of
other
causes
including
drugs if
resistant
0
After each
HD session

36. Pathogenesis
Xerosis
Decrease in
sweat volume Atrophy
Dehydration
Pornanong Aramwit. Updates in Hemodialysis. Chapter 2. September 9, 2015.
15

37. Topical Moisturing & Emollients
Thomas Mettang. Kidney International (2015) 87, 685–691.
Manenti et al. Kidney Int, 2008. 73(4): p. 512.
It has been suggested by several researchers
that the use of emollients with high water
content should be the first-line treatment
• Dexpanthenol
• Glycerol and Paraffin
• If simple emollients fail:
–Evening Primrose oil rich in essential fatty
acids (γ-linolenic acid)
–Bath oil that contains polidocanol
–Cream that contains natural lipids and
endocannabinoids
Pornanong Aramwit. Updates in Hemodialysis. Chapter 2. September 9, 2015.
15

38. Thomas Mettang. Kidney International (2015) 87, 685–691.
Modification: M.Gawad www.NephroTubeCNE.com
Control Ca, Phosphrous, PTH
Pregabalin
(25mg after HD
to 75 mg daily)
if not well
tolerated or
no response
(50 mg daily) !!! Skin cancer
Exclusion of
other
causes
including
drugs if
resistant
0
After each
HD session

39. Pathogenesis – Nervous Conduction
Ca Channel
Thomas Mettang. Kidney International (2015) 87, 685–691.
11

40. Gabapentin / Pregabalin
Thomas Mettang. Kidney International (2015) 87, 685–691.
11

41. 11
J Dermatolog Treat. 2016 Nov;27(6):515-519
n = 54 placebo-
controlled study
100 mg after each HD session, titrated
up to 300 mg, if necessary

42. 11
J Dermatolog Treat. 2016 Nov;27(6):515-519
n = 54 placebo-
controlled study
100 mg after each HD session, titrated
up to 300 mg, if necessary

43. 10
Nephrology (Carlton).
2012 Nov;17(8):710-7

44. 10
Nephrology (Carlton).
2012 Nov;17(8):710-7
Both improved pruritus significantly, and there
was no difference between the study drugs in
terms of efficacy

45. Nephron Clin Pract. 2012;122(3-4):75-9
16 started Pregabalin
21
n = 13
(81%)
09

46. Thomas Mettang. Kidney International (2015) 87, 685–691.
Modification: M.Gawad www.NephroTubeCNE.com
Control Ca, Phosphrous, PTH
Pregabalin
(25mg after HD
to 75 mg daily)
if not well
tolerated or
no response
(50 mg daily) !!! Skin cancer
Exclusion of
other
causes
including
drugs if
resistant
0
After each
HD session

47. Pathogenesis
Opioid Hypothesis
Keiichi Niikura et al. Trends in Pharm Science. Volume 31, Issue 7. July 2010, Pages 299–305
09
↑ Pain
↓ Pain
Ƙ opioid receptor
mµ opioid receptor

48. Pathogenesis
Opioid Hypothesis
Kumagai H et al. In: Itch, Basic Mechanisms and Therapy, New York 2004. p.286.
09
↑ Pain
↓ Pain
Ratio of the µ-
receptor agonist
(beta-endorphin)
to
Ƙ-receptor agonist
(dynorphin-A)
is increased in
hemodialysis
patients
Ƙ opioid receptor
mµ opioid receptor

49. Naltrexone / Nalfurafine /
Nalbuphine, Butorphanol
Kumagai H et al. In: Itch, Basic Mechanisms and Therapy, New York 2004. p.286.
09
↑ Pain
↓ Pain
Ƙ opioid receptor
Naltrexone
mµ-antagonist
Nalfurafine
Ƙ-agonist
mµ opioid receptor

50. Naltrexone (mµ-antagonist)
Peer G et al. Lancet 1996; 348: 1552–1554.14.
n = 15
08

51. Kumagai H et al. Nephrol Dial Transplant 2010; 25: 1251–1257.
Nalfurafine (Ƙ-agonist)
Placebo (n=111)
5 µg (n=144), P = 0.0002
2.5 µg (n=112), P = 0.0001
08

52. Naltrexone / Nalfurafine /
Nalbuphine, Butorphanol
J Am Acad Dermatol. 2006;54(3):527
BMC Nephrol. 2015;16:47
08
↑ Pain
↓ Pain
Ƙ opioid receptor
Naltrexone
mµ-antagonist
Nalfurafine
Ƙ-agonist
mµ opioid receptor Nalbuphine,
Butorphanol
mµ-antagonist
Ƙ-agonist

53. Thomas Mettang. Kidney International (2015) 87, 685–691.
Modification: M.Gawad www.NephroTubeCNE.com
Control Ca, Phosphrous, PTH
Pregabalin
(25mg after HD
to 75 mg daily)
if not well
tolerated or
no response
(50 mg daily) !!! Skin cancer
Exclusion of
other
causes
including
drugs if
resistant
0
After each
HD session

54. PHOTOTHERAPY
UVB vs. UVA
• Broad band UVB phototherapy reported a
marked reduction in pruritus.
• Long-wave UVA radiation treatment did not
improve itch intensity.
• Saltzer et al. Cutis, 1975. 16: p.298-299.
• Gilchrest et al. N Engl J Med, 1977. 297(3): p. 136-138
• Gilchrest et al. Ann Intern Med 1979; 91: 17–21.
• Gilchrest. Int J Dermatol, 1979. 18(9): p. 741-748.
• Blachley et al. Am J Kidney Dis, 1985. 5(5): p.237-241.
• Tan JKL et al. J Amer Acad Dermatol 1991; 25: 811–818.
• Kurban et al. Clin Dermatol, 2008. 26(3): p. 255-264.
04

55. Thomas Mettang. Kidney International (2015) 87, 685–691.
Modification: M.Gawad www.NephroTubeCNE.com
Control Ca, Phosphrous, PTH
Pregabalin
(25mg after HD
to 75 mg daily)
if not well
tolerated or
no response
(50 mg daily) !!! Skin cancer
Exclusion of
other
causes
including
drugs if
resistant
0
After each
HD session

56. Pentoxifylline - Pathogenesis
The American Journal of Gastroenterology 109, 1424-1426 (September 2014)
13

57. Pentoxifylline - Pathogenesis
The American Journal of Gastroenterology 109, 1424-1426 (September 2014)
Anti-inflammatory
13

58. Pentoxifylline - Pathogenesis
The American Journal of Gastroenterology 109, 1424-1426 (September 2014)
Anti-inflammatory
13

59. Pentoxifylline - Pathogenesis
The American Journal of Gastroenterology 109, 1424-1426 (September 2014)
Anti-inflammatory
13

60. Mettang T et al. Nephrol Dial Transplant 2007; 22: 2727–2728.
Pentoxifylline: 600mg IV,
3X/week (at the end of each
dialysis session), for 4 weeks
n = 7 on HD (didn’t respond to
gabapentin or UVB-phototherapy)
3 patients
stopped
treatment
n = 1 Insomnia
n = 2 Nausea
n = 1 Jaundice
Itch score (median; range)
12

61. Check on www.NephroTubeCNE.com
Uremic Pruritus
Basic Science → Evidence → Practice
Mohammed Abdel Gawad
Nephrology Specialist
Kidney & Urology Center (KUC)
Alexandria – EGY
drgawad@gmail.com
17th Annual Conference
Damanhour Nephrology Department
10 / Nov / 2017

62. Talk Outline
• Prevalence
• Itching scales
• Effect on Sleep & QOL
• Diagnosis: Is it uremic pruritus?
• Management approach
• Basic science & evidence of some lines
• Terminology

63. Talk Outline
• Prevalence
• Itching scales
• Effect on Sleep & QOL
• Diagnosis: Is it uremic pruritus?
• Management approach
• Basic science & evidence of some lines
• Terminology

64. Thomas Mettang. Kidney International (2015) 87, 685–691.
03

65. Thomas Mettang. Kidney International (2015) 87, 685–691.
03
More accurately to be termed
‘chronic kidney disease-associated
pruritus’
(CKD-aP)

66. Home Messages

67. Home Messages
• CKDaP is a major problem
• Its prevalence is about 18%
• It affects sleep, QOL, and increases mortality

68. Thomas Mettang. Kidney International (2015) 87, 685–691.
Modification: M.Gawad www.NephroTubeCNE.com
Control Ca, Phosphrous, PTH
Pregabalin
(25mg after HD
to 75 mg daily)
if not well
tolerated or
no response
(50 mg daily) !!! Skin cancer
Exclusion of
other
causes
including
drugs if
resistant
0

69. Thank You