{"title":"肾移植受者饮食盐摄入量与钙调磷酸酶抑制剂肾毒性相关的肾脏结局的相关性","authors":"Satoru Sanada, Saki Katano, Kengo Asami, Hiroyuki Kumata, Satoshi Sekiguchi, Mitsuhiro Sato","doi":"10.1038/s41598-025-11292-4","DOIUrl":null,"url":null,"abstract":"<p><p>Tonicity-responsive enhancer binding protein (TonEBP) protects kidney tubular cells against hypertonicity. Calcineurin inhibitors (CNI) are known to suppress TonEBP by hampering nuclear translocation. Moreover, sodium inversely activates TonEBP. We investigated whether CNI-induced nephrotoxicity in transplant recipients could be due to impaired TonEBP activity, and whether sodium restriction exacerbates the intoxication. Immunohistochemical analysis using biopsy specimens from 128 patients revealed that TonEBP was mainly located in the cytoplasm in cases of CNI nephrotoxicity, while it showed nuclear-cytoplasmic staining in cases of rejection or interstitial fibrosis and tubular atrophy. This suggests that TonEBP transactivation is limited in CNI nephrotoxicity. A retrospective observational analysis of 308 kidney transplant recipients at our institute between 1984 and 2018 showed a positive correlation between dietary salt intake and eGFR slope. A low-salt diet is linked to a rapid annual decline in eGFR, with adjusted odds ratios of 2.40 and a 95% confidence interval of 1.18-4.90. These findings suggest that the recommended salt intake for kidney transplant recipients may require reassessment.</p>","PeriodicalId":21811,"journal":{"name":"Scientific Reports","volume":"15 1","pages":"26466"},"PeriodicalIF":3.9000,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12280067/pdf/","citationCount":"0","resultStr":"{\"title\":\"Correlation between dietary salt intake and renal outcomes related to calcineurin inhibitor nephrotoxicity in kidney transplant recipients.\",\"authors\":\"Satoru Sanada, Saki Katano, Kengo Asami, Hiroyuki Kumata, Satoshi Sekiguchi, Mitsuhiro Sato\",\"doi\":\"10.1038/s41598-025-11292-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Tonicity-responsive enhancer binding protein (TonEBP) protects kidney tubular cells against hypertonicity. Calcineurin inhibitors (CNI) are known to suppress TonEBP by hampering nuclear translocation. Moreover, sodium inversely activates TonEBP. We investigated whether CNI-induced nephrotoxicity in transplant recipients could be due to impaired TonEBP activity, and whether sodium restriction exacerbates the intoxication. Immunohistochemical analysis using biopsy specimens from 128 patients revealed that TonEBP was mainly located in the cytoplasm in cases of CNI nephrotoxicity, while it showed nuclear-cytoplasmic staining in cases of rejection or interstitial fibrosis and tubular atrophy. This suggests that TonEBP transactivation is limited in CNI nephrotoxicity. A retrospective observational analysis of 308 kidney transplant recipients at our institute between 1984 and 2018 showed a positive correlation between dietary salt intake and eGFR slope. A low-salt diet is linked to a rapid annual decline in eGFR, with adjusted odds ratios of 2.40 and a 95% confidence interval of 1.18-4.90. These findings suggest that the recommended salt intake for kidney transplant recipients may require reassessment.</p>\",\"PeriodicalId\":21811,\"journal\":{\"name\":\"Scientific Reports\",\"volume\":\"15 1\",\"pages\":\"26466\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2025-07-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12280067/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Scientific Reports\",\"FirstCategoryId\":\"103\",\"ListUrlMain\":\"https://doi.org/10.1038/s41598-025-11292-4\",\"RegionNum\":2,\"RegionCategory\":\"综合性期刊\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MULTIDISCIPLINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Scientific Reports","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1038/s41598-025-11292-4","RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
Correlation between dietary salt intake and renal outcomes related to calcineurin inhibitor nephrotoxicity in kidney transplant recipients.
Tonicity-responsive enhancer binding protein (TonEBP) protects kidney tubular cells against hypertonicity. Calcineurin inhibitors (CNI) are known to suppress TonEBP by hampering nuclear translocation. Moreover, sodium inversely activates TonEBP. We investigated whether CNI-induced nephrotoxicity in transplant recipients could be due to impaired TonEBP activity, and whether sodium restriction exacerbates the intoxication. Immunohistochemical analysis using biopsy specimens from 128 patients revealed that TonEBP was mainly located in the cytoplasm in cases of CNI nephrotoxicity, while it showed nuclear-cytoplasmic staining in cases of rejection or interstitial fibrosis and tubular atrophy. This suggests that TonEBP transactivation is limited in CNI nephrotoxicity. A retrospective observational analysis of 308 kidney transplant recipients at our institute between 1984 and 2018 showed a positive correlation between dietary salt intake and eGFR slope. A low-salt diet is linked to a rapid annual decline in eGFR, with adjusted odds ratios of 2.40 and a 95% confidence interval of 1.18-4.90. These findings suggest that the recommended salt intake for kidney transplant recipients may require reassessment.
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