Background: Cardiovascular diseases (CVD) is the leading cause of death among maintenance hemodialysis patients, with dyslipidemia being a prevalent complication. The paradoxical relationship between cardiovascular outcomes and established lipid risk markers, such as low-density lipoprotein cholesterol (LDL-C), complicates lipid management in this population. This study investigated Lipoprotein-associated phospholipase A2 (Lp-PLA2), an emerging biomarker known for its proinflammatory and proatherogenic properties, as a potential cardiovascular prognostic marker in this cohort. In this context, the association between Lp-PLA2 levels and cardiovascular outcomes was evaluated, with the aim to facilitate more accurate stratification and identification of high-risk individuals. Methods: From August 2013 to January 2014, 361 hemodialysis patients were prospectively enrolled. Lp-PLA₂ activity and laboratory measures at baseline were quantified. Comorbidities and medications were recorded. All patients were followed until the end of April, 2022. The individual and combined effects of Lp-PLA₂ activity and LDL-C on patient outcomes were examined. The association between Lp-PLA₂ activity and all-cause mortality, cardiovascular mortality, and major adverse cardiovascular events (MACEs) was analyzed. Results: The median Lp-PLA₂ activity was 481.2 U/L. In subjects with Lp-PLA₂ activity over 481.2 U/L, significantly higher total cholesterol (4.89 vs. 3.98 mmol/L; P < 0.001), LDL-C (3.06 vs. 2.22 mmol/L; P < 0.001), and apolipoprotein B (0.95 vs. 0.75 mmol/L; P < 0.001) were observed. Over a median follow-up of 78.1 months, 182 patients died, with 77 cases identified as cardiovascular death, 88 MACEs happened. Cardiovascular mortality and MACEs, but not all-cause mortality, were significantly increased in the high Lp-PLA2 group. Cox regression analyses showed that high Lp-PLA₂ activity was associated with cardiovascular mortality and MACE occurrence. After comprehensive adjustment, high Lp-PLA₂ activity was independently associated with cardiovascular mortality(as a dichotomous variable: HR:2.57, 95%CI:1.58,4.18, P < 0.001; as a continuous variable: HR:1.25, 95%CI:1.10,1.41, P = 0.001) and MACEs(as a dichotomous variable: HR:2.17, 95%CI:1.39,3.40, P = 0.001; as a continuous variable: HR:1.20, 95%CI:1.07,1.36, P = 0.002). When participants were grouped by median Lp-PLA2 activity and LDL-C values, those with high Lp-PLA₂ and low LDL-C had the highest CV mortality. The addition of Lp-PLA2 significantly improved reclassification (as a dichotomous variable NRI = 42.51%, 95%CI: 5.0%,61.33%; as a continuous variable, NRI = 33.32%, 95% CI: 7.47%,56.21%). Conclusions: High Lp-PLA₂ activity is an independent risk factor for cardiovascular mortality and MACEs occurrence in patients on hemodialysis. The combined measures of Lp-PLA₂ and LDL-C help to identify individuals with a higher risk of cardiovascular death.

Ischemia-reperfusion injury (IRI) is the primary cause of acute kidney injury (AKI), which can result in chronic kidney disease (CKD) with renal fibrosis. Magnesium lithospermate B (Mlb), a bioactive compound produced from Salvia miltiorrhiza Bunge, exerts nephroprotective effects against AKI. However, the significance of Mlb in the evolution of IRI-induced AKI in patients with CKD remains unclear. Notably, the specific mechanisms underlying the putative antifibrotic activities of Mlb during this progression remain to be fully elucidated. This study sought to explore the therapeutic benefits of Mlb in AKI-to-CKD progression and uncover the potential mechanisms, with a special interest in its effects on renal fibrosis and cell cycle regulation. Unilateral ischemia/reperfusion (UIR)-induced mouse AKI-to-CKD progression (in vivo) and HK-2 cells with TGF-β-induced fibrosis model (in vitro) were used in the study. The beneficial effects of Mlb on renal fibrosis and cell cycle-related signaling pathways were investigated using histological analysis, molecular assays, network pharmacology, and RNA sequencing. Mlb treatment significantly reduced renal dysfunction, inflammation, apoptosis, and the G2/M phase cell cycle stalling in mice 14 days post-UIR-induced AKI, subsequently improving renal fibrosis. Mechanistically, Mlb promotes the activity of the CDK1/Cyclin B1 signaling pathway, thereby alleviating the G2/M phase cell cycle stalling. Network pharmacology and RNA sequencing analyses identified the KLF5/CDK1/Cyclin B1 signaling pathway as a potential target of the antifibrotic effects of Mlb, which was further verified in both in vivo and in vitro experiments. The KLF5 inhibitor ML264 attenuated the protective effects of Mlb by reducing CDK1/Cyclin B1 expression and reinstating the G2/M phase cell cycle stalling, highlighting the critical role of this pathway in Mlb-mediated renal protection. Mlb decreases renal fibrosis by inhibiting the G2/M phase cell cycle stalling via the KLF5/CDK1/Cyclin B1 signaling pathway during AKI-to-CKD progression. Our findings offer new insight into the therapeutic potential of Mlb in preventing CKD progression following AKI and identify a previously unrecognized mechanism involving the KLF5/CDK1/Cyclin B1 pathway.

Background: Acute kidney injury (AKI) is a major complication of cardiac surgery, particularly in patients with pre-existing chronic kidney disease (CKD), who are at higher risk due to their compromised renal function. This study investigated the association between the triglyceride–glucose (TyG) index, a marker of insulin resistance, and postoperative AKI in CKD patients undergoing cardiac surgery to enhance risk stratification and perioperative management. Methods: This retrospective study included 542 patients with impaired renal function (estimated glomerular filtration rate (eGFR) 15–60 mL/min/1.73 m2) undergoing cardiac surgery from January 2018 to December 2019. The TyG index was calculated as Ln(fasting triglycerides [mg/dL] × fasting blood glucose [mg/dL]/2), and outcomes were defined as postoperative AKI (per Kidney Disease: Improving Global Outcomes (KDIGO) criteria), in-hospital mortality, and length of hospital stay. Multivariate logistic regression and subgroup analyses assessed the association between TyG and these endpoints. Results: Among the 542 patients, 55.7% developed AKI, and the in-hospital mortality rate was 7.6%. In the multivariate regression analysis, the odds ratio for AKI with each unit increase in LnTyG was 0.43 (95% CI 0.02–8.70, p = 0.579), while in the standardized TyG, it was 0.96 (95% CI 0.77–1.21, p = 0.754). Subgroup analyses, stratified by age, sex, CKD stage, and diabetes status, revealed no significant associations across all strata (all p for interaction > 0.05). Conclusion: The TyG index is not significantly associated with AKI or prognosis after cardiac surgery in patients with kidney dysfunction. Further studies are needed to elucidate the role of insulin resistance in the pathogenesis of AKI.

Background/Objectives: Hemodialysis-induced myocardial stunning (HIMS) is a frequent complication in patients undergoing maintenance hemodialysis, characterized by transient left ventricular dysfunction due to ischemic episodes. Mitochondrial dysfunction and fluctuations in key ions such as potassium (K⁺) and calcium (Ca²⁺) are implicated in the pathogenesis of HIMS. This study aims to investigate the role of mitochondrial dysfunction and the protective potential of mitochondrial ATP-sensitive potassium channels (mitoK_ATP) in mitigating HIMS. Methods: A 5/6 nephrectomy rat model was established to mimic chronic kidney disease and the subsequent HIMS. The effects of mitoK_ATP channel modulators were evaluated by administering diazoxide (DZX), a mitoK_ATP opener, and 5-hydroxydecanoate (5-HD), a mitoK_ATP blocker, before hemodialysis. Mitochondrial function was assessed by measuring membrane potential, ATP synthase activity, and intramitochondrial Ca²⁺ levels. Myocardial function was evaluated using speckle tracking echocardiography. Results: Rats undergoing hemodialysis exhibited significant reductions in left ventricular strain and synchrony. DZX administration significantly improved mitochondrial function and reduced myocardial strain compared to controls. Conversely, 5-HD worsened mitochondrial swelling and disrupted myocardial function. Higher K⁺ and Ca²⁺ concentrations in the dialysate were associated with improved mitochondrial energy metabolism and myocardial strain. Conclusions: Mitochondrial dysfunction and ion imbalances during hemodialysis are key contributors to HIMS. The activation of mitoK_ATP channels provides mitochondrial protection and may serve as a potential therapeutic strategy to mitigate HIMS.