|
1
|
Chang J, Liang Y, Sun P, Fang X, Sun Q. Molecular and Cellular Mechanisms Linking Chronic Kidney Disease and Sarcopenia in Aging: An Integrated Perspective. Clin Interv Aging 2025; 20:449-458. [PMID: 40226833 PMCID: PMC11992981 DOI: 10.2147/cia.s516704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Accepted: 03/29/2025] [Indexed: 04/15/2025] Open
Abstract
Chronic kidney disease (CKD) and sarcopenia are prevalent conditions among the aging population, contributing significantly to morbidity and mortality. CKD exacerbates sarcopenia through complex molecular and cellular mechanisms, including chronic inflammation, oxidative stress, uremic toxin accumulation, protein-energy wasting, and hormonal dysregulation. This review explores the interplay between CKD and sarcopenia, focusing on key pathways such as mTOR signaling, the AMPK-FOXO axis, and myostatin/activin pathways that regulate muscle protein metabolism. Additionally, mitochondrial dysfunction and impaired autophagy emerge as critical contributors to muscle wasting. Clinical implications include identifying biomarkers such as interleukin-6, tumor necrosis factor-alpha, myostatin, and Klotho for diagnosis and monitoring, while potential therapeutic strategies involve targeting the AMPK/mTOR pathway, enhancing mitochondrial function, and inhibiting myostatin activity. Emerging approaches, including multi-omics technologies and AI-driven personalized treatment models, offer innovative solutions for understanding and managing the CKD-sarcopenia axis. This review underscores the need for integrated therapeutic strategies and multidisciplinary collaboration to mitigate muscle wasting and improve outcomes in CKD patients. By bridging molecular insights with clinical applications, this work aims to inform future research and translational efforts in addressing this critical healthcare challenge.
Collapse
Affiliation(s)
- Jing Chang
- Department of Internal Medicine, Beijing Chao-yang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China
| | - Yuer Liang
- Department of Nephrology, Beijing Chao-yang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China
| | - Pingping Sun
- Department of Internal Medicine, Beijing Chao-yang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China
| | - Xiangyang Fang
- Department of Internal Medicine, Beijing Chao-yang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China
| | - Qianmei Sun
- Department of Nephrology, Beijing Chao-yang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China
| |
Collapse
|
|
2
|
Tuo J, Li Z, Xie L. Association between triglyceride-glucose index and clinical outcomes among patients with chronic kidney disease: a meta-analysis. BMC Nephrol 2025; 26:61. [PMID: 39915738 PMCID: PMC11804066 DOI: 10.1186/s12882-025-03984-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Accepted: 01/24/2025] [Indexed: 02/09/2025] Open
Abstract
PURPOSE To identify the relationship of triglyceride-glucose (TyG) index with clinical outcomes in chronic kidney disease (CKD) patients based on current available evidence. METHODS PubMed, EMBASE, Web of Science and CNKI databases were searched up to August 31, 2024. Primary outcome was the all-cause mortality. Secondary outcomes included the coronary artery disease (CAD) mortality, CKD progression, risk of severe coronary artery stenosis (SCAS), major adverse cardiovascular event (MACE), coronary artery calcification (CAC) progression, end-stage renal disease (ESRD), and nonalcoholic fatty liver disease (NAFLD). The hazard ratio (HR) and odds ratio (OR) with 95% confidence interval (CI) were combined to assess the predictive role of TyG index for above clinical outcomes among CKD patients. All statistical analysis was performed by STATA 15.0 version. RESULTS Twelve studies with 26,530 cases were included. Pooled results indicated that elevated TyG index was significantly related to increased risk for all-cause mortality (HR = 1.22, 95% CI: 1.13-1.31, P<0.001). Besides, high TyG index was also associated with the CAD mortality (HR = 1.19, 95% CI: 1.04-1.36, P = 0.011), occurrence of CKD progression (HR = 1.52, 95% CI: 1.36-1.70, P<0.001), SCAS (OR = 1.79, 95% CI: 1.13-2.83, P = 0.013), MACE (OR = 1.68, 95% CI: 1.11-2.54, P = 0.014), CAC progression (OR = 1.55, 95% CI: 1.06-1.76, P = 0.02), CAD (OR = 2.865, 95% CI: 1.681-4.885, P<0.001), ESRD (OR = 1.49, 95% CI: 1.12-1.99, P = 0.006) and NAFLD (OR = 4.903, 95% CI: 3.046-7.893, P<0.001). CONCLUSION High TyG index predicts poor clinical outcomes and might serve as a novel prognostic indicator among CKD patients. However, more studies are still needed to verify above findings.
Collapse
Affiliation(s)
- Jinli Tuo
- Department of Nephrology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, 610041, China
| | - Zhong Li
- Department of Nephrology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, 610041, China
| | - Linshen Xie
- Department of Nephrology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, 610041, China.
| |
Collapse
|
|
3
|
Corsello A, Trovato CM, Dipasquale V, Proverbio E, Milani GP, Diamanti A, Agostoni C, Romano C. Malnutrition management in children with chronic kidney disease. Pediatr Nephrol 2025; 40:15-24. [PMID: 38954039 PMCID: PMC11584524 DOI: 10.1007/s00467-024-06436-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Revised: 06/04/2024] [Accepted: 06/05/2024] [Indexed: 07/04/2024]
Abstract
Chronic kidney disease (CKD) encompasses diverse conditions such as congenital anomalies, glomerulonephritis, and hereditary nephropathies, necessitating individualized nutritional interventions. Early detection is pivotal due to the heightened risk of adverse outcomes, including compromised growth and increased healthcare costs. The nutritional assessment in pediatric CKD employs a comprehensive, multidisciplinary approach, considering disease-specific factors, growth metrics, and dietary habits. The prevalence of malnutrition, as identified through diverse tools and guidelines, underscores the necessity for regular and vigilant monitoring. Nutritional management strategies seek equilibrium in calorie intake, protein requirements, and electrolyte considerations. Maintaining a well-balanced nutritional intake is crucial for preventing systemic complications and preserving the remaining kidney function. The nuanced landscape of enteral nutrition, inclusive of gastrostomy placement, warrants consideration in scenarios requiring prolonged support, with an emphasis on minimizing risks for optimized outcomes. In conclusion, the ongoing challenge of managing nutrition in pediatric CKD necessitates continuous assessment and adaptation. This review underscores the significance of tailored dietary approaches, not only to foster growth and prevent complications but also to enhance the overall quality of life for children grappling with CKD.
Collapse
Affiliation(s)
- Antonio Corsello
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
- Pediatric Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
| | - Chiara Maria Trovato
- Hepatology Gastroenterology and Nutrition Unit, Bambino Gesù Children Hospital, Rome, Italy
| | - Valeria Dipasquale
- Pediatric Gastroenterology and Cystic Fibrosis Unit, Department of Human Pathology in Adulthood and Childhood "G. Barresi", University of Messina, Messina, Italy
| | - Emanuele Proverbio
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
- Pediatric Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Gregorio Paolo Milani
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
- Pediatric Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Antonella Diamanti
- Hepatology Gastroenterology and Nutrition Unit, Bambino Gesù Children Hospital, Rome, Italy
| | - Carlo Agostoni
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
- Pediatric Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Claudio Romano
- Pediatric Gastroenterology and Cystic Fibrosis Unit, Department of Human Pathology in Adulthood and Childhood "G. Barresi", University of Messina, Messina, Italy
| |
Collapse
|
|
4
|
Jv M, Zhang J, Han Y, Yang A, Zhu Y. Association of triglyceride glucose-body mass index and left ventricular hypertrophy in patients with IgA nephropathy: a retrospective study. Eur J Med Res 2024; 29:627. [PMID: 39726054 DOI: 10.1186/s40001-024-02234-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Accepted: 12/17/2024] [Indexed: 12/28/2024] Open
Abstract
INTRODUCTION IgA nephropathy (IgAN) is one of the most prevalent forms of glomerulonephritis worldwide, particularly affecting 40-50% of the East Asian population. Cardiovascular mortality represents a leading cause of death in patients with IgAN. Left ventricular hypertrophy (LVH) serves as a predictor of heart failure and cardiovascular mortality. Previous studies have indicated that Triglyceride glucose-body mass index (TyG-BMI), a surrogate marker for insulin resistance surrogates, correlated with the development of LVH. However, there is a lack of information available regarding the association between TyG-BMI and LVH in patients with IgAN. This study aims to explore the relationship between TyG-BMI and LVH in this population. METHODS This retrospective study was conducted in the Fifth Affiliated Hospital of Sun Yat-sen University recruiting inpatients with renal biopsy-confirmed IgAN who were over the age of 18 years. Left ventricular dimensions were assessed through echocardiography. Linear regression and multivariate logistic regression analyses were performed using R language software and SPSS to investigate the association between TyG-BMI levels and LVH risk. Statistical significance was set at p < 0.05. RESULTS A total of 327 patients with IgAN were enrolled in this study. Left ventricular mass index (LVMI) was positively correlated with TyG-BMI index (corr. coefficient: 0.453, p < 0.001) and inversely correlated with eGFR (corr. coefficient: -0.392, p < 0.001). After adjusting for age, gender, smoking, alcohol use, hemoglobin, low-density lipoprotein cholesterol, Scr, and urine output, advanced age and higher levels of hemoglobin and Scr were independently associated with increased TyG-BMI (p < 0.05). The odds ratios of the highest quartile of TyG-BMI compared with the lowest quartile were 8.39 (95%CI 1.66-42.39; p = 0.010). CONCLUSIONS Our findings indicated that the TyG-BMI level was positively correlated with LVMI. A high TyG-BMI level was independently associated with an increased risk of LVH in patients with IgAN. TyG-BMII demonstrated predictive ability for LVH in IgAN patients.
Collapse
Affiliation(s)
- Menglei Jv
- Department of Nephrology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
| | - Jun Zhang
- Department of Otolaryngology Head and Neck Surgery, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
| | - Yuzhang Han
- Department of Nephrology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China
| | - Anni Yang
- Department of Otolaryngology Head and Neck Surgery, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China.
| | - Ye Zhu
- Department of Nephrology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China.
| |
Collapse
|
|
5
|
Chen T, Liu Y, Wu S, Long S, Feng L, Lu W, Chen W, Hong G, Zhou L, Wang F, Luo Y, Zou H, Liu W. The association of RBP4 with chronic kidney diseases in southern Chinese population. Front Endocrinol (Lausanne) 2024; 15:1381060. [PMID: 39698033 PMCID: PMC11652128 DOI: 10.3389/fendo.2024.1381060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Accepted: 11/13/2024] [Indexed: 12/20/2024] Open
Abstract
Background Retinol binding protein 4 (RBP4), as a novel adipokine, has been proven to be highly related to insulin resistance, obesity, diabetes, hypertension, hyperuricemia and other metabolic diseases, which are all risk factors for chronic kidney disease (CKD). However, there is a lack of sufficient studies to explore the relationship between RBP4 and CKD, and no reports have described the predictive value of RBP4 for CKD. This study was designed to clarify the relationship between RBP4 and CKD and its potential predictive value. Methods Our team has conducted a large-scale cross-sectional survey that contained 2117 individuals on the southern coast of China. Correlation test, logistic regression analysis were used to evaluate the association between RBP4 and CKD. Receiver operating characteristic (ROC) were used to evaluate the optimal cut-off and predictive value of RBP4 for predicting CKD. Results By using the quartile grouping method, the population was divided into four groups according to the RBP4 level. As the RBP4 level increased, the prevalence of CKD also gradually increased among different groups. RBP4 was also correlated with various metabolic risk factors, such as blood glucose, blood lipids, blood pressure, waist circumference, uric acid, and with kidney function indicators such as creatinine, urine protein. Logistic regression analysis found that after adjusting for confounders, RBP4 remained significantly associated with CKD, independent of metabolic risk factors. ROC analysis showed that RBP4 as a single index, AUC (0.666) was superior to Scr, FBG, Log HOMA-IR, WC, TG, VLDL-C, UA, HDL-C, LDL-C, and that combining RBP4 indicator and other common risk factors of CKD can improve the accuracy for predicting CKD. Conclusion This study found that the RBP4 was strongly correlated with CKD, RBP4 may become a valuable marker and have strong power for predicting CKD.
Collapse
Affiliation(s)
- Tong Chen
- Department of Nephrology, South China Hospital of Shenzhen University, Shenzhen, China
- Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National Regional Key Technology Engineering Laboratory for Medical Ultrasound School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, China
- Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China
| | - Yu Liu
- Department of Nephrology, South China Hospital of Shenzhen University, Shenzhen, China
- Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National Regional Key Technology Engineering Laboratory for Medical Ultrasound School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, China
| | - Shiquan Wu
- Department of Nephrology, South China Hospital of Shenzhen University, Shenzhen, China
| | - Siyu Long
- Department of Nephrology, South China Hospital of Shenzhen University, Shenzhen, China
| | - Ling Feng
- Department of Nephrology, Shenzhen Hospital, Southern Medical University, Shenzhen, China
| | - Wenqian Lu
- School of Medicine, The Chinese University of Hong Kong, Shenzhen, China
| | - Wenya Chen
- Department of Nephrology, South China Hospital of Shenzhen University, Shenzhen, China
| | - Guoai Hong
- Department of Nephrology, South China Hospital of Shenzhen University, Shenzhen, China
| | - Li Zhou
- Department of Nephrology, South China Hospital of Shenzhen University, Shenzhen, China
| | - Fang Wang
- Department of Nephrology, South China Hospital of Shenzhen University, Shenzhen, China
| | - Yuechan Luo
- Department of Nephrology, South China Hospital of Shenzhen University, Shenzhen, China
| | - Hequn Zou
- Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China
- School of Medicine, The Chinese University of Hong Kong, Shenzhen, China
| | - Weihua Liu
- Department of Nephrology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fujian, China
| |
Collapse
|
|
6
|
Luo P, Li D, Guo Y, Meng X, Kan R, Pan L, Xiang Y, Mao B, He Y, Wang S, Yang Y, Liu Z, Xie J, Zhang B, He W, Hu S, Zhou X, Yu X. Associations of physiologic subtypes based on HOMA2 indices of β-cell function and insulin sensitivity with the risk of kidney function decline, cardiovascular disease, and all-cause mortality from the 4C study. Cardiovasc Diabetol 2024; 23:401. [PMID: 39511523 PMCID: PMC11546320 DOI: 10.1186/s12933-024-02496-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Accepted: 10/31/2024] [Indexed: 11/15/2024] Open
Abstract
BACKGROUND Previous studies have been limited by their inability to differentiate between the effects of insulin sensitivity and β-cell function on the risk of kidney function decline, cardiovascular disease (CVD), and all-cause mortality. To address this knowledge gap, we aimed to investigate whether the physiological subtypes based on homeostasis model assessment-2 (HOMA2) indices of β-cell function (HOMA2-B) and insulin sensitivity (HOMA2-S) could be used to identify individuals with subsequently high or low of clinical outcome risk. METHODS This retrospective cohort study included 7,317 participants with a follow-up of up to 5 years. Based on HOMA2 indices, participants were categorized into four physiologic subtypes: the normal phenotype (high insulin sensitivity and high β-cell function), the insulinopenic phenotype (high insulin sensitivity and low β-cell function), the hyperinsulinaemic phenotype (low insulin sensitivity and high β-cell function), and the classical phenotype (low insulin sensitivity and low β-cell function). The outcomes included kidney function decline, CVD events (fatal and nonfatal), and all-cause mortality. Cox regression models were used to calculate hazard ratios (HRs) for outcomes, and spline models were used to examine the dose-dependent associations of HOMA2-B and HOMA2-S with outcomes. RESULTS A total of 1,488 (20.3%) were classified as normal, 2,179 (29.8%) as insulinopenic, 2,173 (29.7%) as hyperinsulinemic, and 1,477 (20.2%) as classical subtypes. Compared with other physiological subtypes, the classical subtype presented the highest risk of kidney function decline (classical vs. normal HR 11.50, 95% CI 4.31-30.67). The hyperinsulinemic subtype had the highest risk of CVD and all-cause mortality (hyperinsulinemic vs. normal: fatal CVD, HR 6.56, 95% CI 3.09-13.92; all-cause mortality, HR 4.56, 95% CI 2.97-7.00). Spline analyses indicated the dose-dependent associations of HOMA2-B and HOMA2-S with outcomes. CONCLUSIONS The classical subtype had the strongest correlation with the risk of kidney function decline, and the hyperinsulinemic subtype had the highest risk of CVD and all-cause mortality, which should be considered for interventions with precision medicine.
Collapse
Affiliation(s)
- Peiqiong Luo
- Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China
- Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, 430030, Hubei, China
| | - Danpei Li
- Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China
- Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, 430030, Hubei, China
| | - Yaming Guo
- Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China
- Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, 430030, Hubei, China
| | - Xiaoyu Meng
- Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China
- Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, 430030, Hubei, China
| | - Ranran Kan
- Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China
- Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, 430030, Hubei, China
| | - Limeng Pan
- Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China
- Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, 430030, Hubei, China
| | - Yuxi Xiang
- Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China
- Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, 430030, Hubei, China
| | - Beibei Mao
- Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China
- Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, 430030, Hubei, China
| | - Yi He
- Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China
- Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, 430030, Hubei, China
| | - Siyi Wang
- Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China
- Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, 430030, Hubei, China
| | - Yan Yang
- Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China
- Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, 430030, Hubei, China
| | - Zhelong Liu
- Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China
- Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, 430030, Hubei, China
| | - Junhui Xie
- Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China
- Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, 430030, Hubei, China
| | - Benping Zhang
- Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China
- Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, 430030, Hubei, China
| | - Wentao He
- Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China
- Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, 430030, Hubei, China
| | - Shuhong Hu
- Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China
- Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, 430030, Hubei, China
| | - Xinrong Zhou
- Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China
- Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, 430030, Hubei, China
| | - Xuefeng Yu
- Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China.
- Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, 430030, Hubei, China.
| |
Collapse
|
|
7
|
Nayak SS, Kuriyakose D, Polisetty LD, Patil AA, Ameen D, Bonu R, Shetty SP, Biswas P, Ulrich MT, Letafatkar N, Habibi A, Keivanlou MH, Nobakht S, Alotaibi A, Hassanipour S, Amini-Salehi E. Diagnostic and prognostic value of triglyceride glucose index: a comprehensive evaluation of meta-analysis. Cardiovasc Diabetol 2024; 23:310. [PMID: 39180024 PMCID: PMC11344391 DOI: 10.1186/s12933-024-02392-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Accepted: 08/05/2024] [Indexed: 08/26/2024] Open
Abstract
OBJECTIVE The present umbrella review aims to collate and summarize the findings from previous meta-analyses on the Triglyceride and Glucose (TyG) Index, providing insights to clinicians, researchers, and policymakers regarding the usefulness of this biomarker in various clinical settings. METHODS A comprehensive search was conducted in PubMed, Scopus, and Web of Science up to April 14, 2024, without language restrictions. The AMSTAR2 checklist assessed the methodological quality of the included meta-analyses. Statistical analyses were performed using Comprehensive Meta-Analysis (CMA) software. RESULTS A total of 32 studies were finally included. The results revealed significant associations between the TyG index and various health outcomes. For kidney outcomes, a high TyG index was significantly associated with an increased risk of contrast-induced nephropathy (CIN) (OR = 2.24, 95% CI: 1.82-2.77) and chronic kidney disease (CKD) (RR = 1.46, 95% CI: 1.32-1.63). High TyG index was significantly associated with an increased risk of type 2 diabetes mellitus (T2DM) (RR = 3.53, 95% CI: 2.74-4.54), gestational diabetes mellitus (GDM) (OR = 2.41, 95% CI: 1.48-3.91), and diabetic retinopathy (DR) (OR = 2.34, 95% CI: 1.31-4.19). Regarding metabolic diseases, the TyG index was significantly higher in patients with obstructive sleep apnea (OSA) (SMD = 0.86, 95% CI: 0.57-1.15), metabolic syndrome (MD = 0.83, 95% CI: 0.74-0.93), and non-alcoholic fatty liver disease (NAFLD) (OR = 2.36, 95% CI: 1.88-2.97) compared to those without these conditions. In cerebrovascular diseases, a higher TyG index was significantly associated with an increased risk of dementia (OR = 1.14, 95% CI: 1.12-1.16), cognitive impairment (OR = 2.31, 95% CI: 1.38-3.86), and ischemic stroke (OR = 1.37, 95% CI: 1.22-1.54). For cardiovascular outcomes, the TyG index showed significant associations with an increased risk of heart failure (HF) (HR = 1.21, 95% CI: 1.12-1.30), atrial fibrillation (AF) (SMD = 1.22, 95% CI: 0.57-1.87), and hypertension (HTN) (RR = 1.52, 95% CI: 1.25-1.85). CONCLUSION The TyG index is a promising biomarker for screening and predicting various medical conditions, particularly those related to insulin resistance and metabolic disorders. However, the heterogeneity and methodological quality of the included studies suggest the need for further high-quality research to confirm these findings and refine the clinical utility of the TyG index.
Collapse
Affiliation(s)
- Sandeep Samethadka Nayak
- Division of Hospital Medicine, Department of Internal Medicine, Bridgeport Hospital, Yale New Heaven, Bridgeport, CT, USA
| | - Dona Kuriyakose
- St. Joseph's Mission Hospital, Kollam District, Anchal, Kerala, India
| | - Lakshmi D Polisetty
- Division of Hospital Medicine, Department of Internal Medicine, Bridgeport Hospital, Yale New Heaven, Bridgeport, CT, USA
- Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, John Dempsey Hospital, University of Connecticut, Bridgeport, CT, USA
| | - Anjali Avinash Patil
- Rajarshee Chhatrapati Shahu Maharaj Government Medical College Kolhapur Shenda park, Kolhapur, Maharashtra, India
| | - Daniyal Ameen
- Division of Hospital Medicine, Department of Internal Medicine, Bridgeport Hospital, Yale New Heaven, Bridgeport, CT, USA
| | - Rakshita Bonu
- Vydehi Institute of Medical Sciences and Research Centre, Bengaluru. 82, Nallurahalli Main Road, Whitefield, Bengaluru, Karnataka, India
| | - Samatha P Shetty
- Director of Capacity Management, NYC Health Hospitals, Elmhurst, USA
| | - Pubali Biswas
- Vydehi Institute of Medical Sciences and Research Centre, Bengaluru. 82, Nallurahalli Main Road, Whitefield, Bengaluru, Karnataka, India
| | - Micheal T Ulrich
- Riverside University Health System Medical Center, Moreno Valley, CA, USA
| | | | - Arman Habibi
- Guilan University of Medical Sciences, Rasht, Iran
| | | | - Sara Nobakht
- Guilan University of Medical Sciences, Rasht, Iran
| | | | - Soheil Hassanipour
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, P.O. Box: 41448-95655, Rasht, Iran
| | | |
Collapse
|
|
8
|
Lin L, Pan X, Feng Y, Yang J. Chronic kidney disease combined with metabolic syndrome is a non-negligible risk factor. Ther Adv Endocrinol Metab 2024; 15:20420188241252309. [PMID: 39071115 PMCID: PMC11273817 DOI: 10.1177/20420188241252309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Accepted: 04/10/2024] [Indexed: 07/30/2024] Open
Abstract
Metabolic syndrome (MetS) is a group of conditions characterized by hypertension (HTN), hyperglycaemia or insulin resistance (IR), hyperlipidaemia, and abdominal obesity. MetS is associated with a high incidence of cardiovascular events and mortality and is an independent risk factor for chronic kidney disease (CKD). MetS can cause CKD or accelerate the progression of kidney disease. Recent studies have found that MetS and kidney disease have a cause-and-effect relationship. Patients with CKD, those undergoing kidney transplantation, or kidney donors have a significantly higher risk of developing MetS than normal people. The present study reviewed the possible mechanisms of MetS in patients with CKD, including the disorders of glucose and fat metabolism after kidney injury, IR, HTN and the administration of glucocorticoid and calcineurin inhibitors. In addition, this study reviewed the effect of MetS in patients with CKD on important target organs such as the kidney, heart, brain and blood vessels, and the treatment and prevention of CKD combined with MetS. The study aims to provide strategies for the diagnosis, treatment and prevention of CKD in patients with MetS.
Collapse
Affiliation(s)
- Lirong Lin
- Department of Nephrology, The Third Affiliated Hospital of Chongqing Medical University (General Hospital), Chongqing, China
| | - Xianfeng Pan
- Department of Nephrology, Chongqing Kaizhou District People’s Hospital of Chongqing, Chongqing, China
| | - Yuanjun Feng
- Department of Nephrology, Guizhou Aerospace Hospital, Guizhou 563000, China
| | - Jurong Yang
- Department of Nephrology, The Third Affiliated Hospital of Chongqing Medical University (General Hospital), Chongqing 401120, China
| |
Collapse
|
|
9
|
Dave BP, Chorawala MR, Shah IV, Shah NN, Bhagat SU, Prajapati BG, Thakkar PC. From diabetes to diverse domains: the multifaceted roles of GLP-1 receptor agonists. Mol Biol Rep 2024; 51:835. [PMID: 39042283 DOI: 10.1007/s11033-024-09793-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2024] [Accepted: 07/09/2024] [Indexed: 07/24/2024]
Abstract
Glucagon-like Peptide-1 (GLP-1) receptor agonists (GLP-1RAs) emerged as a primary treatment for type-2 diabetes mellitus (T2DM), however, their multifaceted effects on various target organs beyond glycemic control opened a new era of treatment. We conducted a comprehensive literature search using databases including Scopus, Google Scholar, PubMed, and the Cochrane Library to identify clinical, in-vivo, and in-vitro studies focusing on the diverse effects of GLP-1 receptor agonists. Eligible studies were selected based on their relevance to the varied roles of GLP-1RAs in T2DM management and their impact on other physiological functions. Numerous studies have reported the efficacy of GLP-1RAs in improving outcomes in T2DM, with demonstrated benefits including glucose-dependent insulinotropic actions, modulation of insulin signaling pathways, and reductions in glycemic excursions. Additionally, GLP-1 receptors are expressed in various tissues and organs, suggesting their widespread physiological functions beyond glycemic control potentially include neuroprotective, anti-inflammatory, cardioprotective, and metabolic benefits. However, further scientific studies are still underway to maximize the benefits of GLP-1RAs and to discover additional roles in improving health benefits. This article sought to review not only the actions of GLP1RAs in the treatment of T2DM but also explore its effects on potential targets in other disorders.
Collapse
Affiliation(s)
- Bhavarth P Dave
- Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Opp. Gujarat University, Ahmedabad, Gujarat, 380009, India
| | - Mehul R Chorawala
- Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Opp. Gujarat University, Ahmedabad, Gujarat, 380009, India
| | - Ishika V Shah
- Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Opp. Gujarat University, Ahmedabad, Gujarat, 380009, India
| | - Nidhi N Shah
- Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Opp. Gujarat University, Ahmedabad, Gujarat, 380009, India
| | - Shivam U Bhagat
- Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Opp. Gujarat University, Ahmedabad, Gujarat, 380009, India
| | - Bhupendra G Prajapati
- Department of Pharmaceutics and Pharmaceutical Technology, Shree S. K. Patel College of Pharmaceutical Education & Research, Ganpat University, Mehsana, Gujarat, India.
- Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, 73000, Thailand.
| | - Pratik C Thakkar
- Department of Physiology, Faculty of Medical & Health Sciences, Manaaki Mānawa - The Centre for Heart Research, University of Auckland, 85 Park Road, Auckland, 1142, New Zealand.
| |
Collapse
|
|
10
|
Marrone G, Cornali K, Di Lauro M, Ceravolo MJ, Di Marco L, Manca di Villahermosa S, Mitterhofer AP, Noce A. Innovative Treatments to Counteract Endothelial Dysfunction in Chronic Kidney Disease Patients. Biomedicines 2024; 12:1085. [PMID: 38791047 PMCID: PMC11117580 DOI: 10.3390/biomedicines12051085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 05/02/2024] [Accepted: 05/09/2024] [Indexed: 05/26/2024] Open
Abstract
In chronic kidney disease (CKD) patients, several risk factors contribute to the development of endothelial dysfunction (ED), which can be described as an alteration in the cell structure or in the function of the endothelium. Among the well-known CKD-related risk factors capable of altering the production of endothelium-derived relaxing factors, we include asymmetric dimethylarginine increase, reduced dimethylarginine dimethylamine hydrolase enzyme activity, low-grade chronic systemic inflammation, hyperhomocysteinemia, oxidative stress, insulin resistance, alteration of calcium phosphorus metabolism, and early aging. In this review, we also examined the most important techniques useful for studying ED in humans, which are divided into indirect and direct methods. The direct study of coronary endothelial function is considered the gold standard technique to evaluate if ED is present. In addition to the discussion of the main pharmacological treatments useful to counteract ED in CKD patients (namely sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonist), we elucidate innovative non-pharmacological treatments that are successful in accompanying the pharmacological ones. Among them, the most important are the consumption of extra virgin olive oil with high intake of minor polar compounds, adherence to a plant-dominant, low-protein diet (LPD), an adaptive physical activity program and, finally, ketoanalogue administration in combination with the LPD or the very low-protein diet.
Collapse
Affiliation(s)
- Giulia Marrone
- Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy (K.C.); (L.D.M.); (S.M.d.V.); (A.P.M.)
| | - Kevin Cornali
- Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy (K.C.); (L.D.M.); (S.M.d.V.); (A.P.M.)
| | - Manuela Di Lauro
- Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy (K.C.); (L.D.M.); (S.M.d.V.); (A.P.M.)
| | - Maria Josè Ceravolo
- Nephrology and Dialysis Unit, Department of Systems Medicine, University Hospital of Rome Tor Vergata, 00133 Rome, Italy
| | - Luca Di Marco
- Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy (K.C.); (L.D.M.); (S.M.d.V.); (A.P.M.)
| | - Simone Manca di Villahermosa
- Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy (K.C.); (L.D.M.); (S.M.d.V.); (A.P.M.)
- Nephrology and Dialysis Unit, Department of Systems Medicine, University Hospital of Rome Tor Vergata, 00133 Rome, Italy
| | - Anna Paola Mitterhofer
- Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy (K.C.); (L.D.M.); (S.M.d.V.); (A.P.M.)
- Nephrology and Dialysis Unit, Department of Systems Medicine, University Hospital of Rome Tor Vergata, 00133 Rome, Italy
| | - Annalisa Noce
- Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy (K.C.); (L.D.M.); (S.M.d.V.); (A.P.M.)
- Nephrology and Dialysis Unit, Department of Systems Medicine, University Hospital of Rome Tor Vergata, 00133 Rome, Italy
| |
Collapse
|
|
11
|
Al-Shahrani GS, Belali TM. Frequency of drug-resistant bacterial isolates among pregnant women with UTI in maternity and children's hospital, Bisha, Saudi Arabia. Sci Rep 2024; 14:7397. [PMID: 38548851 PMCID: PMC10978862 DOI: 10.1038/s41598-024-58275-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Accepted: 03/27/2024] [Indexed: 04/01/2024] Open
Abstract
Urinary tract infections (UTIs) are one of the most prevalent bacterial infections affecting humans, with a higher incidence among women. Pregnant women are at an increased risk of developing UTIs, which can have detrimental consequences for both the mother and fetus. UTIs can be caused by various bacteria, and the prevalence of drug-resistant UTIs in maternity and children's hospitals is a cause for concern due to the potential for severe complications if left untreated. The primary objective of the current study was to determine the distribution of UTI-causing bacteria and investigate the antibiotic sensitivity patterns of isolated cultures obtained from pregnant women with UTIs at the Maternity and Children's Hospital, Bisha, Saudi Arabia. This cross-sectional study was conducted from October 2021 to October 2023, involving the analysis of urine samples collected from 321 participants who acquired UTIs during pregnancy. Using biochemical tests and standard cultures, the urine samples were examined for pathogenic bacteria and their anti-microbial sensitivity patterns. The study analyzed susceptibility results according to the Clinical Laboratory Standards Institute guidelines (M100, 28th Edition, 2018). Bacterial strains demonstrating resistance to three or more antibiotics were classified as multidrug-resistant (MDR). This study revealed the distribution of UTI-causing bacteria to be as follows: Escherichia coli, 57.01%; Klebsiella pneumoniae, 24.61%; Pseudomonas aeruginosa, 4.36%; Proteus mirabilis and Enterobacter cloacae, 3.74%; Streptococcus agalactiae, 3.11%; Enterococcus faecalis, 2.18%; and Staphylococcus aureus, 1.24%. Antimicrobial susceptibility testing varied among gram-positive and gram-negative bacteria. Gentamicin demonstrated the highest sensitivity among both gram-positive and gram-negative bacteria; piperacillin-tazobactam was the second most effective drug against gram-negative bacteria. The bacterial isolates showed varying susceptibility to different antibiotics, with Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa being mainly sensitive to gentamicin, piperacillin-tazobactam, and ciprofloxacin, respectively. The strategies for reducing the risk of UTIs need to be improved to limit the spread of MDR bacteria. These strategies may include promoting hygienic practices and administering appropriate antibiotics to prevent the emergence and spread of drug-resistant bacteria. Further research is required to monitor the trends in antibiotic resistance among UTI-causing bacteria and develop effective strategies for managing this public health menace.
Collapse
Affiliation(s)
- Ghady S Al-Shahrani
- Faculty of Applied Medical Sciences, University of Bisha, 255, Al Nakhil, 67714, Bisha, Saudi Arabia
| | - Tareg M Belali
- Faculty of Applied Medical Sciences, University of Bisha, 255, Al Nakhil, 67714, Bisha, Saudi Arabia.
| |
Collapse
|
|
12
|
Lee J, Kim MH, Jang JY, Oh CM. Assessment HOMA as a predictor for new onset diabetes mellitus and diabetic complications in non-diabetic adults: a KoGES prospective cohort study. Clin Diabetes Endocrinol 2023; 9:7. [PMID: 37974292 PMCID: PMC10652621 DOI: 10.1186/s40842-023-00156-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Accepted: 11/06/2023] [Indexed: 11/19/2023] Open
Abstract
BACKGROUND Homeostasis model assessment for insulin resistance (HOMA-IR) is a biomarker for type 2 diabetes mellitus (T2DM). However, the role of HOMA-IR in the non-diabetic is unclear. This study aimed to determine whether IR measured HOMA-IR value is associated with new onset diabetes as well as vascular disease and can be used as an early predictor for diabetes and vascular diseases in non-diabetic participants. METHODS From a prospective community-based cohort of 10,030 individuals, 4314 individuals younger than 65 years and without diabetes were enrolled and divided into three groups by baseline HOMA-IR tertiles: low (n = 1454), moderate (n = 1414), and high (n = 1446). The primary outcome was new onset T2DM. Secondary outcomes were chronic kidney disease (CKD) and a composite of coronary artery disease, myocardial infarction, and stroke as macrovascular events. RESULTS The mean age was 51 years. The prevalence of hypertension and cholesterol and HbA1c were higher in the high HOMA-IR group. New onset T2DM (5.8%) and CKD (12.2%) incidence in the high HOMA-IR group was higher than that in the others. The prevalence of macrovascular events did not differ among groups. High-HOMA-IR was an independent risk factor for new onset T2DM (odds ratio 1.86 [1.17-2.96]; p = 0.01) and CKD (1.49 [1.12-1.98]; p = 0.01). CONCLUSIONS High HOMA-IR was an early predictor of new onset T2DM and CKD, regardless of HbA1c in non-diabetic individuals. Further research on the specific cut off value will be needed.
Collapse
Affiliation(s)
- Jibeom Lee
- Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea
| | - Moon-Hyun Kim
- Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Ji-Yong Jang
- Division of Cardiology, National Health Insurance Service Ilsan hospital, Goyang, Republic of Korea.
| | - Chang-Myung Oh
- Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea.
| |
Collapse
|
|
13
|
Kim HI, Park J. Natural Antioxidants in Obesity and Related Diseases. Antioxidants (Basel) 2023; 12:1966. [PMID: 38001819 PMCID: PMC10669253 DOI: 10.3390/antiox12111966] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2023] [Accepted: 11/02/2023] [Indexed: 11/26/2023] Open
Abstract
Obesity is a chronic complex disease defined by excessive adiposity that impairs health [...].
Collapse
Affiliation(s)
- Hyo In Kim
- Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA;
| | - Jinbong Park
- Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
| |
Collapse
|
|
14
|
Braga PC, Bernardino RL, Guerra-Carvalho B, Carrageta DF, Oliveira PF, Rodrigues AS, Alves MG. The progression from mild to severe hyperglycemia coupled with insulin resistance causes mitochondrial dysfunction and alters the metabolic secretome of epithelial kidney cells. Exp Cell Res 2023; 431:113744. [PMID: 37648074 DOI: 10.1016/j.yexcr.2023.113744] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Revised: 08/08/2023] [Accepted: 08/11/2023] [Indexed: 09/01/2023]
Abstract
Diabetic nephropathy (DN) and insulin resistance (IR) in kidney cells are considered main causes for end-stage renal failure. However, it is unclear how IR affects early stages of the disease. Here, we investigate the impact of mild (11 mM) and severe (22 mM) hyperglycemia, with and without induced IR, on cellular metabolism and mitochondrial bioenergetics in a human kidney cell line (HK-2). IR in HK-2 cells was induced with palmitic acid and cellular cytotoxicity was studied. We evaluated the impact of mild and severe hyperglycemia with and without IR on the metabolic secretome of the cells, their live-cell mitochondria function, mitochondrial membrane potential, and mitochondrial complex activities. Furthermore, we measured fatty acid oxidation and lipid accumulation. Cells cultured under mild hyperglycemic conditions exhibited increased mitochondrial bioenergetic parameters, such as basal respiration, ATP-linked production, maximal respiration capacity, and spare respiration capacity. However, these parameters decreased when cells were cultured under higher glucose concentrations when IR was induced. Our data suggests that progression from mild to severe hyperglycemia induces a metabolic shift, where gluconeogenic amino acids play a crucial role in supplying the energy requirements of HK-2. To our knowledge, this is the first study to evaluate the progression from mild to severe hyperglycemia allied to IR in human kidney cells. This work highlights that this progression leads to mitochondrial dysfunction and alters the metabolic profile of kidney cells. These results identify possible targets for early intervention in DN.
Collapse
Affiliation(s)
- Patrícia C Braga
- Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal; ITR- Laboratory for Integrative and Translational Research in Population Health, Porto, Portugal; Laboratory of Physiology, Department of Imuno-physiology and Pharmacology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.
| | - Raquel L Bernardino
- Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal; ITR- Laboratory for Integrative and Translational Research in Population Health, Porto, Portugal.
| | - Bárbara Guerra-Carvalho
- Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal; ITR- Laboratory for Integrative and Translational Research in Population Health, Porto, Portugal; Laboratory of Physiology, Department of Imuno-physiology and Pharmacology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal; LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Portugal.
| | - David F Carrageta
- Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal; ITR- Laboratory for Integrative and Translational Research in Population Health, Porto, Portugal; Laboratory of Physiology, Department of Imuno-physiology and Pharmacology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.
| | - Pedro F Oliveira
- LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Portugal.
| | - Anabela S Rodrigues
- Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal; ITR- Laboratory for Integrative and Translational Research in Population Health, Porto, Portugal; Department of Nephrology, Santo António Hospital, CHUdSA, Porto, Portugal.
| | - Marco G Alves
- Institute of Biomedicine - iBiMED and Department of Medical Sciences, University of Aveiro, 3810-193, Aveiro, Portugal.
| |
Collapse
|
|
15
|
Curran CS, Kopp JB. The complexity of nicotinamide adenine dinucleotide (NAD), hypoxic, and aryl hydrocarbon receptor cell signaling in chronic kidney disease. J Transl Med 2023; 21:706. [PMID: 37814337 PMCID: PMC10563221 DOI: 10.1186/s12967-023-04584-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Accepted: 09/30/2023] [Indexed: 10/11/2023] Open
Abstract
Early-stage detection of chronic kidney diseases (CKD) is important to treatment that may slow and occasionally halt CKD progression. CKD of diverse etiologies share similar histologic patterns of glomerulosclerosis, tubular atrophy, and interstitial fibrosis. Macro-vascular disease and micro-vascular disease promote tissue ischemia, contributing to injury. Tissue ischemia promotes hypoxia, and this in turn activates the hypoxia-inducible transcription factors (HIFs). HIF-1α and HIF-2α, share a dimer partner, HIF-1β, with the aryl hydrocarbon receptor (AHR) and are each activated in CKD and associated with kidney cellular nicotinamide adenine dinucleotide (NAD) depletion. The Preiss-Handler, salvage, and de novo pathways regulate NAD biosynthesis and gap-junctions regulate NAD cellular retention. In the Preiss-Handler pathway, niacin forms NAD. Niacin also exhibits crosstalk with HIF and AHR cell signals in the regulation of insulin sensitivity, which is a complication in CKD. Dysregulated enzyme activity in the NAD de novo pathway increases the levels of circulating tryptophan metabolites that activate AHR, resulting in poly-ADP ribose polymerase activation, thrombosis, endothelial dysfunction, and immunosuppression. Therapeutically, metabolites from the NAD salvage pathway increase NAD production and subsequent sirtuin deacetylase activity, resulting in reduced activation of retinoic acid-inducible gene I, p53, NF-κB and SMAD2 but increased activation of FOXO1, PGC-1α, and DNA methyltransferase-1. These post-translational responses may also be initiated through non-coding RNAs (ncRNAs), which are additionally altered in CKD. Nanoparticles traverse biological systems and can penetrate almost all tissues as disease biomarkers and drug delivery carriers. Targeted delivery of non-coding RNAs or NAD metabolites with nanoparticles may enable the development of more effective diagnostics and therapies to treat CKD.
Collapse
Affiliation(s)
- Colleen S Curran
- National Heart Lung and Blood Institute, NIH, BG 10 RM 2C135, 10 Center Drive, Bethesda, MD, 20814, USA.
| | | |
Collapse
|
|
16
|
Akbari A, McIntyre CW. Recent Advances in Sodium Magnetic Resonance Imaging and Its Future Role in Kidney Disease. J Clin Med 2023; 12:4381. [PMID: 37445416 PMCID: PMC10342976 DOI: 10.3390/jcm12134381] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Accepted: 06/20/2023] [Indexed: 07/15/2023] Open
Abstract
Sodium imbalance is a hallmark of chronic kidney disease (CKD). Excess tissue sodium in CKD is associated with hypertension, inflammation, and cardiorenal disease. Sodium magnetic resonance imaging (23Na MRI) has been increasingly utilized in CKD clinical trials especially in the past few years. These studies have demonstrated the association of excess sodium tissue accumulation with declining renal function across whole CKD spectrum (early- to end-stage), biomarkers of systemic inflammation, and cardiovascular dysfunction. In this article, we review recent advances of 23Na MRI in CKD and discuss its future role with a focus on the skin, the heart, and the kidney itself.
Collapse
Affiliation(s)
- Alireza Akbari
- Robarts Research Institute, Western University, London, ON N6A 3K7, Canada;
- Lilibeth Caberto Kidney Clinic Research Unit, London Health Sciences Centre, London, ON N6A 5W9, Canada
| | - Christopher W. McIntyre
- Robarts Research Institute, Western University, London, ON N6A 3K7, Canada;
- Lilibeth Caberto Kidney Clinic Research Unit, London Health Sciences Centre, London, ON N6A 5W9, Canada
- Departments of Medicine, Pediatrics and Medical Biophysics, Western University, London, ON N6A 3K7, Canada
| |
Collapse
|
|
17
|
Nabipoorashrafi SA, Adeli A, Seyedi SA, Rabizadeh S, Arabzadeh Bahri R, Mohammadi F, Yadegar A, Nakhjavani M, Esteghamati A. Comparison of insulin resistance indices in predicting albuminuria among patients with type 2 diabetes. Eur J Med Res 2023; 28:166. [PMID: 37161502 PMCID: PMC10170852 DOI: 10.1186/s40001-023-01134-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Accepted: 05/05/2023] [Indexed: 05/11/2023] Open
Abstract
PURPOSE Diabetes is the leading cause of kidney disease. Up to 40% of the population with diabetes experience diabetic kidney disease (DKD). The correlation of DKD with insulin resistance (IR) indices has been shown in previous studies. In this study, the objective was to evaluate surrogate IR indices, including the Triglyceride-Glucose (TyG) index, Visceral Adiposity Index (VAI), Lipid Accumulation Product (LAP), and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) to find the most valuable index for the correlation between albuminuria and IR in the type 2 diabetes (T2D) population. Albuminuria is defined as urine albumin excretion of > 30 mg/day. METHODS In this cross-sectional study, 2934 participants were enrolled and evaluated for urinary albumin excretion, and albuminuria was detected in 526 of the entries. The logistic regression models and Receiver Operating Characteristic (ROC) curve analysis were performed to assess the relationship of TyG index, VAI, LAP, and HOMA-IR's with albuminuria in patients with T2D. RESULTS The TyG index had the highest association (OR 1.67) with the presence of albuminuria in patients with T2D, followed by HOMA-IR (OR 1.127), VAI (OR 1.028), and LAP (OR 1.004). These four indices remained independent after adjustment for multiple confounders. Based on the ROC curve, TyG revealed the best area under the curve (AUC) for revealing albuminuria with sufficient accuracy (AUC: 0.62) in comparison with other measured indices. The calculated TyG index cut-off point for the presence of albuminuria was 9.39. CONCLUSION Among the indices, TyG index had the most significant correlation with albuminuria in patients with T2D.
Collapse
Affiliation(s)
- Seyed Ali Nabipoorashrafi
- Endocrinology and Metabolism Research Center (EMRC), School of Medicine, Vali-Asr Hospital, P.O.Box 13145784, Tehran, Iran
| | - Azam Adeli
- Endocrinology and Metabolism Research Center (EMRC), School of Medicine, Vali-Asr Hospital, P.O.Box 13145784, Tehran, Iran
| | - Seyed Arsalan Seyedi
- Endocrinology and Metabolism Research Center (EMRC), School of Medicine, Vali-Asr Hospital, P.O.Box 13145784, Tehran, Iran
| | - Soghra Rabizadeh
- Endocrinology and Metabolism Research Center (EMRC), School of Medicine, Vali-Asr Hospital, P.O.Box 13145784, Tehran, Iran
| | - Razman Arabzadeh Bahri
- Endocrinology and Metabolism Research Center (EMRC), School of Medicine, Vali-Asr Hospital, P.O.Box 13145784, Tehran, Iran
| | - Fatemeh Mohammadi
- Endocrinology and Metabolism Research Center (EMRC), School of Medicine, Vali-Asr Hospital, P.O.Box 13145784, Tehran, Iran
| | - Amirhossein Yadegar
- Endocrinology and Metabolism Research Center (EMRC), School of Medicine, Vali-Asr Hospital, P.O.Box 13145784, Tehran, Iran
| | - Manouchehr Nakhjavani
- Endocrinology and Metabolism Research Center (EMRC), School of Medicine, Vali-Asr Hospital, P.O.Box 13145784, Tehran, Iran
| | - Alireza Esteghamati
- Endocrinology and Metabolism Research Center (EMRC), School of Medicine, Vali-Asr Hospital, P.O.Box 13145784, Tehran, Iran.
| |
Collapse
|
|
18
|
Lin WR, Liu KH, Ling TC, Wang MC, Lin WH. Role of antidiabetic agents in type 2 diabetes patients with chronic kidney disease. World J Diabetes 2023; 14:352-363. [PMID: 37122432 PMCID: PMC10130897 DOI: 10.4239/wjd.v14.i4.352] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Revised: 01/10/2023] [Accepted: 04/04/2023] [Indexed: 04/12/2023] Open
Abstract
Insulin resistance is a condition in which the target tissues have a decreased response to insulin signaling, resulting in glucose uptake defect, and an increased blood sugar level. Pancreatic beta cells thus enhance insulin production to compensate. This situation may cause further beta cell dysfunction and failure, which can lead diabetes mellitus (DM). Insulin resistance is thus an important cause of the development of type 2 DM. Insulin resistance has also been found to have a strong relationship with cardiovascular disease and is common in chronic kidney disease (CKD) patients. The mechanisms of insulin resistance in CKD are complex and multifactorial. They include physical inactivity, inflammation and oxidative stress, metabolic acidosis, vitamin D deficiency, adipose tissue dysfunction, uremic toxins, and renin-angiotensin-aldosterone system activation. Currently, available anti-diabetic agents, such as biguanides, sulfonylureas, thiazolidinediones, alfa-glucosidase inhibitors, glucagon-like peptide-1-based agents, and sodium-glucose co-transporter-2 inhibitors, have different effects on insulin resistance. In this short review, we describe the potential mechanisms of insulin resistance in CKD patients. We also review the interaction of currently available anti-diabetic medications with insulin resistance.
Collapse
Affiliation(s)
- Wei-Ren Lin
- Division of Nephrology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 704, Taiwan
| | - Kuan-Hung Liu
- Division of Nephrology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 704, Taiwan
| | - Tsai-Chieh Ling
- Division of Nephrology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 704, Taiwan
| | - Ming-Cheng Wang
- Division of Nephrology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 704, Taiwan
| | - Wei-Hung Lin
- Division of Nephrology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 704, Taiwan
| |
Collapse
|
|
19
|
Méndez L, Muñoz S, Barros L, Miralles-Pérez B, Romeu M, Ramos-Romero S, Torres JL, Medina I. Combined Intake of Fish Oil and D-Fagomine Prevents High-Fat High-Sucrose Diet-Induced Prediabetes by Modulating Lipotoxicity and Protein Carbonylation in the Kidney. Antioxidants (Basel) 2023; 12:antiox12030751. [PMID: 36978999 PMCID: PMC10045798 DOI: 10.3390/antiox12030751] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Revised: 03/12/2023] [Accepted: 03/17/2023] [Indexed: 03/30/2023] Open
Abstract
Obesity has been recognized as a major risk factor for chronic kidney disease, insulin resistance being an early common metabolic feature in patients suffering from this syndrome. This study aims to investigate the mechanism underlying the induction of kidney dysfunction and the concomitant onset of insulin resistance by long-term high-fat and sucrose diet feeding in Sprague Dawley rats. To achieve this goal, our study analyzed renal carbonylated protein patterns, ectopic lipid accumulation and fatty acid profiles and correlated them with biometrical and biochemical measurements and other body redox status parameters. Rats fed the obesogenic diet developed a prediabetic state and incipient kidney dysfunction manifested in increased plasma urea concentration and superior levels of renal fat deposition and protein carbonylation. An obesogenic diet increased renal fat by preferentially promoting the accumulation of saturated fat, arachidonic, and docosahexaenoic fatty acids while decreasing oleic acid. Renal lipotoxicity was accompanied by selectively higher carbonylation of proteins involved in the blood pH regulation, i.e., bicarbonate reclamation and synthesis, amino acid, and glucose metabolisms, directly related to the onset of insulin resistance. This study also tested the combination of antioxidant properties of fish oil with the anti-diabetic properties of buckwheat D-Fagomine to counteract diet-induced renal alterations. Results demonstrated that bioactive compounds combined attenuated lipotoxicity, induced more favorable lipid profiles and counteracted the excessive carbonylation of proteins associated with pH regulation in the kidneys, resulting in an inhibition of the progression of the prediabetes state and kidney disease.
Collapse
Affiliation(s)
- Lucía Méndez
- Instituto de Investigaciones Marinas-Consejo Superior de Investigaciones Científicas (IIM-CSIC), Eduardo Cabello 6, E-36208 Vigo, Spain
| | - Silvia Muñoz
- Instituto de Investigaciones Marinas-Consejo Superior de Investigaciones Científicas (IIM-CSIC), Eduardo Cabello 6, E-36208 Vigo, Spain
| | - Lorena Barros
- Instituto de Investigaciones Marinas-Consejo Superior de Investigaciones Científicas (IIM-CSIC), Eduardo Cabello 6, E-36208 Vigo, Spain
| | - Bernat Miralles-Pérez
- Unidad de Farmacología, Facultad de Medicina y Ciencias de la Salud, Universidad Rovira i Virgili, Sant Llorenç 21, E-43201 Reus, Spain
| | - Marta Romeu
- Unidad de Farmacología, Facultad de Medicina y Ciencias de la Salud, Universidad Rovira i Virgili, Sant Llorenç 21, E-43201 Reus, Spain
| | - Sara Ramos-Romero
- Instituto de Química Avanzada de Catalunya-Consejo Superior de Investigaciones Científicas (IQAC-CSIC), Jordi Girona 18-26, E-08034 Barcelona, Spain
- Departamento de Biología Celular, Fisiología e Inmunología, Facultad de Biología, Universidad de Barcelona, E-08028 Barcelona, Spain
| | - Josep Lluís Torres
- Instituto de Química Avanzada de Catalunya-Consejo Superior de Investigaciones Científicas (IQAC-CSIC), Jordi Girona 18-26, E-08034 Barcelona, Spain
| | - Isabel Medina
- Instituto de Investigaciones Marinas-Consejo Superior de Investigaciones Científicas (IIM-CSIC), Eduardo Cabello 6, E-36208 Vigo, Spain
| |
Collapse
|
|
20
|
Hou YC, Liu YM, Liao MT, Zheng CM, Lu CL, Liu WC, Hung KC, Lin SM, Lu KC. Indoxyl sulfate mediates low handgrip strength and is predictive of high hospitalization rates in patients with end-stage renal disease. Front Med (Lausanne) 2023; 10:1023383. [PMID: 36817773 PMCID: PMC9932816 DOI: 10.3389/fmed.2023.1023383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Accepted: 01/17/2023] [Indexed: 02/05/2023] Open
Abstract
Background and aims Sarcopenia has a higher occurrence rate in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) than in the general population. Low handgrip strength-and not sarcopenia per se-is associated with clinical outcomes in patients with CKD, including cardiovascular mortality and hospitalization. The factors contributing to low handgrip strength are still unknown. Accordingly, this study aimed to determine whether uremic toxins influence low handgrip strength in patients with CKD. Materials and methods This cohort study lasted from August 2018 to January 2020. The participants were divided into three groups: the control group [estimated glomerular filtration rate (eGFR) ≥ 60 ml/min], an advanced CKD group (eGFR = 15-60 ml/min), and an ESRD group (under maintenance renal replacement therapy). All participants underwent handgrip strength measurement, dual-energy X-ray absorptiometry, and blood sampling for myokines (irisin, myostatin, and interleukin 6) and indoxyl sulfate. Sarcopenia was defined according to the Asian Working Group for Sarcopenia consensus as low appendicular skeletal muscle index (appendicular skeletal muscle/height2 of < 7.0 kg/m2 in men and < 5.4 kg/m2 in women) and low handgrip strength (< 28 kg in men and < 18 kg in women). Results Among the study participants (control: n = 16; CKD: n = 17; and ESRD: n = 42), the ESRD group had the highest prevalence of low handgrip strength (41.6 vs. 25% and 5.85% in the control and CKD groups, respectively; p < 0.05). The sarcopenia rate was similar among the groups (12.5, 17.6, and 19.5% for the control, CKD, and ESRD groups, respectively; p = 0.864). Low handgrip strength was associated with high hospitalization rates within the total study population during the 600-day follow-up period (p = 0.02). The predictions for cardiovascular mortality and hospitalization were similar among patients with and without sarcopenia (p = 0.190 and p = 0.094). The serum concentrations of indoxyl sulfate were higher in the ESRD group (227.29 ± 92.65 μM vs. 41.97 ± 43.96 μM and 6.54 ± 3.45 μM for the CKD and control groups, respectively; p < 0.05). Myokine concentrations were similar among groups. Indoxyl sulfate was associated with low handgrip strength in univariate and multivariate logistic regression models [univariate odds ratio (OR): 3.485, 95% confidence interval (CI): 1.372-8.852, p = 0.001; multivariate OR: 8.525, 95% CI: 1.807-40.207, p = 0.007]. Conclusion Handgrip strength was lower in the patients with ESRD, and low handgrip strength was predictive of hospitalization in the total study population. Indoxyl sulfate contributed to low handgrip strength and counteracted the benefits of myokines in patients with CKD.
Collapse
Affiliation(s)
- Yi-Chou Hou
- Division of Nephrology, Department of Internal Medicine, Cardinal Tien Hospital, New Taipei City, Taiwan
- School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan
| | - Yueh-Min Liu
- Department of Nursing, Ching Kuo Institute of Management and Health, Keelung, Taiwan
| | - Min-Ter Liao
- Department of Pediatrics, Taoyuan Armed Forces General Hospital, Hsinchu, Taiwan
- Department of Pediatrics, Tri-Service General Hospital, National Defense Medical Center, Taipei City, Taiwan
| | - Cai-Mei Zheng
- Division of Nephrology, Department of Internal Medicine, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan
- Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan
- Taipei Medical University-Research Center of Urology and Kidney (TMU-RCUK), School of Medicine, College of Medicine, Taipei Medical University, Taipei City, Taiwan
| | - Chien-Lin Lu
- School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan
- Division of Nephrology, Department of Medicine, Fu Jen Catholic University Hospital, School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan
| | - Wen-Chih Liu
- Division of Nephrology, Department of Internal Medicine, Taipei Hospital, Ministry of Health and Welfare, New Taipei City, Taiwan
- Department of Biology and Anatomy, National Defense Medical Center, Taipei City, Taiwan
| | - Kuo-Chin Hung
- Division of Nephrology, Department of Medicine, Min-Sheng General Hospital, Taoyuan City, Taiwan
| | - Shyh-Min Lin
- Division of Radiology, Department of Medicine, Cardinal Tien Hospital, New Taipei City, Taiwan
| | - Kuo-Cheng Lu
- School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan
- Division of Nephrology, Department of Medicine, Fu Jen Catholic University Hospital, School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan
- Division of Nephrology, Department of Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan
| |
Collapse
|
|
21
|
Sharma AK, Mukherjee M, Kumar A, Sharma G, Tabassum F, Akhtar MS, Imam MT, Almalki ZS. Preliminary investigation on impact of intergenerational treatment of resveratrol endorses the development of 'super-pups'. Life Sci 2023; 314:121322. [PMID: 36574941 DOI: 10.1016/j.lfs.2022.121322] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Revised: 12/12/2022] [Accepted: 12/20/2022] [Indexed: 12/25/2022]
Abstract
BACKGROUND Redox biology balances free radical generation and scavenging systems, whereas an imbalanced cellular redox can hasten the onset of various diseases and be regarded as a Pandora's box of ailments. The current study aims to assess the pathophysiological impact of intergenerational resveratrol treatment on diabetes-related cognitive and cardio-renal disorders. MATERIAL AND METHOD Diabetic rats of the first, second, and third generations were subjected to an intergenerational treatment of resveratrol (20 mg/kg/p.o./day) for 5 months. During this period, the second generation of animals (pups of the first generation) was produced. After the adulthood of second-generation rats, they used to produce third-generation rats. The rats of each generation were evaluated for physiological parameters (BMI, litter size, and life expectancy) and the pathological impact of streptozotocin (55 mg/kg/i.p.), cognitive dysfunctions, and cardio-renal injury. RESULTS The intergenerational treatment of resveratrol significantly reduced litter size and improved anthropometric parameters, life expectancy, and blood glucose levels in diabetic animals. Resveratrol treatment ameliorates oxidative stress as measured by increased serum nitrite/nitrate concentrations, SOD activity, reduced glutathione concentrations, total serum antioxidant capacity, and diminished serum TBARS level in diabetic animals. Furthermore, diabetic rats receiving intergenerational resveratrol treatment showed improved cognitive behaviour and cardio-renal functionality when compared to the disease control group. CONCLUSION The intergenerational treatment of resveratrol improved the physiological traits and vital abilities of the heart, kidney, and brain, which endorse its antioxidant potential. Surprisingly, resveratrol treatment increases the second and third generations' resistance to neurobehavioral changes, diabetes, and -associated cardio-renal dysfunction, implying that these generations are "super-pups."
Collapse
Affiliation(s)
- Arun K Sharma
- Department of Cardiovascular Pharmacology, Amity Institute of Pharmacy, Amity University, Gurugram, Haryana 122413, India.
| | - Monalisa Mukherjee
- Molecular Sciences and Engineering Laboratory, Amity Institute of Click Chemistry Research and Studies, Amity University, Noida, Uttar Pradesh 201303, India; Amity Institute of Biotechnology, Amity University Uttar Pradesh, Noida, Uttar Pradesh 201303, India
| | - Ashish Kumar
- Department of Cardiovascular Pharmacology, Amity Institute of Pharmacy, Amity University, Gurugram, Haryana 122413, India
| | - Gunjan Sharma
- Department of Pharmacology, Delhi Pharmaceutical Sciences and Research University, New Delhi 110017, India
| | - Fauzia Tabassum
- Department of Pharmacology, College of Dentistry and Pharmacy, Buraydah Private College, Al Qassim 51418, Saudi Arabia
| | - Md Sayeed Akhtar
- Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia
| | - Mohammad Tarique Imam
- Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam Bin Abdul Aziz University, Al-Kharj 11942, Saudi Arabia
| | - Ziyad Saeed Almalki
- Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam Bin Abdul Aziz University, Al-Kharj 11942, Saudi Arabia
| |
Collapse
|
|
22
|
Sinha S, Haque M. Insulin Resistance and Type 2 Diabetes Mellitus: An Ultimatum to Renal Physiology. Cureus 2022; 14:e28944. [PMID: 36111327 PMCID: PMC9462660 DOI: 10.7759/cureus.28944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/08/2022] [Indexed: 11/24/2022] Open
Abstract
Insulin resistance (IR) is stated as diminished insulin action regardless of hyperinsulinemia. The usual target organs for insulin activities are the liver, skeletal muscle, and adipose tissue. Hence, the vasculature and kidneys are nonconventional target organs as the impacts of insulin on these are comparatively separate from other conventional target organs. Vasodilation is achieved by raising endothelial nitric oxide (NO) generation by initiating the phosphoinositide 3-kinase (PI3K) pathway. In insulin-nonresponsive conditions, this process is defective, and there is increased production of endothelin-1 through the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway, which predominates the NO effects, causing vasoconstriction. Renal tubular cells and podocytes have insulin receptors, and their purposeful importance has been studied, which discloses critical acts of insulin signaling in podocyte survivability and tubular action. Diabetic nephropathy (DN) is a prevalent problem in individuals with hypertension, poor glycemic management, hereditary susceptibility, or glomerular hyperfiltration. DN could be a significant contributing factor to end-stage renal disease (ESRD) that results from chronic kidney disease (CKD). IR and diabetes mellitus (DM) are the constituents of syndrome X and are accompanied by CKD progression. IR performs a key part in syndrome X leading to CKD. However, it is indistinct whether IR individually participates in enhancing the threat to CKD advancement rather than CKD complexity. CKD is an extensive public health problem affecting millions of individuals worldwide. The tremendous spread of kidney disease intensifies people’s health impacts related to communicable and noncommunicable diseases. Chronic disease regulator policies do not include CKD at global, local, and/or general levels. Improved knowledge of the character of CKD-associated problems might aid in reforming diagnosis, prevention, and management.
Collapse
|
|
23
|
Choumessi AT, Saha BUF, Navti LK, Tibi AS, Njeck AT, Nantia EA. Assessment of visceral adiposity index and lipid accumulation product index as markers of chronic kidney disease among diabetic and hypertensive patients at the Bamenda Regional Hospital, Cameroon: a cross-sectional study. Pan Afr Med J 2022; 42:228. [PMID: 36845245 PMCID: PMC9949295 DOI: 10.11604/pamj.2022.42.228.33499] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Accepted: 07/10/2022] [Indexed: 11/11/2022] Open
Abstract
Introduction very limited studies have emphasized the importance of visceral adiposity index (VAI) and lipid accumulation product index (LAPI) in the prevention and management of chronic kidney disease (CKD) especially in diabetic and hypertension patients in developing countries including Cameroon. This study aimed at assessing whether VAI and LAPI are markers of CKD among diabetic and hypertensive patients at the Bamenda Regional Hospital, Cameroon. Methods this analytical cross-sectional study was conducted at Bamenda Regional Hospital and involved 200 diabetic and/or hypertensive patients, including 77 males and 123 females. The participant´s anthropometric indices, biochemical parameters, VAI, LAPI, and glomerular filtration rate were investigated. A structured questionnaire was used to assess some risk factors of CKD and participant lifestyle. Results the overweight (41%) and obesity (34%) statuses were prevalent in the population. A considerable proportion of subjects had elevated total cholesterol (46%), low-density lipoprotein (LDL) cholesterol (37.50%), triglycerides (24.5%), urea (40.5%) and creatinine (53.5%) levels. Stage 1 to 3 CKD was largely present in the elderly (>54-year-old) affecting the majority of patients (57.5%). Low education level and lack of physical activity were significantly associated with the prevalence of CKD (p < 0.001). On the contrary to creatinine (unadjusted OR = 1.36; 95% CI: 1.13-1.62), urea (unadjusted OR = 1.02; 95% CI: 1.01-1.03), HDL (unadjusted OR = 0.87; 95% CI: 0.78-0.97), total cholesterol/HDL ratio (unadjusted OR = 1.38; 95% CI; 1.12-1.71), VAI (unadjusted OR = 1.13; 95% CI: 1.05-1.22) and LAPI (unadjusted OR = 1.00; 95% CI: 1.00-1.00) were significantly associated with CKD status of the patients while HDL was negatively associated (unadjusted OR = 0.87; 95% CI: 0.78-0.97). The 9.905 and 5679 cut-offs of VAI and LAPI respectively for CKD discrimination obtained high sensitivity (75.0%) and specificity (≥79.6%). Conclusion visceral adiposity index and LAPI were associated with CKD among diabetic and hypertensive patients. Visceral adiposity index and LAPI could be user-friendly tools for the early diagnosis of CKD among these categories of patients in Cameroon.
Collapse
Affiliation(s)
| | | | - Lifoter Kenneth Navti
- Department of Biochemistry, Faculty of Science, University of Bamenda, Bambili, Cameroon
| | - Ateh Sheron Tibi
- Department of Biochemistry, Faculty of Science, University of Bamenda, Bambili, Cameroon
| | - Anweck Thecla Njeck
- Department of Biochemistry, Faculty of Science, University of Bamenda, Bambili, Cameroon
| | - Edouard Akono Nantia
- Department of Biochemistry, Faculty of Science, University of Bamenda, Bambili, Cameroon,Corresponding author: Edouard Akono Nantia, Department of Biochemistry, Faculty of Science, University of Bamenda, Bambili, Cameroon.
| |
Collapse
|
|
24
|
Lee CL, Liu WJ, Tsai SF. Development and Validation of an Insulin Resistance Model for a Population with Chronic Kidney Disease Using a Machine Learning Approach. Nutrients 2022; 14:nu14142832. [PMID: 35889789 PMCID: PMC9319821 DOI: 10.3390/nu14142832] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 07/06/2022] [Accepted: 07/06/2022] [Indexed: 02/01/2023] Open
Abstract
Background: Chronic kidney disease (CKD) is a complex syndrome without a definitive treatment. For these patients, insulin resistance (IR) is associated with worse renal and patient outcomes. Until now, no predictive model using machine learning (ML) has been reported on IR in CKD patients. Methods: The CKD population studied was based on results from the National Health and Nutrition Examination Survey (NHANES) of the USA from 1999 to 2012. The homeostasis model assessment of IR (HOMA-IR) was used to assess insulin resistance. We began the model building process via the ML algorithm (random forest (RF), eXtreme Gradient Boosting (XGboost), logistic regression algorithms, and deep neural learning (DNN)). We compared different receiver operating characteristic (ROC) curves from different algorithms. Finally, we used SHAP values (SHapley Additive exPlanations) to explain how the different ML models worked. Results: In this study population, 71,916 participants were enrolled. Finally, we analyzed 1,229 of these participants. Their data were segregated into the IR group (HOMA IR > 3, n = 572) or non-IR group (HOMR IR ≤ 3, n = 657). In the validation group, RF had a higher accuracy (0.77), specificity (0.81), PPV (0.77), and NPV (0.77). In the test group, XGboost had a higher AUC of ROC (0.78). In addition, XGBoost also had a higher accuracy (0.7) and NPV (0.71). RF had a higher accuracy (0.7), specificity (0.78), and PPV (0.7). In the RF algorithm, the body mass index had a much larger impact on IR (0.1654), followed by triglyceride (0.0117), the daily calorie intake (0.0602), blood HDL value (0.0587), and age (0.0446). As for the SHAP value, in the RF algorithm, almost all features were well separated to show a positive or negative association with IR. Conclusion: This was the first study using ML to predict IR in patients with CKD. Our results showed that the RF algorithm had the best AUC of ROC and the best SHAP value differentiation. This was also the first study that included both macronutrients and micronutrients. We concluded that ML algorithms, particularly RF, can help determine risk factors and predict IR in patients with CKD.
Collapse
Affiliation(s)
- Chia-Lin Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 407219, Taiwan;
- Department of Medical Research, Taichung Veterans General Hospital, Taichung 407219, Taiwan;
- Department of Public Health, College of Public Health, China Medical University, Taichung 406040, Taiwan
- School of Medicine, National Yang-Ming University, Taipei 112304, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung 402204, Taiwan
| | - Wei-Ju Liu
- Department of Medical Research, Taichung Veterans General Hospital, Taichung 407219, Taiwan;
| | - Shang-Feng Tsai
- School of Medicine, National Yang-Ming University, Taipei 112304, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung 402204, Taiwan
- Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 407219, Taiwan
- Department of Life Science, Tunghai University, Taichung 407224, Taiwan
- Correspondence: ; Tel.: +88-(64)-23592525 (ext. 3046); Fax: +88-(64)-23594980
| |
Collapse
|
|
25
|
Elsaid A, Samir Eid O, Said SB, Zahran RF. Association of NOS3 (rs 2070744) and SOD2Val16Ala (rs4880) gene polymorphisms with increased risk of ESRD among Egyptian patients. JOURNAL OF GENETIC ENGINEERING AND BIOTECHNOLOGY 2021; 19:158. [PMID: 34661767 PMCID: PMC8523625 DOI: 10.1186/s43141-021-00260-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Accepted: 10/02/2021] [Indexed: 11/10/2022]
Abstract
BACKGROUND Chronic kidney Failure (CKD), particularly End-Stage Renal Disease (ESRD), may be serious ill-health related to a high death rate. Uremic syndrome leads to increased oxidative stress, inflammation, and dyslipidemia. Our study aimed at identifying the association of NOS3 (rs 2070744) and SOD2 Val16Ala (rs4880) gene polymorphisms within ESRD Egyptian patients. METHODS This work was conducted on 100 ESRD and 16 CKD Egyptian patients who were compared to 100 healthy controls. DNA was genotyped for these variants using the (T-ARMS-PCR) technique. RESULTS ESRD patients showed a significant association of the genotype of NOS3 gene polymorphism compared with healthy controls (P = 0.032). In the contrast, the present study revealed that no statistically significant differences were found among the CKD, ESRD, and control groups as regards the SOD2 genotypes (P = 0.064). CONCLUSIONS Our findings indicated a significant association between NOS3 (rs 2070744) gene polymorphism and increased risk of ESRD and CKD among Egyptian patients.
Collapse
Affiliation(s)
- Afaf Elsaid
- Genetics Unit, Children Hospital, Mansoura University, Mansoura, Egypt
| | - Omnia Samir Eid
- Department of Chemistry, Biochemistry Division, Faculty of Science, Damietta University, New-Damietta, Egypt
| | - Samy B Said
- Department of Chemistry, Faculty of Science, Damietta University, New-Damietta, 34517, Egypt
| | - Rasha F Zahran
- Department of Chemistry, Biochemistry Division, Faculty of Science, Damietta University, New-Damietta, Egypt.
| |
Collapse
|
|
26
|
Mahmoud T, Borgi L. The Interplay Between Nutrition, Metabolic, and Endocrine Disorders in Chronic Kidney Disease. Semin Nephrol 2021; 41:180-188. [PMID: 34140096 DOI: 10.1016/j.semnephrol.2021.03.012] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
The kidneys are responsible for maintaining our bodies' homeostasis through excretion, biodegradation, and synthesis of different hormones. Therefore, a decline in renal function often results in significant derangements in hormone levels. The most common metabolic and endocrine abnormalities seen in patients with chronic kidney disease include deficiencies in erythropoietin, calcitriol, triiodothyronine, testosterone, and estrogen. In addition, accumulation of hormones such as adiponectin, leptin, triglycerides, and prolactin also is seen. Subsequently, this can lead to the development of a wide range of clinical consequences including but not limited to anemia, hyperparathyroidism, insulin resistance, anorexia-cachexia, infertility, bone disorders, and cardiovascular diseases. These disorders can negatively affect the prognosis and quality of life of patients with chronic kidney disease, and, thus, early diagnosis, nutritional intervention, and pharmacologic treatment is imperative.
Collapse
Affiliation(s)
- Tala Mahmoud
- Faculty of Medicine, University of Balamand, Beirut, Lebanon
| | - Lea Borgi
- Renal Division, Brigham and Women's Hospital, Boston, MA.
| |
Collapse
|
|
27
|
Morioka T, Mori K, Emoto M. Is Stiffness Parameter β Useful for the Evaluation of Atherosclerosis?~ Its Clinical Implications, Limitations, and Future Perspectives ~. J Atheroscler Thromb 2021; 28:435-453. [PMID: 33583910 PMCID: PMC8193788 DOI: 10.5551/jat.rv17047] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Atherosclerosis comprises two components, atherosis and sclerosis, characterized by morphological wall thickening and functional stiffening, respectively, of the arterial wall. In recent years, much interest has been directed to the role of functional changes in large arteries, i.e., increased stiffness or decreased elasticity, on the development of cardiovascular diseases. In fact, the clinical evaluation of arterial stiffness is increasingly performed in patients with cardiovascular risk factors. Local arterial stiffness is measured using an ultrasound technique implemented with an echo-tracking system at the common carotid and femoral arteries. Several indices of local arterial stiffness are obtained by ultrasound, among which stiffness parameter β is unique because it is the least affected by blood pressure at the time of measurement. Evidence from cross-sectional studies indicates that increased stiffness parameter β is associated with a number of cardiovascular risk factors, such as older age, smoking, insufficient physical activity, hypertension, obesity, metabolic syndrome, insulin resistance, type 2 diabetes, chronic kidney disease, and comorbid cardiovascular disease. Results from several prospective observational studies also suggest that carotid stiffness parameter β is a useful surrogate marker of cardiovascular events and/or mortality, although the results differ depending on the characteristics of the study subjects. Furthermore, several interventional studies have shown that carotid stiffness parameter β improved after lifestyle modification or drug treatment. In this review, we summarize the current evidence of stiffness parameter β of the carotid artery and discuss its clinical implications as a marker of vascular health or as a predictor of cardiovascular outcomes.
Collapse
Affiliation(s)
- Tomoaki Morioka
- Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine
| | - Katsuhito Mori
- Department of Nephrology, Osaka City University Graduate School of Medicine
| | - Masanori Emoto
- Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine
| |
Collapse
|
|
28
|
Sahathevan S, Khor BH, Ng HM, Abdul Gafor AH, Mat Daud ZA, Mafra D, Karupaiah T. Understanding Development of Malnutrition in Hemodialysis Patients: A Narrative Review. Nutrients 2020; 12:E3147. [PMID: 33076282 PMCID: PMC7602515 DOI: 10.3390/nu12103147] [Citation(s) in RCA: 106] [Impact Index Per Article: 21.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Revised: 10/11/2020] [Accepted: 10/13/2020] [Indexed: 12/15/2022] Open
Abstract
Hemodialysis (HD) majorly represents the global treatment option for patients with chronic kidney disease stage 5, and, despite advances in dialysis technology, these patients face a high risk of morbidity and mortality from malnutrition. We aimed to provide a novel view that malnutrition susceptibility in the global HD community is either or both of iatrogenic and of non-iatrogenic origins. This categorization of malnutrition origin clearly describes the role of each factor in contributing to malnutrition. Low dialysis adequacy resulting in uremia and metabolic acidosis and dialysis membranes and techniques, which incur greater amino-acid losses, are identified modifiable iatrogenic factors of malnutrition. Dietary inadequacy as per suboptimal energy and protein intakes due to poor appetite status, low diet quality, high diet monotony index, and/or psychosocial and financial barriers are modifiable non-iatrogenic factors implicated in malnutrition in these patients. These factors should be included in a comprehensive nutritional assessment for malnutrition risk. Leveraging the point of origin of malnutrition in dialysis patients is crucial for healthcare practitioners to enable personalized patient care, as well as determine country-specific malnutrition treatment strategies.
Collapse
Affiliation(s)
- Sharmela Sahathevan
- Dietetics Program, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia;
| | - Ban-Hock Khor
- Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaakob Latif, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia; (B.-H.K.); (A.H.A.G.)
| | - Hi-Ming Ng
- School of Medicine, Faculty of Health & Medical Sciences, Taylor’s University Lakeside Campus, No 1, Jalan Taylors, Subang Jaya 47500, Malaysia;
| | - Abdul Halim Abdul Gafor
- Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaakob Latif, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia; (B.-H.K.); (A.H.A.G.)
| | - Zulfitri Azuan Mat Daud
- Department of Dietetics, Faculty of Medicine & Health Sciences, Universiti Putra Malaysia, UPM Serdang 43400, Malaysia;
| | - Denise Mafra
- Post Graduation Program in Medical Sciences and Post-Graduation Program in Cardiovascular Sciences, (UFF), Federal Fluminense University Niterói-Rio de Janeiro (RJ), Niterói-RJ 24033-900, Brazil;
| | - Tilakavati Karupaiah
- School of BioSciences, Faculty of Health & Medical Sciences, Taylor’s University Lakeside Campus, No 1, Jalan Taylors, Subang Jaya 47500, Malaysia
| |
Collapse
|
|
29
|
Vesa CM, Popa L, Popa AR, Rus M, Zaha AA, Bungau S, Tit DM, Corb Aron RA, Zaha DC. Current Data Regarding the Relationship between Type 2 Diabetes Mellitus and Cardiovascular Risk Factors. Diagnostics (Basel) 2020; 10:E314. [PMID: 32429441 PMCID: PMC7277953 DOI: 10.3390/diagnostics10050314] [Citation(s) in RCA: 62] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2020] [Revised: 05/06/2020] [Accepted: 05/14/2020] [Indexed: 02/06/2023] Open
Abstract
Reducing cardiovascular risk (CVR) is the main focus of diabetes mellitus (DM) management nowadays. Complex pathogenic mechanisms that are the subject of this review lead to early and severe atherosclerosis in DM patients. Although it is not a cardiovascular disease equivalent at the moment of diagnosis, DM subjects are affected by numerous cardiovascular complications, such as acute coronary syndrome, stroke, or peripheral artery disease, as the disease duration increases. Therefore, early therapeutic intervention is mandatory and recent guidelines focus on intensive CVR factor management: hyperglycaemia, hypertension, and dyslipidaemia. Most important, the appearance of oral or injectable antidiabetic medication such as SGLT-2 inhibitors or GLP-1 agonists has proven that an antidiabetic drug not only reduces glycaemia, but also reduces CVR by complex mechanisms. A profound understanding of intimate mechanisms that generate atherosclerosis in DM and ways to inhibit or delay them are of the utmost importance in a society where cardiovascular morbidity and mortality are predominant.
Collapse
Affiliation(s)
- Cosmin Mihai Vesa
- Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania; (C.M.V.); (R.A.C.A.); (D.C.Z.)
| | - Loredana Popa
- Department II of Internal Medicine, Clinical County Emergency Hospital of Oradea, 410169 Oradea; Romania; (L.P.); (A.R.P.); (M.R.)
| | - Amorin Remus Popa
- Department II of Internal Medicine, Clinical County Emergency Hospital of Oradea, 410169 Oradea; Romania; (L.P.); (A.R.P.); (M.R.)
- Department of Medical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
| | - Marius Rus
- Department II of Internal Medicine, Clinical County Emergency Hospital of Oradea, 410169 Oradea; Romania; (L.P.); (A.R.P.); (M.R.)
- Department of Medical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
| | - Andreea Atena Zaha
- Faculty of Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400000 Cluj Napoca, Romania;
| | - Simona Bungau
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania;
| | - Delia Mirela Tit
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania;
| | - Raluca Anca Corb Aron
- Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania; (C.M.V.); (R.A.C.A.); (D.C.Z.)
| | - Dana Carmen Zaha
- Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania; (C.M.V.); (R.A.C.A.); (D.C.Z.)
| |
Collapse
|
|
30
|
William JH, Morales A, Rosas SE. When ESKD complicates the management of diabetes mellitus. Semin Dial 2020; 33:209-222. [PMID: 32274852 DOI: 10.1111/sdi.12873] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Given the increased incidence and prevalence of ESKD (end-stage kidney disease) attributed to diabetes mellitus, it is important to consider the physiological and global sociodemographic factors that give rise to unique challenges in providing excellent care to this population. The individual with diabetes and ESKD faces alterations of glucose homeostasis that require close therapeutic attention, as well as the consideration of safe and effective means of maintaining glycemic control. Implementation of routine monitoring of blood glucose and thoughtful alteration of the individual's hypoglycemic drug regimen must be employed to reduce the risk of neurological, cardiovascular, and diabetes-specific complications that may arise as a result of ESKD. Titration of insulin therapy may become quite challenging, as kidney replacement therapy often significantly impacts insulin requirements. New medications have significantly improved the ability of the clinician to provide effective therapies for the management of diabetes, but have also raised an equal amount of uncertainty with respect to their safety and efficacy in the ESKD population. Additionally, the clinician must consider the challenges related to the delivery of kidney replacement therapy, and how inter-modality differences may impact glycemic control, diabetes, and ESKD-related complications, and issues surrounding dialysis vascular access creation.
Collapse
Affiliation(s)
- Jeffrey H William
- Nephrology Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Alexander Morales
- Nephrology Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Sylvia E Rosas
- Nephrology Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.,Kidney and Hypertension Unit, Joslin Diabetes Center, Boston, MA, USA
| |
Collapse
|
|
31
|
Inhibition of tumor necrosis factor-α enhanced the antifibrotic effect of empagliflozin in an animal model with renal insulin resistance. Mol Cell Biochem 2020; 466:45-54. [PMID: 31933108 DOI: 10.1007/s11010-020-03686-x] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2019] [Accepted: 01/04/2020] [Indexed: 01/25/2023]
Abstract
Insulin resistance (IR) has emerged as one of the main risk factors for renal fibrosis (RF) that represents a common stage in almost all chronic kidney disease. The present study aims to investigate the inhibitory effect of empagliflozin (EMPA "a sodium-glucose co-transporter 2 inhibitor") and infliximab [IFX "a tumor necrosis factor-α (TNF-α) antibody"] on RF in rats with induced IR. IR was induced by adding 10% fructose in drinking water for 20 weeks. Thereafter, fructose-induced IR rats were concurrently treated with EMPA (30 mg/kg), IFX (1 dose 5 mg/kg), or EMPA + IFX for 4 weeks, in addition to IR control group (received 10% fructose in water) and normal control (NC) group. Rats with IR displayed hyperglycemia, deterioration in kidney functions, glomerulosclerosis, and collagen fiber deposition in renal tissues as compared to NC. This was associated with downregulation of the renal sirtuin 1 (Sirt 1) expression along with higher renal tissue TNF-α and transforming growth factor-β1 (TGF-β1) levels. Both EMPA and IFX significantly modulated the aforementioned fibrotic cytokines, upregulated the renal Sirt 1 expression, and attenuated RF compared to IR control group. Of note, IFX effect was superior to that of EMPA. However, the combination of EMPA and IFX alleviated RF to a greater extent surpassing the monotherapy. This may be attributed to the further upregulation of renal Sirt 1 in addition to the downregulation of fibrotic cytokines. These findings suggest that the combination of EMPA and IFX offers additional benefits and may represent a promising therapeutic option for RF.
Collapse
|
|
32
|
Kulkarni S, Lenin M, Ramesh R, Delphine SCW, Velu K. Evaluation of Single-Nucleotide Polymorphisms of Transcription Factor 7-Like 2 and ATP2B1 Genes as Cardiovascular Risk Predictors in Chronic Kidney Disease. Int J Appl Basic Med Res 2019; 9:221-225. [PMID: 31681547 PMCID: PMC6822321 DOI: 10.4103/ijabmr.ijabmr_92_19] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Revised: 04/01/2019] [Accepted: 07/30/2019] [Indexed: 11/12/2022] Open
Abstract
Introduction: Cardiovascular disease (CVD) is the primary cause of morbidity and premature mortality in chronic kidney disease (CKD). The transcription factor 7-like 2 (TCF7L2) gene product TCF4 is a transcription factor that acts as a downstream effector in the canonical Wnt signaling pathway and may be important in the development of both type 2 diabetes and renal development and disease. It is, therefore, plausible that mutations in this gene could manifest themselves in reduced kidney function or kidney disease through their effects on hyperglycemia as well as independent of this mechanism. The ATP2B1 gene encodes the plasma membrane calcium ATPase isoform 1, which removes bivalent calcium ions from eukaryotic cells against very large concentration gradients and is responsible for controlling the contraction and dilation of vascular smooth muscles. Aim and Objectives: The aims of this study are (1) to evaluate single-nucleotide polymorphisms (SNPs) of TCF7L2 gene as cardiovascular risk predictors in CKD and (2) to evaluate SNPs of ATP2B1 gene as cardiovascular risk predictors in CKD. Subjects and Methods: Fifty clinically diagnosed CKD patients in the age group between 20 and 60 years of both genders were selected as cases and fifty healthy participants from the master health checkup department were selected as controls. Genomic DNA was extracted based on the spin column kit method. The DNA samples were stored at −20°C until analysis. Genotyping for TCF7L2 gene rs7903146 (C/T) and ATP2B1 gene rs11105354 (A/G) was carried out through polymerase chain reaction. Results: T allele frequency was observed in 12 controls and 23 cases (odds ratio [OR] = 2.2, 95% confidence interval [CI]: 1.0–4.7). CC genotype was observed in 38 controls and 27 cases and CT genotype in 22 cases and 12 controls. A allele was found in 38 cases and 23 controls (OR = 2, 95% CI: 1.1–3.8). The mean values of cholesterol, low-density lipoprotein, triglycerides, glucose, insulin, urea, and creatinine were high in cases when compared to controls. Conclusion: T allele of TCF7L2 gene rs7903146 (C/T) and A allele of ATP2B1 (A/G) gene rs11105354 (A/G) are associated with CVD in CKD patients.
Collapse
Affiliation(s)
- Sweta Kulkarni
- Department of Biochemistry, Mahatma Gandhi Medical College and Research Institute, Sri Balaji Vidyapeeth (Deemed to be University), Puducherry, India
| | - M Lenin
- Center for Interdisciplinary Research Facility, Sri Balaji Vidyapeeth, Puducherry, India
| | - R Ramesh
- Department of Biochemistry, JIPMER, Puducherry, India
| | - Silvia Cr Wilma Delphine
- Department of Biochemistry, Aakash Institute of Medical Sciences and Research Centre, Bengaluru, Karnataka, India
| | - Kuzhandai Velu
- Department of Biochemistry, Mahatma Gandhi Medical College and Research Institute, Sri Balaji Vidyapeeth (Deemed to be University), Puducherry, India
| |
Collapse
|
|
33
|
Ajayi EIO, Molehin OR, Oloyede OI, Kumar V, Amara VR, Kaur J, Karpe P, Tikoo K. Liver mitochondrial membrane permeability modulation in insulin-resistant, uninephrectomised male rats by Clerodendrum volubile P. Beauv and Manihot esculenta Crantz. CLINICAL PHYTOSCIENCE 2019. [DOI: 10.1186/s40816-019-0124-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AbstractBackgroundNon-alcoholic fatty liver disease, which occurs in people who are not alcohol drinkers, describes some of the pathogenic conditions that may be in the least characterized by simple steatosis or can be as serious as non-alcoholic steatohepatitis and cirrhosis. Its mechanistic pathogenesis has been said to arise from insulin resistance and oxidative stress, which may be compounded by obesity. An experimental model showing, systemic insulin resistance, obesity and accumulated hepatic fatty acids was created in adult male rats using high-fat diet manipulation and surgical removal of the left kidney (uninephrectomy). This study sought to identify the impact of these multiple burdens on the liver mitochondrial membrane permeability transition pore opening, and the possible in vitro effects of the extracts ofClerodendrum volubileandManihot esculentaleaves on the membrane permeabilization.ResultsThe results indicated that the methanolic extract ofClerodendrum volubileleaf inhibited mitochondrial membrane pore opening in the insulin resistance condition or when it is followed by uni-nephrectomy, while the ethanolic extract ofManihot esculentaleaf does the same in the insulin resistance condition both prior to and following uni-nephrectomy.ConclusionSince the vegetable extracts were able to abrogate mitochondrial pore opening at low concentrations, the structural integrity of the mitochondria can possibly be restored over time if treated by the vegetable extracts. Research efforts should, therefore, be made to harness the drugability of the bioactives of these vegetables for use in the treatment of non-alcoholic fatty liver disease arising from insulin resistance and renal failure.
Collapse
|
|
34
|
Hyperhomocysteinemia Associated with Low Muscle Mass, Muscle Function in Elderly Hemodialysis Patients: An Analysis of Multiple Dialysis Centers. BIOMED RESEARCH INTERNATIONAL 2019; 2019:9276097. [PMID: 31281847 PMCID: PMC6590600 DOI: 10.1155/2019/9276097] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/22/2019] [Accepted: 05/23/2019] [Indexed: 11/18/2022]
Abstract
Background The hyperhomocysteinemia was with high prevalence and has been considered as a risk factor for cardiovascular disease in hemodialysis patients. These patients also experienced a high risk of muscle wasting caused by the comorbidity, malnutrition, and low physical activity. We investigated the associations of homocysteinemia with muscle mass, muscle function in elderly hemodialysis patients. Methods A clinical cross-sectional study was conducted on 138 hemodialysis patients aged 65 years and above in seven hospital-based hemodialysis centers in Taiwan. The data on anthropometry, laboratory, and 3-day dietary intake was examined. The skeletal muscle mass (SMM) was measured by the bioelectrical impedance analysis; the SMM was adjusted by height or weight as SMMHt2 (kg/m2) and SMMWt (%). Muscle function was defined as handgrip strength (HGS) (kg) measured by handgrip dynamometer. Statistical analyses were conducted using simple regression and multivariable stepwise regression analysis. Results In the total sample, 74.6 % of hemodialysis patients were hyperhomocysteinemia (≥ 15 μmol/L). The means of SMMHt2, SMMWt, arm lean mass, hand grip strength, and muscle quality were 8.7 ± 1.2, 37.7 ± 5.6, 1.7 ± 0.5, 21.1 ± 7.4, and 10.0 ± 3.0, respectively. The multivariable stepwise regression analysis showed that homocysteinemia level was significantly inversely associated with SMMWt (B-coeff. = -0.03, p = 0.02) in hemodialysis patients above 65 years old, but not with muscle function. Conclusions Hyperhomocysteinemia is common and associated with decreased muscle mass in the elderly hemodialysis patients. Future studies are suggested to explore the impact of the homocysteine-lowering therapy on muscle decline.
Collapse
|
|
35
|
Vadalà M, Castellucci M, Guarrasi G, Terrasi M, La Blasca T, Mulè G. Retinal and choroidal vasculature changes associated with chronic kidney disease. Graefes Arch Clin Exp Ophthalmol 2019; 257:1687-1698. [PMID: 31147842 DOI: 10.1007/s00417-019-04358-3] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2018] [Revised: 05/04/2019] [Accepted: 05/14/2019] [Indexed: 01/13/2023] Open
Abstract
PURPOSE Retinal and choroidal microvascular changes can be related to renal impairment in hypertension and chronic kidney disease (CKD). The study examines the association between retinochoroidal parameters and renal impairment in hypertensive, non-diabetic patients. METHODS This is a cross-sectional study on Caucasian patients with systemic arterial hypertension with different levels of renal function. All subjects were studied by blood chemistry, urine examination, microalbuminuria and blood pressure. Complete eye examination was completed with swept source optical coherence tomography (SS-OCT) and optical coherence tomography angiography (OCTA) scans of macular region. Patients were divided in groups: LowGFR and HighGFR and CKD- and CKD+, according to the value of glomerular filtrate (GFR) and albuminuria. LowGFR and CKD+ groups included patients with clinical kidney impairment. RESULTS One hundred and twenty eyes of 120 hypertensive patients were evaluated. The mean retinal thickness was thinner in CKD+ versus CKD- group (p < 0.009). LowGFR and CKD+ groups showed thinner choroidal values than HighGFR (p < 0.02) and CKD- (p < 0.001) groups. OCTA showed lower density in LowGFR than in HighGFR group (p < 0.001) and in CKD+ versus CKD- group (p < 0.001). Albuminuria was inversely related to choroidal and retinal thickness measures (p < 0.001) and to the indices of superficial parafoveal (p < 0.05) and foveal (p < 0.05) vascular densities. CONCLUSIONS CKD is associated with retinal thinning, eGFR and decreasing renal function with progressive reduction of choroidal and retinal vascular density. SS-OCT and OCTA documented close association between CKD and reduction of both choroidal thickness and paracentral retinal vascular density in hypertensive patients.
Collapse
Affiliation(s)
- Maria Vadalà
- Dipartimento di Biomedicina Sperimentale e Neuroscienze cliniche, Sezione di Oftalmologia, University of Palermo, Via Liborio Giuffrè 13, 90127, Palermo, Italy.
| | - Massimo Castellucci
- Dipartimento di Biomedicina Sperimentale e Neuroscienze cliniche, Sezione di Oftalmologia, University of Palermo, Via Liborio Giuffrè 13, 90127, Palermo, Italy
| | - Giulia Guarrasi
- Dipartimento di Biomedicina Sperimentale e Neuroscienze cliniche, Sezione di Oftalmologia, University of Palermo, Via Liborio Giuffrè 13, 90127, Palermo, Italy
| | - Micol Terrasi
- Dipartimento di Biomedicina Sperimentale e Neuroscienze cliniche, Sezione di Oftalmologia, University of Palermo, Via Liborio Giuffrè 13, 90127, Palermo, Italy
| | - Tiziana La Blasca
- Dipartimento Biomedico di Medicina Interna e Specialistica, Università di Palermo, Palermo, Italy
| | - Giuseppe Mulè
- Dipartimento Biomedico di Medicina Interna e Specialistica, Università di Palermo, Palermo, Italy
| |
Collapse
|
|
36
|
Schrauben SJ, Jepson C, Hsu JY, Wilson FP, Zhang X, Lash JP, Robinson BM, Townsend RR, Chen J, Fogelfeld L, Kao P, Landis JR, Rader DJ, Hamm LL, Anderson AH, Feldman HI. Insulin resistance and chronic kidney disease progression, cardiovascular events, and death: findings from the chronic renal insufficiency cohort study. BMC Nephrol 2019; 20:60. [PMID: 30786864 PMCID: PMC6383235 DOI: 10.1186/s12882-019-1220-6] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2018] [Accepted: 01/17/2019] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Insulin resistance contributes to the metabolic syndrome, which is associated with the development of kidney disease. However, it is unclear if insulin resistance independently contributes to an increased risk of chronic kidney disease (CKD) progression or CKD complications. Additionally, predisposing factors responsible for insulin resistance in the absence of diabetes in CKD are not well described. This study aimed to describe factors associated with insulin resistance and characterize the relationship of insulin resistance to CKD progression, cardiovascular events and death among a cohort of non-diabetics with CKD. METHODS Data was utilized from Chronic Renal Insufficiency Cohort Study participants without diabetes (N = 1883). Linear regression was used to assess associations with insulin resistance, defined using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). The relationship of HOMA-IR, fasting glucose, hemoglobin A1c (HbA1c), and C-peptide with CKD progression, cardiovascular events, and all-cause mortality was examined with Cox proportional hazards models. RESULTS Novel positive associations with HOMA-IR included serum albumin, uric acid, and hemoglobin A1c. After adjustment, HOMA-IR was not associated with CKD progression, cardiovascular events, or all-cause mortality. There was a notable positive association of one standard deviation increase in HbA1c with the cardiovascular endpoint (HR 1.16, 95% CI: 1.00-1.34). CONCLUSION We describe potential determinants of HOMA-IR among a cohort of non-diabetics with mild-moderate CKD. HOMA-IR was not associated with renal or cardiovascular events, or all-cause mortality, which adds to the growing literature describing an inconsistent relationship of insulin resistance with CKD-related outcomes.
Collapse
Affiliation(s)
- Sarah J Schrauben
- Division of Renal-Electrolyte and Hypertension, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, 19103, PA, USA. .,Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19103, USA.
| | - Christopher Jepson
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19103, USA.,Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
| | - Jesse Y Hsu
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19103, USA.,Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
| | - F Perry Wilson
- Department of Medicine, Yale School of Medicine, New Haven, CT, USA
| | - Xiaoming Zhang
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19103, USA.,Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
| | - James P Lash
- Department of Medicine, University of Illinois at Chicago College of Medicine, Chicago, IL, USA
| | - Bruce M Robinson
- Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI; Arbor Research Collaborative for Health, Ann Arbor, MI, USA
| | - Raymond R Townsend
- Division of Renal-Electrolyte and Hypertension, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, 19103, PA, USA
| | - Jing Chen
- Department of Medicine, Tulane University School of Medicine, New Orleans, Lousiana, USA
| | - Leon Fogelfeld
- Department of Medicine, Rush University Medical Center, Chicago, IL, USA
| | - Patricia Kao
- Deparment of Medicine, Washington University School of Medicine in Saint Louis, St. Louis, MO, USA
| | - J Richard Landis
- Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19103, USA.,Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
| | - Daniel J Rader
- Division of Renal-Electrolyte and Hypertension, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, 19103, PA, USA
| | - L Lee Hamm
- Department of Medicine, Tulane University School of Medicine, New Orleans, Lousiana, USA
| | - Amanda H Anderson
- Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.,Tulane University, School of Public Health and Tropical Medicine, New Orleans, LA, USA
| | - Harold I Feldman
- Division of Renal-Electrolyte and Hypertension, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, 19103, PA, USA.,Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19103, USA.,Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
| |
Collapse
|
|
37
|
Sagmeister MS, Taylor AE, Fenton A, Wall NA, Chanouzas D, Nightingale PG, Ferro CJ, Arlt W, Cockwell P, Hardy RS, Harper L. Glucocorticoid activation by 11β-hydroxysteroid dehydrogenase enzymes in relation to inflammation and glycaemic control in chronic kidney disease: A cross-sectional study. Clin Endocrinol (Oxf) 2019; 90:241-249. [PMID: 30358903 PMCID: PMC6334281 DOI: 10.1111/cen.13889] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2018] [Revised: 10/02/2018] [Accepted: 10/22/2018] [Indexed: 02/02/2023]
Abstract
OBJECTIVE Patients with chronic kidney disease (CKD) have dysregulated cortisol metabolism secondary to changes in 11β-hydroxysteroid dehydrogenase (11β-HSD) enzymes. The determinants of this and its clinical implications are poorly defined. METHODS We performed a cross-sectional study to characterize shifts in cortisol metabolism in relation to renal function, inflammation and glycaemic control. Systemic activation of cortisol by 11β-HSD was measured as the metabolite ratio (tetrahydrocortisol [THF]+5α-tetrahydrocortisol [5αTHF])/tetrahydrocortisone (THE) in urine. RESULTS The cohort included 342 participants with a median age of 63 years, median estimated glomerular filtration rate (eGFR) of 28 mL/min/1.73 m2 and median urine albumin-creatinine ratio of 35.5 mg/mmol. (THF+5αTHF)/THE correlated negatively with eGFR (Spearman's ρ = -0.116, P = 0.032) and positively with C-reactive protein (ρ = 0.208, P < 0.001). In multivariable analysis, C-reactive protein remained a significant independent predictor of (THF+5αTHF)/THE, but eGFR did not. Elevated (THF+5αTHF)/THE was associated with HbA1c (ρ = 0.144, P = 0.008) and diabetes mellitus (odds ratio for high vs low tertile of (THF+5αTHF)/THE 2.57, 95% confidence interval 1.47-4.47). Associations with diabetes mellitus and with HbA1c among the diabetic subgroup were independent of eGFR, C-reactive protein, age, sex and ethnicity. CONCLUSIONS In summary, glucocorticoid activation by 11β-HSD in our cohort comprising a spectrum of renal function was associated with inflammation and impaired glucose control.
Collapse
Affiliation(s)
- Michael S. Sagmeister
- Institute of Inflammation and AgeingUniversity of BirminghamBirminghamUK
- Department of Renal MedicineUniversity Hospitals Birmingham NHS Foundation TrustBirminghamUK
| | - Angela E. Taylor
- Institute of Metabolism and Systems ResearchUniversity of BirminghamBirminghamUK
| | - Anthony Fenton
- Institute of Inflammation and AgeingUniversity of BirminghamBirminghamUK
- Department of Renal MedicineUniversity Hospitals Birmingham NHS Foundation TrustBirminghamUK
| | - Nadezhda A. Wall
- Institute of Clinical SciencesUniversity of BirminghamBirminghamUK
| | - Dimitrios Chanouzas
- Institute of Inflammation and AgeingUniversity of BirminghamBirminghamUK
- Department of Renal MedicineUniversity Hospitals Birmingham NHS Foundation TrustBirminghamUK
| | - Peter G. Nightingale
- Institute of Translational MedicineUniversity Hospitals Birmingham NHS Foundation TrustBirminghamUK
| | - Charles J. Ferro
- Department of Renal MedicineUniversity Hospitals Birmingham NHS Foundation TrustBirminghamUK
| | - Wiebke Arlt
- Institute of Metabolism and Systems ResearchUniversity of BirminghamBirminghamUK
| | - Paul Cockwell
- Department of Renal MedicineUniversity Hospitals Birmingham NHS Foundation TrustBirminghamUK
| | - Rowan S. Hardy
- Institute of Metabolism and Systems ResearchUniversity of BirminghamBirminghamUK
- Institute of Inflammation and Ageing, ARUK Rheumatoid Arthritis Centre of Excellence, and MRC ARUK Centre for Musculoskeletal AgeingUniversity of BirminghamBirminghamUK
| | - Lorraine Harper
- Department of Renal MedicineUniversity Hospitals Birmingham NHS Foundation TrustBirminghamUK
- Institute of Clinical SciencesUniversity of BirminghamBirminghamUK
| |
Collapse
|
|
38
|
Suassuna PGDA, de Paula RB, Sanders-Pinheiro H, Moe OW, Hu MC. Fibroblast growth factor 21 in chronic kidney disease. J Nephrol 2018; 32:365-377. [DOI: 10.1007/s40620-018-0550-y] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Accepted: 10/15/2018] [Indexed: 01/10/2023]
|
|
39
|
Fayed A, El Nokeety MM, Heikal AA, Abdulazim DO, Naguib MM, Sharaf El Din UAA. Fibroblast growth factor-23 is a strong predictor of insulin resistance among chronic kidney disease patients. Ren Fail 2018; 40:226-230. [PMID: 29619868 PMCID: PMC6014287 DOI: 10.1080/0886022x.2018.1455594] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
Insulin resistance (IR) is very common among chronic kidney disease (CKD) patients. Disturbance in mineral and bone metabolism (MBD) seems to play a role in the pathogenesis of insulin resistance. Fibroblast growth factor-23 (FGF23) is evolving as the most important link between MBD and many pathologic sequences of CKD. The aim was to evaluate IR in pre-dialysis CKD patients looking for a possible association to mineral metabolism among CKD patients. A total of 100 stage 3–5 CKD patients were selected beside 20 normal control subjects. Homeostatic model assessment of insulin resistance (HOMA-IR) was used to assess IR in selected cases. Both groups were compared for fasting blood glucose (FBG), fasting blood insulin (FBI), HOMA-IR, estimated glomerular filtration rate (eGFR), serum calcium (Ca), phosphorus (P), 25 hydroxy vitamin D (25 OH vit D), parathormone (PTH), and uric acid (UA). Correlation study between HOMA_IR and different studied parameters was performed. HOMA-IR is significantly higher in CKD (8.87 ± 3.48 vs. 3.97 ± 0.34 in CKD vs. control, respectively, p < .001). In addition CKD patients have significantly higher FGF23 (235 ± 22.96 vs. 139 ± 12.3 pg/mL, p < .001), PTH (76.9 ± 15.27 vs. 47.9 ± 2.52 pg/mL, p < .001), P (4.3 ± 0.67 vs. 3.6 ± 0.23 mg/dL, p < .001), and UA (5 ± 1.22 vs. 4.85 ± 0.48 mg/dL, p < .001) and significantly lower Ca (8.2 ± 0.3 vs. 8.9 ± 0.33 mg/dL, p < .001), and 25 (OH) vit D (17 ± 5.63 vs. 37 ± 3.43 ng/mL, p < .001). Stepwise linear regression analysis revealed that BMI, GFR, Ca, P, and FGF23 were the only significant predictors of HOMA IR. Increased IR in CKD is a consequence of the uremic status and is intimately associated with disturbed phosphate metabolism and FGF23. Further studies are needed to look for an underlying mechanism.
Collapse
Affiliation(s)
- Ahmed Fayed
- a Nephrology Unit, Internal Medicine Department, School of Medicine , Cairo University , Cairo , Egypt
| | - Mahmoud M El Nokeety
- a Nephrology Unit, Internal Medicine Department, School of Medicine , Cairo University , Cairo , Egypt
| | - Ahmed A Heikal
- b Internal Medicine Department, School of Medicine , Cairo University , Cairo , Egypt
| | - Dina O Abdulazim
- c Rheumatology and Rehabilitation Department, School of Medicine , Cairo University , Cairo , Egypt
| | - Mervat M Naguib
- d Endocrinology Unit, Internal Medicine Department, School of Medicine , Cairo University , Cairo , Egypt
| | - Usama A A Sharaf El Din
- a Nephrology Unit, Internal Medicine Department, School of Medicine , Cairo University , Cairo , Egypt
| | | |
Collapse
|
|
40
|
Both insulin resistance and metabolic syndrome accelerate the progression of chronic kidney disease among Chinese adults: results from a 3-year follow-up study. Int Urol Nephrol 2018; 50:2239-2244. [DOI: 10.1007/s11255-018-1934-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2018] [Accepted: 07/06/2018] [Indexed: 10/28/2022]
|
|
41
|
Coverdale JPC, Katundu KGH, Sobczak AIS, Arya S, Blindauer CA, Stewart AJ. Ischemia-modified albumin: Crosstalk between fatty acid and cobalt binding. Prostaglandins Leukot Essent Fatty Acids 2018; 135:147-157. [PMID: 30103926 PMCID: PMC6109191 DOI: 10.1016/j.plefa.2018.07.014] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2018] [Revised: 07/17/2018] [Accepted: 07/17/2018] [Indexed: 02/06/2023]
Abstract
Myocardial ischemia is difficult to diagnose effectively with still few well-defined biochemical markers for identification in advance, or in the absence of myocardial necrosis. "Ischemia-modified albumin" (IMA), a form of albumin displaying reduced cobalt-binding affinity, is significantly elevated in ischemic patients, and the albumin cobalt-binding (ACB) assay can measure its level indirectly. Elucidating the molecular mechanism underlying the identity of IMA and the ACB assay hinges on understanding metal-binding properties of albumin. Albumin binds most metal ions and harbours four primary metal binding sites: site A, site B, the N-terminal site (NTS), and the free thiol at Cys34. Previous efforts to clarify the identity of IMA and the causes for its reduced cobalt-binding capacity were focused on the NTS site, but the degree of N-terminal modification could not be correlated to the presence of ischemia. More recent work suggested that Co2+ ions as used in the ACB assay bind preferentially to site B, then to site A, and finally to the NTS. This insight paved the way for a new consistent molecular basis of the ACB assay: albumin is also the main plasma carrier for free fatty acids (FFAs), and binding of a fatty acid to the high-affinity site FA2 results in conformational changes in albumin which prevent metal binding at site A and partially at site B. Thus, this review advances the hypothesis that high IMA levels in myocardial ischemia and many other conditions originate from high plasma FFA levels hampering the binding of Co2+ to sites A and/or B. This is supported by biophysical studies and the co-association of a range of pathological conditions with positive ACB assays and high plasma FFA levels.
Collapse
Affiliation(s)
| | - Kondwani G H Katundu
- School of Medicine, University of St Andrews, St Andrews, United Kingdom; College of Medicine, University of Malawi, Blantyre, Malawi
| | - Amélie I S Sobczak
- School of Medicine, University of St Andrews, St Andrews, United Kingdom
| | - Swati Arya
- School of Medicine, University of St Andrews, St Andrews, United Kingdom
| | | | - Alan J Stewart
- School of Medicine, University of St Andrews, St Andrews, United Kingdom.
| |
Collapse
|
|
42
|
Wang Y, Wei RB, Yang Y, Su TY, Huang MJ, Li P, Chen XM. Valsartan Alleviates Insulin Resistance in Skeletal Muscle of Chronic Renal Failure Rats. Med Sci Monit 2018; 24:2413-2419. [PMID: 29679000 PMCID: PMC5933205 DOI: 10.12659/msm.909910] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2018] [Accepted: 04/10/2018] [Indexed: 01/26/2023] Open
Abstract
BACKGROUND Studies on insulin resistance (IR) in chronic kidney disease (CKD) patients are rare, and its exact mechanism remains unclear. In this study, we explored the molecular mechanism of IR with chronic renal failure (CRF) and interventions to alleviate IR in patients with CRF. MATERIAL AND METHODS In vivo and in vitro models of CRF were established by 5/6 nephrectomy and urea stimulation C2C12 cells, respectively. Based on the CRF model, angiotensin II (Ang II) and valsartan groups were established to observe the effect of drug intervention on IR. Western blot assays were performed to detect the expression and phosphorylation of IRS-1 and Akt, which are 2 critical proteins in the insulin signaling pathway. RESULTS Both urea stimulation and 5/6 nephrectomy induced glucose uptake disorder in skeletal muscle cells (P<0.01). Skeletal muscle IR was aggravated in the Ang II group (P<0.05) but alleviated in the valsartan group (P<0.01). Regardless of the experimental method (in vivo or in vitro), tyrosine phosphorylation of IRS-1 and Akt were significantly lower (P<0.01) and serine phosphorylation was significantly higher (P<0.01) in the model group than in the sham/control group. Compared to the model group, additional Ang II aggravated abnormal phosphorylation (P<0.05); conversely, additional valsartan alleviated abnormal phosphorylation to some extent (P<0.05). CONCLUSIONS There is skeletal muscle insulin resistance in the presence of CRF. This phenomenon can be aggravated by Ang II and partially relieved by valsartan. One of the mechanisms of IR in CRF patients may be associated with the critical proteins in the IRS-PI3k-Akt pathway by changing their phosphorylation levels.
Collapse
Affiliation(s)
- Yang Wang
- Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, P.R. China
| | - Ri-Bao Wei
- Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, P.R. China
| | - Yue Yang
- Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, P.R. China
- Renal Division of China-Japan Friendship Hospital, Beijing, P.R. China
| | - Ting-Yu Su
- Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, P.R. China
| | - Meng-Jie Huang
- Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, P.R. China
| | - Ping Li
- Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, P.R. China
| | - Xiang-Mei Chen
- Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, P.R. China
| |
Collapse
|
|
43
|
Metabolic Syndrome and Chronic Renal Disease. DISEASES (BASEL, SWITZERLAND) 2018. [PMID: 29364162 DOI: 10.3390/diseases6010012.] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background: The influence of metabolic syndrome (MetS) on kidneys is related to many complications. We aimed to assess the association between MetS and chronic renal disease defined by a poor estimated glomerular filtration rate (eGFR) and/or the presence of microalbuminuria/macroalbuminuria. METHODS 149 patients (77 males/72 females) were enrolled in the study. Chronic renal disease was defined according to KDIGO 2012 criteria based on eGFR category and classified albuminuria. MetS was studied as a dichotomous variable (0 to 5 components) including hypertension, waist circumference, low HDL-cholesterol, high triglycerides, and high glucose. Results: The association between clustering MetS and both classified eGFR and classified albuminuria (x² = 50.3, p = 0.001 and x² = 26.9, p = 0.003 respectively) was found to be significant. The MetS presence showed an odds 5.3-fold (1.6-17.8) higher for low eGFR and 3.2-fold (1.2-8.8) higher for albuminuria in combination with the presence of diabetes mellitus, which also increased the risk for albuminuria by 3.5-fold (1.1-11.3). Albuminuria was significantly associated with high triglycerides, hypertension, high glucose (x² = 11.8, p = 0.003, x² = 11.4, p = 0.003 and x² = 9.1, p = 0.01 respectively), and it was mildly associated with a low HDL-C (x² = 5.7, p = 0.06). A significant association between classified eGFR and both high triglycerides and hypertension (x² = 9.7, p = 0.04 and x² = 16.1, p = 0.003 respectively) was found. Conclusion: The clustering of MetS was significantly associated with chronic renal disease defined by both classified eGFR and albuminuria. The definition of impaired renal function by classified albuminuria was associated with more MetS components rather than the evaluation of eGFR category. MetS may contribute to the manifestation of albuminuria in patients with diabetes mellitus.
Collapse
|
|
44
|
Raikou VD, Gavriil S. Metabolic Syndrome and Chronic Renal Disease. Diseases 2018; 6:E12. [PMID: 29364162 PMCID: PMC5871958 DOI: 10.3390/diseases6010012] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2017] [Revised: 01/20/2018] [Accepted: 01/22/2018] [Indexed: 02/07/2023] Open
Abstract
Background: The influence of metabolic syndrome (MetS) on kidneys is related to many complications. We aimed to assess the association between MetS and chronic renal disease defined by a poor estimated glomerular filtration rate (eGFR) and/or the presence of microalbuminuria/macroalbuminuria. METHODS 149 patients (77 males/72 females) were enrolled in the study. Chronic renal disease was defined according to KDIGO 2012 criteria based on eGFR category and classified albuminuria. MetS was studied as a dichotomous variable (0 to 5 components) including hypertension, waist circumference, low HDL-cholesterol, high triglycerides, and high glucose. Results: The association between clustering MetS and both classified eGFR and classified albuminuria (x² = 50.3, p = 0.001 and x² = 26.9, p = 0.003 respectively) was found to be significant. The MetS presence showed an odds 5.3-fold (1.6-17.8) higher for low eGFR and 3.2-fold (1.2-8.8) higher for albuminuria in combination with the presence of diabetes mellitus, which also increased the risk for albuminuria by 3.5-fold (1.1-11.3). Albuminuria was significantly associated with high triglycerides, hypertension, high glucose (x² = 11.8, p = 0.003, x² = 11.4, p = 0.003 and x² = 9.1, p = 0.01 respectively), and it was mildly associated with a low HDL-C (x² = 5.7, p = 0.06). A significant association between classified eGFR and both high triglycerides and hypertension (x² = 9.7, p = 0.04 and x² = 16.1, p = 0.003 respectively) was found. Conclusion: The clustering of MetS was significantly associated with chronic renal disease defined by both classified eGFR and albuminuria. The definition of impaired renal function by classified albuminuria was associated with more MetS components rather than the evaluation of eGFR category. MetS may contribute to the manifestation of albuminuria in patients with diabetes mellitus.
Collapse
Affiliation(s)
- Vaia D Raikou
- Department of Nephrology, Doctors' Hospital, 26 Kefallinias, 11257 Athens, Greece.
| | - Sotiris Gavriil
- Department of Weight-Surgery, Doctors' Hospital, 11257 Athens, Greece.
| |
Collapse
|
|
45
|
Martin B, Caron N, Jadot I, Colombaro V, Federici G, Depommier C, Declèves AÉ. Evaluation of inducible nitric oxide synthase inhibition on kidney function and structure in high-fat diet-induced kidney disease. Exp Physiol 2017; 103:125-140. [PMID: 28944982 DOI: 10.1113/ep086594] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2017] [Accepted: 08/25/2017] [Indexed: 12/15/2022]
Abstract
NEW FINDINGS What is the central question of this study? The metabolic pathways regulating the effects of obesity on the kidney remain unknown. We sought to determine whether inducible nitric oxide synthase (iNOS) is involved in the underlying mechanisms of high-fat diet-induced kidney disease using a specific iNOS inhibitor, N6-(1-iminoethyl)-l-lysine hydrochloride (L-NIL). What is the main finding and its importance? We did not demonstrate an upregulation of iNOS renal expression after high caloric intake, suggesting that iNOS might not be a crucial player in the development of obesity-induced kidney disease. Although L-NIL treatment clearly ameliorated systemic metabolic parameters, the effect on loss of renal function, impairment of tubular integrity, oxidative stress and inflammation appeared to be more moderate. Central obesity is related to caloric excess, promoting deleterious cellular responses in targeted organs. Nitric oxide (NO) has been determined as a key player in the pathogenesis of metabolic diseases. Here, we investigated the implication of inducible NO synthase (iNOS) in the development of obesity-induced kidney disease. C57Bl/6 male mice were randomized to a low-fat diet (LFD) or a high-fat diet (HFD) and treated with N6-(1-iminoethyl)-l-lysine hydrochloride (L-NIL), a specific iNOS inhibitor, for 16 weeks. Mice fed an HFD exhibited a significant increase in body weight, fasting blood glucose and plasma concentrations of non-esterified fatty acids, triglyceride and insulin. Inhibition of iNOS prevented these changes in mice fed an HFD. Interestingly, the significant increase in albuminuria and mesangial matrix expansion were not ameliorated with L-NIL, whereas a significant decrease in proteinuria, N-acetyl-β-d-glucosaminidase excretion and renal triglyceride content were found, suggesting that iNOS inhibition is more suitable for tubular function than glomerular function. The urinary concentration of hydrogen peroxide, a stable product of reactive oxygen species production, that was found to be increased in mice fed an HFD, was significantly reduced with L-NIL. Finally, despite a moderate effect of L-NIL on inflammatory processes in the kidney, we demonstrated a positive impact of this treatment on adipocyte hypertrophy and on adipose tissue inflammation. These results suggest that inhibition of iNOS leads to a moderate beneficial effect on kidney function in mice fed an HFD. Further studies are needed for better understanding of the role of iNOS in obesity-induced kidney disease.
Collapse
Affiliation(s)
- Blanche Martin
- Molecular Physiology Research Unit-URPHYM, University of Namur (UNamur), Namur, Belgium
| | - Nathalie Caron
- Molecular Physiology Research Unit-URPHYM, University of Namur (UNamur), Namur, Belgium
| | - Inès Jadot
- Molecular Physiology Research Unit-URPHYM, University of Namur (UNamur), Namur, Belgium
| | - Vanessa Colombaro
- Molecular Physiology Research Unit-URPHYM, University of Namur (UNamur), Namur, Belgium
| | - Gabrielle Federici
- Molecular Physiology Research Unit-URPHYM, University of Namur (UNamur), Namur, Belgium
| | - Clara Depommier
- Molecular Physiology Research Unit-URPHYM, University of Namur (UNamur), Namur, Belgium
| | - Anne-Émilie Declèves
- Molecular Physiology Research Unit-URPHYM, University of Namur (UNamur), Namur, Belgium.,Laboratory of Molecular Biology, University of Mons (UMONS), Mons, Belgium
| |
Collapse
|
|
46
|
Role of ESAT-6 in renal injury by regulating microRNA-155 expression via TLR4/MyD88 signaling pathway in mice with Mycobacterium tuberculosis infection. Biosci Rep 2017; 37:BSR20170021. [PMID: 28655852 PMCID: PMC5529202 DOI: 10.1042/bsr20170021] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2017] [Revised: 06/22/2017] [Accepted: 06/23/2017] [Indexed: 02/06/2023] Open
Abstract
The study aims to investigate the underlying mechanism involved in the early secretory antigenic target-6 (ESAT-6) in renal injury through regulation of the expression of miR-155 through the oll-like receptor (TLR)-4 (TLR4)/myeloid differentiation factor 88 (MyD88) signaling pathway in Mycobacterium tuberculosis (MTB)-infected mice. Sixty C57BL/6 mice with MTB-induced renal injury were randomly assigned into control, MTB, mimic, inhibitor, inhibitor + ESAT6, and inhibitor + ESAT6 + TAK242 groups. Body weight, the ratio of kidney weight to body weight (Kw/Bw), blood urea nitrogen (BUN), and serum creatinine (Scr) of mice were measured. Flow cytometry was used to detect renal activation in mice. Expressions of miR-155 and ESAT6 were detected by quantitative real-time PCR (qRT-PCR), and Western blotting was used to examine the expressions of ESAT6, TLR4, and MyD88. Expressions of tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), and interferon-γ (IFN-γ) were measured by qRT-PCR and ELISA. Compared with the control group, the BUN and Scr levels as well as the expression levels of miR-155, TLR4, MyD88, TNF-α, IL-17, and IFN-γ increased, while Kw/Bw decreased in the MTB and mimic groups. In comparison with the MTB group, the above indexes except Kw/Bw were elevated in the mimic group, but were reduced in the inhibitor group, while the Kw/Bw dropped in the mimic group but increased in the inhibitor group. Compared with the inhibitor group, the Kw/Bw decreased while the rest of the indexes increased in the inhibitor + ESAT6 group. ESAT6 may induce renal injury by promoting miR-155 expression through the TLR-4/MyD88 signaling pathway in MTB-infected mice.
Collapse
|
|
47
|
Dion F, Dumayne C, Henley N, Beauchemin S, Arias EB, Leblond FA, Lesage S, Lefrançois S, Cartee GD, Pichette V. Mechanism of insulin resistance in a rat model of kidney disease and the risk of developing type 2 diabetes. PLoS One 2017; 12:e0176650. [PMID: 28459862 PMCID: PMC5411038 DOI: 10.1371/journal.pone.0176650] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2017] [Accepted: 04/13/2017] [Indexed: 12/19/2022] Open
Abstract
Chronic kidney disease is associated with homeostatic imbalances such as insulin resistance. However, the underlying mechanisms leading to these imbalances and whether they promote the development of type 2 diabetes is unknown. The effect of chronic kidney disease on insulin resistance was studied on two different rat strains. First, in a 5/6th nephrectomised Sprague-Dawley rat model of chronic kidney disease, we observed a correlation between the severity of chronic kidney disease and hyperglycemia as evaluated by serum fructosamine levels (p<0.0001). Further, glucose tolerance tests indicated an increase of 25% in glycemia in chronic kidney disease rats (p<0.0001) as compared to controls whereas insulin levels remained unchanged. We also observed modulation of glucose transporters expression in several tissues such as the liver (decrease of ≈40%, p≤0.01) and muscles (decrease of ≈29%, p≤0.05). Despite a significant reduction of ≈37% in insulin-dependent glucose uptake in the muscles of chronic kidney disease rats (p<0.0001), the development of type 2 diabetes was never observed. Second, in a rat model of metabolic syndrome (Zucker Leprfa/fa), chronic kidney disease caused a 50% increased fasting hyperglycemia (p<0.0001) and an exacerbated glycemic response (p<0.0001) during glucose challenge. Similar modulations of glucose transporters expression and glucose uptake were observed in the two models. However, 30% (p<0.05) of chronic kidney disease Zucker rats developed characteristics of type 2 diabetes. Thus, our results suggest that downregulation of GLUT4 in skeletal muscle may be associated with insulin resistance in chronic kidney disease and could lead to type 2 diabetes in predisposed animals.
Collapse
Affiliation(s)
- François Dion
- Centre de recherche de l’Hôpital Maisonneuve-Rosemont, Faculté de Médecine, Centre affilié à l’Université de Montréal, Montréal, Québec, Canada
- Département de pharmacologie, Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada
- * E-mail: (VP); (FD)
| | - Christopher Dumayne
- Centre de recherche de l’Hôpital Maisonneuve-Rosemont, Faculté de Médecine, Centre affilié à l’Université de Montréal, Montréal, Québec, Canada
- Département de pharmacologie, Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada
| | - Nathalie Henley
- Centre de recherche de l’Hôpital Maisonneuve-Rosemont, Faculté de Médecine, Centre affilié à l’Université de Montréal, Montréal, Québec, Canada
| | - Stéphanie Beauchemin
- Centre de recherche de l’Hôpital Maisonneuve-Rosemont, Faculté de Médecine, Centre affilié à l’Université de Montréal, Montréal, Québec, Canada
| | - Edward B. Arias
- School of Kinesiology, University of Michigan, Ann Arbor, Michigan, United States of America
| | - François A. Leblond
- Centre de recherche de l’Hôpital Maisonneuve-Rosemont, Faculté de Médecine, Centre affilié à l’Université de Montréal, Montréal, Québec, Canada
| | - Sylvie Lesage
- Centre de recherche de l’Hôpital Maisonneuve-Rosemont, Faculté de Médecine, Centre affilié à l’Université de Montréal, Montréal, Québec, Canada
- Département de microbiologie, infectiologie et immunologie, Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada
| | - Stéphane Lefrançois
- Centre INRS-Institut Armand-Frappier, Institut National de la Recherche Scientifique, Laval, Québec, Canada
- Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada
| | - Gregory D. Cartee
- School of Kinesiology, University of Michigan, Ann Arbor, Michigan, United States of America
| | - Vincent Pichette
- Centre de recherche de l’Hôpital Maisonneuve-Rosemont, Faculté de Médecine, Centre affilié à l’Université de Montréal, Montréal, Québec, Canada
- Département de pharmacologie, Faculté de Médecine, Université de Montréal, Montréal, Québec, Canada
- * E-mail: (VP); (FD)
| |
Collapse
|
|
48
|
Sumi T, Oguri M, Fujimaki T, Horibe H, Kato K, Matsui K, Takeuchi I, Murohara T, Yamada Y. Association of renal function with clinical parameters and conditions in a longitudinal population-based epidemiological study. Biomed Rep 2017; 6:242-250. [PMID: 28357080 PMCID: PMC5351156 DOI: 10.3892/br.2016.831] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2016] [Accepted: 11/28/2016] [Indexed: 12/29/2022] Open
Abstract
The aim of the present study was to examine the association of renal function with clinical parameters and conditions in the general population. Study subjects comprised 6,027 community-dwelling individuals who were recruited to the Inabe Health and Longevity Study: A longitudinal genetic epidemiological study of atherosclerotic, cardiovascular and metabolic diseases. The cutoff value, which was used to divide the subjects into those with normal and those with low estimated glomerular filtration rate (eGFR), was 60 ml/min/1.73 m2. Bonferroni's correction was applied to establish the statistical significance of the association. Longitudinal analysis using the generalized linear mixed-effect model, following adjustments for age and gender, revealed that the eGFR was significantly associated (P<0.0017) with serum levels of triglycerides, low-density lipoprotein cholesterol, uric acid, blood glycosylated hemoglobin content, fasting plasma glucose and body mass index. These parameters decreased curvilinearly with increases in eGFR. Furthermore, eGFR correlated positively with serum levels of high-density lipoprotein (HDL) cholesterol. Longitudinal analysis using the generalized estimating equation following adjustment for age and gender indicated a significant association (P<0.0024) between eGFR and prevalence of hypertension, type 2 diabetes mellitus, hypo-HDL cholesterolemia, hyperuricemia and obesity. Thus, low eGFR results in detrimental effects on various clinical parameters and conditions, resulting in increased risk of hypertension, dyslipidemia, type 2 diabetes mellitus, hyperuricemia and obesity.
Collapse
Affiliation(s)
- Takuya Sumi
- Department of Cardiology, Graduate School of Medicine, Nagoya University, Nagoya, Aichi 466-8560, Japan
| | - Mitsutoshi Oguri
- Department of Cardiology, Kasugai Municipal Hospital, Kasugai, Aichi 486-8510, Japan
| | - Tetsuo Fujimaki
- Department of Cardiovascular Medicine, Inabe General Hospital, Inabe, Mie 511-0428, Japan
| | - Hideki Horibe
- Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi, Gifu 507-0042, Japan
| | - Kimihiko Kato
- Department of Internal Medicine, Meitoh Hospital, Nagoya, Aichi 465-0025, Japan
| | - Kota Matsui
- Department of Biostatistics, Graduate School of Medicine, Nagoya University, Nagoya, Aichi 464-8601, Japan
| | - Ichiro Takeuchi
- Department of Computer Science, Graduate School of Engineering, Nagoya Institute of Technology, Nagoya, Aichi 466-8555, Japan
- Core Research for Evolutionary Science and Technology (CREST), Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan
| | - Toyoaki Murohara
- Department of Cardiology, Graduate School of Medicine, Nagoya University, Nagoya, Aichi 466-8560, Japan
| | - Yoshiji Yamada
- Core Research for Evolutionary Science and Technology (CREST), Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan
- Department of Human Functional Genomics, Life Science Research Center, Mie University, Tsu, Mie 514-8507, Japan
| |
Collapse
|
|
49
|
Huh JH, Yadav D, Kim JS, Son JW, Choi E, Kim SH, Shin C, Sung KC, Kim JY. An association of metabolic syndrome and chronic kidney disease from a 10-year prospective cohort study. Metabolism 2017; 67:54-61. [PMID: 28081778 DOI: 10.1016/j.metabol.2016.11.003] [Citation(s) in RCA: 68] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2016] [Revised: 10/03/2016] [Accepted: 11/02/2016] [Indexed: 11/22/2022]
Abstract
OBJECTIVE Although metabolic abnormalities have been considered important risk factors of chronic kidney disease (CKD), the impact of metabolic syndrome (MS) and insulin resistance on renal function deterioration is poorly understood. We investigated the association between MS and incident CKD/rapid decline of estimated glomerular filtration rate (eGFR) in a 10-year population-based longitudinal study. MATERIAL AND METHODS Among 10,030 subjects, 6065 without history of CKD or cardiovascular disease at baseline were analyzed using data generated from the Ansan-Ansung cohort of the Korean Genome Epidemiology Study. Participants were categorized into two groups based on the presence of MS at baseline. Incident CKD was defined as eGFR <60ml/min per 1.73m2, and rapid decline of eGFR was defined as >3ml/min per 1.73m2/yr over 10years. RESULTS During the 10-year follow-up period, CKD developed in 893 subjects (14.7%). Compared to subjects without MS, the odds ratio (OR; 95% confidence interval, CI) of incident CKD in those with MS was 1.38 (1.16-1.64) after controlling for confounding factors. The risk of rapid decline of eGFR was also higher in subjects with MS than those without MS (OR: 1.20, 95% CI: 1.04-1.39). In addition, we found that higher levels of homeostatic model assessment of insulin resistance (HOMA-IR) were associated with incident CKD and rapid decline of eGFR independently of traditional CKD risk factors (OR: 1.24, 95% CI: 1.04-1.47). CONCLUSION Both MS and insulin resistance were independent risk factors of incident CKD and rapid decline of eGFR in healthy Korean population.
Collapse
Affiliation(s)
- Ji Hye Huh
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University, Wonju College of Medicine, Wonju, Republic of Korea
| | - Dhananjay Yadav
- Department of Preventive Medicine, Yonsei University, Wonju College of Medicine, Wonju, Republic of Korea
| | - Jae Seok Kim
- Division of Nephrology, Department of Internal Medicine, Yonsei University, Wonju College of Medicine, Wonju, Republic of Korea
| | - Jung-Woo Son
- Division of Cardiology, Department of Internal Medicine, Yonsei University, Wonju College of Medicine, Wonju, Republic of Korea
| | - Eunhee Choi
- Institute of Life Style Medicine, Yonsei University, Wonju College of Medicine, Wonju, Republic of Korea,.
| | - Seong Hwan Kim
- Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Gyeonggi, South Korea
| | - Chol Shin
- Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Gyeonggi, South Korea
| | - Ki-Chul Sung
- Division of Cardiology, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jang Young Kim
- Division of Cardiology, Department of Internal Medicine, Yonsei University, Wonju College of Medicine, Wonju, Republic of Korea,.
| |
Collapse
|
|
50
|
Leyco T, Ryanputra D, Peh R, Ponce A, Khoo CM. Glycaemic Control after Metformin Discontinuation in Diabetic Patients with a Declining Renal Function. J Diabetes Res 2017; 2017:2769819. [PMID: 29230420 PMCID: PMC5694578 DOI: 10.1155/2017/2769819] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2017] [Revised: 09/18/2017] [Accepted: 10/09/2017] [Indexed: 12/29/2022] Open
Abstract
Metformin is contraindicated in diabetic patients with declining renal function. This study examined the glycaemic control in diabetic patients with chronic kidney disease when metformin was discontinued. This was a retrospective study. We screened 2032 diabetic patients who attended the Diabetes Clinic at a tertiary hospital between 1 September 2014 and 30 September 2015. We analyzed the data on 69 patients whom metformin was discontinued due to declining renal function and had a complete 6-month follow-up. There was no significant difference in the HbA1c and body weight at 6-month follow-up compared to baseline after metformin discontinuation. The eGFR was significantly lower at 6-month follow-up compared to baseline. Upon metformin discontinuation, the majority of patients had their diabetes medication uptitrated (in particular insulin or sulphonylurea). Patients with an improved glycaemia at 6-month follow-up had further declined in eGFR compared to patients with worsened glycaemia. 17% of the study patients experienced hypoglycaemia. Upon metformin discontinuation, glycaemic control could be optimised with uptitration but should be balanced against the risk of hypoglycaemia. Further improvement in the glycaemic control might indicate further deterioration in the renal function.
Collapse
Affiliation(s)
- Theresa Leyco
- Department of Medicine, National University Hospital, Singapore
| | - Davin Ryanputra
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Ray Peh
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Alexphil Ponce
- Higher Education Department, Centre for International Education, Cebu, Philippines
| | - Chin Meng Khoo
- Department of Medicine, National University Hospital, Singapore
| |
Collapse
|