{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T16:04:47Z","timestamp":1786982687549,"version":"build-2736575974"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T00:00:00Z","timestamp":1744329600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T00:00:00Z","timestamp":1744329600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["CEN Case Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Autosomal dominant polycystic kidney disease (ADPKD), the most prevalent inherited kidney disorder, progresses inexorably to end-stage kidney disease (ESKD) with the vasopressin V2-receptor antagonist tolvaptan serving as a primary treatment option since 2014. While dapagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, was approved for treating chronic kidney disease in August 2021, its renoprotective effects in ADPKD remain uncertain due to potential vasopressin stimulation. We evaluated four Japanese ADPKD patients receiving combination therapy with tolvaptan and dapagliflozin for over two years. A 74-year-old woman (Mayo Class 1D, CKD stage 4) showed improved estimated glomerular filtration rate (eGFR) decline from \u2212 1.39 to \u2212 0.66\u00a0mL\/min\/1.73\u00a0m\n                    <jats:sup>2<\/jats:sup>\n                    \/year. A 62-year-old woman (Mayo Class 1B, CKD stage 3b) demonstrated eGFR decline improvement from \u2212 1.02 to \u2212 0.66\u00a0mL\/min\/1.73\u00a0m\n                    <jats:sup>2<\/jats:sup>\n                    \/year. A 39-year-old man (Mayo Class 1C, CKD stage 3a) exhibited significant improvement from \u2212 5.00 to \u2212 1.35\u00a0mL\/min\/1.73\u00a0m\n                    <jats:sup>2<\/jats:sup>\n                    \/year. A 45-year-old woman (Mayo Class 1D, CKD stage 3b) showed marked improvement from \u2212 14.12 to \u2212 0.22\u00a0mL\/min\/1.73\u00a0m\n                    <jats:sup>2<\/jats:sup>\n                    \/year. While eGFR decline decelerated in the control group, the combination therapy group showed more pronounced improvements. Height-adjusted total kidney volume (htTKV) in the group combination therapy showed variable responses: two patients experienced volume increases (+\u20094.03%,\u2009+\u20093.65%\/year), while two showed decreases (\u2212 0.45%, \u2212 3.65%\/year). These cases suggest potential renoprotective benefits from combining tolvaptan and dapagliflozin in ADPKD patients. Careful monitoring of renal cyst enlargement is warranted with concurrent dapagliflozin use. Further research is needed to confirm these preliminary findings and establish optimal patient selection criteria for combination therapy.\n                  <\/jats:p>","DOI":"10.1007\/s13730-025-00990-7","type":"journal-article","created":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T08:40:53Z","timestamp":1744360853000},"page":"500-506","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Renoprotective effects of combination therapy with tolvaptan and dapagliflozin in autosomal dominant polycystic kidney disease: a four-case series"],"prefix":"10.1007","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-0876-3311","authenticated-orcid":false,"given":"Junji","family":"Nishida","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayuko","family":"Yamakawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoko","family":"Miura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Yasutomi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,11]]},"reference":[{"issue":"4","key":"990_CR1","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1159\/000045214","volume":"80","author":"E Higashihara","year":"1998","unstructured":"Higashihara E, et al. Prevalence and renal prognosis of diagnosed autosomal dominant polycystic kidney disease in Japan. Nephron. 1998;80(4):421\u20137. https:\/\/doi.org\/10.1159\/000045214. (PMID: 9832641).","journal-title":"Nephron"},{"key":"990_CR2","unstructured":"Hanafusa N, et al. on behalf of Japanese Society for Dialysis Therapy Renal Data Registry Committee. 2022 Annual Dialysis Data Report, JSDT Renal Data Registry. (in Japanese). Journal of Japanese Society for Dialysis Therapy 2022;56(12):473\u2013536."},{"key":"990_CR3","doi-asserted-by":"publisher","unstructured":"Heerspink HJL, et al.; DAPA-CKD Trial Committees and Investigators. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020 Oct 8;383(15):1436\u20131446. https:\/\/doi.org\/10.1056\/NEJMoa2024816. Epub 2020 Sep 24. PMID: 32970396.","DOI":"10.1056\/NEJMoa2024816"},{"key":"990_CR4","unstructured":"EMPA-KIDNEY Collaborative Group; Herrington WG, et al. Empagliflozin in Patients with Chronic Kidney Disease. N Engl J Med 2022. 10.1056\/ NEJMoa2204233"},{"key":"990_CR5","unstructured":"Kei Fukamizu, et al. Japanese Society of Nephrology Recommendation on the correct use of SGLT2 inhibitors in the treatment of CKD. (in Japanese). The Japanese Journal of Nephrology 2023;65(1):1\u201310."},{"key":"990_CR6","unstructured":"Narita K, Study Group on Intractable Renal Disorders, Research Project on Policy for Intractable Diseases. Evidence-based clinical practice guideline for polycystic kidney disease (PKD) 2020. Tokyo: Tokyo Igakusha; 2020."},{"key":"990_CR7","doi-asserted-by":"publisher","unstructured":"Kanda Y. Investigation of the freely available easy-to-use software 'EZR' for medical statistics. Bone Marrow Transplant. 2013 Mar;48(3):452\u20138. https:\/\/doi.org\/10.1038\/bmt.2012.244. Epub 2012 Dec 3. 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(PMID: 20205482).","journal-title":"Drugs"},{"key":"990_CR10","doi-asserted-by":"publisher","unstructured":"Palmer BF, Clegg DJ. Kidney-Protective Effects of SGLT2 Inhibitors. Clin J Am Soc Nephrol. 2023 Feb 1;18(2):279\u2013289. https:\/\/doi.org\/10.2215\/CJN.09380822. Epub 2022 Oct 20. PMID: 36220189; PMCID: PMC10103214.","DOI":"10.2215\/CJN.09380822"},{"key":"990_CR11","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.mito.2021.02.016","volume":"58","author":"B Afsar","year":"2021","unstructured":"Afsar B, et al. Mitochondrion-driven nephroprotective mechanisms of novel glucose lowering medications. Mitochondrion. 2021;58:72\u201382. https:\/\/doi.org\/10.1016\/j.mito.2021.02.016. (Epub 2021 Mar 5 PMID: 33677060).","journal-title":"Mitochondrion"},{"issue":"4","key":"990_CR12","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1016\/j.cmet.2021.02.016","volume":"33","author":"T Sen","year":"2021","unstructured":"Sen T, Heerspink HJL. A kidney perspective on the mechanism of action of sodium glucose co-transporter 2 inhibitors. Cell Metab. 2021;33(4):732\u20139. https:\/\/doi.org\/10.1016\/j.cmet.2021.02.016. (Epub 2021 Mar 9 PMID: 33691091).","journal-title":"Cell Metab"},{"key":"990_CR13","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1016\/S2213-8587(20)30300-4","volume":"8","author":"M Oshima","year":"2020","unstructured":"Oshima M, et al. Effects of canagliflozin on anaemia in patients with type 2 diabetes and chronic kidney disease: a post-hoc analysis from the CREDENCE trial. Lancet Diabetes Endocrinol. 2020;8:903\u201314.","journal-title":"Lancet Diabetes Endocrinol"},{"key":"990_CR14","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1161\/CIRCULATIONAHA.120.050391","volume":"143","author":"PS Jhund","year":"2021","unstructured":"Jhund PS, et al. Efficacy of dapagliflozin on renal function and outcomes in patients with heart failure with reduced ejection fraction: results of DAPA-HF. 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Salsalate, but not metformin or canagliflozin, slows kidney cyst growth in an adult-onset mouse model of polycystic kidney disease. EBioMedicine. 2019 Sep;47:436\u2013445. https:\/\/doi.org\/10.1016\/j.ebiom.2019.08.041. Epub 2019 Aug 28. PMID: 31473186; PMCID: PMC6796518.","DOI":"10.1016\/j.ebiom.2019.08.041"},{"key":"990_CR18","doi-asserted-by":"publisher","unstructured":"Patel\u00a0DM, Dahl\u00a0NK.\u00a0Examining the role of novel CKD therapies for the ADPKD patient.\u00a0Kidney360 2021;2:1036\u201341. https:\/\/doi.org\/10.34067\/KID.0007422020.","DOI":"10.34067\/KID.0007422020"},{"issue":"19","key":"990_CR19","doi-asserted-by":"publisher","first-page":"6341","DOI":"10.3390\/jcm12196341","volume":"12","author":"F Morioka","year":"2023","unstructured":"Morioka F, et al. Short-term dapagliflozin administration in autosomal dominant polycystic kidney disease-a retrospective single-arm case series study. 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