{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T11:03:06Z","timestamp":1792839786264,"version":"4.5.0"},"reference-count":31,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2012,4,16]],"date-time":"2012-04-16T00:00:00Z","timestamp":1334534400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2012,6]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Adefovir and tenofovir are nucleotide analogues used as long\u2010term therapy of chronic hepatitis B. Side effects are few, but prolonged and high\u2010dose therapy has been associated with proximal renal tubular dysfunction (<jats:styled-content style=\"fixed-case\">RTD<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To assess the incidence of <jats:styled-content style=\"fixed-case\">RTD<\/jats:styled-content> during long\u2010term nucleotide therapy of chronic hepatitis B.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 51 patients being treated at the <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>linical <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>enter, <jats:styled-content style=\"fixed-case\">N<\/jats:styled-content>ational <jats:styled-content style=\"fixed-case\">I<\/jats:styled-content>nstitutes of <jats:styled-content style=\"fixed-case\">H<\/jats:styled-content>ealth were studied. Diagnosis of <jats:styled-content style=\"fixed-case\">RTD<\/jats:styled-content> required <jats:italic>de novo<\/jats:italic> appearance of at least three of five features: hypophosphataemia, hypouricaemia, serum creatinine elevation, proteinuria or glucosuria.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 51 patients treated for 1\u201310 (mean 7.4) years with adefovir (<jats:italic>n<\/jats:italic>\u00a0=\u00a042), tenofovir (<jats:italic>n<\/jats:italic>\u00a0=\u00a04) or adefovir followed by tenofovir (<jats:italic>n<\/jats:italic>\u00a0=\u00a05), 7 (14%) developed <jats:styled-content style=\"fixed-case\">RTD<\/jats:styled-content>. Time to onset ranged from 22 to 94 (mean 49) months with an estimated 10\u2010year cumulative rate of 15%. All seven had low urinary percent maximal tubular reabsorption of phosphate (&lt;82%). Patients with <jats:styled-content style=\"fixed-case\">RTD<\/jats:styled-content> were older (58 vs. 44\u00a0years; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.01) and had lower baseline glomerular filtration rates (82 vs. 97\u00a0cc\/min; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.08) compared to those without; but did not differ in other features. Six patients with <jats:styled-content style=\"fixed-case\">RTD<\/jats:styled-content> were switched to entecavir, all subsequently had improvements in serum phosphate (2.0\u20133.0\u00a0mg\/dL), creatinine (1.6\u20131.1\u00a0mg\/dL), uric acid (2.7\u20133.8\u00a0mg\/dL) and proteinuria.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Renal tubular dysfunction develops in 15% of patients treated with adefovir or tenofovir for 2\u20139\u00a0years and is partially reversible with change to other antivirals. Monitoring for serum phosphate, creatinine and urinalysis is prudent during long\u2010term adefovir and tenofovir therapy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1365-2036.2012.05093.x","type":"journal-article","created":{"date-parts":[[2012,4,17]],"date-time":"2012-04-17T01:38:51Z","timestamp":1334626731000},"page":"1317-1325","source":"Crossref","is-referenced-by-count":135,"title":["Renal tubular dysfunction during long\u2010term adefovir or tenofovir therapy in chronic hepatitis <scp>B<\/scp>"],"prefix":"10.1111","volume":"35","author":[{"given":"N.","family":"Gara","sequence":"first","affiliation":[{"name":"Liver Diseases Branch National Institute of Diabetes and Digestive and Kidney Diseases Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X.","family":"Zhao","sequence":"additional","affiliation":[{"name":"Biostatistics, Intramural Research National Institute of Diabetes and Digestive and Kidney Diseases Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. T.","family":"Collins","sequence":"additional","affiliation":[{"name":"Skeletal Clinical Studies Unit, Craniofacial and Skeletal Diseases Branch National Institute of Dental and Craniofacial Research Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. H.","family":"Chong","sequence":"additional","affiliation":[{"name":"Skeletal Clinical Studies Unit, Craniofacial and Skeletal Diseases Branch National Institute of Dental and Craniofacial Research Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. E.","family":"Kleiner","sequence":"additional","affiliation":[{"name":"Pathology Branch National Cancer Institute, National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Jake Liang","sequence":"additional","affiliation":[{"name":"Liver Diseases Branch National Institute of Diabetes and Digestive and Kidney Diseases Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. G.","family":"Ghany","sequence":"additional","affiliation":[{"name":"Liver Diseases Branch National Institute of Diabetes and Digestive and Kidney Diseases Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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