The prevalence of chronic kidney disease (CKD) is increasing globally, especially in elderly patients. 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 (300–350 g) 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 µg/day), and (IV) CKD treated with a higher KP-13 dose (intraperitoneal 26 µg/day). Treatments were administered daily from week 3 for 10 days. After 13 weeks, KP-13 increased systemic blood pressure, accentuating diastolic dysfunction’s 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 (Il6, Tnf), fibrosis (Col1), and apoptosis markers (Bax/Bcl2) relative to the CKD group. In summary, KP-13’s influence on CKD and uremic cardiomyopathy encompassed heightened blood pressure and potentially activated inflammatory and apoptotic pathways in the left ventricle.

慢性肾病 （CKD） 的患病率在全球范围内不断增加，尤其是在老年患者中。尿毒症性心肌病是 CKD 的常见心血管并发症，以左心室肥厚 （LVH）、舒张功能障碍和纤维化为特征。Kisspeptins 及其受体 KISS1R 对肾脏病理生理学产生关键影响，并调节各种器官系统中与年龄相关的病理。KISS1R 激动剂，包括 kisspeptin-13 （KP-13），有望成为年龄相关生物过程和肾脏相关疾病的新型治疗剂。我们的调查旨在阐明 KP-13 对 CKD 和尿毒症心肌病轨迹的影响。雄性 Wistar 大鼠 （300-350 g） 被随机分为四组：（I） 假手术，（II） 5/6 肾切除术诱导的 CKD，（III） CKD 接受低剂量 KP-13 （腹膜内 13 μg/天），以及 （IV） 用较高 KP-13 剂量处理的 CKD （腹膜内 26 μg/天）。从第 3 周开始每天进行治疗，持续 10 天。13 周后，KP-13 使全身血压升高，突出了舒张功能障碍的超声心动图指标，并加强了 CKD 相关标志物，例如血清尿素水平、肾小球肥大和肾小管扩张。值得注意的是，KP-13 不会加剧循环尿毒症毒素水平、肾脏炎症或纤维化标志物。相比之下，较高的 KP-13 剂量与后壁和前壁厚度减少相关，加上心肌细胞横截面积减少和炎症 （Il6、Tnf） 、纤维化 （Col1） 和细胞凋亡标志物 （Bax/Bcl2） 相对于 CKD 组同时升高。 总之，KP-13 对 CKD 和尿毒症性心肌病的影响包括血压升高和可能激活左心室的炎症和凋亡通路。