Beyond traditional biomarkers: do serum cystatin C and urinary cystatin B improve diagnostic precision in feline and canine renal disease? A systematic review and meta-analysis

Chronic kidney disease (CKD) is the most common nephropathy in cats and dogs, particularly in elderly animals, whereas acute kidney injury (AKI) represents an abrupt-onset condition associated with high morbidity and mortality. Serum creatinine and urea are widely used for renal function assessment; however, they exhibit low sensitivity for the early detection of renal dysfunction. In this context, alternative biomarkers, such as serum cystatin C (sCysC) and urinary cystatin B (uCysB), have been investigated as potential diagnostic tools. The present study conducted a meta-analysis, following PRISMA guidelines, to evaluate the performance of these biomarkers in cats with CKD and dogs with AKI. Three studies on sCysC and two on uCysB were included, comparing diseased cats and dogs with healthy controls, only one article on uCysB in cats met the inclusion and exclusion criteria and was analyzed qualitatively. The meta-analysis demonstrated a consistent increase in sCysC in cats with CKD, with a large effect size, indicating moderate and stable discriminatory ability. Conversely, uCysB showed a marked elevation in dogs with AKI, with effect sizes exceeding thresholds for strong clinical relevance, suggesting a strong association with tubular injury. However, high heterogeneity was observed among uCysB studies, along with relevant methodological limitations, including predominant comparisons with healthy animals. It is concluded that sCysC has limited utility in current clinical practice, with no proven superiority over creatinine or symmetric dimethylarginine (SDMA), whereas uCysB emerges as a promising biomarker for AKI, although its clinical application still depends on more robust prospective studies.