Background: Mild cognitive impairment (MCI) is regarded as a transition phase between normal aging and Alzheimer's disease (AD). Identification of novel and non-invasive biomarkers that can distinguish AD at an early stage from MCI is warranted for therapeutic and support planning. The goal of this study was to identify the differences of serum metabolomic profiles between MCI and early-stage AD, which could be potential non-invasive biomarkers for early diagnosis of AD. Methods: The subjects enrolled in the study were classified into two diagnostic groups: MCI (n = 40) and early-stage AD (n = 40). Targeted metabolomics analysis of serum samples was performed using the Biocrates Absolute-IDQ P180 kit. Targeted metabolic data were analyzed by TargetLynx, and MetIDQ software was applied to integrate the metabolites by automated calculation of metabolite concentrations. Results: The datasets of targeted metabolite analysis were analyzed by the orthogonal-projection-to-latent-structure–discriminant-analysis (OPLS-DA) model. The OPLS-DA score plots demonstrated considerable separation between the MCI and early-stage AD patients. The levels of pimelylcarnitine, putrescine, SM (OH) C24:1, and SM C24:0 were significantly lower, whereas the levels of acetylornithine, methionine sulfoxide, and PC ae C44:3 were significantly higher in early-stage AD patients as compared with MCI patients. Receiver operating characteristic curve analysis of a combination of three lipid metabolites [SM (OH) C24:1, SM C24:0, and PC ae C44:3] showed an acceptable discrimination between the early-stage AD and MCI patients (area under the curve = 0.788). Conclusions: Our results characterized the differences of serum metabolic profiles between MCI and early-stage AD patients. The positive findings from this study indicate that the minimally invasive method of blood sampling may help to identify patients with AD at an early stage from those with MCI.

Dietary leucine supplementation has been explored for the therapeutic intervention of obesity and obesity-induced metabolic dysfunctions. In this study, we aim to examine the effects of dietary leucine supplementation in db/db mice. Mice were treated with or without leucine (1.5% w/v) in drinking water for 12 weeks. The leucine supplement was found to reduce insulin resistance and hepatic steatosis in db/db mice. Using Nuclear Magnetic Resonance (NMR)-based lipidomics, we found that the reduction of hepatic triglyceride synthesis was correlated with attenuated development of fatty liver. In addition, diabetic nephropathy (DN) was also ameliorated by leucine. Using liquid chromatography–time-of-flight mass spectrometry (LC-TOF MS)-based urine metabolomics analysis, we found that the disturbance of the tricarboxylic acid (TCA) cycle was reversed by leucine. The beneficial effects of leucine were probably due to AMP-activated protein kinase (AMPK) activation in the liver and kidneys of db/db mice. Thus, dietary leucine supplementation may potentially be a nutritional intervention to attenuate hepatic steatosis and early DN in type II diabetes.

Background: Patients with diabetic kidney disease (DKD) are at higher risk of hypoglycemia than diabetic patients without DKD. We aimed to investigate the temporal trends of severe hypoglycemia in advanced DKD patients transitioning to dialysis and examine risk factors associated with severe hypoglycemia. We also investigated the association of severe hypoglycemia episodes with one-year mortality after initiation of dialysis in patients with advanced DKD. Methods: Using the Taiwan National Health Insurance Research Database, 46,779 advanced DKD patients transitioning to dialysis (Peritoneal dialysis 4216, hemodialysis 42,563) between 1997 and 2011 were enrolled. We calculated the rates of severe hypoglycemia from 5 years before dialysis until 10 years after dialysis. Cox proportional hazard model was used to examine the risk factors of post end stage renal disease (ESRD) one-year hypoglycemia and post ESRD one-year mortality in advanced DKD patients transitioning to dialysis. Results: We found that 11.5% of advanced DKD patients had at least one episode of severe hypoglycemia the year leading up to dialysis initiation. Multivariate analysis revealed hemodialysis compared with peritoneal dialysis, stroke, use of sulfonylurea, glinide, and insulin were associated with higher risk of severe hypoglycemia one year after transitioning to dialysis. Increased frequency of severe hypoglycemia-related hospitalizations was associated with incrementally higher mortality risk one year after transitioning to dialysis (Pre-ESRD hypoglycemia: Hazard ratios: 1.28 (1.18–1.38, p < 0.001), 1.64 (1.49–1.81, p < 0.001) for one, two hypoglycemia-related hospitalizations, respectively; post-ESRD hypoglycemia: HRs of 1.56 (1.40–1.73, p < 0.001), 1.72 (1.39–2.12, p < 0.001) for one, two hypoglycemia-related hospitalizations, respectively (reference group: no hypoglycemia related hospitalization)). Conclusions: Among advanced DKD patients, we observed a progressive elevated risk of hypoglycemia during the critical dialysis transition period. Increased frequency of severe hypoglycemia-related hospitalizations was associated with higher mortality risk one year after transitioning to dialysis. Further study of glycemic management strategies which prevent hypoglycemia during the critical transition period are warranted.

Background: Statins are commonly used for cardiovascular disease (CVD) prevention. Observational studies reported the effects on sepsis prevention and mortality improvement. Patients with chronic kidney disease (CKD) are at high risk for CVD and infectious diseases. Limited information is available for statin use in patients with non-dialysis CKD stage V.Method: The retrospective observational study included patients with non-dialysis CKD stage V, with either de novo statin use or none. Patients who were prior statin users and had prior cardiovascular events were excluded. The key outcomes were infection-related hospitalization, major adverse cardiovascular events (MACE) (non-fatal myocardial infarction, hospitalization for heart failure, or non-fatal stroke), and all-cause mortality. The data were retrieved from the Chang Gung Research Database (CGRD) from January 2001 to December 2019. Analyses were conducted with Cox proportional hazard regression models in the propensity score matching (PSM) cohort.Result: A total of 20,352 patients with CKD stage V were included (1,431 patients were defined as de novo statin users). After PSM, 1,318 statin users were compared with 1,318 statin non-users. The infection-related hospitalization (IRH) rate was 79.3 versus 94.3 per 1,000 person-years in statin users and statin non-users, respectively [hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.74–0.93, p = 0.002]. The incidence of MACE was 38.9 versus 55.9 per 1,000 person-years in statin users and non-users, respectively (HR, 0.72; 95% CI 0.62–0.83, p < 0.001). The all-cause mortality did not differ between statin users and non-users, but statin users had lower infection-related mortality than non-users (HR, 0.59; 95% CI 0.38–0.92, p = 0.019).Conclusion:De novo use of statin in patients with non-dialysis CKD stage V reduced the incidence of cardiovascular events, hospitalization, and mortality for infectious disease. The study results reinforced the benefits of statin in a wide range of patients with renal impairment before maintenance dialysis.

BACKGROUND: Chronic hepatitis B and C infections are major causes of morbidity and mortality in end-stage kidney disease (ESKD) patients on hemodialysis (HD). The Fibrosis-4 (FIB-4) score is a non-invasive method to evaluate chronic liver disease. However, it is unclear whether there is a connection between the FIB-4 score and major adverse cardiovascular events (MACEs) and mortality in patients on HD. This study investigates the relationship between FIB-4 scores, MACEs, and mortality in HD patients. METHODS: A 5-year retrospective study included 198 HD patients with chronic hepatitis B and C from Chang Gung Memorial Hospital. FIB-4 scores were categorized into high (>2.071), middle (1.030~2.071), and low (<1.030) tertiles for cross-sectional analyses. MACEs and mortality were tracked longitudinally. RESULTS: Patients with high FIB-4 scores had lower hemoglobin and albumin levels. Cox multivariate analysis showed that high FIB-4 scores (aHR: 1.589) and diabetes mellitus (aHR: 5.688) were significant factors for all-cause mortality. The optimal FIB-4 score for 5-year mortality was 2.942. FIB-4 scores were not significant for predicting 5-year MACEs. CONCLUSIONS: High FIB-4 scores are associated with increased 5-year all-cause mortality risk in HD patients with chronic hepatitis virus infection.

Renal leptospirosis caused by leptospiral infection is characterised by tubulointerstitial nephritis and tubular dysfunction, resulting in acute and chronic kidney injury. Metabolomic and transcriptomic data from a murine model of Leptospira infection were analysed to determine whether metabolomic data from urine were associated with transcriptome changes relevant to kidney injury caused by Leptospira infection. Our findings revealed that 37 metabolites from the urine of L. interrogans-infected mice had significantly different concentrations than L. biflexa-infected and non-infected control mice. Of these, urinary L-carnitine and acetyl-L-carnitine levels were remarkably elevated in L. interrogans-infected mice. Using an integrated pathway analysis, we found that L-carnitine and acetyl-L-carnitine were involved in metabolic pathways such as fatty acid activation, the mitochondrial L-carnitine shuttle pathway, and triacylglycerol biosynthesis that were enriched in the renal tissues of the L. interrogans-infected mice. This study highlights that L-carnitine and acetyl-L-carnitine are implicated in leptospiral infection-induced kidney injury, suggesting their potential as metabolic modulators.