Tanshinone IIA elevates serum soluble klotho levels and decreases cardiovascular events in patients on maintenance hemodialysis: a prospective before-after study

Abstract

Background: Cardiovascular disease (CVD) is the most common adverse event of maintenance hemodialysis (MHD), in which serum soluble klotho plays a vital role. Tanshinone IIA (tan) has been used to protect the cardiovascular system for hundreds of years. This study was performed to investigate the effects of tan on klotho level and cardiovascular events of MHD patients.Methods: Totally 112 patients were enrolled in this study, and their demographic, clinical, and laboratory characteristics were collected at admission. Serum soluble klotho, carotid intima-media thickness (CIMT), and abdominal aorta calcification (AAC) level were measured to determine their relationship. Seventy-one patients were given sodium tan sulfonate injection according to their willingness, while 41 patients were not given any specific treatment. The endpoint events were recorded, including cardiovascular mortality, nonfatal cardiovascular events, and all-cause mortality.Results: All patients were divided into two groups on whether the level of serum soluble klotho was more than medium or not. CIMT and AAC grade showed significant differences between 2 groups (group of low level of klotho versus group of high level of klotho, CIMT: 1.03±0.22 vs. 0.85±0.20 mm, P<0.001; AAC grade: 5.04±3.93 vs. 1.69±2.30 points, P<0.001). All patients were followed up for at least one year.The results revealed that using tan improved the level of serum soluble klotho (490.23±153.97 pg/mL after using tan versus 444.49±143.32 pg/mL before using tan, P=0.042). Kaplan-Meier curves showed that cardiovascular event-free survival was significantly higher in patients given tan (P=0.040) compared with patients not given tan.Conclusions: Tan effectively increases the level of serum soluble klotho and further reduces the incidence of cardiovascular events in MHD patients.

Correlation Between Soluble Klotho and Vascular Calcification in Chronic Kidney Disease: A Meta-Analysis and Systematic Review

“…Ten publications, involving 1,204 participants were eligible according to the inclusion and exclusion criteria (Kitagawa et al, 2013;Buiten et al, 2014;Cai et al, 2015;Di Lullo et al, 2015;Morita et al, 2015;Krishnasamy et al, 2017;Zheng et al, 2018;Koga et al, 2020;Xu et al, 2020;Chen et al, 2021). All included studies had observational or cross-sectional design.…”

“…Primary features of the included studies and baseline information on participants are shown in Table 1. Among these studies, five reported correlation coefficients (r) pertaining to the association between sKlotho level and VC using Pearson correlation or Spearman correlation analysis (Cai et al, 2015;Di Lullo et al, 2015;Krishnasamy et al, 2017;Zheng et al, 2018;Koga et al, 2020); five reported ORs and CIs pertaining to the association between sKlotho level and VC according to multivariate logistic regression analysis (Cai et al, 2015;Morita et al, 2015;Zheng et al, 2018;Koga et al, 2020;Chen et al, 2021); one study only reported a β-value in multivariate logistic regression analysis (Kitagawa et al, 2013); and two studies reported β-values and CIs pertaining to the association between sKlotho level and VC according to multivariate linear regression analysis (Buiten et al, 2014;Xu et al, 2020). Regarding the correlation between sKlotho and non-VC clinical findings among the included studies, one study reported ORs and CIs pertaining to the association between sKlotho level and vascular dysfunction (Kitagawa et al, 2013) or cardiovascular events (Buiten et al, 2014) according to multivariate logistic regression analysis.…”

“…One study reported HRs and CIs pertaining to the association between sKlotho level and all-cause mortality according to Cox regression analysis (Zheng et al, 2018). Another study reported β-values and CIs pertaining to the association between sKlotho level and carotid intima-media thickness according to multivariate linear regression analysis (Xu et al, 2020). However, no studies reported results on the association between VC and clinical outcomes.…”

“…The pooled effector OR was [3.27 (1.70, 6.30)] with no heterogeneity (I 2 = 0%, p = 0.48) (Figure 5A) and [1.05 (1.01, 1.09)] with moderate heterogeneity (I 2 = 63%, p = 0.10) (Figure 5B) according to whether sKlotho was treated as a categorical or continuous variable, respectively. Two studies reported β-values pertaining to the association between sKlotho level and VC using multivariate linear regression analysis after adjusting for similar confounders (Buiten et al, 2014;Xu et al, 2020). Indirect ORs and CIs were calculated using exp(β).…”

“…According to another study, each 100-pg/mL increase in sKlotho level was associated with a 40% reduction in risk of arterial stiffness (Kitagawa et al, 2013). Interestingly, Xu et al reported that treatment with tanshinone IIA effectively decreased cardiovascular events in CKD patients, and the beneficial effect exerted by tanshinone IIA was ascribed to the elevation in sKlotho level (Xu et al, 2020). Because of significant differences in nature among these studies, they were unable to be combined to generate pooled effectors.…”