{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:11:14Z","timestamp":1790835074844,"version":"4.1.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T00:00:00Z","timestamp":1689638400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The use of cyclosporin A (CsA) is hampered by the development of nephrotoxicity including hypertension, which is partially dependent on renal sodium retention. To address this issue, we have investigated in vivo sodium reabsorption in different nephron segments of CsA-treated rats through micropuncture study coupled to expression analyses of sodium transporters. To translate the findings in rats to human, kidney-transplanted patients having CsA treatment were enrolled in the study.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Adult male Sprague\u2013Dawley rats were treated with CsA (15\u2009mg\/kg\/day) for 21\u00a0days, followed by micropuncture study and expression analyses of sodium transporters. CsA-treated kidney-transplanted patients with resistant hypertension were challenged with 50\u00a0mg furosemide.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>CsA-treated rats developed hypertension associated with reduced glomerular filtration rate. In vivo microperfusion study demonstrated a significant decrease in rate of absolute fluid reabsorption in the proximal tubule but enhanced sodium reabsorption in the thick ascending limb of Henle's loop (TAL). Expression analyses of sodium transporters at the same nephron segments further revealed a reduction in Na+-H+ exchanger isoform 3 (NHE3) in the renal cortex, while TAL-specific, furosemide-sensitive Na+-K+-2Cl\u2212 cotransporter (NKCC2) and NHE3 were significantly upregulated in the inner stripe of outer medulla. CsA-treated patients had a larger excretion of urinary NKCC2 protein at basal condition, and higher diuretic response to furosemide, showing increased FeNa+, FeCl\u2212 and FeCa2+ compared with both healthy controls and FK506-treated transplanted patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Altogether, these findings suggest that up-regulation of NKCC2 along the TAL facilitates sodium retention and contributes to the development of CsA-induced hypertension.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ndt\/gfad161","type":"journal-article","created":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T16:07:06Z","timestamp":1689696426000},"page":"297-304","source":"Crossref","is-referenced-by-count":10,"title":["Cyclosporin-induced hypertension is associated with the up-regulation of Na+-K+-2Cl\u2212 cotransporter (NKCC2)"],"prefix":"10.1093","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5134-3826","authenticated-orcid":false,"given":"Giovanna","family":"Capolongo","sequence":"first","affiliation":[{"name":"Department of Translational Medical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d , Naples , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Damiano","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine and Animal Productions, University of Naples , Naples , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Suzumoto","sequence":"additional","affiliation":[{"name":"Biogem, Institute of Molecular Biology and Genetics , Ariano Irpino , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Zacchia","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d , Naples , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Rizzo","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d , Naples , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrica","family":"Zona","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d , Naples , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa Maria","family":"Pollastro","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Campania \u201cLuigi Vanvitelli\u201d , Naples , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariadelina","family":"Simeoni","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University 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