岩津 好隆

Chronic renal failure (CRF) is associated with the development of cardiovascular disease (CVD). Paraoxonase 1 (PON1), an antioxidant enzyme, shows cardioprotective properties and has been proposed as a therapeutic marker for CRF. A systematic analysis of the literature assessing the association between PON1 activity and renal replacement therapy (RRT) of CRF is currently lacking. Therefore, we set out to perform a meta-analysis of the available data on PON1 in RRT of CRF. We searched three electronic databases for studies on PON1 activity in CRF patients with RRT such as hemodialysis (HD), peritoneal dialysis (PD), or renal transplantation (RTx), published before June 2023. A random-effects and network meta-analysis were performed. A total of 53 studies were eligibly identified. Compared to CRF patients without RRT, RTx patients had higher paraoxonase activity (standard mean difference (SMD), 1.76, 95% confidence interval (CI), 0.76–2.75), followed by HD (SMD, 0.73; 95% CI, 0.02–1.45) and PD patients. Likewise, RTx patients had higher arylesterase activity (SMD, 1.84, 95% CI, 0.18–3.50), followed by HD and PD patients. Also, paraoxonase activity was increased after HD (SMD, 0.59, 95% CI, 0.16–1.03). In conclusion, the overall data demonstrated that PON1 activity is higher in CRF patients with RRT, particularly RTx, followed by that of HD and PD. Measuring PON1 activity can also be included to the paraclinical toolbox for the management of RRT, in addition to the understanding of CRF-related pathophysiology. Regarding the selection of RRT types and their potential to prevent CVD, more research is required.

Calciprotein particles (CPPs) are colloids composed of solid-phase calcium-phosphate and serum protein fetuin-A. CPPs form a polydispersed system with different particle size and density. CPPs with specific physical properties can induce calcification and innate immune responses in cultured cells. In hemodialysis patients, blood CPP levels were reported to correlate with vascular calcification and inflammation. However, little is known about relation between these disorders and physical properties of CPPs. Here, we show that the association between physical properties of plasma CPPs and serum levels of inflammatory cytokines/chemokines in 78 hemodialysis out-patients by cross-sectional study. Patients with cardiovascular disease (CVD) had significantly higher high density CPP (H-CPP) levels than patients without CVD but not low density CPP (L-CPP). Seven cytokines/chemokines (EGF, eotaxin, IL-8, IP-10, MCP-1, MIP-1, MIP-1β and TNFα) were detectable in the serum samples from > 95% of the patients. In multivariate regression analysis, H-CPP was positively associated with eotaxin after adjusting for age, gender, smoking, serum phosphate and FGF23. L-CPP was negatively associated with IL-8 after adjusting for age, gender, serum albumin, phosphate and FGF23. High H-CPP levels were associated with pro-inflammatory response, whereas L-CPPs were associated with anti-inflammatory response. CPPs with different physical properties may impact differently on pathophysiology in HD patients.