Role of Dysregulated Ion Channels in Sensory Neurons in Chronic Kidney Disease-Associated Pruritus
Identifieur interne : 000697 ( Pmc/Curation ); précédent : 000696; suivant : 000698Role of Dysregulated Ion Channels in Sensory Neurons in Chronic Kidney Disease-Associated Pruritus
Auteurs : Akishi Momose ; Micihihiro Yabe ; Shigetoshi Chiba ; Kenjirou Kumakawa ; Yasuo Shiraiwa ; Hiroki Mizukami [Japon]Source :
- Medicines [ 2305-6320 ] ; 2019.
Abstract
Url:
DOI: 10.3390/medicines6040110
PubMed: 31766242
PubMed Central: 6963506
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Role of Dysregulated Ion Channels in Sensory Neurons in Chronic Kidney Disease-Associated Pruritus</title><author><name sortKey="Momose, Akishi" sort="Momose, Akishi" uniqKey="Momose A" first="Akishi" last="Momose">Akishi Momose</name><affiliation><nlm:aff id="af1-medicines-06-00110">Department of Urology, Jusendo General Hospital, Koriyama 9638585, Japan;<email>m.yabe@jusendo.or.jp</email> (M.Y.);<email>s.chiba@jusendo.or.jp</email> (S.C.);<email>k.kumakawa@jusendo.or.jp</email> (K.K.);<email>y.shiraiwa@jusendo.or.jp</email> (Y.S.)</nlm:aff></affiliation></author><author><name sortKey="Yabe, Micihihiro" sort="Yabe, Micihihiro" uniqKey="Yabe M" first="Micihihiro" last="Yabe">Micihihiro Yabe</name><affiliation><nlm:aff id="af1-medicines-06-00110">Department of Urology, Jusendo General Hospital, Koriyama 9638585, Japan;<email>m.yabe@jusendo.or.jp</email> (M.Y.);<email>s.chiba@jusendo.or.jp</email> (S.C.);<email>k.kumakawa@jusendo.or.jp</email> (K.K.);<email>y.shiraiwa@jusendo.or.jp</email> (Y.S.)</nlm:aff></affiliation></author><author><name sortKey="Chiba, Shigetoshi" sort="Chiba, Shigetoshi" uniqKey="Chiba S" first="Shigetoshi" last="Chiba">Shigetoshi Chiba</name><affiliation><nlm:aff id="af1-medicines-06-00110">Department of Urology, Jusendo General Hospital, Koriyama 9638585, Japan;<email>m.yabe@jusendo.or.jp</email> (M.Y.);<email>s.chiba@jusendo.or.jp</email> (S.C.);<email>k.kumakawa@jusendo.or.jp</email> (K.K.);<email>y.shiraiwa@jusendo.or.jp</email> (Y.S.)</nlm:aff></affiliation></author><author><name sortKey="Kumakawa, Kenjirou" sort="Kumakawa, Kenjirou" uniqKey="Kumakawa K" first="Kenjirou" last="Kumakawa">Kenjirou Kumakawa</name><affiliation><nlm:aff id="af1-medicines-06-00110">Department of Urology, Jusendo General Hospital, Koriyama 9638585, Japan;<email>m.yabe@jusendo.or.jp</email> (M.Y.);<email>s.chiba@jusendo.or.jp</email> (S.C.);<email>k.kumakawa@jusendo.or.jp</email> (K.K.);<email>y.shiraiwa@jusendo.or.jp</email> (Y.S.)</nlm:aff></affiliation></author><author><name sortKey="Shiraiwa, Yasuo" sort="Shiraiwa, Yasuo" uniqKey="Shiraiwa Y" first="Yasuo" last="Shiraiwa">Yasuo Shiraiwa</name><affiliation><nlm:aff id="af1-medicines-06-00110">Department of Urology, Jusendo General Hospital, Koriyama 9638585, Japan;<email>m.yabe@jusendo.or.jp</email> (M.Y.);<email>s.chiba@jusendo.or.jp</email> (S.C.);<email>k.kumakawa@jusendo.or.jp</email> (K.K.);<email>y.shiraiwa@jusendo.or.jp</email> (Y.S.)</nlm:aff></affiliation></author><author><name sortKey="Mizukami, Hiroki" sort="Mizukami, Hiroki" uniqKey="Mizukami H" first="Hiroki" last="Mizukami">Hiroki Mizukami</name><affiliation wicri:level="1"><nlm:aff id="af2-medicines-06-00110">Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki 0368563, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki 0368563</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31766242</idno><idno type="pmc">6963506</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6963506</idno><idno type="RBID">PMC:6963506</idno><idno type="doi">10.3390/medicines6040110</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000697</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000697</idno><idno type="wicri:Area/Pmc/Curation">000697</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000697</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Role of Dysregulated Ion Channels in Sensory Neurons in Chronic Kidney Disease-Associated Pruritus</title><author><name sortKey="Momose, Akishi" sort="Momose, Akishi" uniqKey="Momose A" first="Akishi" last="Momose">Akishi Momose</name><affiliation><nlm:aff id="af1-medicines-06-00110">Department of Urology, Jusendo General Hospital, Koriyama 9638585, Japan;<email>m.yabe@jusendo.or.jp</email> (M.Y.);<email>s.chiba@jusendo.or.jp</email> (S.C.);<email>k.kumakawa@jusendo.or.jp</email> (K.K.);<email>y.shiraiwa@jusendo.or.jp</email> (Y.S.)</nlm:aff></affiliation></author><author><name sortKey="Yabe, Micihihiro" sort="Yabe, Micihihiro" uniqKey="Yabe M" first="Micihihiro" last="Yabe">Micihihiro Yabe</name><affiliation><nlm:aff id="af1-medicines-06-00110">Department of Urology, Jusendo General Hospital, Koriyama 9638585, Japan;<email>m.yabe@jusendo.or.jp</email> (M.Y.);<email>s.chiba@jusendo.or.jp</email> (S.C.);<email>k.kumakawa@jusendo.or.jp</email> (K.K.);<email>y.shiraiwa@jusendo.or.jp</email> (Y.S.)</nlm:aff></affiliation></author><author><name sortKey="Chiba, Shigetoshi" sort="Chiba, Shigetoshi" uniqKey="Chiba S" first="Shigetoshi" last="Chiba">Shigetoshi Chiba</name><affiliation><nlm:aff id="af1-medicines-06-00110">Department of Urology, Jusendo General Hospital, Koriyama 9638585, Japan;<email>m.yabe@jusendo.or.jp</email> (M.Y.);<email>s.chiba@jusendo.or.jp</email> (S.C.);<email>k.kumakawa@jusendo.or.jp</email> (K.K.);<email>y.shiraiwa@jusendo.or.jp</email> (Y.S.)</nlm:aff></affiliation></author><author><name sortKey="Kumakawa, Kenjirou" sort="Kumakawa, Kenjirou" uniqKey="Kumakawa K" first="Kenjirou" last="Kumakawa">Kenjirou Kumakawa</name><affiliation><nlm:aff id="af1-medicines-06-00110">Department of Urology, Jusendo General Hospital, Koriyama 9638585, Japan;<email>m.yabe@jusendo.or.jp</email> (M.Y.);<email>s.chiba@jusendo.or.jp</email> (S.C.);<email>k.kumakawa@jusendo.or.jp</email> (K.K.);<email>y.shiraiwa@jusendo.or.jp</email> (Y.S.)</nlm:aff></affiliation></author><author><name sortKey="Shiraiwa, Yasuo" sort="Shiraiwa, Yasuo" uniqKey="Shiraiwa Y" first="Yasuo" last="Shiraiwa">Yasuo Shiraiwa</name><affiliation><nlm:aff id="af1-medicines-06-00110">Department of Urology, Jusendo General Hospital, Koriyama 9638585, Japan;<email>m.yabe@jusendo.or.jp</email> (M.Y.);<email>s.chiba@jusendo.or.jp</email> (S.C.);<email>k.kumakawa@jusendo.or.jp</email> (K.K.);<email>y.shiraiwa@jusendo.or.jp</email> (Y.S.)</nlm:aff></affiliation></author><author><name sortKey="Mizukami, Hiroki" sort="Mizukami, Hiroki" uniqKey="Mizukami H" first="Hiroki" last="Mizukami">Hiroki Mizukami</name><affiliation wicri:level="1"><nlm:aff id="af2-medicines-06-00110">Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki 0368563, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki 0368563</wicri:regionArea></affiliation></author></analytic><series><title level="j">Medicines</title><idno type="eISSN">2305-6320</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><bold>Background:</bold> We investigated ion channels at the skin, including peripheral nerve endings, which serve as output machines and molecular integrators of many pruritic inputs mainly received by multiple G protein-coupled receptors (GPCRs). <bold>Methods:</bold> Based on the level of chronic kidney disease–associated pruritus (CKD-aP), subjects were divided into two groups: non-CKD-aP (no or slight pruritus; n = 12) and CKD-aP (mild, moderate, or severe pruritus; n = 11). Skin samples were obtained from the forearm or elbow during operations on arteriovenous fistulas. We measured ion channels expressed at the skin, including peripheral nerve endings by RT-PCR: Nav1.8, Kv1.4, Cav2.2, Cav3.2, BK<sub>Ca</sub>, Anoctamin1, TRPV1, TRPA1, and ASIC. <bold>Results:</bold> Expression of Cav3.2, BK<sub>Ca</sub>, and anoctamin1 was significantly elevated in patients with CKD-aP. On the other hand, expression of TRPV1 was significantly reduced in these patients. We observed no significant difference in the levels of Cav2.2 or ASIC between subjects with and without CKD-aP. TRPA1, Nav1.8, and Kv1.4 were not expressed. <bold>Conclusions:</bold> It was concluded that this greater difference in the expression of ion channels in the skin tissue including, specially cutaneous peripheral nerve endings in CKD patients with CKD-aP may increase generator potential related to itching.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Momose, A" uniqKey="Momose A">A. Momose</name></author><author><name sortKey="Yabe, M" uniqKey="Yabe M">M. Yabe</name></author><author><name sortKey="Chiba, S" uniqKey="Chiba S">S. Chiba</name></author><author><name sortKey="Kumakawa, K" uniqKey="Kumakawa K">K. Kumakawa</name></author><author><name sortKey="Shiraiwa, Y" uniqKey="Shiraiwa Y">Y. Shiraiwa</name></author><author><name sortKey="Kusumi, T" uniqKey="Kusumi T">T. Kusumi</name></author><author><name sortKey="Mizukami, H" uniqKey="Mizukami H">H. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Medicines (Basel)</journal-id><journal-id journal-id-type="iso-abbrev">Medicines (Basel)</journal-id><journal-id journal-id-type="publisher-id">medicines</journal-id><journal-title-group><journal-title>Medicines</journal-title></journal-title-group><issn pub-type="epub">2305-6320</issn><publisher><publisher-name>MDPI</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31766242</article-id><article-id pub-id-type="pmc">6963506</article-id><article-id pub-id-type="doi">10.3390/medicines6040110</article-id><article-id pub-id-type="publisher-id">medicines-06-00110</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Role of Dysregulated Ion Channels in Sensory Neurons in Chronic Kidney Disease-Associated Pruritus</article-title></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="true">https://orcid.org/0000-0002-1342-6997</contrib-id><name><surname>Momose</surname><given-names>Akishi</given-names></name><xref ref-type="aff" rid="af1-medicines-06-00110">1</xref><xref rid="c1-medicines-06-00110" ref-type="corresp">*</xref></contrib><contrib contrib-type="author"><name><surname>Yabe</surname><given-names>Micihihiro</given-names></name><xref ref-type="aff" rid="af1-medicines-06-00110">1</xref></contrib><contrib contrib-type="author"><name><surname>Chiba</surname><given-names>Shigetoshi</given-names></name><xref ref-type="aff" rid="af1-medicines-06-00110">1</xref></contrib><contrib contrib-type="author"><name><surname>Kumakawa</surname><given-names>Kenjirou</given-names></name><xref ref-type="aff" rid="af1-medicines-06-00110">1</xref></contrib><contrib contrib-type="author"><name><surname>Shiraiwa</surname><given-names>Yasuo</given-names></name><xref ref-type="aff" rid="af1-medicines-06-00110">1</xref></contrib><contrib contrib-type="author"><name><surname>Mizukami</surname><given-names>Hiroki</given-names></name><xref ref-type="aff" rid="af2-medicines-06-00110">2</xref></contrib></contrib-group><aff id="af1-medicines-06-00110"><label>1</label>Department of Urology, Jusendo General Hospital, Koriyama 9638585, Japan;<email>m.yabe@jusendo.or.jp</email> (M.Y.);<email>s.chiba@jusendo.or.jp</email> (S.C.);<email>k.kumakawa@jusendo.or.jp</email> (K.K.);<email>y.shiraiwa@jusendo.or.jp</email> (Y.S.)</aff><aff id="af2-medicines-06-00110"><label>2</label>Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki 0368563, Japan</aff><author-notes><corresp id="c1-medicines-06-00110"><label>*</label>Correspondence: <email>a.momose@jusendo.or.jp</email></corresp></author-notes><pub-date pub-type="epub"><day>13</day><month>11</month><year>2019</year></pub-date><pub-date pub-type="collection"><month>12</month><year>2019</year></pub-date><volume>6</volume><issue>4</issue><elocation-id>110</elocation-id><history><date date-type="received"><day>12</day><month>9</month><year>2019</year></date><date date-type="accepted"><day>11</day><month>11</month><year>2019</year></date></history><permissions><copyright-statement>© 2019 by the authors.</copyright-statement><copyright-year>2019</copyright-year><license license-type="open-access"><license-p>Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>).</license-p></license></permissions><abstract><p><bold>Background:</bold> We investigated ion channels at the skin, including peripheral nerve endings, which serve as output machines and molecular integrators of many pruritic inputs mainly received by multiple G protein-coupled receptors (GPCRs). <bold>Methods:</bold> Based on the level of chronic kidney disease–associated pruritus (CKD-aP), subjects were divided into two groups: non-CKD-aP (no or slight pruritus; n = 12) and CKD-aP (mild, moderate, or severe pruritus; n = 11). Skin samples were obtained from the forearm or elbow during operations on arteriovenous fistulas. We measured ion channels expressed at the skin, including peripheral nerve endings by RT-PCR: Nav1.8, Kv1.4, Cav2.2, Cav3.2, BK<sub>Ca</sub>, Anoctamin1, TRPV1, TRPA1, and ASIC. <bold>Results:</bold> Expression of Cav3.2, BK<sub>Ca</sub>, and anoctamin1 was significantly elevated in patients with CKD-aP. On the other hand, expression of TRPV1 was significantly reduced in these patients. We observed no significant difference in the levels of Cav2.2 or ASIC between subjects with and without CKD-aP. TRPA1, Nav1.8, and Kv1.4 were not expressed. <bold>Conclusions:</bold> It was concluded that this greater difference in the expression of ion channels in the skin tissue including, specially cutaneous peripheral nerve endings in CKD patients with CKD-aP may increase generator potential related to itching.</p></abstract><kwd-group><kwd>uremic pruritus</kwd><kwd>ion channels</kwd><kwd>cell signaling</kwd><kwd>Cav3.2 calcium channel</kwd><kwd>RT-PCR</kwd><kwd>skin</kwd></kwd-group></article-meta></front><floats-group><table-wrap id="medicines-06-00110-t001" orientation="portrait" position="float"><object-id pub-id-type="pii">medicines-06-00110-t001_Table 1</object-id><label>Table 1</label><caption><p>Definitions of Shiratori’s itch severity scores.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="center" valign="top" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Score (Severity)</th><th align="left" valign="top" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Daytime Symptoms</th><th align="left" valign="top" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Nighttime Symptoms</th></tr></thead><tbody><tr><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">4 (severe)</td><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Intolerable itching, worsened instead of relieved by scratching. Cannot focus on work or study</td><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Can hardly sleep because of itching. Scratching all the time, but itching intensifies with scratching</td></tr><tr><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">3 (moderate)</td><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Scratching even in the presence of others. Irritation as a result of itching, continuous scratching</td><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Wake up because of itching. Can fall asleep again after scratching, but continue to scratch unconsciously while sleeping </td></tr><tr><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">2 (mild)</td><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Itch sensation is relieved by light, occasional scratching. Not too disturbing</td><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Feel somewhat itchy, which is relieved by scratching. Do not wake up because of itch sensations</td></tr><tr><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">1 (slight)</td><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Feel itchy sometimes, but tolerable without scratching</td><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Feel slightly itchy when going to sleep, but do not need to scratch. Sleeping well</td></tr><tr><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">0 (no symptoms)</td><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Hardly feel itchy or do not feel itchy at all</td><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Hardly feel itchy or do not feel itchy at all</td></tr></tbody></table></table-wrap><table-wrap id="medicines-06-00110-t002" orientation="portrait" position="float"><object-id pub-id-type="pii">medicines-06-00110-t002_Table 2</object-id><label>Table 2</label><caption><p>Gene Assays ID.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" valign="top" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Gene Name</th><th align="left" valign="top" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Assay ID</th></tr></thead><tbody><tr><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">ASIC1(acid sensing ion channel subunit 1)</td><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Hs00952807_m1</td></tr><tr><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Anoctamin 1</td><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Hs00216121_m1</td></tr><tr><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">CACNA 1B (Cav2.2)</td><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Hs04996252_m1</td></tr><tr><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">CACNA1H (Cav3.2)</td><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Hs01103527_m1</td></tr><tr><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">KCNA4 (Kv1.4)</td><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Hs00937357_s1</td></tr><tr><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">KCNMA1 (BK<sub>Ca</sub>)</td><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Hs01119504_m1</td></tr><tr><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">SCN10A (Nav1.8)</td><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Hs01045151_m1</td></tr><tr><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">TRPA1 </td><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Hs00175798_m1</td></tr><tr><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">TRPV1 </td><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Hs00218912_m1</td></tr><tr><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">beta-2-microglobulin </td><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">Hs00187842_m1</td></tr></tbody></table><table-wrap-foot><fn><p>Pre-made TaqMan<sup>®</sup> Gene Expression Assays for human were used (Thermo Fisher Scientific, Waltham, MA, USA).</p></fn></table-wrap-foot></table-wrap><table-wrap id="medicines-06-00110-t003" orientation="portrait" position="float"><object-id pub-id-type="pii">medicines-06-00110-t003_Table 3</object-id><label>Table 3</label><caption><p>Patient characteristics.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Characteristic</th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Non-Pruritus<break></break>(n = 12)</th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Pruritus<break></break>(n = 11)</th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1"><italic>p</italic> Value</th></tr></thead><tbody><tr><td align="left" valign="middle" rowspan="1" colspan="1">Degree of pruritus</td><td align="left" valign="middle" rowspan="1" colspan="1">none, slight</td><td align="left" valign="middle" rowspan="1" colspan="1">mild, moderate, severe</td><td align="left" valign="middle" rowspan="1" colspan="1"></td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Gender (F/M)</td><td align="left" valign="middle" rowspan="1" colspan="1">4/8</td><td align="left" valign="middle" rowspan="1" colspan="1">4/7</td><td align="left" valign="middle" rowspan="1" colspan="1">>0.05</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Age (y.o.)</td><td align="left" valign="middle" rowspan="1" colspan="1">68 ± 10</td><td align="left" valign="middle" rowspan="1" colspan="1">68 ± 10</td><td align="left" valign="middle" rowspan="1" colspan="1">>0.05</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Original disease <break></break>(DM/CGN/PCK/unknown)</td><td align="left" valign="middle" rowspan="1" colspan="1">7/1/2/2</td><td align="left" valign="middle" rowspan="1" colspan="1">9/1/0/1</td><td align="left" valign="middle" rowspan="1" colspan="1">>0.05</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">HBV/HCV (n)</td><td align="left" valign="middle" rowspan="1" colspan="1">0/1</td><td align="left" valign="middle" rowspan="1" colspan="1">0/0</td><td align="left" valign="middle" rowspan="1" colspan="1">>0.05</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Duration of HD (days) </td><td align="left" valign="middle" rowspan="1" colspan="1">23 (0–12779)</td><td align="left" valign="middle" rowspan="1" colspan="1">9 (0–5318)</td><td align="left" valign="middle" rowspan="1" colspan="1">>0.05</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Albumin (d/dL)</td><td align="left" valign="middle" rowspan="1" colspan="1">3.2 ± 0.6</td><td align="left" valign="middle" rowspan="1" colspan="1">3.3 ± 0.4</td><td align="left" valign="middle" rowspan="1" colspan="1">>0.05</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Corrected Ca (mg/dL)</td><td align="left" valign="middle" rowspan="1" colspan="1">8.8 ± 1.1</td><td align="left" valign="middle" rowspan="1" colspan="1">8.9 ± 0.6</td><td align="left" valign="middle" rowspan="1" colspan="1">>0.05</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">iP (mg/dl)</td><td align="left" valign="middle" rowspan="1" colspan="1">5.0 ± 1.8</td><td align="left" valign="middle" rowspan="1" colspan="1">5.7 ± 1.3</td><td align="left" valign="middle" rowspan="1" colspan="1">>0.05</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">i-PTH (pg/mL)</td><td align="left" valign="middle" rowspan="1" colspan="1">219 ± 126</td><td align="left" valign="middle" rowspan="1" colspan="1">233 ± 135</td><td align="left" valign="middle" rowspan="1" colspan="1">>0.05</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">hsCRP (mg/dL)</td><td align="left" valign="middle" rowspan="1" colspan="1">0.17 (0.02–1.44)</td><td align="left" valign="middle" rowspan="1" colspan="1">0.32 (0.04–8.00)</td><td align="left" valign="middle" rowspan="1" colspan="1">>0.05</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Ferritin (ng/mL)</td><td align="left" valign="middle" rowspan="1" colspan="1">119 ± 84</td><td align="left" valign="middle" rowspan="1" colspan="1">130 ± 59</td><td align="left" valign="middle" rowspan="1" colspan="1">>0.05</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">Anti-pruritic therapy (nalfurafine, urea, predonisolone, crotamiton, diphenhydramine)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">7 (58%)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">3 (27%)</td><td align="left" valign="top" style="border-bottom:solid thin" rowspan="1" colspan="1">>0.05</td></tr></tbody></table><table-wrap-foot><fn><p>Values are presented as means ± SD, median (range), or numbers (percentages). <italic>p</italic>-values were calculated using the unpaired t-test, Mann-Whitney U-test, or chi-square test. DM, diabetes mellitus; CGN, chronic glomeluronephritis; PCK, polycystic kidney; hsCRP, hypersensitivity C-reactive protein.</p></fn></table-wrap-foot></table-wrap><table-wrap id="medicines-06-00110-t004" orientation="portrait" position="float"><object-id pub-id-type="pii">medicines-06-00110-t004_Table 4</object-id><label>Table 4</label><caption><p>Relative expression levels.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="center" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Gene Name</th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1"></th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Non-Pruritus</th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1">Pruritus</th><th align="left" valign="middle" style="border-top:solid thin;border-bottom:solid thin" rowspan="1" colspan="1"><italic>p</italic>-Value</th></tr></thead><tbody><tr><td align="left" valign="middle" rowspan="1" colspan="1">Cav3.2</td><td align="left" valign="middle" rowspan="1" colspan="1">CACNA 1H</td><td align="left" valign="middle" rowspan="1" colspan="1">0.948 (0.660–1.809) (n = 6)</td><td align="left" valign="middle" rowspan="1" colspan="1">2.490 (0.910–4.993) (n = 6)</td><td align="left" valign="middle" rowspan="1" colspan="1">0.039</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Cav2.2</td><td align="left" valign="middle" rowspan="1" colspan="1">CACNA 1B</td><td align="left" valign="middle" rowspan="1" colspan="1">1.344 (0.038–19.186) (n = 5)</td><td align="left" valign="middle" rowspan="1" colspan="1">0.089 (0.066–0.977) (n = 3)</td><td align="left" valign="middle" rowspan="1" colspan="1">>0.05</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Anoctamin1</td><td align="left" valign="middle" rowspan="1" colspan="1">TMEM 16A</td><td align="left" valign="middle" rowspan="1" colspan="1">1.094 (0.653–1.517) (n = 10)</td><td align="left" valign="middle" rowspan="1" colspan="1">1.528 (0.819–6.733) (n = 11)</td><td align="left" valign="middle" rowspan="1" colspan="1">0.009</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">ASIC1</td><td align="left" valign="middle" rowspan="1" colspan="1"></td><td align="left" valign="middle" rowspan="1" colspan="1">0.796 (0.505–3.000) (n = 8)</td><td align="left" valign="middle" rowspan="1" colspan="1">2.962 (0.334–14.189) (n = 7)</td><td align="left" valign="middle" rowspan="1" colspan="1">>0.05</td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Kv1.4</td><td align="left" valign="middle" rowspan="1" colspan="1">KCNA4</td><td align="left" valign="middle" rowspan="1" colspan="1">No date</td><td align="left" valign="middle" rowspan="1" colspan="1">No date</td><td align="left" valign="middle" rowspan="1" colspan="1"></td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">Na1.8</td><td align="left" valign="middle" rowspan="1" colspan="1">SCN10A </td><td align="left" valign="middle" rowspan="1" colspan="1">No date</td><td align="left" valign="middle" rowspan="1" colspan="1">No date</td><td align="left" valign="middle" rowspan="1" colspan="1"></td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">TRPA1</td><td align="left" valign="middle" rowspan="1" colspan="1"></td><td align="left" valign="middle" rowspan="1" colspan="1">No date</td><td align="left" valign="middle" rowspan="1" colspan="1">No date</td><td align="left" valign="middle" rowspan="1" colspan="1"></td></tr><tr><td align="left" valign="middle" rowspan="1" colspan="1">TRPV1</td><td align="left" valign="middle" rowspan="1" colspan="1"></td><td align="left" valign="middle" rowspan="1" colspan="1">1.013 (0.804–1.223) (n = 3)</td><td align="left" valign="middle" rowspan="1" colspan="1">0.394 (0.256–0.463) (n = 3)</td><td align="left" valign="middle" rowspan="1" colspan="1">0.048</td></tr><tr><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">KCa1.1 (BK<sub>Ca</sub>) </td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">KCNMA1</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.911 (0.526–1.685) (n = 7)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">2.657 (0.664–4.042) (n = 7)</td><td align="left" valign="middle" style="border-bottom:solid thin" rowspan="1" colspan="1">0.020</td></tr></tbody></table><table-wrap-foot><fn><p>Values are expressed as median (range). <italic>p</italic>-values were calculated using the unpaired <italic>t</italic>-test. 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