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Uremic cardiomyopathy is a common cardiovascular complication of CKD, characterized by left ventricular hypertrophy (LVH), diastolic dysfunction, and fibrosis. Kisspeptins and their receptor, KISS1R, exert a pivotal influence on kidney pathophysiology and modulate age-related pathologies across various organ systems. KISS1R agonists, including kisspeptin-13 (KP-13), hold promise as novel therapeutic agents within age-related biological processes and kidney-related disorders. Our investigation aimed to elucidate the impact of KP-13 on the trajectory of CKD and uremic cardiomyopathy. Male Wistar rats (300\u2013350\u00a0g) were randomized into four groups: (I) sham-operated, (II) 5\/6 nephrectomy-induced CKD, (III) CKD subjected to a low dose of KP-13 (intraperitoneal 13\u00a0\u00b5g\/day), and (IV) CKD treated with a higher KP-13 dose (intraperitoneal 26\u00a0\u00b5g\/day). Treatments were administered daily from week 3 for 10\u00a0days. After 13\u00a0weeks, KP-13 increased systemic blood pressure, accentuating diastolic dysfunction\u2019s echocardiographic indicators and intensifying CKD-associated markers such as serum urea levels, glomerular hypertrophy, and tubular dilation. Notably, KP-13 did not exacerbate circulatory uremic toxin levels, renal inflammation, or fibrosis markers. In contrast, the higher KP-13 dose correlated with reduced posterior and anterior wall thickness, coupled with diminished cardiomyocyte cross-sectional areas and concurrent elevation of inflammatory (<jats:italic>Il6, Tnf<\/jats:italic>), fibrosis (<jats:italic>Col1<\/jats:italic>), and apoptosis markers (<jats:italic>Bax\/Bcl2<\/jats:italic>) relative to the CKD group. In summary, KP-13\u2019s influence on CKD and uremic cardiomyopathy encompassed heightened blood pressure and potentially activated inflammatory and apoptotic pathways in the left ventricle.<\/jats:p>","DOI":"10.1007\/s11357-023-01017-8","type":"journal-article","created":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T13:04:14Z","timestamp":1700571854000},"page":"2463-2488","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Role of the kisspeptin-KISS1R axis in the pathogenesis of chronic kidney disease and uremic cardiomyopathy"],"prefix":"10.1007","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5812-715X","authenticated-orcid":false,"given":"Hoa","family":"Dinh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4197-4579","authenticated-orcid":false,"given":"Zsuzsanna Z. 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