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NNH Clinical Protocol

[PROTOCOL_TITLE]

[Brief one or two sentence description of what this protocol does, who it's for, and which guideline(s) and source paper it draws from.]

📚 [Primary guideline citation]📄 [Source paper citation]⚠️ For NNH clinical staff only
Step 1

[Picker step title — e.g. Select the procedure / Select the indication]

[One sentence guiding the clinician on what they're choosing.]

[OPTION_1_TITLE][short tag][OPTION_2_TITLE][short tag][OPTION_3_TITLE][short tag][OPTION_4_TITLE][short tag][OPTION_5_TITLE][short tag][OPTION_6_TITLE][short tag]
Recommendation

—

Choose a different procedure
Clinical decision support, not a substitute for clinical judgment. Verify allergies, drug interactions, and renal/hepatic dose adjustments before administration. [Replace this sentence with protocol-appropriate caveats about evidence quality, regulatory grade, or guideline limitations.]

Reference

[Primary reference — author list. Title in italics. Journal year;volume(issue):pages. doi:...]

[Secondary reference — e.g. relevant society guideline.]

Pathophysiology at a glance

The itch cascade in chronic kidney disease

CKD-associated pruritus is rarely a skin problem alone. It begins with a compromised barrier and is amplified by systemic inflammation and neural sensitization, ending in disrupted sleep and a measurable loss of quality of life.

Healthy skin

Intact barrier, balanced hydration and sensation

Baseline

Xerosis

Sweat-gland and barrier dysfunction, dry cracked skin

Stage 1

Inflammation

Systemic Th1 shift, rising IL-2, IL-6 and TNF-alpha

Stage 2

Neuropathic itch

Opioid imbalance and peripheral or central sensitization

Stage 3

Sleep disruption

Nocturnal scratching, fragmented sleep, daytime fatigue

Stage 4

Reduced quality of life

Depression, social withdrawal, lower treatment adherence

Outcome
40–60%of hemodialysis patients

Report some degree of itch, and roughly a quarter describe it as moderate to severe. Pruritus is markedly under-reported unless clinicians ask directly.

Mettang T, Kremer AE. Kidney Int. 2015. DOPPS pruritus data.

Why it matters: a mortality signal

Moderate to severe CKD-aP
Poor sleep · depression · chronic inflammation
Independently associated with higher mortality

In large dialysis cohorts, more severe pruritus tracks with worse sleep, more depression, and higher all-cause mortality, which reframes itch as a clinical quality marker rather than a cosmetic complaint.

Association, not causation. Mettang & Kremer, Kidney Int. 2015.

Pathophysiology Explorer

The Itch Engine

CKD-associated pruritus is multifactorial. Select a mechanism to see how it feeds itch generation. The same patient often has several drivers at once, which is why single-agent therapy frequently falls short.

Central driverCKD-Associated Pruritus
Select a mechanism

How itch is generated

Tap any node in the Itch Engine above to see how that mechanism lowers the itch threshold and drives the scratch-itch cycle.

Most patients have more than one active driver.

Diagnostic Workup Navigator

Is this truly CKD-associated pruritus?

CKD-aP is a diagnosis of attribution, not exclusion alone, but common mimics and co-existing causes are easy to miss. Check what applies, then read the stratified read-out.

Supportive Features that fit CKD-aP

Red flags Suggesting another or added cause

Dermatologic

Hepatic

Hematologic

Endocrine / Infectious / Malignancy

Make your selections above

As you check supportive features and red flags, this read-out classifies the picture as likely CKD-aP, a possible alternate diagnosis, or a mixed etiology.

    Severity Assessment

    How severe is it? (WI-NRS)

    The 24-hour Worst Itching Numerical Rating Scale anchors severity and is the same instrument used in the pivotal trials. Sleep and daily-life impact escalate urgency even at lower scores.

    0 none10 worst imaginable
    0
    NoneMildModSevV.Sev
    None

    Set the worst-itch score to classify severity and see the matched starting recommendations.

      Treatment Pyramid

      A stepped approach, built on a wide base

      Every level rests on the one below it. Foundational care and a thorough workup are never skipped, even when reaching for systemic therapy. Select a level for evidence, dosing, and pearls.

      Foundational Measures

      Fix the modifiable drivers first

      Before and alongside any drug, work the three foundational domains. Check what you have addressed; the dashboard tracks how much modifiable ground is covered.

      Skin care

      Dialysis optimization

      CKD-MBD optimization

      A planning aid, not a clinical record. Targets follow standard dialysis adequacy and KDIGO CKD-MBD guidance, individualized to the patient.

      Medication Navigator

      Choosing a systemic agent

      Ranked by strength of evidence in CKD-associated pruritus. Select an agent for dosing, onset, benefits, risks, and its role in the pathway.

      Difelikefalin Deep Dive

      Korsuva: turning the opioid balance toward kappa

      Itch is promoted by mu-opioid activity and suppressed by kappa-opioid signaling. Difelikefalin is a peripherally restricted kappa agonist, the only FDA-approved therapy for moderate-to-severe CKD-aP in hemodialysis.

      Mechanism, interactively

      Mu receptor Endogenous opioidsPromotes itch
      Kappa receptorDifelikefalin targetSuppresses itch
      Itch signalHigh

      Trial responder rates

      Dialysis-unit workflow

      1Order

      0.5 mcg/kg dry body weight, three times weekly with each HD. Supplied as a single-dose vial.

      2Administer

      IV bolus into the venous line of the dialysis circuit at the end of each session, during or after rinse-back.

      3Monitor

      Track WI-NRS response over 8 to 12 weeks; watch for GI and CNS effects; reassess if no benefit.

      Common adverse effects

      DiarrheaDizzinessVomiting

      Hemodialysis only. Difelikefalin has not been studied in peritoneal dialysis and is not approved or dosed for PD patients.

      Refractory Navigator

      When standard therapy is not enough

      Before labeling itch refractory, confirm the standard steps have truly been tried and adhered to. Then weigh the options below by evidence strength.

      Confirm what has failed

      0 of 4 confirmed. Re-treat any gap before escalating.

      NNH Clinical Workflow

      From symptom to longitudinal follow-up

      A single repeatable pathway that ties the tools above together, from the first report of itch through ongoing monitoring.

      Clinical pearls

      Take it with you

      References

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