Fast Facts: Kidney Itch

CKD-associated pruritus: under-recognized and under-treated

H. Rayner, N. Sukul

• Publisher: S. Karger
• Year: 2022
• ISBN:
  9783318065138
• Topic: Medizin
• Subtopic: Nephrologie

Chronic kidney disease-associated pruritus, also known as uremic pruritus and in this book called 'kidney itch', is defined as itching suffered by people with chronic kidney disease who have no other condition to explain it. Repeated scratching causes trauma, bleeding and, eventually, scarring of the skin. Kidney itch can also have far-reaching effects on quality of life, with patients' work and social life commonly affected. Even though kidney itch is common, it often goes undiagnosed, and when recognized, it is often inadequately treated or not treated at all. 'Fast Facts: Kidney Itch' describes the problem of kidney itch in detail, documents its impact on people's lives, reviews the current understanding of its pathophysiology, and then sets out an evidence-based approach to its assessment and management. Table of Contents: • Clinical features • Causes • How common is kidney itch and who is most at risk? • The wider impact • Approach to management

5Approach to management

Assessment

You are unlikely to know if someone is suffering from kidney itch unless you ask them. Many people do not talk about their itch symptoms with clinicians. If you adopt the habit of asking every person at every consultation: ‘Are you bothered by itching?’, you may be surprised by the answers you get.

For people treated with dialysis, a question about itching should be routinely included in the regular health reviews carried out by the dialysis team. If an individual is bothered by itching, consider it to be due to kidney disease unless there is an alternative explanation.

The next step is to assess the severity of the itch with the following questions.

•How much are you bothered by itching? Slightly, moderately, very much or extremely?’

•How bad is your itching out of 10, where 10 is the worst itching you can imagine?’

•Where on your body do you itch?’

•Do you make yourself bleed by scratching?’

You should then enquire about symptoms that are associated with itching.

•How does the itching affect your life?’

•How well do you sleep?’

•Do your legs feel restless?’

•Do you feel down (blue) or depressed?’

Treatment principles

All people with chronic itch should be encouraged to use moisturizing cream or emollient for the dry skin that very often accompanies it.¹ Treatment should then be guided by the severity of the itch.

Individuals with any of the following have severe itch:

•severity score of 7 or more out of 10

•widespread itching

•bleeding from scratching

•sleep disturbed by itching

•depressed about itching and its effects on their life.

Offer systemic treatment as first-line therapy to people with severe kidney itch.

Individuals with less severe or localized itching may wish to continue with topical moisturizing cream or emollient alone.

All people with kidney itch should be reviewed regularly to monitor the severity of their itching. Of hemodialysis patients responding to a DOPPS survey who were not at all or somewhat bothered by itching, 22% became at least moderately bothered 1 year later.²

How should I judge clinical trial evidence about therapies?

Many substances have been studied as possible treatments for kidney itch. Keep the points outlined in Table 5.1 in mind when judging whether a clinical trial provides reliable evidence.

TABLE 5.1

Judging the reliability of evidence from a clinical trial

Is there a placebo control?

There is a considerable placebo effect from most treatments for itching, so the efficacy of a substance can only be judged by comparison against a placebo.

Is there regression toward the mean?

Kidney itch typically varies in severity over time, so any reduction in itch may be the natural easing after an especially severe period.

Is there an adequate washout period between treatments?

In trials where different treatments are used sequentially, the effect of the first may linger and still be present when the next substance is started. This is especially the case for systemic treatments that are excreted by the kidneys.

Is the number of participants large enough to show a difference with confidence?

The size of the sample needed depends on the magnitude of the effect. If the treatment is very effective, a relatively small sample may be enough to show a clear difference from placebo.

How severe is the itching at baseline in the study population?

The individuals in the trial should match the patient you are planning to treat. A treatment that has been shown to help those who are severely affected may not be right for those less badly affected.

How large is the effect?

A treatment may have an effect that is big enough to be statistically significant but too small to be of benefit to the patient.

Are the side effects of the treatment clearly described?

An effective treatment that carries a high risk of very unpleasant or serious side effects may not be an attractive choice. The side effects must also be compared with those of the control as the nocebo effect can be surprisingly large.

Does the study measure other outcomes that matter to patients?

Measurement of the effect on the patient’s wider quality of life is very helpful for assessing the usefulness of a treatment.

The most rigorous and comprehensive review of treatments for kidney itch has been published by Cochrane³ and is 174 pages long. It applied strict criteria for assessing the quality of all available studies of interventions for itch in people with advanced CKD. Its conclusions highlight the need for a rethink of current practice.

Which systemic treatment is most effective?

Table 5.2 summarizes the results of high-quality trials of systemic treatments for kidney itch.³ To put these results in context, it has been suggested that the minimum clinically important difference for improvement of itch on a VAS from 0 to 10 cm is 1.4 cm.⁴

Gabapentin and pregabalin. Although gabapentin and pregabalin were designed as GABA analogs, they do not bind to GABA receptors, do not convert into GABA or another GABA receptor agonist in vivo, and do not modulate GABA transport or metabolism. Instead, they inhibit voltage-gated calcium channels in neuronal membranes.⁵

Both drugs have been shown to significantly reduce kidney itch in clinical trials (Figure 5.1).

TABLE 5.2

Summary of high-quality placebo-controlled trials of systemic treatments for CKD-associated itch

Treatment	Mean change in itch compared with placebo on a 0–10 cm VAS	Number of participants (number of RCTs)
GABA analogs
Gabapentin,	4.95 cm lower than placebo	297 (5)
pregabalin	95% CI 5.46–4.44 lower
κ-opioid agonists
Nalfurafine,	1.05 cm lower than place...