Met Tang 2014

Uremic pruritusThomas Mettang1 and Andreas E. Kremer2

1Department of Nephrology, Deutsche Klinik fur Diagnostik, Wiesbaden, Germany and 2Department of Medicine 1, Friedrich-AlexanderUniversity of Erlangen-Nuremberg, Erlangen, Germany

Uremic pruritus or chronic kidney disease-associated pruritus

(CKD-aP) remains a frequent and compromising symptom in

patients with advanced or end-stage renal disease, strongly

reducing the patient’s quality of life. More than 40% of

patients undergoing hemodialysis suffer from chronic

pruritus; half of them complain about generalized pruritus.

The pathogenesis of CKD-aP remains obscure. Parathormone

and histamine as well as calcium and magnesium salts have

been suspected as pathogenetic factors. Newer hypotheses

are focusing on opioid-receptor derangements and

microinflammation as possible causes of CKD-aP, although

until now this could not be proven. Pruritus may be

extremely difficult to control, as therapeutic options are

limited. The most consequential approaches to treatment

are: topical treatment with or without anti-inflammatory

compounds or systemic treatment with (a) gabapentin,

(b) l-opioid receptor antagonists and j-agonists, (c) drugs

with an anti-inflammatory action, (d) phototherapy, or

(e) acupuncture. A stepwise approach is suggested starting

with emollients and gabapentin or phototherapy as first-line

treatments. In refractory cases, more experimental options as

l-opioid-receptor—antagonists (i.e., naltrexone) or j-opioid-

receptor agonist (nalfurafine) may be chosen. In desperate

cases, patients suitable for transplantation might be set on

‘high urgency’-status, as successful kidney transplantation

will relieve patients from CKD-aP.

Kidney International advance online publication, 8 January 2014;

doi:10.1038/ki.2013.454

KEYWORDS: chronic kidney disease; hemodialysis; itch; peritoneal dialysis;

uremic pruritus

Uremic pruritus or more accurately termed ‘chronic kidneydisease-associated pruritus’ (CKD-aP) remains a frequentand compromising symptom in patients with advanced orend-stage renal disease.1 The prevalence and the burden ofthis symptom are often underestimated by nephrologists.2

Effective treatment options are limited because of a lownumber of randomized, placebo-controlled trials with mostof them reporting only limited therapeutic success. In addition,several times in the past, reports on putative effective noveltreatment options were followed by studies with contradic-tory results.3–6 The lack of effective treatment modalities alsoresults from a still incomplete knowledge of the underlyingpathophysiological mechanisms. This review highlights therecent clinical and experimental findings focusing on thepathogenesis and current treatment options of CKD-aP.

CLINICAL FEATURES OF CKD-aP

Intensity and spatial distribution of pruritus in patients withchronic renal insufficiency may vary significantly over time.The degree of CKD-aP may range from sporadic discomfortto complete restlessness during day- and nighttime stronglyreducing the patient’s quality of life. The skin of affectedpatients is often unchanged, resembling that of patientswithout pruritus, which in most cases presents dry and scaly.In contrast to dermatological pruritus, primary skin lesionsare not observed in patients with CKD-aP. However,excoriations with and without impetigo, linear crusts,papules, ulcerations, and less commonly prurigo nodularismay be seen as secondary skin changes due to intensescratching activity (Figure 1a–c). Up to 50% of patients withCKD-aP complain about generalized pruritus.7,8 In theremaining patients, CKD-aP seems to affect predominantlyback, face, and shunt arm, respectively.9 Interestingly, inabout 25% of patients pruritus is reported most severeduring or immediately after dialysis. Once patients havedeveloped CKD-aP, this symptom will in most cases last formonth or years.10 In patients with generalized pruritus, othercauses such as dermatological, hepatobiliary, hematological,endocrinological, neurological and psychiatric disorders,drug intake as well as solid tumors need to be ruled out.

The diagnosis of CKD-aP may be challenging. Many patientswith CKD in advanced stages (IV–V) are suffering from otherdiseases, such as cardiovascular diseases, diabetes mellitus,chronic liver or hematological diseases, which by itself or bymedication given to treat these entities may provoke itch.

http://www.kidney-international.org m i n i r e v i e w

& 2013 International Society of Nephrology

Correspondence: Thomas Mettang, Department of Nephrology, Deutsche

Klinik fur Diagnostik, Aukammallee 33, Wiesbaden 65191, Germany.

E-mail: [email protected]

Received 3 March 2013; revised 14 August 2013; accepted 22 August

2013

Kidney International 1

http://dx.doi.org/10.1038/ki.2013.454

http://www.kidney-international.org

mailto:[email protected]

In some cases, the clinical appearance (localization, pattern,quality of itch, and so on) may be helpful to categorize theitch in these patients. Quite often, however, a definitivediagnosis cannot be established and treatment has to beinitiated according to considerations of likelihood.

Epidemiology

Although in the early days of dialysis treatment, CKD-aP wasa very common problem afflicting up to 85% of patients11 itsincidence declined to 50–60% in the late eighties.12 However,numbers are difficult to compare as chronic itch has rarely

been analyzed and instruments used to assess the intensity ofitch diverge.

A recent large-scale investigation on several thousand patientsreported that 440% of patients undergoing hemodialysissuffer from chronic pruritus1 (Figure 2). This study uncovered ahigher mortality of patients suffering from pruritus. However,when controlled for sleep disturbance this correlation did notremain statistically significant. Severe pruritus is, however, veryrare in pediatric patients on dialysis (Figure 3).13 Data on theprevalence of CKD-aP in patients undergoing peritonealdialysis are rather scarce. The few reports available, however,permit the conclusion that patients undergoing peritonealdialysis are similarly affected by pruritus as patients onhemodialysis.12,14 Although prevalence of pruritus has declinedduring the last decades potentially by improved hemodialysistechniques, this symptom remains a major clinical symptomand in severe cases often a medical challenge.

Etiopathology

The pathogenesis of CKD-aP remains obscure.15 Varioussubstances have been discussed as potential pruritogens in

Figure 1 | Typical skin changes observed in patients sufferingfrom chronic kidney disease-associated pruritus (CKD-aP).(a) Scratch marks with excoriations at the lower leg. (b) Typicalhyperkeratotic partly excoriated nodules (prurigo nodularis) locatedon the forearm. (c) Deep scars and prurigo nodules at the shouldersand back of a female patient.

30

20

10

0

Pat

ient

s (%

)

Somewhat1768/2105

Notn=1555/2135

Moderately1066/1339

Very much925/994

Extremely715/698

2629 29 29

18 1815 14

1210

45% / 42%

DOPPSI / DOPPSII

Degree of being bothered by itchiness

I II I II I II I II I II

Figure 2 | Prevalence and intensity of uremic pruritus accordingto DOPPS-data from 1996 to 1999 (I) and 2002 to 2003 (II) (afterPisoni et al.1). DOPPS, Dialysis Outcome and Practice Patterns Study.

Patients on dialysis Patients with uremic pruritus

Patients > 18 yearsPatients ≤ 18 years

95

505

199

18

9.1%

18.8%

Num

ber

of p

atie

nts

P = 0.0013

600

500

400

300

200

100

0

Figure 3 | Prevalence of uremic pruritus in children on dialysis(18 years or younger) and in adult dialysis patients (older than18 years). Prevalence of uremic pruritus in children is significantlylower than in adult patients (w2 test according to Schwab et al.13).

m i n i r e v i e w T Mettang and AE Kremer: Uremic pruritus

2 Kidney International

chronic renal diseases; however, a causal relation could neverbe established. Among others, parathormone and histaminewere investigated more closely as presumable pruritogenicfactors. Parathormone is believed to be a possiblepathogenetic factor based on the observation that persistentpruritus in patients with secondary hyperparathyroidismimproved after parathyroidectomy.16,17 In contrast,parathormone did not elicit any cutaneous reaction uponintradermal application in humans and could not be detectedin skin biopsies of affected patients.18

Stockenhuber et al.19 observed increased levels of histaminein patients with CKD-aP and suggested that accumulation ofthis classical pruritogen would have a key role. Nevertheless,contradictory data on the impact of histamine have beenreported.12 The absence of typical skin changes such as whealsand the regularly observed therapeutic failure of antihista-mines in patients with CKD-aP challenge the concept ofhistamine as a major pruritogen.20 Interestingly, increasedlevels of tryptase, another substance released by mast cells wereobserved in patients with CKD-aP.21

The impact of xenobiotic agents and uremia toxins hasnot yet been established. There is also some controversyabout the influence of other factors, that is, increased tissueconcentrations of vitamin A and metastatic microcalcifica-tions caused by calcium and magnesium salts.22

Xerosis of the skin is described in a large number ofpatients with renal failure and was suspected as a significantpathogenetic factor in CKD-aP. However, many patients withmarked xerosis do not necessarily suffer from itch but thosewho do often do better by moisturizing and rehydrating theskin. Thus, it is likely that xerosis adds to the intensity of itchif CKD-aP is present.23

Special attention has been focused on neuropathic changes,nerve proliferations of the pruritus-mediating cells, and centralnervous alterations. Similar to cholestatic pruritus, enhancedstimulation of the central m-opioid receptors by cumulatedendorphins or cumulated endogenic morphines has beensuggested as a cause for CKD-aP. This hypothesis wasunderlined by the observation in a single study showing asubstantial amelioration of itching in uremic patients after the

oral application of the m-opioid receptor antagonist naltrex-one.5 This positive anti-pruritic effect could, however, not beconfirmed in a large-scale study of our group on hemodialysispatients presenting with pruritus. A more recent hypothesis onCKD-aP reported on an imbalance between the activities ofthe mostly antagonistic acting m- and k-opioid receptors infavor of m-receptor activation. For this reason, application of ak-agonist was recommended for the treatment.

More recent research points to microinflammation onskin and probably systemic level as an etiopathologicallyrelevant factor in CKD-aP. In this regard, elevated levels ofc-reactive protein were observed in serum of hemodialysispatients with chronic pruritus;24,25 furthermore, relativelyincreased proinflammatory relevant TH1-cells and raisedinterleukin-6 concentrations could be detected in thesepatients by our study group.25 Figure 4 summarizes thepotential pathogenic factors in CKD-aP.

Treatment options

Pruritus may be extremely vexing at times and difficult tocontrol. Therapeutic options in CKD-aP are, however,limited. Most studies on this symptom are not reliablebecause of inadequate documentation of patient’s character-istics, concomitant diseases, therapeutic measures taken, andoften very low case numbers. Moreover, effects that mightbe statistically significant may not necessarily be clinicallyrelevant and vice versa. To give an example, a reduction ofitch intensity from 8 to 6 on a visual analog scale (VAS), eventhough not statistically significant, might mean a greatimprovement in the torture of itch, whereas a reduction from3.5 to 2.5 may be statistically significant without a subjectiveimprovement for the patient. Owing to a meticulous study byStaender et al. done in 192 patients with pruritus, theminimal clinical important difference is 1.40 for theimprovement of pruritus on a VAS ranging from 0 to 10(personal communication).

For future studies, improved strategies for the assessmentof itch are required that do better reflect the burden ofsuffering of our patients.

In the following, the most consequential approaches totreatment are presented:� Topical treatment� Gabapentin� Systemic treatment with m-opioid receptor antagonists andk-agonists

� Drugs with an anti-inflammatory action� Phototherapy� Acupuncture� Others

Table 1 summarizes most of the randomized controlledtrials on the above-mentioned treatment options.

TOPICAL TREATMENT

Daily topical treatment using rehydrating emollients shouldbe regarded as baseline therapy. Addition of cooling

Stimuli

• Parathormone• Histamine• Tryptase• Xenobiotica• Uremic toxins• Cytokines• Inflammation

CNS

• Opioid disbalance• Psychological factors

Supplemental influences

– Scaly skin, dry skin– Serological factors

Neuropathy

Nerve-proliferation

Figure 4 | Schematic synopsis of potential pathogenic factors inchronic kidney disease-associated pruritus (CKD-aP). CNS, centralnervous system.


T Mettang and AE Kremer: Uremic pruritus m i n i r e v i e w

substances such as menthol to emollients may furtherimprove its antipruritic effect. However, properly controlledstudies are lacking.

Tacrolimus ointments

Topical treatment with tacrolimus has been shown tocompletely or partially resolve eczema and pruritus in atopicdermatitis.26 As microinflammatory processes may beinvolved in the pathogenesis of CKD-aP, we tested thisdrug in a preliminary study of three patients on peritonealdialysis with severe CKD-aP. Patients applied tacrolimus0.03% ointment twice daily to the most affected areas for aperiod of 7 days and scored itch intensity on a VAS before,during, and after treatment. Tacrolimus ointment stronglyimproved pruritus during treatment period; however,pruritus rose back to baseline values within days after endof treatment.27 Our observation was confirmed in a proof ofconcept study by Kuypers et al.28 reporting about 25 patientstreated with tacrolimus ointment for a period of 6 weeks witha reduction of itch intensity by 43%. A more recent double-blind, vehicle-controlled study conducted on 22 hemodialysispatients with pruritus29 showed a strong reduction of itchintensity in both the verum and vehicle group of about 80%.A difference between tacrolimus and vehicle could not bedemonstrated. However, the highly unexpected improvementon the basic cream (vehicle) could not be explained by theauthors. One should note that no serious adverse reactionswere seen in this study using either tacrolimus or the carrier.

Gamma linolenic acid ointment

In a study conducted by Chen et al.30, a cream containinghigh concentrations of gamma linolenic acid (GLA), anessential fatty acid derived from certain plant seed oils, wastested on 17 patients with CKD-aP. In this randomized

double-blind, placebo-controlled, crossover study patientswere treated for 6 weeks, with a washout period of 2 weeks inbetween the two treatment phases. Paired analysis showedthat the intensity of pruritus was significantly reducedfollowing GLA treatment whereas pruritus scores afterplacebo treatment revealed a nonsignificant reduction. Thisinvestigation suggests that GLA can exert an improvedantipruritic effect over vehicle and may serve as a usefuladjunct in providing symptomatic relief. It was speculatedthat the mechanism of action of this therapeutic agent maybe the formation of anti-inflammatory acting prostaglandins,which are derived from the ‘prodrug’ GLA.

SYSTEMIC TREATMENT

Gabapentin and pregabalin. Gabapentin, an anticonvul-sant and centrally acting calcium-channel-blocker, has beenshown to exert a pain-modulating effect in patients withneuropathic pain. In a study by Gunal et al.31 involving25 patients on hemodialysis with CKD-aP, 300 mg of oralgabapentin administered three times weekly for 4 weeks wassafe and highly effective in reducing pruritus. Itch intensity asdetermined by a VAS dropped from 8.4 before treatment to1.2 after 4 weeks of treatment. Similar results could beobtained in another double-blind, controlled, crossover studytreating 34 patients with 100 mg gabapentin orally threetimes a week.32 Our group has seen comparable beneficialeffects in the use of gabapentin. As this drug is largely welltolerated, it should be considered as a promising treatmentoption in the management of CKD-aP if topical treatment isineffective. There are a couple of reports that pregabalin isreducing CKD-aP. One recent trial suggests that patientson dialysis not responding to or not tolerating gabapentinmight be switched to pregabalin with good success andtolerability.33

Table 1 | Selection of most important randomized, placebo-controlled trials in patients with CKD-aP

Author Intervention/medication DesignNumber of

patients treatedDuration oftreatment Results

Gunal et al.31 Gabapentin 300 mg p.o. three times a week RCT crossover 25 4 Weeks Highly significant effectRazeghi et al.32 Gabapentin 100 mg p.o. three times a week RCT crossover 34 4 Weeks Highly significant effectWikstrom et al.34 Nalfurafine 5mg i.v. three times a week Meta-analysis

of two RCTs144 2–4 Weeks Significant effect

Kumagai et al.35 Nalfurafine 2.5 vs. 5mg p.o. daily RCT 337 2 Weeks Significant effectPeer et al.5 Naltrexone 50 mg p.o. daily RCT crossover 15 7 Days Highly significant effectPauli-Magnus et al.6 Naltrexone 50 mg p.o. daily RCT crossover 23 28 Days No effect (no difference

between placebo and verum)Silva et al.37 Thalidomide100 mg p.o. daily RCT 29 7 Days Moderate but significant effect

(Po0.05)Duo41 Electro-acupuncture 3� weekly Controlled (sham

acupuncture)6 2 Weeks Significant effect

Che-Yi et al.42 Acupuncture 3� weekly Controlled (shamacupuncture)

40 1 Month Significant effect

Ko et al.40 Photo therapy (UVB-narrow band) Single blinded 21 6 Weeks No significant effectDuque et al.29 Tacrolimus 0.01%-ointment daily 2� daily Vehicle controlled 22 4 Weeks No significant difference

between vehicle and verumChen et al.30 2.2% Gamma linolenic acid–containing

ointment 3�dailyRCT crossover 17 2 Weeks Significant effect (Po0.0001)

Abbreviations: CKD-aP, chronic kidney disease-associated pruritus; i.v., intravenous; RCT, randomized controlled trial; UVB, ultraviolet light B.



l-Opioid receptor antagonists

Naltrexone. A placebo-controlled, double-blind, cross-over trial by Peer et al.5 showed that administration of oralnaltrexone for 1 week led to an almost complete resolution ofpruritus in 15 patients with severe CKD-aP. However, whentrying to confirm these results by a 4-week lasting placebo-controlled, double-blind, crossover study in 23 patients withsevere CKD-aP, we failed to demonstrate a significant effectof treatment with a daily dose of 50 mg naltrexone comparedwith placebo. Itch intensity decreased by 29.2% duringnaltrexone and by 16.9% during placebo treatment asdetermined by VAS without being statistically significant.6

The findings of Peer et al.5 are in sharp contrast to theresults of our study and cannot be explained by differencesin patients compliance, naltrexone dose, or study design,as both studies were randomized, placebo-controlled,double-blind, and crossover trials. The studies merelydiffered as to the intensity of pruritus in the evaluatedgroups. Although the trial by Peer et al. exclusivelyconcentrated on patients most seriously afflicted withpruritus (mean VAS 10), the mean intensity of pruritus inour patients was found to be VAS 6. This and otherdifferences, for instance, regarding hemodialysis treatment,the material used, divergent lifestyle, eating habits, andenvironmental circumstances in different parts of the worldmay well have been involved in causing these contradictingresults.

j-Opioid receptor agonists

As k-opioid receptors primarily mediate m-opioid receptor-antagonistic effects, and as k-agonistic drugs are known tosuppress morphine-induced itch, it was assumed that thesesubstances might be capable of alleviating pruritus. Thesesubstances are likely to act on spinal cord level by inhibitingthe itch impulse transmitted by the first neuron.

Nalfurafine. Nalfurafine is a highly selective k-opioid-receptor agonist. A meta-analysis of two randomized double-blind and placebo-controlled studies on a total of 144hemodialysis patients with CKD-aP corroborated an anti-pruritic effect of nalfurafine. In these studies, the substancewas administered as a short infusion following hemodialysisthree times weekly for a total period of 4 weeks. A moderate,but significant effect of nalfurafine could be demonstrated.34

In another randomized, prospective, placebo-controlledphase-III-study a total of 337 hemodialysis patients withpruritus were treated orally with nalfurafine hydrochlorideat doses of 2.5 or 5mg daily for 2 weeks.35 On treatmentwith the test substance, the itch intensity, measured by VAS(0–100 mm), significantly decreased by 22 (5mg) and 23 mm(2.5 mg), respectively, after 7 days of application, while itmerely dropped by 13 mm in the placebo group. However,the incidence of undesired drug actions (insomnia inparticular) was substantially higher in both verum groups(35.1% on 5mg and 25% on 2.5 mg) compared with theplacebo group (16.2%). Moreover, the effect of medicationwas wearing off fast once treatment was stopped.

Pentoxifylline

Suggesting that CKD-aP is mediated by systemic micro-inflammation, we investigated the use of pentoxifylline inseven hemodialysis patients with CKD-aP who did notrespond to treatment with gabapentin or ultraviolet light B(UVB)-phototherapy. Pentoxifylline, a weak tumor necrosisfactor-alpha inhibitor, was administered at 600 mg intrave-nously three times a week (at the end of each dialysis session)for 4 weeks. Those patients tolerating the drug experienced analmost complete resolution of pruritus, which continued for atleast 4 weeks after cessation of therapy. However, four patientsdiscontinued therapy due to treatment-related or -unrelatedhealth problems.36 Considering the rather modest tolerance ofthe agent at least with the dose chosen, this approach may onlybe recommended in severe refractory cases.

Thalidomide

Thalidomide, which is currently used as an immunomodu-lator to treat graft-versus-host reactions and myeloma,suppresses production of tumor necrosis factor-alpha andmay therefore be effective in the treatment of CKD-aP.37

A placebo-controlled, crossover, randomized double-blindstudy of thalidomide for the treatment of refractory uremicpruritus demonstrated improvements in itch scores inapproximately 55% of patients in both phases of the trial.Aside from the suppression of tumor necrosis factor-alpha, acentrally abating effect might be responsible for beneficialantipruritic effects.

PHOTOTHERAPY

In the late 1970s, Gilchrest et al.38 reported on theeffectiveness of sunburn-spectrum UVB-phototherapy onpatients with CKD-aP. Although long-wave UVA radiationtreatment did not improve itch intensity, 9 of 10 subjectstreated with UVB phototherapy reported a marked reductionin pruritus. Subsequently, a series of studies explored theeffectiveness of phototherapy in CKD-aP, particularly usingradiation with broadband UVB. According to a meta-analysisby Tan et al.39, the most promising phototherapy for uremicitch is UVB radiation, whereas UVA does not appear to beeffective. More recent research suggested that side effects ofnarrow-band UVB-radiation were less frequent and treatmentis just as effective as treatment using broadband UVB.However, in newer studies the effectiveness of narrow-bandUVB-radiation could not be verified.40 The risk forskin malignancies following UVB irradiation and long-termsystemic immunosuppression remains a matter of debate,especially in immunocompromised patients suffering fromadvanced disease or in those scheduled to receive immuno-suppressive treatment after renal transplantation. Thus,patients should be carefully evaluated before consideringUVB therapy.

ACUPUNCTURE

An interesting approach to treat CKD-aP is acupuncture.Electro-acupuncture or sham-electro-stimulation was applied



to six patients on hemodialysis in a blinded manner ina study by Duo41. Patients on acupuncture showed asignificantly higher reduction in pruritus determined by ascore than the sham-treated patients. In another study, 40patients with CKD-aP were treated with acupuncture eitherat the Quchi (LI11) acupoint or at a non-acupoint 2 cmlateral thrice weekly for 1 month. Patients treated using thecorrect acupoint revealed a substantial reduction in pruritususing a score regarding severity, distribution, and sleepdisturbance ending up with maximum 45 points (38.3±4.3,17.3±5.5, and 16.5±4.9 start vs. 4 weeks vs. 12 weeks later),whereas pruritus in patients with sham-acupuncture did notchange substantially (38.3±4.3, 37.5±3.2 and 37.1±5start vs. 4 weeks vs. 12 weeks later).42 Given these results,acupuncture at least in experienced hands might be a usefultool in the treatment of CKD-aP.

OTHERS

Many other substances such as orally applied activatedcharcoal, erythropoietin, and ondansentron have beenreported to be effective in case reports or case series, however,their beneficial effects could not be proven in randomized-controlled trials.43

Treatment of CKD-aP remains a frustrating endeavor andcontinues to present a significant therapeutic challenge.Besides topical treatment, gabapentin, immunomodulatory

drugs, and kappa-receptor agonists may be helpful in severecases. A stepwise approach is suggested in choosing atherapeutic modality, and whenever possible, treatmentshould be initiated with the drug exhibiting the mostfavorable safety and efficacy profiles (Figure 5). In desperatecases patients principally eligible for a kidney transplant maybe switched to ‘high urgency’ status, which will decrease theirwaiting time. In most cases, successful kidney transplantationwill relieve patients from CKD-aP.44 Figure 5 shows apotential therapeutic algorithm of CKD-aP.

PERSPECTIVES

During the last decade basic research on pruritus hasconsiderably emerged. Besides novel insights into centralitch processing, peripheral itch-signaling neurons, receptors,and intracellular signaling pathways could be identified. Itbecame apparent that different forms of itch are conveyed bydistinct pathways and that various mechanisms and factorsare involved in the pathogenesis of pruritus.45 Beside mastcells, eosinophilic granulocytes may contribute on skin levelto itch by release of neurotrophins, neuropeptides, and theircytotoxic granule proteins. Another interesting approachwould be to study the role of novel receptors being involvedin itch induction such as the mas-related G-protein coupledreceptors being activated by histamine and the anti-malariadrug chloroquine, the protease-activated receptors 2 and 4,which can be altered by exogenous and endogenous proteasesand the recently described histamine-4-receptor. Which ofthose cells and receptors may have a role in CKD-aP warrantfurther investigations. Thus, development of a causal phar-macological treatment for those patients remains on thedistant horizon.

DISCLOSURETM has served as a scientific consultant for FMC and receivedspeakers honorary from Roche, Amgen, Sanofi, and Baxter. AEKdeclared no competing interests.

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international results from the Dialysis Outcomes and Practice PatternsStudy (DOPPS). Nephrol Dial Transplant 2006; 21: 3495–3505.

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7. Narita I, Alchi B, Omori K et al. Etiology and prognostic significance ofsevere uremic pruritus in chronic hemodialysis patients. Kidney Int 2006;69: 1626–1632.

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among patients undergoing maintenance hemodialysis. Arch Dermatol1982; 118: 154–156.

Exclusion of other causes for pruritus

Assessment of severityof pruritus

WeakMoisturing ointment

oil bath

Moisturing ointment /oil bath

Increase doseof dialysis

KtV < 1.2

KtV > 1.2

Quality of dialysis(Kt/V)

Persisting

Persisting

Persisting

and

Gabapentin100-300 mg or

or or

or orUVB

phototherapyCharcoal(6g/die)

Nalfurafine2.5 – 5.0 mg p.o.

Naltrexone Tacrolimus ointment (Electro-) acupuncture

Consider kidney transplantation

Severe

Figure 5 | Therapeutic algorithm in chronic kidneydisease-associated pruritus (CKD-aP). Kt/V, urea clearance inrelation to urea distribution volume; UVB, ultraviolet light B.



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Met Tang 2014