{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:52:54Z","timestamp":1791273174623,"version":"4.1.0"},"reference-count":60,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","funder":[{"name":"Israel Science Foundation","award":["2030\/21"],"award-info":[{"award-number":["2030\/21"]}],"id":[{"id":"https:\/\/ror.org\/04sazxf24","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Israel Science Foundation","award":["2825\/22"],"award-info":[{"award-number":["2825\/22"]}],"id":[{"id":"https:\/\/ror.org\/04sazxf24","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Israel Science Foundation","award":["1394\/25"],"award-info":[{"award-number":["1394\/25"]}],"id":[{"id":"https:\/\/ror.org\/04sazxf24","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2026,10]]},"abstract":"\n Key Points<\/jats:title>\n \n \n \n Maternal ketosis disrupted nephrogenesis, reduced proliferation, and suppressed Myc and cell cycle signaling.<\/jats:p>\n <\/jats:list-item>\n \n Offspring exhibited persistent kidney deficits, including reduced nephron endowment and compromised long-term kidney function.<\/jats:p>\n <\/jats:list-item>\n \n Gestational ketosis developmental risks highlighted the need for metabolic monitoring and dietary guidance during pregnancy.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n The increasing popularity of ketogenic diets raises concerns regarding their safety during pregnancy. While mild ketosis is a common metabolic adaptation in gestation, the effect of diet-induced, supraphysiological ketosis on fetal kidney development remains unknown. We aimed to investigate the effects of maternal ketosis on offspring nephrogenesis and long-term kidney outcomes.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Two complementary murine models were used: maternal exposure to a ketogenic diet or\n \u03b2<\/jats:italic>\n -hydroxybutyrate supplementation throughout gestation. Offspring were evaluated at birth and during postnatal development. Kidney structure and function were assessed using nephron counts, kidney size, and serum markers of kidney function and injury. Nephron progenitor cell (NPC) dynamics were examined using RNA sequencing, gene set enrichment analysis, immunostaining, and quantitative PCR to assess proliferation and inflammation-related markers.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Both the ketogenic diet and\n \u03b2<\/jats:italic>\n -hydroxybutyrate supplementation models induced maternal ketosis and reduced offspring nephron number. Offspring exhibited impaired kidney function, which was more pronounced in the ketogenic diet group. Transcriptomic analysis of NPCs revealed downregulation of cell cycle and Myc signaling pathways, alongside upregulation of inflammatory pathways, including TNF-\n \u03b1<\/jats:italic>\n \/NF-\u03baB signaling. Immunostaining confirmed reduced NPC proliferation and c-Myc expression, alongside increased TNF-\n \u03b1<\/jats:italic>\n expression. Although postnatal NPC proliferation partially recovered after reversion to a normal diet, it was insufficient to rescue the nephron endowment deficit.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Maternal ketosis disrupted nephrogenesis by suppressing c-Myc signaling and activating inflammatory pathways in NPCs, leading to a congenital nephron deficit and compromised adult kidney function.<\/jats:p>\n <\/jats:sec>","DOI":"10.1681\/asn.0000001126","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T16:04:58Z","timestamp":1778083498000},"page":"2132-2145","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":1,"title":["Gestational Ketosis Compromises Nephron Endowment and Long-Term Kidney Function in Offspring"],"prefix":"10.1681","volume":"37","author":[{"given":"Athar","family":"Amleh","sequence":"first","affiliation":[{"name":"Pediatric Nephrology Unit, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel"},{"name":"Wohl Institute for Translational Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1802-8768","authenticated-orcid":false,"given":"Yaniv","family":"Makayes","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology Unit, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel"},{"name":"Wohl Institute for Translational Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eden","family":"Abergel","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology Unit, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel"},{"name":"Wohl Institute for Translational Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6745-4337","authenticated-orcid":false,"given":"Dan Binyamin","family":"Varshavsky","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology Unit, Hadassah Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel"},{"name":"Wohl Institute for Translational Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadar","family":"Benyamini","sequence":"additional","affiliation":[{"name":"Bioinformatic Unit of the I-CORE, Hebrew University of Jerusalem, Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inbar","family":"Plaschkes","sequence":"additional","affiliation":[{"name":"Bioinformatic Unit of the I-CORE, Hebrew University of Jerusalem, Jerusalem, 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