Rat models for arterial calcification associated with chronic kidney disease: a systematic review and meta-analysis

Arterial calcification represents a major burden in chronic kidney disease (CKD) and is an independent risk factor for cardiovascular diseases (CVD). Rodent models are essential for preclinical research on arterial calcification mechanisms and potential therapeutic interventions, permitting longitudinal analysis of disease progression, which is ethically unfeasible in humans. In this study, we specifically focused on rat models as representative rodent models, given their well-established use in cardiovascular research. Through systematic literature screening, we identified 470 studies employing rat models to investigate arterial calcification, with these models designed to simulate various pathological conditions. Our analysis revealed that arterial calcification was predominantly induced through kidney impairment, vitamin D overload, or mechanical and chemical vessel damage. Female rats were significantly underrepresented across studies, highlighting a considerable sex bias in experimental design. Particular emphasis was given to CKD-associated arterial calcification models, which accounted for about 60% of the identified studies. A meta-analysis of 67 CKD-related studies identified several significant factors influencing arterial calcification. Dietary phosphate concentration, male sex, and the use of Sprague-Dawley rats were associated with enhanced arterial calcification development. Nephrectomy-based approaches demonstrated superior efficacy and reliability in arterial calcification induction compared to adenine-based models. However, the analysis was limited by substantial heterogeneity across studies, potential publication bias, and inconsistent reporting of experimental parameters.These findings underscore the critical need for standardized reporting of experimental procedures and results to enhance the applicability of animal studies in meta-analyses and improve their translational value.