Background: Few studies have investigated the relationship between the anion gap, including the corrected anion gap, and patient mortality in intensive care units (ICUs) without restricting the analysis to specific diseases or medical specialties. Our primary objective was to investigate the association between the anion gap and ICU mortality using multiple open-access databases. Methods: We identified 4229 subjects from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, whose entries were from between 2008 and 2019. For each patient, the anion gap and corrected anion gap were calculated, and the study sample was divided into tertile groups (T) according to these levels. The association between the anion gap and in-hospital mortality was assessed using hazard ratios (HRs) and 95% confidence intervals (CIs) derived from a multivariable-adjusted Cox proportional hazards model. Besides MIMIC-IV, we also incorporated study samples from two other databases (MIMIC-III and electronic ICU) to calculate summary HRs using a random-effects meta-analysis. Results: Within MIMIC-IV, 1015 patients (24%) died during an average follow-up period of 15.5 days. The fully adjusted HRs and 95% CIs for T2 and T3, relative to T1, were 1.31 (95% CI 1.08–1.58) and 1.54 (95% CI 1.24–1.90), respectively. When grouped by corrected anion gap, the results remained statistically significant. In the meta-analysis, the summary HRs and 95% CIs for T2 and T3 were 1.24 (95% CI 1.08–1.43) and 1.55 (95% CI 1.33–1.82), respectively. Conclusions: Both the anion gap and corrected anion gap were associated with in-hospital mortality regardless of specific diseases or medical specialties.

Mitochondrial homeostasis is controlled by biogenesis, dynamics, and mitophagy. Mitochondrial dysfunction plays a central role in cardiovascular and renal disease and omega-3 fatty acids (FAs) are beneficial for cardiovascular disease. We investigated whether omega-3 fatty acids (FAs) regulate mitochondrial biogenesis, dynamics, and mitophagy in the kidney and heart of adenine-induced uremic rats. Eighteen male Sprague Dawley rats were divided into normal control, adenine control, and adenine with omega-3 FA groups. Using Western blot analysis, the kidney and heart expression of mitochondrial homeostasis-related molecules, including peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), dynamin-related protein 1 (Drp1), and phosphatase and tensin homolog-induced putative kinase 1 (PINK1) were investigated. Compared to normal, serum creatinine and heart weight/body weight in adenine control were increased and slightly improved in the omega-3 FA group. Compared to the normal controls, the expression of PGC-1α and PINK1 in the kidney and heart of the adenine group was downregulated, which was reversed after omega-3 FA supplementation. Drp1 was upregulated in the kidney but downregulated in the heart in the adenine group. Drp1 expression in the heart recovered in the omega-3 FA group. Mitochondrial DNA (mtDNA) was decreased in the kidney and heart of the adenine control group but the mtDNA of the heart was recovered in the omega-3 FA group. Drp1, which is related to mitochondrial fission, may function oppositely in the uremic kidney and heart. Omega-3 FAs may be beneficial for mitochondrial homeostasis by activating mitochondrial biogenesis and PINK1-dependent mitophagy in the kidney and heart of uremic rats.

Background: Individuals receiving maintenance hemodialysis (HD) are at particularly high risk for cardiovascular disease. Although olive oil intake has been associated with cardiovascular benefits, the effects of stir-fried olive oil on erythrocyte membrane fatty acid (FA) composition in patients undergoing HD have not been adequately investigated. This study aimed to compare the effects of stir-fried and non-stir-fried olive oil on changes in erythrocyte membrane FA composition in patients undergoing HD.Methods: In this single-blind randomized trial, 31 patients undergoing HD received lunch meals containing extra virgin olive oil for 12 weeks. Meals were prepared using one of two methods: the olive oil was either used during stir-frying or added after cooking without heat exposure. Erythrocyte membrane FA profiles were assessed at baseline and after the 12-week intervention using gas chromatography.Results: A total of 27 participants completed the study. Overall caloric intake and animal-derived lipid intake did not differ between the groups. In the stir-fried olive oil group, erythrocyte membrane trans-oleic acid levels increased significantly after 12 weeks. In contrast, the non-stir-fried olive oil group showed significant increases in saturated FAs, including stearic acid, along with a higher arachidonic acid-to-eicosapentaenoic acid ratio and increased serum albumin levels.Conclusions: Stir-fried olive oil increased trans-oleic acid levels in erythrocyte membrane FA composition, whereas non-stir-fried olive oil improved serum albumin levels. These findings suggest that preparation methods may be as important as the oil itself, with non-stir-fried olive oil offering a potentially useful nutritional strategy for patients undergoing HD.

Patients with chronic kidney disease (CKD) face a substantial cardiovascular burden, with altered erythrocyte membrane fatty acids (FAs) representing potential markers of adverse outcomes. However, comprehensive evaluations according to varying levels of kidney function remain limited. This retrospective pooled analysis evaluated the association between kidney function decline, erythrocyte FA profiles, and estimated enzymatic indices (surrogate product-to-precursor ratios) across eight distinct cohorts (N = 282: 33 healthy controls, 131 non-dialysis CKD, 118 end-stage kidney disease). Generalized linear mixed models accounted for inter-cohort heterogeneity with study source as a random intercept, adjusting for age, sex, diabetes, and serum albumin. With declining kidney function, erythrocyte membrane oleic acid exhibited a stepwise increase alongside an elevated elongation of very long-chain fatty acids protein 6 index, whereas linoleic acid and the stearoyl-CoA desaturase 18 index progressively decreased. Multivariable models confirmed that estimated glomerular filtration rate was an independent predictor of oleic (β = −0.012, 95% CI: −0.024 to −0.0003, p = 0.044) and linoleic (β = 0.016, 95% CI: 0.004 to 0.028, p = 0.012) acid levels. In conclusion, kidney dysfunction is independently associated with an altered membrane FA composition, characterized by an increase in monounsaturated FAs and a decline in essential polyunsaturated FAs. These findings suggest a potential link between declining kidney function and altered lipid metabolism, providing a basis for further studies exploring targeted nutritional interventions in CKD.

Myostatin is associated with inflammatory processes; however, its renal expression and impact on mitochondrial homeostasis during chronic kidney disease (CKD) remain poorly defined. This study investigated whether omega-3 fatty acids (FAs) modulate renal myostatin and mitochondrial integrity under uremic conditions using both in vivo and in vitro models. In rats with adenine-induced CKD, omega-3 FA supplementation attenuated the increase in renal myostatin expression. Uremia was associated with impaired mitochondrial homeostasis, evidenced by decreased peroxisome proliferator-activated receptor gamma coactivator-1 alpha levels and increased dynamin-related protein 1 levels, alongside the upregulation of mitophagy and inflammatory markers. Furthermore, mitochondrial structural damage and reduced mitochondrial DNA (mtDNA) content were observed in uremic kidneys. Omega-3 FA treatment partially reversed these alterations, restored mtDNA levels, and preserved mitochondrial cristae integrity. In vitro, HK-2 cells treated with indoxyl sulfate exhibited increases in myostatin expression and mitochondrial impairment, which were mitigated by eicosapentaenoic acid, docosahexaenoic acid, or their combination. These findings suggest that omega-3 FAs exert protective effects against uremia-induced renal injury by suppressing myostatin and preserving mitochondrial homeostasis, specifically by modulating biogenesis, dynamics, and structural integrity. Consequently, omega-3 FAs may serve as a potential therapeutic strategy with which to preserve mitochondrial homeostasis in patients with CKD.