{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T06:48:18Z","timestamp":1768027698930,"version":"3.49.0"},"reference-count":27,"publisher":"Pharmaceutical Society of Japan","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biological &amp; Pharmaceutical Bulletin","Biol. Pharm. Bull."],"published-print":{"date-parts":[[2026,1,10]]},"DOI":"10.1248\/bpb.b25-00465","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T22:09:10Z","timestamp":1767996550000},"page":"84-89","source":"Crossref","is-referenced-by-count":0,"title":["Long-Term Use of Proton Pump Inhibitors Affects Blood Levels of Indoxyl Sulfate in Japanese Patients with Chronic Kidney Disease"],"prefix":"10.1248","volume":"49","author":[{"given":"Kotaro","family":"Kawamoto","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Japan Community Healthcare Organization Sapporo Hokushin Hospital, 6\u20132\u20131 Atsubetsuchuo 2-jo, Atsubetsu-ku, Sapporo 004\u20138618, Japan"},{"name":"Division of Biochemistry, Department of Molecular Biosciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, 1757 Kanazawa, Tobetsu-cho, Ishikari-gun, Hokkaido 061\u20130293, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shota","family":"Kadomura","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Japan Community Healthcare Organization Hokkaido Hospital, 8\u20133\u201318, Nakanoshima 1-jo, Toyohira-ku, Sapporo 062\u20138618, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maki","family":"Nabeki","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Japan Community Healthcare Organization Sapporo Hokushin Hospital, 6\u20132\u20131 Atsubetsuchuo 2-jo, Atsubetsu-ku, Sapporo 004\u20138618, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroaki","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Japan Community Healthcare Organization Sapporo Hokushin Hospital, 6\u20132\u20131 Atsubetsuchuo 2-jo, Atsubetsu-ku, Sapporo 004\u20138618, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kanji","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Japan Community Healthcare Organization Sapporo Hokushin Hospital, 6\u20132\u20131 Atsubetsuchuo 2-jo, Atsubetsu-ku, Sapporo 004\u20138618, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manabu","family":"Noda","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrinology, Japan Community Healthcare Organization Sapporo Hokushin Hospital, 6\u20132\u20131 Atsubetsuchuo 2-jo, Atsubetsu-ku, Sapporo 004\u20138618, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hajime","family":"Masuda","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrinology, Japan Community Healthcare Organization Sapporo Hokushin Hospital, 6\u20132\u20131 Atsubetsuchuo 2-jo, Atsubetsu-ku, Sapporo 004\u20138618, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shirou","family":"Tsuchida","sequence":"additional","affiliation":[{"name":"Division of Biochemistry, Department of Molecular Biosciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, 1757 Kanazawa, Tobetsu-cho, Ishikari-gun, Hokkaido 061\u20130293, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsuya","family":"Itoh","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Japan Community Healthcare Organization Sapporo Hokushin Hospital, 6\u20132\u20131 Atsubetsuchuo 2-jo, Atsubetsu-ku, Sapporo 004\u20138618, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michiya","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutics, Department of Clinical Pharmaceutics, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, 1757 Kanazawa, Tobetsu-cho, Ishikari-gun, Hokkaido 061\u20130293, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"163","reference":[{"key":"1","unstructured":"1) Bikbov B, Purcell CA, Levey AS, <i>et al<\/i>. Global, regional, and national burden of chronic kidney disease, 1990\u20132017: a systematic analysis for the global burden of disease study 2017. <i>Lancet<\/i>, <b>395<\/b>, 709\u2013733 (2020)."},{"key":"2","doi-asserted-by":"crossref","unstructured":"2) Lin CJ, Wu V, Wu PC, Wu CJ. Meta-analysis of the associations of p-cresyl sulfate (PCS) and indoxyl sulfate (IS) with cardiovascular events and all-cause mortality in patients with chronic renal failure. <i>PLOS ONE<\/i>, <b>10<\/b>, e0132589 (2015).","DOI":"10.1371\/journal.pone.0132589"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3) Andr\u00e9 C, Bodeau S, Kamel S, Bennis Y, Caillard P. The AKI-to-CKD transition: the role of uremic toxins. <i>Int. J. Mol. Sci.<\/i>, <b>24<\/b>, 16152 (2023).","DOI":"10.3390\/ijms242216152"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4) Wu IW, Hsu KH, Lee CC, Sun CY, Hsu HJ, Tsai CJ, Tzen CY, Wang YC, Lin CY, Wu MS. p-Cresyl sulphate and indoxyl sulphate predict progression of chronic kidney disease. <i>Nephrol. Dial. Transplant.<\/i>, <b>26<\/b>, 938\u2013947 (2011).","DOI":"10.1093\/ndt\/gfq580"},{"key":"5","unstructured":"5) Niwa T. Uremic toxicity of indoxyl sulfate. <i>Nagoya J. Med. Sci.<\/i>, <b>72<\/b>, 1\u201311 (2010)."},{"key":"6","doi-asserted-by":"crossref","unstructured":"6) Deguchi T, Kusuhara H, Takadate A, Endou H, Otagiri M, Sugiyama Y. Characterization of uremic toxin transport by organic anion transporters in the kidney. <i>Kidney Int.<\/i>, <b>65<\/b>, 162\u2013174 (2004).","DOI":"10.1111\/j.1523-1755.2004.00354.x"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7) Mangin D, Lawson J, Cuppage J, Shaw E, Ivanyi K, Davis A, Risdon C. Legacy drug-prescribing patterns in primary care. <i>Ann. Fam. Med.<\/i>, <b>16<\/b>, 515\u2013520 (2018).","DOI":"10.1370\/afm.2315"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8) Ishida M, Tsuchiya M, Naito J, Kawazoe H, Watanabe D, Nonaka Y, Sano M, Sakai H, Suzuki A, Kumada K, Okura H, Shimizu M, Iihara H. Vonoprazan-associated nephrotoxicity: extensive real-world evidence from spontaneous adverse drug reaction reports. <i>Kidney Int.<\/i>, <b>102<\/b>, 666\u2013668 (2022).","DOI":"10.1016\/j.kint.2022.06.007"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9) Lazarus B, Chen Y, Wilson FP, Sang Y, Chang AR, Coresh J, Grams ME. Proton pump inhibitor use and the risk of chronic kidney disease. <i>JAMA Intern. Med.<\/i>, <b>176<\/b>, 238\u2013246 (2016).","DOI":"10.1001\/jamainternmed.2015.7193"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10) Wijarnpreecha K, Thongprayoon C, Chesdachai S, Panjawatanana P, Ungprasert P, Cheungpasitporn W. Associations of proton-pump inhibitors and H2 receptor antagonists with chronic kidney disease: a meta-analysis. <i>Dig. Dis. Sci.<\/i>, <b>62<\/b>, 2821\u20132827 (2017).","DOI":"10.1007\/s10620-017-4725-5"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11) Nagata N, Nishijima S, Miyoshi-Akiyama T, Kojima Y, Kimura M, Aoki R, Ohsugi M, Ueki K, Miki K, Iwata E, Hayakawa K, Ohmagari N, Oka S, Mizokami M, Itoi T, Kawai T, Uemura N, Hattori M. Population-level metagenomics uncovers distinct effects of multiple medications on the human gut microbiome. <i>Gastroenterology<\/i>, <b>163<\/b>, 1038\u20131052 (2022).","DOI":"10.1053\/j.gastro.2022.06.070"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12) Chioukh R, Noel-Hudson MS, Ribes S, Fournier N, Becquemont L, Verstuyft C. Proton pump inhibitors inhibit methotrexate transport by renal basolateral organic anion transporter hOAT3. <i>Drug Metab. Dispos.<\/i>, <b>42<\/b>, 2041\u20132048 (2014).","DOI":"10.1124\/dmd.114.058529"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13) El Chamieh C, Larabi IA, Laville SM, Jacquelinet C, Combe C, Fouque D, Laville M, Frimat L, Pecoits-Filho R, Lange C, Stengel B, Alencar De Pinho N, Alvarez JC, Massy ZA, Liabeuf S. Proton-pump inhibitors and serum concentrations of uremic toxins in patients with chronic kidney disease. <i>Toxins<\/i>, <b>15<\/b>, 276 (2023).","DOI":"10.3390\/toxins15040276"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14) Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, Yamagata K, Tomino Y, Yokoyama H, Hishida A. Revised equations for estimated GFR from serum creatinine in Japan. <i>Am. J. Kidney Dis.<\/i>, <b>53<\/b>, 982\u2013992 (2009).","DOI":"10.1053\/j.ajkd.2008.12.034"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15) Stevens PE, Ahmed SB, Carrero JJ, <i>et al<\/i>. KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease. <i>Kidney Int.<\/i>, <b>105<\/b>, S117\u2013S314 (2024).","DOI":"10.1016\/j.kint.2023.10.018"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16) Motojima M, Hosokawa A, Yamato H, Muraki T, Yoshioka T. Uraemic toxins induce proximal tubular injury <i>via<\/i> organic anion transporter 1-mediated uptake. <i>Br. J. Pharmacol.<\/i>, <b>135<\/b>, 555\u2013563 (2002).","DOI":"10.1038\/sj.bjp.0704482"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17) Jia Y, Zhao L, Wang F, Shang J, Zhao Z. Comparing estimated protein excretion rate and spot urinary protein-creatinine ratio in assessing urinary protein excretion in patients with kidney disease in China: a single center study. <i>Front. Med.<\/i>, <b>12<\/b>, 1517019 (2025).","DOI":"10.3389\/fmed.2025.1517019"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18) Suga H, Ichimura Y, Oda M, Saitoh H. Different correlation between serum levels of indoxyl sulfate and estimated GFR in the elderly with or without dementia. <i>BPB Reports<\/i>, <b>3<\/b>, 102\u2013105 (2020).","DOI":"10.1248\/bpbreports.3.3_102"},{"key":"19","doi-asserted-by":"crossref","unstructured":"19) Yatsunenko T, Rey FE, Manary MJ, <i>et al<\/i>. Human gut microbiome viewed across age and geography. <i>Nature<\/i>, <b>486<\/b>, 222\u2013227 (2012).","DOI":"10.1038\/nature11053"},{"key":"20","doi-asserted-by":"crossref","unstructured":"20) Ephraim E, Cochrane CY, Jewell DE. Varying protein levels influence metabolomics and the gut microbiome in healthy adult dogs. <i>Toxins (Basel)<\/i>, <b>12<\/b>, 517 (2020).","DOI":"10.3390\/toxins12080517"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21) Kato K, Ishida S, Tanaka M, Mitsuyama E, Xiao JZ, Odamaki T. Association between functional lactase variants and a high abundance of Bifidobacterium in the gut of healthy Japanese people. <i>PLOS ONE<\/i>, <b>13<\/b>, e0206189 (2018).","DOI":"10.1371\/journal.pone.0206189"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22) Yu CP, Sweet DH, Peng YH, Hsieh YW, Chao PDL, Hou YC, Lin SP. Effects of nonsteroidal anti-inflammatory drugs on the renal excretion of indoxyl sulfate, a nephro-cardiovascular toxin, in rats. <i>Eur. J. Pharm. Sci.<\/i>, <b>101<\/b>, 66\u201370 (2017).","DOI":"10.1016\/j.ejps.2017.02.007"},{"key":"23","doi-asserted-by":"crossref","unstructured":"23) Sueyoshi M, Fukunaga M, Mei M, Nakajima A, Tanaka G, Murase T, Narita Y, Hirata S, Kadowaki D. Effects of lactulose on renal function and gut microbiota in adenine-induced chronic kidney disease rats. <i>Clin. Exp. Nephrol.<\/i>, <b>23<\/b>, 908\u2013919 (2019).","DOI":"10.1007\/s10157-019-01727-4"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24) Mishima E, Fukuda S, Shima H, Hirayama A, Akiyama Y, Takeuchi Y, Fukuda NN, Suzuki T, Suzuki C, Yuri A, Kikuchi K, Tomioka Y, Ito S, Soga T, Abe T. Alteration of the intestinal environment by lubiprostone is associated with amelioration of adenine-induced CKD. <i>J. Am. Soc. Nephrol.<\/i>, <b>26<\/b>, 1787\u20131794 (2015).","DOI":"10.1681\/ASN.2014060530"},{"key":"25","doi-asserted-by":"crossref","unstructured":"25) Toyama T, Kitagawa K, Oshima M, Kitajima S, Hara A, Iwata Y, Sakai N, Shimizu M, Hashiba A, Furuichi K, Wada T. Age differences in the relationships between risk factors and loss of kidney function: a general population cohort study. <i>BMC Nephrol.<\/i>, <b>21<\/b>, 477 (2020).","DOI":"10.1186\/s12882-020-02121-z"},{"key":"26","doi-asserted-by":"crossref","unstructured":"26) Krukowski H, Valkenburg S, Madella AM, Garssen J, van Bergenhenegouwen J, Overbeek SA, Huys GRB, Raes J, Glorieux G. Gut microbiome studies in CKD: opportunities, pitfalls and therapeutic potential. <i>Nat. Rev. Nephrol.<\/i>, <b>19<\/b>, 87\u2013101 (2023).","DOI":"10.1038\/s41581-022-00647-z"},{"key":"27","doi-asserted-by":"crossref","unstructured":"27) Rivara MB, Zelnick LR, Hoofnagle AN, Newitt R, Tracy RP, Kratz M, Weigle DS, Kestenbaum BR. Diurnal and long-term variation in plasma concentrations and renal clearances of circulating markers of kidney proximal tubular secretion. <i>Clin. Chem.<\/i>, <b>63<\/b>, 915\u2013923 (2017).","DOI":"10.1373\/clinchem.2016.260117"}],"container-title":["Biological and Pharmaceutical Bulletin"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/bpb\/49\/1\/49_b25-00465\/_pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T03:29:49Z","timestamp":1768015789000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/bpb\/49\/1\/49_b25-00465\/_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,10]]},"references-count":27,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.1248\/bpb.b25-00465","relation":{},"ISSN":["0918-6158","1347-5215"],"issn-type":[{"value":"0918-6158","type":"print"},{"value":"1347-5215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,10]]},"article-number":"b25-00465"}}