Cardiorenal Med. 2026 Sep 8:1. doi: 10.1159/crm/abtag009. Online ahead of print.
ABSTRACT
BACKGROUND: Chronic kidney disease (CKD) is increasingly recognized as a systemic disorder characterized by profound metabolic, inflammatory, and endocrine derangements. Among the endocrine abnormalities observed in CKD, hyperprolactinemia and hypothalamic-pituitary-gonadal axis dysfunction are highly prevalent yet frequently underrecognized. Beyond their reproductive implications, both prolactin excess and sex hormone disturbances appear to contribute to the exceptionally high cardiovascular burden observed in patients with CKD and dialysis-dependent kidney failure.
SUMMARY: educed renal clearance, chronic inflammation, altered dopaminergic inhibition, and uremic toxicity contribute to elevated prolactin concentrations across all CKD stages, particularly in patients undergoing hemodialysis and peritoneal dialysis. Simultaneously, CKD induces profound disturbances of the gonadal axis, including hypogonadotropic hypogonadism, testosterone deficiency, menstrual abnormalities, infertility, and reduced estrogen levels. Emerging evidence suggests that prolactin and gonadal dysfunction are not isolated endocrine abnormalities, but rather integral components of a complex neuroendocrine-cardiovascular network. Hyperprolactinemia has been associated with endothelial dysfunction, arterial stiffness, insulin resistance, oxidative stress, inflammation, accelerated atherosclerosis, sympathetic overactivity, and prothrombotic states. Likewise, testosterone and estrogen deficiencies contribute to vascular dysfunction, sarcopenia, frailty, metabolic abnormalities, and increased cardiovascular and all-cause mortality. These alterations may synergistically amplify cardiovascular risk in patients with CKD beyond traditional risk factors. Furthermore, dialysis-related factors and a persistent uremic milieu may perpetuate endocrine dysfunction even in adequately treated patients.
CONCLUSION: Hyperprolactinemia and gonadal dysfunction represent potentially relevant non-traditional cardiovascular risk factors in CKD. Their integration within the broader neuroendocrine-cardiovascular axis provides a novel pathophysiological framework linking endocrine abnormalities, uremic toxicity, and cardiovascular disease. Improved recognition of these disturbances may open new perspectives for cardiovascular risk stratification and targeted therapeutic interventions in CKD and dialysis populations.
PMID:42709646 | DOI:10.1159/crm/abtag009