Elevated Serum Nardilysin Is Inversely Associated with Cardiovascular Disease in Kidney Transplant Recipients.

This observational cohort study measured serum levels of two circulating peptides — Nardilysin (NRDc) and MOTS-c — in 150 participants (118 kidney transplant recipients [KTRs] and 32 age-matched controls) to explore their potential roles as cardiometabolic biomarkers in this high-risk population. Using commercial ELISA kits, the researchers found that median serum NRDc and MOTS-c levels were significantly higher in KTRs compared to controls. Penalized logistic regression revealed an inverse association between elevated NRDc levels and prevalent cardiovascular (CV) disease in KTRs, suggesting that higher NRDc may be associated with lower odds of existing CV disease. KTRs were followed for a median of approximately 29 months, during which renal allograft loss and all-cause mortality were analyzed using Fine-Gray competing risk regression. The authors propose that elevated NRDc and MOTS-c in KTRs may reflect altered metabolic and inflammatory pathways unique to this population. Key limitations include the observational design, the relatively small and single-center cohort, the cross-sectional nature of the CV disease association, and the lack of incident CV event data. The authors acknowledge that longitudinal studies are needed to clarify causal relationships.

Why this grade: This is a single-center observational cohort of only 150 participants with cross-sectional CV disease associations and no randomization or control of confounding, limiting causal inference.