Obstacles to Early Diagnosis and Treatment of Pruritus in Patients with Chronic Kidney Disease: Current Perspectives

Figures & data

Figure 1 PRISMA Flow Diagram of Methodology.

Notes: PRISMA Figure adapted from Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372:n71. Creative Commons.⁷

Table 1 Importance of CKD-aP

PREVALENCE
Nondialysis CKD Patients	Wulczyn et al^Citation9 (CRIC Study)	42%	Severity increased nonlinearly with the progression of renal impairment
	CKDOPPS^Citation10	24% (23–29%)	Prevalence 19% higher in CKD5 compared to CKD3
	(RENINE/PROM)^Citation11	50%
Hemo-Dialysis Patients	Young et al^Citation8	85%
	DOPPS 1996–2004^Citation12 (Phase 1 to 3)	>70%
	DOPPS 1996–2004^Citation13 (Phase 4 to 6)	67%	Moderate to extreme in 37%
	JDOPPS 1999 −2008^Citation14	20–70%	Moderate to extreme in 44% (40–50%)
	LDO^Citation15	60%	14.5% very much bothered with itch
	ITCH National Registry USA^Citation16	84%
	China: pooled prevalence from 11 studies^Citation17	61%
	GEHIS (Germany)^Citation18	25%	Point prevalence 25.2%; lifetime prevalence of 35.2%
	Gatmiri et al (Iran)^Citation19	58%
PD	Tessari et al (Italy)^Citation20	52%	Mode of PD not mentioned
CAPD	Mettang et al^Citation21	50%
UNDER-REPORTING
Rayner et al^Citation22		17% of those with severe itch never reported their symptom to healthcare provider
CLINICAL ADVERSE EFFECTS
Higher mortality^Citation12,Citation13		17% higher mortality risk for patients with moderate to extreme pruritus compared with patients with mild or no pruritus
Reduced HRQoL^Citation12–14,Citation16,Citation18,Citation20,Citation23–28,Citation30
Higher hospitalization rate^Citation13
Higher withdrawal from dialysis^Citation13,Citation15
Decreased chance of employment^Citation13
Restless leg syndrome, chronic pain, sleep disturbance^Citation14,Citation18,Citation21,Citation30,Citation31
Increased use of medications^Citation15

Table 2 Symptom-Cluster of CKD-aP

Itching

Depression

Anxiety

Stress

Fatigue

Pain

Sleep disturbances

Restless leg syndrome

Post-dialysis fatigue

Figure 2 Pathogenic factors of CKD-aP and their interactions.

Table 3 Various Treatments Used in CKD-aP

Mode	Effective	Not Effective or Variable Effect
Topical	Emollients with high water content Emollients with natural lipids and endocannabinoids	GLA-rich 2.2% cream/primrose oil Dead Sea lotion Pramoxine HCl 1% lotion Tacrolimus 0.1% ointment thrice weekly Chinese herb−based cream Capsaicin 0.025% cream Sarna lotion Avena sativa lotion Cromolyn sodium 4% Lidocaine
Physical	Narrow-band UVB	Far-infrared ray
Systemic	Pregabaline Gabapentin Difelikefalin: 0.5 μg/kg IV thrice weekly Nalfurafine HCl 5 μg OD or 5 μg IV post-HD 3×/week Butorphanol 1 mg OD intranasally	Ondansetron 8 mg TDS Naltrexone 50 mg OD Montelukast Nicotinamide 500 mg BID Oral Zinc sulfate Oral cromolyn sodium 135 mg TDS 2 GLA-enriched evening primrose oil capsules BID Thalidomide 100 mg OD Cholestyramine 5 g BID Oral charcoal
Intervention	HFHD; HDF; MCO dialyzers High-permeability HD Renal transplant	Mg-free dialysate Parathyroidectomy
Empirical	Acupuncture	Auricular acupressure Chinese herb

Abbreviations: HFHD, high flux hemodialysis; HDF, hemodiafiltration.

Table 4 Risk Factors and Hazard Ratio of Moderate to Extreme CKD-aP

Risk Factors and HR of Moderate to Extreme CKD-aP*
Male (vs female) 1.10 Ascites (vs no) 1.85 Hepatitis C (vs no) 1.29 WBC count >5400/mL: 1.03−1.2 Serum phosphorus, >5.5: 1.2–1.37 Corrected serum calcium >10.2 g/dl: 1.22 Serum ferritin <100 ng/mL (vs 100–399 ng/mL) 1.03 Smoking (current or stopped smoking <1 year) 1.15 Systemic diseases – lung, neurological, CHF Serum albumin, <3.0 (vs. 3.51 - 4 g/dl): 1.17 Older age, per 10 years older: 1.04

Notes: *Based on DOPPS I & II.

Abbreviations: CHF, congestive heart failure; HR, hazard ratio.

Figure 3 Clinical management of CKD-aP.

Table 5 Areas of Research

Identification of modifiable risk factors Whether the use of preemptive emollients would benefit in delaying the development of CKD-aP Recognition of optimal dialysis dose If different dialyzer membranes have any benefit Research in the area of the symptom cluster Whether calcimimetics have any beneficial role Long-term risk versus the safety of UVB therapy When to use antihistamine drugs and how long Burden in early CKD stages Development of guidelines Epidemiology of pruritus not due to CKD-aP in CKD patients How to bring helpful practice patterns

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