Association of Serum Polyamines with Cardiovascular Events and All-Cause Mortality in Chronic Kidney Disease

Emerging evidence indicates that serum polyamines, including putrescine, spermidine, and spermine, may serve as potential biomarkers for chronic kidney disease (CKD) and its progression. However, the association between serum polyamine levels, cardiovascular (CV) events, and mortality in CKD patients remains poorly understood.

A retrospective cohort study was conducted, involving 297 adult patients with CKD at stages 1-5 from March 2015 to September 2018, with follow-up until May 2023. Serum polyamine levels were quantified using high-performance liquid chromatography and subsequently categorized into quartiles. The Kaplan-Meier curve was employed to assess the survival probabilities of CV events and overall mortality in relation to serum polyamine levels. The relationship between serum polyamines and the risk of cardiovascular disease (CVD) and overall mortality was explored using univariate and multivariate Cox regression analyses. Furthermore, we conducted a competing-risk analysis to investigate the link between serum polyamines and CV events, with mortality as the competing event.

Over a median follow-up of 6.11 years, our findings revealed a negative correlation between putrescine levels and estimated glomerular filtration rate (eGFR), while spermidine and spermine levels were positively correlated with eGFR. The Kaplan-Meier curve demonstrated that serum polyamines were significantly associated with risk of CV events and all-cause mortality. Moreover, Cox regression analyses showed that, in a multivariate Cox model, patients in the highest quartile of putrescine displayed a significantly higher risk of CV events (hazard ratio [HR] 6.972, 95% confidence interval [CI] 2.520-19.294, p < 0.001) compared to those in the lowest quartile. Conversely, higher levels of spermidine were associated with a lower risk of CV events (HR = 0.077, 95% CI 0.022-0.274, p < 0.001), and higher levels of spermine also appeared to reduce the risk of CV events (HR = 0.180, 95% CI 0.061-0.530, p = 0.002). The relationship between serum polyamines and CVD remained robust in the competing risk models. Additionally, in the multivariate model, spermidine and spermine showed a significant protective effect on the risk of overall mortality; however, the protective effect was diminished upon the inclusion of eGFR as a covariate.

Our study demonstrates significant disruption in serum polyamine levels among CKD patients, which correlates with eGFR. Altered polyamine levels are linked to an increased risk of CV events and overall mortality. Thus, serum polyamines may be considered valuable prognostic indicators for CKD patients.