Serum Lipidomic Analysis Reveals Biomarkers and Metabolic Pathways of Thyroid Dysfunction.

Abnormal thyroid hormone secretion is the most important feature of hypothyroidism and plays an important role in lipid metabolism. However, their connection has not been clearly established. This study aimed to identify the serum biomarkers and metabolic pathways associated with hyperthyroidism and hypothyroidism. The study enrolled discovery and validation sets of 175 and 300 participants, respectively, to identify and validate the serum biomarkers of hyperthyroidism and hypothyroidism via ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry lipidomics through univariate and multivariate analyses. Eight and six biomarkers were identified for hyperthyroidism and hypothyroidism, respectively. Spearman correlation analysis was used to assess the correlation between the biomarkers and thyroid dysfunction indicators; subsequently, metabolic pathway and network analyses were performed for these biomarkers. Most biomarkers exhibited significant correlation with thyroid dysfunction indicators, mainly being enriched in the glycerophospholipid (GPL) metabolism. The diagnostic accuracies of the biomarkers and biomarker panels were assessed via receiver operating characteristic curve analysis. All the biomarkers demonstrated good diagnostic performance, and the hyperthyroidism and hypothyroidism biomarker panels reached an area under the curve value of 1.000. The results were validated using the validation set. Therefore, our findings revealed that thyroid dysfunction primarily affects the human metabolism via the GPL metabolism, thus providing a theoretical basis for the clinical prevention and control of thyroid dysfunction.

Androgen deprivation restores ARHGEF2 to promote neuroendocrine differentiation of prostate cancer.

Androgen receptor (AR) plays an important role in the progression of prostate cancer and has been targeted by castration or AR-antagonists. The emergence of castration-resistant prostate cancer (CRPC) after androgen deprivation therapy (ADT) is inevitable. However, it is not entirely clear how ADT fails or how it causes resistance. Through analysis of RNA-seq data, we nominate ARHGEF2 as a pivotal androgen-repressed gene. We show that ARHGEF2 is directly suppressed by androgen/AR. AR occupies the enhancer and communicates with the promoter region of ARHGEF2. Functionally, ARHGEF2 is important for the growth, lethal phenotype, and survival of CRPC cells and tumor xenografts. Correspondingly, AR inhibition or AR antagonist treatment can restore ARHGEF2 expression, thereby allowing prostate cancer cells to induce treatment resistance and tolerance. Overall, our findings provide an explanation for the contradictory clinical results that ADT resistance may be caused by the up-regulation of ARHGEF2 and provide a novel target.

Prognostic Value of Systemic Immune-Inflammation Index among Critically Ill Patients with Acute Kidney Injury: A Retrospective Cohort Study.

Inflammation plays a significant role in the occurrence and development of acute kidney injury (AKI). Evidence regarding the prognostic effect of the systemic immune-inflammation index (SII) in critically ill patients with AKI is scarce. The aim of this study was to assess the association between SII and all-cause mortality in these patients. Detailed clinical data were extracted from the Medical Information Mart for Intensive Care Database (MIMIC)-IV. The primary outcome was set as the in-hospital mortality. A total of 10,764 AKI patients were enrolled in this study. The restricted cubic splines analyses showed a J-shaped curve between SII and the risk of in-hospital and ICU mortality. After adjusting for relevant confounders, multivariate Cox regression analysis showed that both lower and higher SII levels were associated with an elevated risk of in-hospital all-cause mortality. A similar trend was observed for ICU mortality. In summary, we found that the SII was associated in a J-shaped pattern with all-cause mortality among critically ill patients with AKI. SII appears to be have potential applications in the clinical setting as a novel and easily accessible biomarker for predicting the prognosis of AKI patients.

Serum metabolomics study of anxiety disorder patients based on LC-MS.

BACKGROUND: In the current environment of increasing social pressure, anxiety disorder has become a kind of health problem that needs to be solved urgently. However, the pathological mechanism of anxiety is still unclear, the classification of clinical diagnosis and symptoms is complex, and there is still a lack of biomarkers that can be identified and judged. METHODS: This study used LC-MS and non-targeted metabolomics to analyze the clinically collected plasma of 18 samples from anxiety disorder patients and 31 samples from healthy people to screen differential metabolites and perform subsequent metabolic pathway analysis. Binary Logistic regression was used to construct the anxiety disorder diagnosis prediction model and evaluate the prediction efficacy. RESULTS: The results showed that 22 metabolites were disturbed in the plasma of anxiety patients compared with healthy people. These metabolites mainly participate in 6 metabolic pathways. The combined diagnostic factors 4-Acetamidobutanoate, 3-Hydroxysebacic acid, and Cytosine were used to construct the diagnosis prediction model. The prediction probability of the model is 91.8%, the Youden index is 0.889, the sensitivity is 0.889, and the specificity is 1.000, so the prediction effect is good. CONCLUSIONS: This study preliminarily analyzed and explored the differences between plasma samples from patients with anxiety disorder and healthy individuals, increased the types of potential biomarkers for anxiety disorder, and provided a valuable reference for subsequent research related to anxiety disorder.

Circ_0114428 promotes proliferation, fibrosis and EMT process of high glucose-induced glomerular mesangial cells through regulating the miR-185-5p/SMAD3 axis.

Circular RNA (circRNA) has been confirmed to be the key regulators of diabetic nephropathy (DN) progression. However, the role of circ_0114428 in the DN progression remains unclear. Glomerular mesangial cells (GMCs) were treated with high glucose (HG) to mimic DN cell models in vitro. The expression levels of circ_0114428, microRNA (miR)-185-5p, and SMAD3 mRNA were examined by quantitative real-time PCR. Cell proliferation ability was detected by MTT assay, EdU staining and flow cytometry. The protein levels of proliferation marker, fibrosis markers, epithelial-mesenchymal transition (EMT) markers and SMAD3 were measured by western blot assay. The interaction between miR-185-5p and circ_0114428 or SMAD3 was confirmed via dual-luciferase reporter assay, RIP assay and RNA pull-down assay. Our data showed that circ_0114428 was upregulated in HG-induced GMCs. Circ_0114428 overexpression could aggravate the promotion effect of HG on the proliferation, fibrosis and EMT process of GMCs, while its knockdown had an opposite effect. In the terms of mechanisms, circ_0114428 could sponge miR-185-5p to regulate SMAD3. MiR-185-5p inhibitor could reverse the suppressive effect of circ_0114428 knockdown on the proliferation, fibrosis and EMT process in HG-induced GMCs. Also, SMAD3 overexpression abolished the inhibition of miR-185-5p on the proliferation, fibrosis and EMT process in HG-induced GMCs. Taken together, our data suggested that circ_0114428 might promote DN progression by regulating the miR-185-5p/SMAD3 axis.

Functional metabolome profiling may improve individual outcomes in colorectal cancer management implementing concepts of predictive, preventive, and personalized medical approach.

Objectives: Colorectal cancer (CRC) is one of the most common solid tumors worldwide, but its diagnosis and treatment are limited. The objectives of our study were to compare the metabolic differences between CRC patients and healthy controls (HC), and to identify potential biomarkers in the serum that can be used for early diagnosis and as effective therapeutic targets. The aim was to provide a new direction for CRC predictive, preventive, and personalized medicine (PPPM). Methods: In this study, CRC patients (n = 30) and HC (n = 30) were recruited. Serum metabolites were assayed using an ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) technology. Subsequently, CRC cell lines (HCT116 and HCT8) were treated with metabolites to verify their function. Key targets were identified by molecular docking, thermal shift assay, and protein overexpression/inhibition experiments. The inhibitory effect of celastrol on tumor growth was also assessed, which included IC50 analysis, nude mice xenografting, molecular docking, protein overexpression/inhibition experiments, and network pharmacology technology. Results: In the CRC group, 15 serum metabolites were significantly different in comparison with the HC group. The level of glycodeoxycholic acid (GDCA) was positively correlated with CRC and showed high sensitivity and specificity for the clinical diagnostic reference (AUC = 0.825). In vitro findings showed that GDCA promoted the proliferation and migration of CRC cell lines (HCT116 and HCT8), and Poly(ADP-ribose) polymerase-1 (PARP-1) was identified as one of the key targets of GDCA. The IC50 of celastrol in HCT116 cells was 121.1 nM, and the anticancer effect of celastrol was supported by in vivo experiments. Based on the potential of GDCA in PPPM, PARP-1 was found to be significantly correlated with the anticancer functions of celastrol. Conclusion: These findings suggest that GDCA is an abnormally produced metabolite of CRC, which may provide an innovative molecular biomarker for the predictive identification and targeted prevention of CRC. In addition, PARP-1 was found to be an important target of GDCA that promotes CRC; therefore, celastrol may be a potential targeted therapy for CRC via its effects on PARP-1. Taken together, the pathophysiology and progress of tumor molecules mediated by changes in metabolite content provide a new perspective for predictive, preventive, and personalized medical of clinical cancer patients based on the target of metabolites in vivo.Clinical trials registration number: ChiCTR2000039410. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-021-00269-8.

Early Warning of Ischemic Stroke Based on Atherosclerosis Index Combined With Serum Markers.

CONTEXT: Ischemic stroke (IS) is a serious public health problem worldwide, threatening human life and health. Atherosclerosis is the cause of stroke. At present, there are few selective indexes that can be used to evaluate atherosclerosis in the clinic; providers rely mainly on the atherosclerotic index (AI). Disturbance of lipid metabolism is considered to be a key event leading to IS. OBJECTIVE: The purpose of this study was to discover potential biomarkers in the serum of atherosclerosis-induced IS, combined with the AI to provide early warning for the diagnosis of IS. METHODS: In this study, we used nontargeted metabolomics based on ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) to measure the changes in serum metabolites in a group of patients with IS. To verify the reproducibility of candidate biomarkers in the population, we expanded the sample size. RESULTS: Five metabolites were identified, including sphingomyelin (18:0/14:0), 1-Methylpyrrolinium, PC (18:0/18:0), LysoPC (18:0/0:0), and PC (18: 2/18:2). The combination of these 5 metabolic markers has good diagnostic and predictive ability, and the change level of these metabolites is significantly related to IS. Our results also indicate that changes in glycerophospholipid metabolism may indicate an early risk of IS development. CONCLUSION: These findings may contribute to the development of new diagnostic methods of potential biomarkers in serum combined with the AI, thereby providing early warning for the diagnosis of atherosclerosis-induced IS, and may provide a new insights for pathogenesis in IS.

Exosomal circTAOK1 contributes to diabetic kidney disease progression through regulating SMAD3 expression by sponging miR-520h.

BACKGROUND: Diabetic nephropathy (DN) is a frequent diabetes complication with complex pathogenesis. Circular RNA (circRNA) circTAOK1 (also named circ_0003928) has been reported to be upregulated in high glucose (HG)-treated human umbilical vein endothelial cells. Also, exosomal circRNAs can exert significant roles in the pathology of various diseases. This study is designed to explore the role and mechanism of exosomal circTAOK1 on the glomerular mesangial cell (GMC) injury in DN. METHODS: Exosomes were detected by a transmission electron microscope. The protein levels of CD9, CD63, proliferating cell nuclear antigen (PCNA), cyclinD1, α-SMA, fibronectin, E-cadherin, N-cadherin, and SMAD family member 3 (SMAD3) were examined by western blot assay. circTAOK1, microRNA-520h (miR-520h), and SMAD3 levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation and cell cycle progression were detected by cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), and flow cytometry assays. The binding relationship between miR-520h and circTAOK1 or SMAD3 was predicted by Starbase and then verified by a dual-luciferase reporter and RNA immunoprecipitation (RIP), RNA pull-down assays. RESULTS: CircTAOK1 expression was upregulated in the exosomes isolated from HG-treated glomerular epithelial cells (GEC). Moreover, GEC-circTAOK1-Exo could promote proliferation, fibrosis, and epithelial-mesenchymal transition (EMT) of glomerular mesangial cells (GMCs). Mechanically, circTAOK1 could regulate SMAD3 expression by sponging miR-520h, GEO-si-circTAOK1 Exo-induced miR-520h and repressed SMAD3 expression in GMC. CONCLUSION: GEC-circTAOK1-Exo could boost proliferation, fibrosis, and EMT of GMC through targeting the miR-520h/SMAD3 axis, providing new insights into the pathogenesis of DN.

A serum lipidomics study for the identification of specific biomarkers for endometrial polyps to distinguish them from endometrial cancer or hyperplasia.

Endometrial diseases, including endometrial polyps (EP), endometrial cancer (EC) and endometrial hyperplasia (EH), are common gynecological diseases that affect women of childbearing and perimenopausal age. Clinically, biopsy or imaging methods are usually used to screen and diagnose these diseases; however, due to the invasiveness and heterogeneity of these tests, a noninvasive, convenient, objective and accurate biomarker is needed for the differential diagnosis of EP, EC or EH. In the present study, serum samples from 326 patients with endometrial diseases and 225 healthy volunteers were analyzed using nontargeted lipidomics. A combination of multivariate and univariate analyses was used to identify and qualify six, eight and seven potential biomarkers in the sera from patients with EP, EC and EH, respectively. Using a logistic regression algorithm and receiver operating characteristic (ROC) curve analysis, a biomarker panel including four specific EP biomarkers, 6-keto-PGF1α, PA(37:4), LysoPC(20:1) and PS(36:0), showed good classification and diagnostic ability in distinguishing EP from EC or EH. The biomarker panel for distinguishing EP from EC yielded an area under the curve (AUC) of 0.915, sensitivity of 100% and specificity of 72.41%, while that for distinguishing EP from EH yielded an AUC of 1.000, sensitivity of 100% and specificity of 100%. The two diagnostic models also showed good diagnostic abilities in the validation set. Therefore, this biomarker panel can be used as a rapid diagnostic method to assist in imaging examinations and provide a reference for clinicians in the identification and diagnosis of endometrial diseases.

Application of lipidomics strategy to explore aging-related biomarkers and potential anti-aging mechanisms of ginseng.

Aging often leads to an increase risk of age-related diseases, and the development of anti-aging drugs have become the trend and focus of the current scientific research. In this experiment, serum samples from healthy people of different ages were analyzed based on clinical lipidomics, and a total of 10 potential biomarkers in middle-aged and youth group, 20 biomarkers in the youth and the elderly group were obtained. Furthermore, dhSph and dhCer involved above may affect the aging process through sphingolipid metabolic pathway. As the first and rate-limiting step of catalyzing de novo sphingolipid pathway, SPT may play a key role in human anti-aging, which is revealed by lipidomics liposome tracer analysis. The potential active components in ginseng on SPT was further verified by molecular docking virtual screening and atomic force microscope. Four ingredients of ginseng may reduce the levels of metabolites dhSph and dhCer by inhibiting the activity of SPT, and play an anti-aging effect by affecting the sphingolipid metabolism pathway.A clinical trials registration number: ChiCTR1900026836.

Pharmacodynamic substances in Salvia miltiorrhiza for prevention and treatment of hyperlipidemia and coronary heart disease based on lipidomics technology and network pharmacology analysis.

In this study, untargeted lipidomics based on UPLC-Q/TOF-MS, network pharmacology and atomic force microscopy were used to explore the common biomarkers of hyperlipidemia and coronary heart disease, the therapeutic mechanism of the main components of Salvia miltiorrhiza as well as the action mechanism of key lipids. Firstly, the serum samples of 30 healthy people, 30 patients with coronary heart disease and 30 patients with hyperlipidemia were analyzed by using lipidomics technology to obtain biomarkers which can be used to link hyperlipidemia and coronary heart disease and to find potential targets; then, the key components and core targets of Salvia miltiorrhiza intervention in hyperlipidemia and coronary heart disease were analyzed by network pharmacology, the results were verified by atomic force microscopy. It showed that SMS2 might be the key target. And through network pharmacology and atomic force microscope analysis, it can be inferred that salvianolic acid A can combine with SMS2 to play a therapeutic role.

Cleavage rules of mass spectrometry fragments and rapid identification of chemical components of Radix Paeoniae Alba using UHPLC-Q-TOF-MS.

INTRODUCTION: Radix Paeoniae Alba (RPA) presents several pharmacological effects, including analgesia, liver protection, and toxicity reduction. RPA consists mostly of monoterpenes and their glycosides, tannins, flavonoids, and organic acids, with monoterpenes being the main active pharmaceutical ingredients. OBJECTIVE: To establish an effective method for rapid classification and identification of the main monoterpenes, flavonoids, and organic acids in RPA. METHODS: We used ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) and data post-processing technology to rapidly classify and identify the monoterpenoids, flavonoids, and organic acids in RPA. We also summarised the diagnostic product ions and neutral losses of monoterpenoids, flavonoids, and organic acids in RPA reported in the literature. RESULTS: We identified 24 components, namely 18 monoterpenoids, one flavonoid, and five organic acids. CONCLUSION: In this study, we analysed the chemically active pharmaceutical ingredients and assessed the quality of RPA. In addition, we demonstrated that UHPLC-Q-TOF-MS can be used to qualitatively classify and identify the variety of chemical components of traditional Chinese medicines (TCMs) to a certain extent. Moreover, we confirmed that mass spectrometry can be used to identify the components of TCMs.

Rapid classification and identification of chemical constituents in Epimedium koreanum Nakai by UPLC-Q-TOF-MS combined with data post-processing techniques.

INTRODUCTION: Epimedium koreanum Nakai (EKN), is a well-known Chinese herbal medicine for the treatment of osteoporosis, immunosuppression, tumours and cardiovascular diseases. Comprehensive component identification is essential for elucidation of its pharmacological mechanism and quality control. However, its complex chemical composition has caused certain difficulties in the analysis of this traditional Chinese medicine (TCM). Therefore, there is an urgent need to establish a method for rapid classification and identification of EKN chemical components. OBJECTIVE: To establish a method for rapid classification and identification of the main components of flavonoids, organic acids and alkaloids in EKN. METHODS: The samples were analysed by ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and data post-processing techniques. The UPLC system used a BEH C18 column to separate the total extract of EKN. The mobile phase consisted of 0.1% formic acid in water and acetonitrile, and the EKN extract was analysed by gradient elution at a flow rate of 0.4 mL/min. In both the positive and negative ion modes, the fragment information was obtained and compared with those of the characteristic fragmentations and neutral losses described in the literature to quickly identify the target compounds. RESULTS: Finally, we successfully screened out 51 chemical components, including 40 flavonoids, nine organic acids, and two alkaloids. CONCLUSION: The established method not only comprehensively analysed the chemical compositions of EKN, solved the difficult problems of analysis and identification of the complex chemical compositions of the TCM, but also further promoted the development of the application of chemical compositions of TCM.

An Approach to Identify Individual Functional Single Nucleotide Polymorphisms and Isoform MicroRNAs.

MicroRNAs (miRNAs) and single nucleotide polymorphisms (SNPs) play important roles in disease risk and development, especially cancer. Importantly, when SNPs are located in pre-miRNAs, they affect their splicing mechanism and change the function of miRNAs. To improve disease risk assessment, we propose an approach and developed a software tool, IsomiR_Find, to identify disease/phenotype-related SNPs and isomiRs in individuals. Our approach is based on the individual's samples, with SNP information extracted from the 1000 Genomes Project. SNPs were mapped to pre-miRNAs based on whole-genome coordinates and then SNP-pre-miRNA sequences were constructed. Moreover, we developed matpred2, a software tool to identify the four splicing sites of mature miRNAs. Using matpred2, we identified isomiRs and then verified them by searching within individual miRNA sequencing data. Our approach yielded biomarkers for biological experiments, mined functions of miRNAs and SNPs, improved disease risk assessment, and provided a way to achieve individualized precision medicine.

The effect of hemodialysis on ocular changes in patients with the end-stage renal disease.

Background: Numerous metabolic parameters can be changed during hemodialysis in the end-stage renal disease (ESRD) caused by systemic diseases, such as diabetes mellitus, hypertension. Some ocular parameters also can be variable due to the changes after hemodialysis. This study evaluates the effects of ocular parameters, including best-corrected visual acuity (BCVA), intraocular pressure (IOP), central macular thickness (CMT), subfoveal choroidal thickness (SFCT), retinal arteriolar caliber (RAC), retinal venular calibre (RVC), in ESRD patients following hemodialysis. Materials and methods: Two-hundred and two ESRD patients were recruited resulting in 404 eyes evaluations. All patients underwent hemodialysis in the Dialysis Unit of the Second Hospital of Tianjin Medical University. BCVA, CMT, IOP, SFCT, RAC and RVC were evaluated before and after hemodialysis. Systemic parameters were collected such as age, body weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), duration of hemodialysis, body weight changes, high density lipoprotein cholesterol (HDLC), low density lipoprotein cholesterol (LDLC), very low density lipoprotein cholesterol (VLDLC), glycosylated hemoglobin (HbA1c). Results: The causes of ESRD patients included chronic glomerulonephritis (n = 65), diabetes mellitus (n = 60), hypertensive nephrosclerosis (n = 37), and other causes (n = 40). In our study, BCVA (p = .817), CMT (p = .252) and IOP (p = .978) did not significantly change after hemodialysis. SFCT significantly decreased from 254.29 ± 69.36 µm to 235.54 ± 659.90 µm (p = .002) following hemodialysis. SFCT changes were significantly correlated with SBP (p = .042) and body weight changes (p = .044). The RAC and RVC were dilated significantly (p = .033, p = .007). RVC changes were correlated with baseline DBP (p = .003), HDLC (p = .009), LDLC (p = .004) and changes in DBP (p = .037) and body weight (p = .001). Conclusion: Hemodialysis can affect various ocular parameters including SFCT, RAC and RVC, which changed significantly following hemodialysis. Whereas BCVA, IOP and CMT did not change after hemodialysis in ESRD patients. The systemic compensatory mechanisms of the changes in SBP, DBP, body weight following hemodialysis need further study.

Androgen deprivation therapy with chemotherapy or abiraterone for patients with metastatic hormone-naive prostate cancer: a systematic review and meta-analysis.

Patients with metastasis prostate cancer underwent androgen deprivation therapy (ADT) in the considering of the leading role of androgen receptor pathway. However, the resistance occurred within 1 year or more. The combination of cytotoxic chemotherapy and abiraterone for ADT therapy was performed in recent randomized controlled trials. The meta-analysis was focused on the treatment comparisons between additional treatment with ADT and ADT alone. A significant difference was observed that the overall survival benefit of early and active additional treatment with ADT in patients with hormone-sensitive metastatic prostate cancer. However, a great proportion of patients with metastatic disease have metastases after receiving ADT. It will be important to further improve the treatment options.

Correlation of Caveolin-1 With Vascular Intimal Thickness for Different Locations of Catheter Tips in a Dog Model.

INTRODUCTION: Many studies have reported increased intimal thickness around the catheter tip after catheterization. Caveolin-1 is a protein in the endothelial cell that acts as a shear sensor causing vascular remodeling. This study aimed to elucidate the suitability of different catheter locations and determine the role of caveolin-1 in canine models. MATERIALS AND METHODS: Tunneled silicone 14.5-F catheters were inserted into the left jugular vein and right femoral vein in 8 dogs. The dogs were separated into 2 groups by catheter location and were followed up for 28 days. All dogs underwent extracorporeal circulation 3 times a week. After animal sacrifice, histological and immunohistochemical assays were performed to measure specific cell populations. RESULTS: There were higher catheter dysfunction rates and lower blood flow rates in the right femoral vein group compared to the left jugular vein group. There was intimal hyperplasia around the catheter tip in both groups with no significant difference between the two groups. There were caveolin-1 expression in the intimal layer of venous wall around the catheter tip location sites in both groups. CONCLUSIONS: These findings indicate that different catheter tip locations may influence catheter function and specific targeting of caveonlin-1 could be a strategy of possible future novel therapies for catheter-related vein stenosis.

Abnormal ankle-brachial index and risk of cardiovascular or all-cause mortality in patients with chronic kidney disease: a meta-analysis.

Prognostic role of ankle-brachial index (ABI) in patients with chronic kidney disease (CKD) is controversial. We aimed to evaluate whether abnormal ABI was an independent predictor of cardiovascular or all-cause mortality in CKD patients with or without hemodialysis by conducting a meta-analysis. We systematically searched Pubmed and Embase databases for prospective observational studies that investigated baseline abnormal ABI and subsequent cardiovascular or all-cause mortality risk in CKD patients with or without hemodialysis. An ABI value of 0.9 to 1.3 was defined as normal. Pooled hazard risk (HR) with 95% confidence interval (CI) was calculated for the abnormal vs. normal ABI category. Six studies enrolling 5820 patients were identified and analyzed. Overall, abnormal ABI was associated with an increased risk of all-cause mortality (HR 2.26; 95% CI 1.60-3.18) and cardiovascular mortality (HR 3.58; 95% CI 2.53-5.06). Subgroup analysis indicated that patients with abnormally low ABI increased by 2.45-fold all-cause mortality and 5.18-fold cardiovascular mortality. Similarly, an abnormally high ABI increased by 1.94-fold all-cause mortality and 4.04-fold cardiovascular mortality. In addition, the effect of abnormal ABI on all-cause mortality was more pronounced among hemodialysis patients (HR 3.06; 95% CI 2.30-4.07) but not in CKD patients (HR 1.42; 95% CI 0.98-2.05). Abnormally low and high ABI are independently associated with cardiovascular or all-cause mortality risk in maintenance hemodialysis patients. This meta-analysis highlighted an U-shaped relationship between ABI and mortality risk in CKD patients undergoing hemodialysis. However, findings of this meta-analysis were undermined by the small number of included studies.