Role of the kisspeptin-KISS1R axis in the pathogenesis of chronic kidney disease and uremic cardiomyopathy.
Hoa DinhZsuzsanna Z A KovácsMerse KisKlaudia KupeczAnita SejbenGergő SzűcsFanni Magdolna MárványköviAndrea SiskaMarah FreiwanSzonja Polett PósaZsolt GallaKatalin Eszter IbosÉva BodnárGülsüm Yilmaz LauberAna Isabel Antunes GoncalvesEylem AcarAndrás KristonFerenc KovácsPéter HorváthZsolt BozsóGábor TóthImre FöldesiPéter Béla MonostoriGábor CserniBruno Karl PodesserAndrea LehoczkiPeter PokreiszAttila KissLászló DuxKrisztina CsabafiMárta SárközyPublished in: GeroScience (2023)
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.
Keyphrases
- chronic kidney disease
- end stage renal disease
- blood pressure
- left ventricular
- oxidative stress
- heart failure
- low dose
- cross sectional
- escherichia coli
- high glucose
- mitral valve
- cell death
- rheumatoid arthritis
- machine learning
- hypertensive patients
- squamous cell carcinoma
- pulmonary hypertension
- magnetic resonance
- radiation therapy
- magnetic resonance imaging
- artificial intelligence
- double blind
- clinical trial
- physical activity
- liver fibrosis
- endoplasmic reticulum stress
- coronary artery disease
- heart rate
- pulmonary artery
- metabolic syndrome
- transcatheter aortic valve replacement
- stress induced
- aortic valve
- induced apoptosis
- preterm birth
- aortic stenosis
- gestational age
- pi k akt