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Su Z, Luo Z, Wu D, Liu W, Li W, Yin Z, Xue R, Wu L, Cheng Y, Wan Q. Causality between diabetes and membranous nephropathy: Mendelian randomization. Clin Exp Nephrol 2025; 29:227-235. [PMID: 39375304 DOI: 10.1007/s10157-024-02566-8] [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: 07/11/2024] [Accepted: 09/11/2024] [Indexed: 10/09/2024]
Abstract
BACKGROUND Membranous nephropathy (MN) has not yet been fully elucidated regarding its relationship with Type I and II Diabetes. This study aims to evaluate the causal effect of multiple types of diabetes and MN by summarizing the evidence from the Mendelian randomization (MR) study. METHODS The statistical data for MN was obtained from a GWAS study encompassing 7979 individuals. Regarding diabetes, fasting glucose, fasting insulin, and HbA1C data, we accessed the UK-Biobank, within family GWAS consortium, MAGIC, FinnGen database, MRC-IEU, and Neale Lab, which provided sample sizes ranging from 17,724 to 298,957. As a primary method in this MR analysis, we employed the Inverse Variance Weighted (IVW), Weighted Median, Weighted mode, MR-Egger, Mendelian randomization pleiotropy residual sum, and outlier (MR-PRESSO) and Leave-one-out sensitivity test. Reverse MR analysis was utilized to investigate whether MN affects Diabetes. Meta-analysis was applied to combine study-specific estimates. RESULTS It has been determined that type 2 diabetes, gestational diabetes, type 1 diabetes with or without complications, maternal diabetes, and insulin use pose a risk to MN. Based on the genetic prediction, fasting insulin, fasting blood glucose, and HbA1c levels were not associated with the risk of MN. No heterogeneity, horizontal pleiotropy, or reverse causal relationships were found. The meta-analysis results further validated the accuracy. CONCLUSIONS The MR analysis revealed the association between MN and various subtypes of diabetes. This study has provided a deeper understanding of the pathogenic mechanisms connecting MN and diabetes.
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Affiliation(s)
- Zhihang Su
- Department of Nephrology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, 3002 Sungang West Road, Shenzhen, 518000, China
| | - Ziqi Luo
- Department of Endocrinology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China
| | - Di Wu
- Department of Nephrology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, 3002 Sungang West Road, Shenzhen, 518000, China
| | - Wen Liu
- Department of Nephrology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, 3002 Sungang West Road, Shenzhen, 518000, China
| | - Wangyang Li
- Department of Nephrology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, 3002 Sungang West Road, Shenzhen, 518000, China
| | - Zheng Yin
- Department of Nephrology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, 3002 Sungang West Road, Shenzhen, 518000, China
| | - Rui Xue
- Department of Nephrology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, 3002 Sungang West Road, Shenzhen, 518000, China
| | - Liling Wu
- Department of Nephrology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, 3002 Sungang West Road, Shenzhen, 518000, China
| | - Yuan Cheng
- Department of Nephrology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, 3002 Sungang West Road, Shenzhen, 518000, China
| | - Qijun Wan
- Department of Nephrology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, 3002 Sungang West Road, Shenzhen, 518000, China.
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Cao BN, Zhang CY, Wang Z, Wang YX. Causal relationship between 412 gut microbiota, 1,400 blood metabolites, and diabetic nephropathy: a randomized Mendelian study. Front Endocrinol (Lausanne) 2025; 15:1450428. [PMID: 39897958 PMCID: PMC11782027 DOI: 10.3389/fendo.2024.1450428] [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: 06/17/2024] [Accepted: 12/16/2024] [Indexed: 02/04/2025] Open
Abstract
Objective The aim of this study was to investigate the causal relationship between microbiota, diabetic nephropathy, and blood metabolites through a randomized Mendelian study. Methods In this study, we used 412 microbiota as exposures, 1,400 blood metabolites as intermediaries, and diabetic nephropathy as the outcome. We conducted a two-way Mendelian randomization (MR) analysis to explore the causal relationship between microbiota and diabetic nephropathy, followed by mediation analyses and two-step MR to identify potential blood metabolites. Results There is a causal relationship between microbiota and diabetic nephropathy. Specific bacteria and metabolites, such as Escherichia coli str. K-12 substr. MG1655, Listeria monocytogenes 10403S, g_Adlercreutzia, g_Haemophilus, g_Bacteroides, and Escherichia coli CFT073, and metabolites like pyrraline, glycocholenate sulfate, alpha-ketoglutarate, tetradecadienoate (14:2), Cys-gly oxidized, methylsuccinate, and various others, were identified. Escherichia coli str. K-12 substr. MG1655 is positively related to alpha-ketoglutarate levels, while alpha-ketoglutarate levels and Sphingomyelin (d18:1/18:1, d18:2/18:0) are negatively related. The bacterial microbiota involved in fatty acid oxidation is associated with diabetic kidney disease (DKD) progression, positively correlated with glycocholenate sulfate levels, and negatively correlated with the phosphate linoleyl-tetraenyl-glycerol (18:2 to 20:4) ratio. Additionally, Listeria monocytogenes 10403S is positively correlated with N-acetyl-isoputreanine and negatively correlated with X-12462. Anaerobic fermentation-related bacteria were positively related to N-acetylcarnitine and 5-acetylamino-6-formyluracil and negatively correlated with 5-acetamino-6-amino-3-methyluracil (X-24243). Escherichia coli CFT073 was positively associated with X-16580. Interactions between Bacillus species and metabolites such as d18:1/18:1, d18:2/18:0, 2-aminophenol sulfate, and cholate were negative when compared to tetradecadienoate (14:2). g_Adlercreutzia is positively correlated with N-delta-acetylornithine, methylsuccinate, and N-acetyl-isoputreanine but negatively correlated with N-acetylglucosamine and N-acetylgalactosamine. g_Haemophilus was positively associated with arachidoylcarnitine but negatively correlated with X-24531. The results were heterogeneous and multi-efficacious. Conclusions For the first time, MR analysis provides supportive evidence for a bidirectional causal relationship between microbiota and diabetic nephropathy and identifies specific genes associated with the disease. The results suggest that probiotic therapy may play a significant role in preventing diabetic nephropathy and improving the quality of life and survival rates of affected patients. Furthermore, this study provides additional evidence of a causal relationship between specific microbiota, diabetic nephropathy, and blood metabolites.
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Affiliation(s)
- Bo-Ning Cao
- Endocrinology Department, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Cai-Yan Zhang
- General Surgery Department, The General Hospital of The People's Liberation Army, Beijing, China
| | - Zhen Wang
- Endocrinology Department, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Yao-Xian Wang
- Endocrinology Department, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Administrative Department, Renal Research Institution of Beijing University of Chinese Medicine, Beijing, China
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El aameri M, Jaghror I, Meskini N, Benchehida H, Eladha I, Chakit M, Norelhoda A, Taib B, Taboz Y. Chronic complications of type 2 diabetes and associated factors: a cross-sectional study at the Moulay Hassan Hospital in Kenitra, Morocco. Pan Afr Med J 2024; 49:84. [PMID: 40027088 PMCID: PMC11871885 DOI: 10.11604/pamj.2024.49.84.42930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2024] [Accepted: 11/06/2024] [Indexed: 03/05/2025] Open
Abstract
Introduction all around the world, type 2 diabetes is considered a metabolic disease that generates complications that can be very serious, even fatal, over time, especially if not properly managed. Clinical and biological parameters in blood glucose levels will be assessed in this study (N=300 patients). We assess the prevalence of complications caused by diabetes including diabetic retinopathy, nephropathy, neuropathy, and cardiovascular diseases. Type 2 diabetes is an incurred disease, but it can be managed. Self-therapeutic education is therefore imperative and highly recommended. Methods this study was carried out at the Moulay Hassan Hospital in Kenitra (Morocco) using a self-administered questionnaire targeting chronic complications caused by diabetes. Descriptive statistical analysis was followed to determine frequencies and percentages for complications and we carried out univariable and multivariable regression analysis to determine factors associated with complications. Results the study highlights clinical and bioclinical features. Mean age of patients (58.51±13.11 year with standard deviation: 13,113), hypertension (45.7%), glycemia (1.85±0.64 g/l), HbA1c (8.09±1.7%), BMI (26.44±3.4 kg/m2) and chronic complications (41.7%) including retinopathy (16%), nephropathy (4%), neuropathy (3.3%), cardiovascular diseases (16.7%) and amnesia (2%). There was mainly a statistical difference between complications and HTA: (AOR=2.43 (1.52-3.89) (CI=95%) (p=0.000), chronic complications and smoking: (AOR=0.16) (0.04-0.61) (CI=95%) (p=0.007), complications and physical activity: (AOR=3,34) (1.34-7.24) (CI=95%) (p=0.014) and complications and lipid profile: (AOR=4.95) (2.79-8.77) (CI=95%) (p=0.001). Conclusion therapeutic education of type 2 patients with diabetes remains highly recommended, as it improves compliance with non-pharmacological treatment, especially hygienic-dietary measures, and physical activity, and limits the early onset of complications associated with diabetes.
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Affiliation(s)
- Mohammed El aameri
- Faculty of Sciences, Natural Resources and Sustainable Development Laboratory, Ibn Tofail University, Kenitra, Morocco
| | - Imane Jaghror
- Biology and Health Laboratory, Ibn Tofail University, Sciences Faculty, Kenitra, Morocco
| | - Nadia Meskini
- Biology and Health Laboratory, Ibn Tofail University, Sciences Faculty, Kenitra, Morocco
| | - Hiba Benchehida
- Faculty of Sciences, Natural Resources and Sustainable Development Laboratory, Ibn Tofail University, Kenitra, Morocco
| | - Ibtissam Eladha
- Faculty of Sciences, Natural Resources and Sustainable Development Laboratory, Ibn Tofail University, Kenitra, Morocco
| | - Miloud Chakit
- Biology and Health Laboratory, Ibn Tofail University, Sciences Faculty, Kenitra, Morocco
| | - Aroui Norelhoda
- Department of Biology and Health, Cognitive-Behavioral Neurosciences and Applied Nutrition Unit, Kenitra, Morocco
| | - Bouchra Taib
- Faculty of Sciences, Natural Resources and Sustainable Development Laboratory, Ibn Tofail University, Kenitra, Morocco
| | - Youness Taboz
- Department of Biology, Faculty of Science, Ibn Tofail University, Kenitra, Morocco
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Kovacevic S, Zdravkovic V, Blagojevic J, Djordjevic S, Miolski J, Gasic V, Jelovac M, Ugrin M, Pavlovic S, Jesic M. Association of variants in AGTR1, ACE, MTHFR genes with microalbuminuria and risk factors for the onset of diabetic nephropathy in adolescents with type 1 diabetes in the population of Serbia. PLoS One 2024; 19:e0312489. [PMID: 39446857 PMCID: PMC11500908 DOI: 10.1371/journal.pone.0312489] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Accepted: 10/07/2024] [Indexed: 10/26/2024] Open
Abstract
INTRODUCTION Genetic studies may provide valuable information about patients who are at high risk of developing diabetes nephropathy. Before the appearance of albuminuria, there are genetic mutations that can predispose the development of kidney disease. MATERIAL AND METHODS The study included 130 adolescents with type 1 diabetes. Patients were divided into two groups according to the presence of microalbuminuria. This study was performed to examine clinical and laboratory differences between adolescents with type 1 diabetes with and without microalbuminuria and the distribution of the ACE, AGTR1, and MTHFR gene polymorphisms. RESULTS The mean microalbuminuria in the first group 6.41±7.35 significantly differs from the second group 0.82±0.48 (p<0.001). HbA1c, 24-hour proteinuria, and day-time systolic blood pressure were significantly higher in the MA group (p<0.05). Smaller systolic blood pressure percentage nocturnal decline was observed in the microalbuminuric group (p 0.030). The frequencies of the ACE DD, ID, and II genotypes were 12.5%, 50.0%, and 37.5%, respectively, among T1D patients with MA, and 19.3%, 56.1%, 24.6%, in the control group without MA (P = .510). The frequencies of the AGTR1 AA, AC, and CC genotypes were 62.5%, 25.0%, and 12.5% among TID patients with MA, and 49.1%, 43.9%, 8.0%, in the group without MA (p 0.326). The frequencies of the MTHFR CC, CT and TT genotypes were 37.5%, 50.0%, 12.5% among TID patients with MA, and 37.7%, 45.6%, 16.7% in the group without MA (p 0.901). CONCLUSION Our data suggest that common variants in the AGTR1, ACE, and MTHFR genes are not strongly associated with diabetic nephropathy in our patients with type 1 diabetes.
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Affiliation(s)
- Smiljka Kovacevic
- Endocrinology Department, University Children’s Hospital, Belgrade, Serbia
| | - Vera Zdravkovic
- Endocrinology Department, University Children’s Hospital, Belgrade, Serbia
- Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Jelena Blagojevic
- Endocrinology Department, University Children’s Hospital, Belgrade, Serbia
| | - Stefan Djordjevic
- Faculty of Medicine, University of Belgrade, Belgrade, Serbia
- Rheumatology Department, University Children’s Hospital, Belgrade, Serbia
| | - Jelena Miolski
- Department of Pediatrics, General Hospital Stefan Visoki, Smederevska Palanka, Serbia
| | - Vladimir Gasic
- Laboratory for Molecular Biomedicine, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia
| | - Marina Jelovac
- Laboratory for Molecular Biomedicine, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia
| | - Milena Ugrin
- Laboratory for Molecular Biomedicine, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia
| | - Sonja Pavlovic
- Laboratory for Molecular Biomedicine, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia
| | - Maja Jesic
- Endocrinology Department, University Children’s Hospital, Belgrade, Serbia
- Faculty of Medicine, University of Belgrade, Belgrade, Serbia
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Sinha SK, Carpio MB, Nicholas SB. Fiery Connections: Macrophage-Mediated Inflammation, the Journey from Obesity to Type 2 Diabetes Mellitus and Diabetic Kidney Disease. Biomedicines 2024; 12:2209. [PMID: 39457523 PMCID: PMC11503991 DOI: 10.3390/biomedicines12102209] [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: 07/15/2024] [Revised: 09/12/2024] [Accepted: 09/23/2024] [Indexed: 10/28/2024] Open
Abstract
The high prevalence of diabetes mellitus (DM) poses a significant public health challenge, with diabetic kidney disease (DKD) as one of its most serious consequences. It has become increasingly clear that type 2 DM (T2D) and the complications of DKD are not purely metabolic disorders. This review outlines emerging evidence related to the step-by-step contribution of macrophages to the development and progression of DKD in individuals who specifically develop T2D as a result of obesity. The macrophage is a prominent inflammatory cell that contributes to obesity, where adipocyte hypertrophy leads to macrophage recruitment and eventually to the expansion of adipose tissue. The recruited macrophages secrete proinflammatory cytokines, which cause systemic inflammation, glucose dysregulation, and insulin sensitivity, ultimately contributing to the development of T2D. Under such pathological changes, the kidney is susceptible to elevated glucose and thereby activates signaling pathways that ultimately drive monocyte recruitment. In particular, the early recruitment of proinflammatory macrophages in the diabetic kidney produces inflammatory cytokines/chemokines that contribute to inflammation and tissue damage associated with DKD pathology. Macrophage activation and recruitment are crucial inciting factors that also persist as DKD progresses. Thus, targeting macrophage activation and function could be a promising therapeutic approach, potentially offering significant benefits for managing DKD at all stages of progression.
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Affiliation(s)
- Satyesh K. Sinha
- Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA;
- Department of Internal Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USA
| | - Maria Beatriz Carpio
- Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA;
| | - Susanne B. Nicholas
- Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA;
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Guse B, Langenstein J, Bauer N, Hazuchova K. Signalment and laboratory findings in cats with diabetes mellitus in Germany: a retrospective review of laboratory submissions of 129,505 cats. J Feline Med Surg 2024; 26:1098612X241262669. [PMID: 39286966 PMCID: PMC11418620 DOI: 10.1177/1098612x241262669] [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] [Accepted: 05/29/2024] [Indexed: 09/19/2024]
Abstract
OBJECTIVES The aims of this study were to compare signalment and laboratory parameters between diabetic (D) and non-diabetic (ND) cats and poorly-controlled diabetic (PD) and well-controlled diabetic (WD) cats in Germany. METHODS Laboratory data from Antech Lab Germany between 2015 and 2018 were retrospectively analysed. Age, sex, red blood cell count (RBC), creatinine (CREA), alkaline phosphatase (AP), alanine aminotransferase (ALT), bilirubin (BILI), cholesterol (CHOL), triglycerides (TRI), glucose (GLU) and total thyroxine (TT4) were compared between D (fructosamine ⩾340 µmol/l) and ND cats, and PD (fructosamine >500 µmol/l) and WD (fructosamine 340-500 µmol/l) cats. The proportion of cats with anaemia (RBC ⩽4.21 ×1012/l), CREA >250 µmol/l, ALT >455 U/l, AP >315 U/l, BILI ⩾35 µmol/l and TT4 > reference interval (RI) was compared between PD and WD cats. Data are presented as median and interquartile range (IQR) and analysed using non-parametric tests. Significance was P<0.05, and effect size was assessed by Cramér V or r. RESULTS In total, 129,505 cats were included (D: n = 9334 [prevalence 7.2%], WD: n = 5670/9334 [60.7%]). The median age of D and ND cats was 12 years (IQR D 9-14; ND 9-15); there was no difference in sex. A significant difference was found between groups (D vs ND; PD vs WD) for all parameters studied. Considering the effect sizes and medians outside the RI, the only relevant difference was higher CHOL, TRI, AP and GLU in PD compared with WD (CHOL: PD 7.46 [5.85-9.32] vs WD 5.44 [4.32-6.97] mmol/l, P<0.001, r = 0.39; TRI: PD 1.44 [0.84-3.66] vs WD 0.78 [0.5-1.35] mmol/l, P <0.001, r = 0.35; AP: PD 66 [47-92] vs WD 35 [23-59] U/l, P <0.001, r = 0.39; GLU: PD 23.7 [20.15-27.3] vs WD 6.89 [5-11.31] mmol/l, P <0.001, r = 0.69). CONCLUSIONS AND RELEVANCE Laboratory changes in diabetic cats were mild and mainly associated with lipid derangements.
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Affiliation(s)
- Bente Guse
- Clinic for Small Animals (Internal Medicine, Clinical Pathology and Clinical Pathophysiology), Justus-Liebig-University Giessen, Germany
| | | | - Natali Bauer
- Clinic for Small Animals (Internal Medicine, Clinical Pathology and Clinical Pathophysiology), Justus-Liebig-University Giessen, Germany
| | - Katarina Hazuchova
- Clinic for Small Animals (Internal Medicine, Clinical Pathology and Clinical Pathophysiology), Justus-Liebig-University Giessen, Germany
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Ruggiero N, Soliman MAR, Kuo CC, Aguirre AO, Quiceno E, Saleh J, Yeung K, Khan A, Hess RM, Lim J, Smolar DE, Pollina J, Mullin JP. The Effect of Diabetes on Complications after Spinal Fusion: A Systematic Review and Meta-Analysis. World Neurosurg 2024; 185:e976-e994. [PMID: 38460815 DOI: 10.1016/j.wneu.2024.03.008] [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: 02/24/2024] [Accepted: 03/03/2024] [Indexed: 03/11/2024]
Abstract
OBJECTIVE Spinal fusion procedures are used to treat a wide variety of spinal pathologies. Diabetes mellitus (DM) has been shown to be a significant risk factor for several complications following these procedures in previous studies. To the authors' knowledge, this is the first systematic review and meta-analysis elucidating the relationship between DM and complications occurring after spinal fusion procedures. METHODS Systematic literature searches of PubMed and EMBASE were performed from their inception to October 1, 2022, to identify studies that directly compared postfusion complications in patients with and without DM. Studies met the prespecified inclusion criteria if they reported the following data for patients with and without DM: (1) demographics; (2) postspinal fusion complication rates; and (3) postoperative clinical outcomes. The included studies were then pooled and analyzed. RESULTS Twenty-eight studies, with a cumulative total of 18,853 patients (2695 diabetic patients), were identified that met the inclusion criteria. Analysis showed that diabetic patients had significantly higher rates of total number of postoperative complications (odds ratio [OR] = 1.33; 95% confidence interval [CI] = 1.12-1.58; P = 0.001), postoperative pulmonary complications (OR=2.01; 95%CI=1.31-3.08; P = 0.001), postoperative renal complications (OR=2.20; 95%CI=1.27-3.80; P = 0.005), surgical site infection (OR=2.65; 95%CI=2.19-3.20; P < 0.001), and prolonged hospital stay (OR=1.67; 95%CI=1.47-1.90; P < 0.001). CONCLUSIONS Patients with DM had a significantly higher risk of developing complications after spinal fusion, particularly pulmonary and renal complications, in addition to surgical site infections and had a longer length of stay. These findings are important for informed discussions of surgical risks with patients and families before surgery.
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Affiliation(s)
- Nicco Ruggiero
- Jacobs School of Medicine and Biomedical Sciences at University at Buffalo, Buffalo, New York, USA
| | - Mohamed A R Soliman
- Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences at University at Buffalo, Buffalo, New York, USA; Department of Neurosurgery, Buffalo General Medical Center, Kaleida Health, Buffalo, New York, USA; Department of Neurosurgery, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Cathleen C Kuo
- Jacobs School of Medicine and Biomedical Sciences at University at Buffalo, Buffalo, New York, USA
| | - Alexander O Aguirre
- Jacobs School of Medicine and Biomedical Sciences at University at Buffalo, Buffalo, New York, USA
| | - Esteban Quiceno
- Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences at University at Buffalo, Buffalo, New York, USA; Department of Neurosurgery, Buffalo General Medical Center, Kaleida Health, Buffalo, New York, USA
| | - Julian Saleh
- Jacobs School of Medicine and Biomedical Sciences at University at Buffalo, Buffalo, New York, USA
| | | | - Asham Khan
- Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences at University at Buffalo, Buffalo, New York, USA; Department of Neurosurgery, Buffalo General Medical Center, Kaleida Health, Buffalo, New York, USA
| | - Ryan M Hess
- Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences at University at Buffalo, Buffalo, New York, USA; Department of Neurosurgery, Buffalo General Medical Center, Kaleida Health, Buffalo, New York, USA
| | - Jaims Lim
- Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences at University at Buffalo, Buffalo, New York, USA; Department of Neurosurgery, Buffalo General Medical Center, Kaleida Health, Buffalo, New York, USA
| | - David E Smolar
- Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences at University at Buffalo, Buffalo, New York, USA; Department of Neurosurgery, Buffalo General Medical Center, Kaleida Health, Buffalo, New York, USA
| | - John Pollina
- Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences at University at Buffalo, Buffalo, New York, USA; Department of Neurosurgery, Buffalo General Medical Center, Kaleida Health, Buffalo, New York, USA
| | - Jeffrey P Mullin
- Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences at University at Buffalo, Buffalo, New York, USA; Department of Neurosurgery, Buffalo General Medical Center, Kaleida Health, Buffalo, New York, USA.
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Yan S, Wang H, Feng B, Ye L, Chen A. Causal relationship between gut microbiota and diabetic nephropathy: a two-sample Mendelian randomization study. Front Immunol 2024; 15:1332757. [PMID: 38533501 PMCID: PMC10964483 DOI: 10.3389/fimmu.2024.1332757] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Accepted: 02/26/2024] [Indexed: 03/28/2024] Open
Abstract
Objective Emerging evidence has provided compelling evidence linking gut microbiota (GM) and diabetic nephropathy (DN) via the "gut-kidney" axis. But the causal relationship between them hasn't been clarified yet. We perform a Two-Sample Mendelian randomization (MR) analysis to reveal the causal connection with GM and the development of DN, type 1 diabetes nephropathy (T1DN), type 2 diabetes nephropathy (T2DN), type 1 diabetes mellitus (T1DM), and type 2 diabetes mellitus (T2DM). Methods We used summary data from MiBioGen on 211 GM taxa in 18340 participants. Generalized MR analysis methods were conducted to estimate their causality on risk of DN, T1DN, T2DN, T1DM and T2DM from FinnGen. To ensure the reliability of the findings, a comprehensive set of sensitivity analyses were conducted to confirm the resilience and consistency of the results. Results It was showed that Class Verrucomicrobiae [odds ratio (OR) =1.5651, 95%CI:1.1810-2.0742,PFDR=0.0018], Order Verrucomicrobiales (OR=1.5651, 95%CI: 1.1810-2.0742, PFDR=0.0018) and Family Verrucomicrobiaceae (OR=1.3956, 95%CI:1.0336-1.8844, PFDR=0.0296) had significant risk of DN. Our analysis found significant associations between GM and T2DN, including Class Verrucomimicrobiae (OR=1.8227, 95% CI: 1.2414-2.6763, PFDR=0.0139), Order Verrucomimicrobiae (OR=1.5651, 95% CI: 1.8227-2.6764, PFDR=0.0024), Rhodospirillales (OR=1.8226, 95% CI: 1.2412-2.6763, PFDR=0.0026), and Family Verrucomicroniaceae (OR=1.8226, 95% CI: 1.2412-2.6763, PFDR=0.0083). The Eubacteriumprotogenes (OR=0.4076, 95% CI: 0.2415-0.6882, PFDR=0.0021) exhibited a protection against T1DN. Sensitivity analyses confirmed that there was no significant heterogeneity and pleiotropy. Conclusions At the gene prediction level, we identified the specific GM that is causally linked to DN in both T1DM and T2DM patients. Moreover, we identified distinct microbial changes in T1DN that differed from those seen in T2DN, offering valuable insights into GM signatures associated with subtype of nephropathy.
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Affiliation(s)
- Shuxiang Yan
- Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, Institute of Nephrology, The Second Xiangya Hospital at Central South University, Changsha, China
| | - Hua Wang
- Department of Orthopaedics, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
- Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Baiyu Feng
- Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, Institute of Nephrology, The Second Xiangya Hospital at Central South University, Changsha, China
| | - Lin Ye
- Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, Institute of Nephrology, The Second Xiangya Hospital at Central South University, Changsha, China
| | - Anqun Chen
- Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, Institute of Nephrology, The Second Xiangya Hospital at Central South University, Changsha, China
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Vienken J, Ronco C. Quidquid Agis, Prudenter Agas etRespice Finem!* A Tribute to Eberhard Ritz (1938-2023). Blood Purif 2024; 53:418-421. [PMID: 38437800 DOI: 10.1159/000536558] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Accepted: 01/26/2024] [Indexed: 03/06/2024]
Affiliation(s)
| | - Claudio Ronco
- Department of Nephrology, Dialysis and Kidney Transplantation, San Bortolo Hospital, Vicenza, Italy
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10
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Varney MJ, Benovic JL. The Role of G Protein-Coupled Receptors and Receptor Kinases in Pancreatic β-Cell Function and Diabetes. Pharmacol Rev 2024; 76:267-299. [PMID: 38351071 PMCID: PMC10877731 DOI: 10.1124/pharmrev.123.001015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Revised: 12/01/2023] [Accepted: 12/07/2023] [Indexed: 02/16/2024] Open
Abstract
Type 2 diabetes (T2D) mellitus has emerged as a major global health concern that has accelerated in recent years due to poor diet and lifestyle. Afflicted individuals have high blood glucose levels that stem from the inability of the pancreas to make enough insulin to meet demand. Although medication can help to maintain normal blood glucose levels in individuals with chronic disease, many of these medicines are outdated, have severe side effects, and often become less efficacious over time, necessitating the need for insulin therapy. G protein-coupled receptors (GPCRs) regulate many physiologic processes, including blood glucose levels. In pancreatic β cells, GPCRs regulate β-cell growth, apoptosis, and insulin secretion, which are all critical in maintaining sufficient β-cell mass and insulin output to ensure euglycemia. In recent years, new insights into the signaling of incretin receptors and other GPCRs have underscored the potential of these receptors as desirable targets in the treatment of diabetes. The signaling of these receptors is modulated by GPCR kinases (GRKs) that phosphorylate agonist-activated GPCRs, marking the receptor for arrestin binding and internalization. Interestingly, genome-wide association studies using diabetic patient cohorts link the GRKs and arrestins with T2D. Moreover, recent reports show that GRKs and arrestins expressed in the β cell serve a critical role in the regulation of β-cell function, including β-cell growth and insulin secretion in both GPCR-dependent and -independent pathways. In this review, we describe recent insights into GPCR signaling and the importance of GRK function in modulating β-cell physiology. SIGNIFICANCE STATEMENT: Pancreatic β cells contain a diverse array of G protein-coupled receptors (GPCRs) that have been shown to improve β-cell function and survival, yet only a handful have been successfully targeted in the treatment of diabetes. This review discusses recent advances in our understanding of β-cell GPCR pharmacology and regulation by GPCR kinases while also highlighting the necessity of investigating islet-enriched GPCRs that have largely been unexplored to unveil novel treatment strategies.
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Affiliation(s)
- Matthew J Varney
- Department of Biochemistry and Molecular Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Jeffrey L Benovic
- Department of Biochemistry and Molecular Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania
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11
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Ball RL, Bogue MA, Liang H, Srivastava A, Ashbrook DG, Lamoureux A, Gerring MW, Hatoum AS, Kim MJ, He H, Emerson J, Berger AK, Walton DO, Sheppard K, El Kassaby B, Castellanos F, Kunde-Ramamoorthy G, Lu L, Bluis J, Desai S, Sundberg BA, Peltz G, Fang Z, Churchill GA, Williams RW, Agrawal A, Bult CJ, Philip VM, Chesler EJ. GenomeMUSter mouse genetic variation service enables multitrait, multipopulation data integration and analysis. Genome Res 2024; 34:145-159. [PMID: 38290977 PMCID: PMC10903950 DOI: 10.1101/gr.278157.123] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Accepted: 01/10/2024] [Indexed: 02/01/2024]
Abstract
Hundreds of inbred mouse strains and intercross populations have been used to characterize the function of genetic variants that contribute to disease. Thousands of disease-relevant traits have been characterized in mice and made publicly available. New strains and populations including consomics, the collaborative cross, expanded BXD, and inbred wild-derived strains add to existing complex disease mouse models, mapping populations, and sensitized backgrounds for engineered mutations. The genome sequences of inbred strains, along with dense genotypes from others, enable integrated analysis of trait-variant associations across populations, but these analyses are hampered by the sparsity of genotypes available. Moreover, the data are not readily interoperable with other resources. To address these limitations, we created a uniformly dense variant resource by harmonizing multiple data sets. Missing genotypes were imputed using the Viterbi algorithm with a data-driven technique that incorporates local phylogenetic information, an approach that is extendable to other model organisms. The result is a web- and programmatically accessible data service called GenomeMUSter, comprising single-nucleotide variants covering 657 strains at 106.8 million segregating sites. Interoperation with phenotype databases, analytic tools, and other resources enable a wealth of applications, including multitrait, multipopulation meta-analysis. We show this in cross-species comparisons of type 2 diabetes and substance use disorder meta-analyses, leveraging mouse data to characterize the likely role of human variant effects in disease. Other applications include refinement of mapped loci and prioritization of strain backgrounds for disease modeling to further unlock extant mouse diversity for genetic and genomic studies in health and disease.
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Affiliation(s)
- Robyn L Ball
- The Jackson Laboratory, Bar Harbor, Maine 04609, USA;
| | - Molly A Bogue
- The Jackson Laboratory, Bar Harbor, Maine 04609, USA
| | | | - Anuj Srivastava
- The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut 06032, USA
| | - David G Ashbrook
- University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA
| | | | | | - Alexander S Hatoum
- Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, Missouri 63130, USA
- Artificial Intelligence and the Internet of Things Institute, Washington University School of Medicine, St. Louis, Missouri 63110, USA
| | - Matthew J Kim
- University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada
| | - Hao He
- The Jackson Laboratory, Bar Harbor, Maine 04609, USA
| | - Jake Emerson
- The Jackson Laboratory, Bar Harbor, Maine 04609, USA
| | | | | | | | | | | | | | - Lu Lu
- University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA
| | - John Bluis
- The Jackson Laboratory, Bar Harbor, Maine 04609, USA
| | - Sejal Desai
- The Jackson Laboratory, Bar Harbor, Maine 04609, USA
| | | | - Gary Peltz
- Department of Anesthesia, Pain and Perioperative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA
| | - Zhuoqing Fang
- Department of Anesthesia, Pain and Perioperative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA
| | | | - Robert W Williams
- University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA
| | - Arpana Agrawal
- Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA
| | - Carol J Bult
- The Jackson Laboratory, Bar Harbor, Maine 04609, USA
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12
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Azagew AW, Beko ZW, Mekonnen CK. Determinants of diabetic nephropathy among diabetic patients in Ethiopia: Systematic review and meta-analysis. PLoS One 2024; 19:e0297082. [PMID: 38306369 PMCID: PMC10836702 DOI: 10.1371/journal.pone.0297082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Accepted: 12/22/2023] [Indexed: 02/04/2024] Open
Abstract
INTRODUCTION Diabetic nephropathy (DN) is a long-term kidney disease among diabetic patients. It is the leading cause of end-stage renal failure. In Ethiopia, DN affects the majority of diabetic populations, but there were inconsistent findings about the determinant factors across the studies. METHODS We have accessed studies using PubMed, Embase, EBSCO, Web of Science, OVID, and search engines including Google and Google Scholar published up to June 2023. The study populations were diabetic patients with nephropathy. The quality of each included article was assessed using the Newcastle-Ottawa quality assessment scale. The odds ratios of risk factors were pooled using a random-effect meta-analysis model. Heterogeneity was assessed using the Cochrane Q statistics and I-Square (I2). The publication bias was detected using the funnel plot and/or Egger's test (p< 0.05). Trim and fill analysis was carried out to treat the publication bias. The protocol has been registered with the reference number CRD42023434547. RESULTS A total of sixteen articles were used for this reviewed study. Of which, eleven articles were used for advanced age, ten articles for duration of diabetic illness, ten articles for poor glycemic control, and eleven articles for having co-morbid hypertension. Diabetic patients with advanced age (AOR = 1.11, 95% CI: 1.03-120, I2 = 0.0%, p = 0.488), longer duration of diabetic illness (AOR = 1.23, 95% CI = 1.05-1.45, I2 = 0.0%, p = 0.567), poor glycemic control (AOR = 2.57, 95% CI: 1.07-6.14; I2 = 0.0%, p = 0.996), and having co-morbid hypertension (AOR = 4.03, 95% CI: 2.00-8.12, I2 = 0.0%, p = 0.964) were found to be factors associated with DN. CONCLUSIONS The findings of the study revealed that diabetic patients with advanced age, longer duration of diabetic illness, poor glycemic control status, and co-morbid hypertension were the determinant factors of DN. Therefore, treatment of co-morbid hypertension and high blood glucose and regular screening of renal function should be implemented to detect, treat, and reduce the progression of DN. Furthermore, healthcare workers should give due attention to diabetes with advanced age and a longer duration of diabetes illness to prevent the occurrence of DN.
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Affiliation(s)
- Abere Woretaw Azagew
- Department of Medical Nursing, School of Nursing, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Zerko Wako Beko
- Department of Medical Nursing, School of Nursing, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Chilot Kassa Mekonnen
- Department of Medical Nursing, School of Nursing, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
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13
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Yuan N, Diao J, Dong J, Yan Y, Chen Y, Yan S, Liu C, He Z, He J, Zhang C, Wang H, Wang M, He F, Xiao W. Targeting ROCK1 in diabetic kidney disease: Unraveling mesangial fibrosis mechanisms and introducing myricetin as a novel antagonist. Biomed Pharmacother 2024; 171:116208. [PMID: 38286036 DOI: 10.1016/j.biopha.2024.116208] [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: 11/22/2023] [Revised: 01/05/2024] [Accepted: 01/22/2024] [Indexed: 01/31/2024] Open
Abstract
Diabetic kidney disease (DKD) stands as a pressing health challenge, with mesangial cell fibrosis identified as a pivotal hallmark leading to glomerular sclerosis. Gaining a deeper grasp on the molecular dynamics behind this can potentially introduce groundbreaking therapeutic avenues. Recent revelations from studies on ROCK1-deficient mice, which displayed resilience against high-fat diet (HFD)-induced glomerulosclerosis and mitochondrial fragmentation, spurred our hypothesis regarding ROCK1's potential role in mesangial cell fibrosis. Subsequent rigorous experiments corroborated our theory, highlighting the critical role of ROCK1 in orchestrating mesangial cell proliferation and fibrosis, especially in high-glucose settings. Mechanistically, ROCK1 inhibition led to a notable hindrance in the high-glucose-triggered MAPK signaling pathway, particularly emphasizing the ROCK1/ERK/P38 axis. To translate this understanding into potential therapeutic interventions, we embarked on a comprehensive drug screening journey. Leveraging molecular modeling techniques, Myricetin surfaced as an efficacious inhibitor of ROCK1. Dose-dependent in vitro assays substantiated Myricetin's prowess in curtailing mesangial cell proliferation and fibrosis via ROCK1/ERK/P38 pathway. In vivo verifications paralleled these findings, with Myricetin treatment resulting in significant renal function enhancements and diminished DKD pathological markers, all pivoted around the ROCK1/ERK/P38 nexus. These findings not only deepen our comprehension of DKD molecular underpinnings but also elevate ROCK1 to the pedestal of a promising therapeutic beacon. Concurrently, Myricetin is spotlighted as a potent natural contender, heralding a new era in DKD therapeutic design.
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Affiliation(s)
- Ningning Yuan
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Jianxin Diao
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Jiamei Dong
- Department of Pharmacy, Zhuhai People's Hospital, Zhuhai Hospital Affiliated With Jinan University, Jinan University, Zhuhai 519000, Guangdong, China
| | - Yangtian Yan
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Yuchi Chen
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Shihua Yan
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Changshun Liu
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Zhuoen He
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Jinyue He
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Chi Zhang
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Hao Wang
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Mingqing Wang
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China.
| | - Fei He
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China.
| | - Wei Xiao
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China; Ministry of Education, Guangdong Pharmaceutical University, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangdong Pharmaceutical University, Guangzhou, Guangdong, 510006, China.
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14
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Chen C, Xie Z, Ni Y, He Y. Screening immune-related blood biomarkers for DKD-related HCC using machine learning. Front Immunol 2024; 15:1339373. [PMID: 38318171 PMCID: PMC10838782 DOI: 10.3389/fimmu.2024.1339373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Accepted: 01/05/2024] [Indexed: 02/07/2024] Open
Abstract
Background Diabetes mellitus is a significant health problem worldwide, often leading to diabetic kidney disease (DKD), which may also influence the occurrence of hepatocellular carcinoma (HCC). However, the relationship and diagnostic biomarkers between DKD and HCC are unclear. Methods Using public database data, we screened DKD secretory RNAs and HCC essential genes by limma and WGCNA. Potential mechanisms, drugs, and biomarkers for DKD-associated HCC were identified using PPI, functional enrichment, cMAP, and machine learning algorithms, and a diagnostic nomogram was constructed. Then, ROC, calibration, and decision curves were used to evaluate the diagnostic performance of the nomograms. In addition, immune cell infiltration in HCC was explored using CIBERSORT. Finally, the detectability of critical genes in blood was verified by qPCR. Results 104 DEGs associated with HCC using WGCNA were identified. 101 DEGs from DKD were predicated on secreting into the bloodstream with Exorbase datasets. PPI analysis identified three critical modules considered causative genes for DKD-associated HCC, primarily involved in inflammation and immune regulation. Using lasso and RM, four hub genes associated with DKD-associated HCC were identified, and a diagnostic nomogram confirmed by DCA curves was established. The results of immune cell infiltration showed immune dysregulation in HCC, which was associated with the expression of four essential genes. PLVAP was validated by qPCR as a possible blood-based diagnostic marker for DKD-related HCC. Conclusion We revealed the inflammatory immune pathways of DKD-related HCC and developed a diagnostic nomogram for HCC based on PLVAP, C7, COL15A1, and MS4A6A. We confirmed with qPCR that PLVAP can be used as a blood marker to assess the risk of HCC in DKD patients.
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Affiliation(s)
- Chao Chen
- Engineering Research Center of Natural Medicine, Ministry of Education, Advanced Institute of Natural Sciences, Beijing Normal University at Zhuhai, Zhuhai, China
- Instrumentation and Service Center for Science and Technology, Beijing Normal University at Zhuhai, Zhuhai, China
| | - Zhinan Xie
- Medical Engineering Department, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Ying Ni
- Engineering Research Center of Natural Medicine, Ministry of Education, Advanced Institute of Natural Sciences, Beijing Normal University at Zhuhai, Zhuhai, China
| | - Yuxi He
- Department of Pediatrics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China
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15
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Rai B, Maurya PK, Srivastava M, Mishra P, Asif MH, Tiwari S. An In-Silico Approach to Identify Therapeutic Target and Markers Associated with Diabetic Nephropathy. Curr Diabetes Rev 2024; 21:e100622205872. [PMID: 35702773 DOI: 10.2174/1573399819666220610191935] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 03/29/2022] [Accepted: 04/07/2022] [Indexed: 11/22/2022]
Abstract
BACKGROUND Renal disease in T2DM could arise independently of hyperglycemia, aka non diabetic kidney disease. Its prevalence ranges from 33% to 72.5% among T2DM patients. Specific molecular signatures that distinguish Diabetic Nephropathy from NDKD (FSGS) in T2DM might provide new targets for CKD management. METHODS Five original GEO microarray DN and FSGS datasets were evaluated (GSE111154, GSE96804, GSE125779, GSE129973 and GSE121233). Each of the three groups (DN, FSGS, and Controls) had equal renal transcriptome data (n=32) included in the analysis to eliminate bias. The DEGs were identified using TAC4.0. Pathway analysis was performed on the discovered genes aligned to official gene symbols using Reactome, followed by functional gene enrichment analysis using Funrich, Enrichr..STRING and Network analyst investigated PPI, followed by Webgestalt's pathway erichment. Finally, using the Targetscan 7.0 and DIANA tools, filtered differential microRNAs downregulated in DN were evaluated for target identification. RESULT Between the three groups, DN, FSGS, and Control, a total of 194 DEGs with foldchange, >2 & <-2 and P-value 0.01 were found in the renal transcriptome. In comparison to control, 45 genes were elevated, particularly in DN, whereas 43 were upregulated specifically in FSGS. DN datasets were compared to FSGS in a separate analysis. FABP4, EBF1, ADIRF, and ART4 were shown to be among the substantially up-regulated genes unique to DN in both analyses. The transcriptional regulation of white adipocytes was discovered by pathway analysis. CONCLUSION The molecular markers revealed might be employed as specific targets in the aetiology of DN, as well as in T2DM patients' therapeutic care.
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Affiliation(s)
- Bhuvnesh Rai
- Department of Molecular Medicine and Biotechnology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Pramod Kumar Maurya
- Department of Molecular Medicine and Biotechnology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Medha Srivastava
- Department of Molecular Medicine and Biotechnology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Prabhakar Mishra
- Department of Biostatistics and Health, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Mehar Hasan Asif
- Genetics and Biotechnology Division, CSIR-National Botanical Research Institute, Lucknow, India
| | - Swasti Tiwari
- Department of Molecular Medicine and Biotechnology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
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16
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Yazdanpanah Z, Salehi-Abargouei A, Mozaffari Z, Hemayati R. The effect of green tea ( Camellia sinensis) on lipid profiles and renal function in people with type 2 diabetes and nephropathy: a randomized controlled clinical trial. Front Nutr 2023; 10:1253275. [PMID: 38162524 PMCID: PMC10755896 DOI: 10.3389/fnut.2023.1253275] [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: 07/05/2023] [Accepted: 11/27/2023] [Indexed: 01/03/2024] Open
Abstract
Introduction Diabetic nephropathy is one of the most important microvascular complications of diabetes. Despite the modern treatments, herbs or medicinal plants have gained wide attention. One of these herbs is green tea (Camellia sinensis), which may have an impact on renal function, lipid profiles, and HbA1c. However, the evidence for this is unclear and limited. The present study aimed to evaluate the effect of different doses of green tea on these parameters in type 2 diabetes patients (T2DM) with nephropathy. Methods Sixty-six individuals with T2DM nephropathy (aged 30-70 years) were randomly assigned to receive three cups of green tea/day (n = 22), two cups of green tea/day (n = 22), and the control group (n = 22) for 12 weeks. Lipid profiles, glycated hemoglobin A1c (HbA1c), and renal markers were measured before and after intervention. Data were analyzed using SPSS software version 23. One-way analysis of variance (ANOVA), least significant difference (LSD) post hoc, and analysis of covariance were used to compare quantitative variables. Results In total, 64 participants completed the study. Consuming three cups of infusion green tea per day (7.5 gr) led to a significant reduction in serum levels of total cholesterol (p = 0.009) and HbA1c (p = 0.006) and increased in high-density lipoprotein cholesterol (HDL-C) (p = 0.02) compared with the control group who did not drink green tea. However, no significant differences were observed for other variables. Conclusion In general, it was found that drinking three cups of green tea infusion (7.5 gr) per day produced beneficial effects on some lipid profiles and HbA1c without any adverse effects on renal function in patients with T2DM nephropathy. More studies are needed to fully elucidate these findings. Clinical trial registration Iranian Registry of Clinical Trials (www.irct.ir) under registry number: IRCT2014020114538N2.
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Affiliation(s)
- Zeinab Yazdanpanah
- Research Center for Food Hygiene and Safety, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Amin Salehi-Abargouei
- Research Center for Food Hygiene and Safety, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
- Yazd Cardiovascular Research Center, Non-communicable Diseases Research Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Zohre Mozaffari
- Department of Internal Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Roya Hemayati
- Department of Internal Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
- Diabetes Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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17
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Halimi S. Épidémiologie des maladies rénales chez les patients diabétiques et place des marqueurs. MÉDECINE DES MALADIES MÉTABOLIQUES 2023; 17:614-626. [DOI: 10.1016/j.mmm.2023.10.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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18
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Alzahrani AM, Alshareef RJ, Balubaid MM, Alzahrani M, Alsoubhi M, Shaheen M. Perception and attitude of type 2 diabetic patients toward insulin therapy in the primary care of National Guard for Health Affairs (NGHA) in Jeddah, Saudi Arabia. J Family Med Prim Care 2023; 12:2768-2773. [PMID: 38186793 PMCID: PMC10771210 DOI: 10.4103/jfmpc.jfmpc_2484_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 05/05/2023] [Accepted: 07/18/2023] [Indexed: 01/09/2024] Open
Abstract
Purpose/Background Our study explores and determines the perception toward insulin among patients with diabetes in the National Guard for Health Affairs (NGHA), Jeddah, the Kingdom of Saudi Arabia (KSA), and aims to gain insight into the causes of refusal. Patients with type 2 diabetes (T2D) are likely to need the use of insulin to keep blood glucose levels within normal range and delay the onset of diabetes-related problems. Individuals with diabetes may be hesitant to begin insulin therapy if they have a negative attitude toward it, which might add to the delay in beginning treatment. Materials and Methods A cross-sectional study was conducted in the primary healthcare centers of the NGHA in Jeddah, Saudi Arabia. Data were collected through a validated self-administered questionnaire that was divided into three sections, with a total of 32 questions. The first section concerned demographic data, the second part was directed toward insulin users, and the last section was directed toward non-insulin patients. Results and Conclusion Our study collected 314 responses. Males constituted 54.8% of participants and insulin users resembled 45.7%. According to our study, important deterrents to starting insulin therapy among non-insulin users included the following: the cost of insulin, the pain associated with injections, the difficulty in maintaining food control while on insulin treatment, scarring at the injection site, and the weight gain impact. Factors that were found to influence compliance to insulin therapy among insulin users included fear of weight gain and self-administration of insulin.
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Affiliation(s)
- Abdullah M. Alzahrani
- Department of Family Medicine, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Jeddah, Saudi Arabia
- Department of Health Science, College of Medicine King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
- King Abdullah International Medical Research Center, Jeddah, Saudi Arabia
| | - Reem J. Alshareef
- Department of Family Medicine, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Jeddah, Saudi Arabia
| | - Marwan M. Balubaid
- Department of Health Science, College of Medicine King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
| | - Mohammed Alzahrani
- Department of Health Science, College of Medicine King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
| | - Mohammed Alsoubhi
- Department of Health Science, College of Medicine King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
| | - Mostafa Shaheen
- Department of Health Science, College of Medicine King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
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19
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D Y, Sk SR, R NK, Pa A. Association Between Monocyte-to-High-Density Lipoprotein (HDL) Cholesterol Ratio and Proteinuria in Patients With Type 2 Diabetes Mellitus: A Prospective Observational Study. Cureus 2023; 15:e45783. [PMID: 37872916 PMCID: PMC10590622 DOI: 10.7759/cureus.45783] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/18/2023] [Indexed: 10/25/2023] Open
Abstract
Background Diabetes mellitus (DM) refers to a group of metabolic disorders that share the phenotype of hyperglycemia. "Diabetic nephropathy (DN)" is a microvascular complication of DM, and it is the leading cause of end-stage renal failure. Increased urinary albumin excretion (UAE) and a decrease in glomerular filtration rate (GFR) are associated with DN along with elevated blood pressure and end-stage renal disease (ESRD). The purpose of this study is to analyze the prognostic significance of the monocyte-to-high-density lipoprotein (HDL) cholesterol ratio (MHR) in DN patients. Materials and methods This prospective observational study was carried out over a period of 1.5 years, with patients being followed up for three months. One hundred twenty participants were enrolled and allotted into groups based on the measure of urine albumin-to-creatinine ratio (UACR). The participants were categorized into healthy individuals, normoalbuminuric diabetic patients, microalbuminuric diabetic patients, and macroalbuminuric diabetic patients group. The MHR, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were estimated and compared between the baseline measurements. Conclusion The MHR, NLR, and PLR showed a positive correlation with UACR levels which could serve as an inflammatory marker and be used as an inexpensive and accessible prognostic marker in DN patients.
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Affiliation(s)
- Yashilha D
- Department of General Medicine, Faculty of Medicine and Health Sciences, SRM Institute of Science and Technology, SRM Medical College Hospital and Research Centre, Kattankulathur, IND
| | - Shini Rubina Sk
- Department of Pharmacy Practice, Faculty of Medicine and Health Sciences, SRM Institute of Science and Technology, SRM College of Pharmacy, Kattankulathur, IND
| | - Nanda Kumar R
- Department of General Medicine, Faculty of Medicine and Health Sciences, SRM Institute of Science and Technology, SRM Medical College Hospital and Research Centre, Kattankulathur, IND
| | - Anuba Pa
- Department of Pharmacy Practice, Faculty of Medicine and Health Sciences, SRM Institute of Science and Technology, SRM College of Pharmacy, Kattankulathur, IND
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Ball RL, Bogue MA, Liang H, Srivastava A, Ashbrook DG, Lamoureux A, Gerring MW, Hatoum AS, Kim M, He H, Emerson J, Berger AK, Walton DO, Sheppard K, Kassaby BE, Castellanos F, Kunde-Ramamoorthy G, Lu L, Bluis J, Desai S, Sundberg BA, Peltz G, Fang Z, Churchill GA, Williams RW, Agrawal A, Bult CJ, Philip VM, Chesler EJ. GenomeMUSter mouse genetic variation service enables multi-trait, multi-population data integration and analyses. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.08.08.552506. [PMID: 37609331 PMCID: PMC10441370 DOI: 10.1101/2023.08.08.552506] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/24/2023]
Abstract
Hundreds of inbred laboratory mouse strains and intercross populations have been used to functionalize genetic variants that contribute to disease. Thousands of disease relevant traits have been characterized in mice and made publicly available. New strains and populations including the Collaborative Cross, expanded BXD and inbred wild-derived strains add to set of complex disease mouse models, genetic mapping resources and sensitized backgrounds against which to evaluate engineered mutations. The genome sequences of many inbred strains, along with dense genotypes from others could allow integrated analysis of trait - variant associations across populations, but these analyses are not feasible due to the sparsity of genotypes available. Moreover, the data are not readily interoperable with other resources. To address these limitations, we created a uniformly dense data resource by harmonizing multiple variant datasets. Missing genotypes were imputed using the Viterbi algorithm with a data-driven technique that incorporates local phylogenetic information, an approach that is extensible to other model organism species. The result is a web- and programmatically-accessible data service called GenomeMUSter ( https://muster.jax.org ), comprising allelic data covering 657 strains at 106.8M segregating sites. Interoperation with phenotype databases, analytic tools and other resources enable a wealth of applications including multi-trait, multi-population meta-analysis. We demonstrate this in a cross-species comparison of the meta-analysis of Type 2 Diabetes and of substance use disorders, resulting in the more specific characterization of the role of human variant effects in light of mouse phenotype data. Other applications include refinement of mapped loci and prioritization of strain backgrounds for disease modeling to further unlock extant mouse diversity for genetic and genomic studies in health and disease.
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21
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Alarfaj RM, Alayed D. Knowledge and Practice of Use of Insulin Therapy Among Patients With Type 2 Diabetes Attending Primary Health Care Centers, Riyadh, Saudi Arabia: A Cross-Sectional Study. Cureus 2023; 15:e35486. [PMID: 37007415 PMCID: PMC10057695 DOI: 10.7759/cureus.35486] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/23/2023] [Indexed: 02/27/2023] Open
Abstract
OBJECTIVE The objective of this study was to explore the level of knowledge and practice of insulin therapy among patients with type 2 diabetes in Saudi Arabia. MATERIALS AND METHODS In this cross-sectional study, 400 pretested structured questionnaires were administered through an interview with patients in a primary health care center. Responses from 324 participants (81% response rate) were analyzed. The questionnaire comprised three main sections: sociodemographic data, a knowledge assessment, and a practice assessment. The total knowledge score was calculated out of 10: 7-10 was excellent, 5.5-6.9 was satisfactory, and less than 5.5 was poor. RESULT Approximately 57% of the participants were ≤ 59 years old, and 56.3% were females. The mean knowledge score was 6.5 (+/-1.6). Participants showed an overall good practice, with 92.5 rotating the site of injection, 83.3% sterilizing the site, and 95.7% taking insulin regularly. The knowledge level was influenced effectively by gender, marital status, educational level, job, frequency of follow-up, having visited a diabetic educator, duration of insulin therapy, and experiencing a hypoglycemic event (p-value <0.05). Knowledge was revealed to significantly influence self-insulin administration, meal-skipping after taking insulin, use of home glucose monitoring, keeping snacks nearby, and taking insulin in relation to meals (p-value <0.05). In some of the practice parameters, patients with high knowledge scores had better practice. CONCLUSION Knowledge of patients with type 2 diabetes mellitus was satisfactory, with significant differences in knowledge according to gender, marital status, educational level, occupation, duration of diabetes, frequency of follow-up, visiting a diabetic educator, and having an experience of the hypoglycemic episode. Participants showed overall good practice, with better practice being associated with a higher knowledge score.
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22
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Advances in the Pharmacological Management of Diabetic Nephropathy: A 2022 International Update. Biomedicines 2023; 11:biomedicines11020291. [PMID: 36830828 PMCID: PMC9953496 DOI: 10.3390/biomedicines11020291] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 12/24/2022] [Accepted: 01/17/2023] [Indexed: 01/26/2023] Open
Abstract
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD) worldwide. Its pathogenesis encompasses functional alterations involving elevated intraglomerular and systemic pressure, increased activity of the renin-angiotensin system (RAS) and oxidative stress, and the eventual development of renal fibrosis. The management of DN involves the optimization of blood pressure (BP) and blood glucose targets. However, treatment of these risk factors slows down but does not stop the progression of DN. Innovative pharmacologic therapies for dyslipidemia and type 2 diabetes mellitus (T2DM) could play a key role in bridging this gap and attenuating the residual risk of DN beyond traditional risk factor management. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), sodium-glucose cotransporter-2 inhibitors (SGLT-2is), and inhibitors of mineralocorticoid receptor-mediated sodium reabsorption are recently introduced drug classes that have been shown to have positive effects on kidney function in individuals with T2DM. The aim of this review is to provide an update on the therapeutic options available in order to prevent or slow the onset and progression of DN in diabetic patients.
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23
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Nakade Y, Iwata Y, Sakai N, Mita M, Nakane M, Hamase K, Suda W, Toyama T, Kitajima S, Hara A, Shimizu M, Ogushi C, Furuichi K, Koshino Y, Morita H, Hattori M, Wada T. Increased levels of oral Streptococcus-derived D-alanine in patients with chronic kidney disease and diabetes mellitus. Sci Rep 2022; 12:21773. [PMID: 36526888 PMCID: PMC9758232 DOI: 10.1038/s41598-022-26175-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Accepted: 12/12/2022] [Indexed: 12/23/2022] Open
Abstract
The number of patients on hemodialysis is increasing globally; diabetes mellitus (DM) complications is the major cause of hemodialysis in patients with chronic kidney disease (CKD). The D-amino acid (AA) profile is altered in patients with CKD; however, it has not been studied in patients with CKD and DM. Furthermore, bacteria responsible for altering the D-AA profile are not well understood. Therefore, we examined the D-AA profiles and associated bacteria in patients with CKD, with and without DM. We enrolled 12 healthy controls and 54 patients with CKD, with and without DM, and determined their salivary, stool, plasma, and urine chiral AA levels using two-dimensional high-performance liquid chromatography. We performed 16S rRNA gene sequencing analysis of the oral and gut microbiota to determine the association between the abundance of bacterial species and D-AA levels. Plasma D-alanine and D-serine levels were higher in patients with CKD than in healthy adults (p < 0.01), and plasma D-alanine levels were higher in patients with CKD and DM than in those without DM. The abundance of salivary Streptococcus, which produced D-alanine, increased in patients with CKD and DM and was positively correlated with plasma D-alanine levels. Patients with CKD and DM had unique oral microbiota and D-alanine profiles. Plasma D-alanine is a potential biomarker for patients with CKD and DM.
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Affiliation(s)
- Yusuke Nakade
- grid.9707.90000 0001 2308 3329Department of Nephrology and Laboratory Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641 Japan ,grid.9707.90000 0001 2308 3329Department of Clinical Laboratory, Kanazawa University, 13-1 Takara-machi, Kanazawa, Japan
| | - Yasunori Iwata
- grid.9707.90000 0001 2308 3329Department of Nephrology and Laboratory Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641 Japan ,grid.9707.90000 0001 2308 3329Division of Infection Control, Kanazawa University, 13-1 Takara-machi, Kanazawa, Japan
| | - Norihiko Sakai
- grid.9707.90000 0001 2308 3329Department of Nephrology and Laboratory Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641 Japan ,grid.9707.90000 0001 2308 3329Division of Blood Purification, Kanazawa University, 13-1 Takara-machi, Kanazawa, Japan
| | - Masashi Mita
- grid.511730.1KAGAMI Co., Ltd., 7-18 Saitobaiohiruzu Center 308, Ibaragi, Osaka Japan
| | - Maiko Nakane
- grid.511730.1KAGAMI Co., Ltd., 7-18 Saitobaiohiruzu Center 308, Ibaragi, Osaka Japan
| | - Kenji Hamase
- grid.177174.30000 0001 2242 4849Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Japan
| | - Wataru Suda
- grid.509459.40000 0004 0472 0267RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa Japan ,grid.26999.3d0000 0001 2151 536XGraduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba Japan
| | - Tadashi Toyama
- grid.9707.90000 0001 2308 3329Department of Nephrology and Laboratory Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641 Japan
| | - Shinji Kitajima
- grid.9707.90000 0001 2308 3329Department of Nephrology and Laboratory Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641 Japan
| | - Akinori Hara
- grid.9707.90000 0001 2308 3329Department of Nephrology and Laboratory Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641 Japan
| | - Miho Shimizu
- grid.9707.90000 0001 2308 3329Department of Nephrology and Laboratory Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641 Japan
| | - Chikako Ogushi
- grid.9707.90000 0001 2308 3329Department of Clinical Laboratory, Kanazawa University, 13-1 Takara-machi, Kanazawa, Japan
| | - Kengo Furuichi
- grid.411998.c0000 0001 0265 5359Department of Nephrology, Kanazawa Medical University, 1-1 Uchinada, Kahoku, Ishikawa Japan
| | - Yoshitaka Koshino
- Department of Internal Medicine, Mizuho Hospital, 422-1 Tsubata, Kahoku, Ishikawa Japan
| | - Hidetoshi Morita
- grid.261356.50000 0001 1302 4472Graduate School of Environmental and Life Science, Okayama University, 1-1-1 Tsushima-naka, Okayama, Japan
| | - Masahira Hattori
- grid.509459.40000 0004 0472 0267RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa Japan ,grid.26999.3d0000 0001 2151 536XGraduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba Japan
| | - Takashi Wada
- grid.9707.90000 0001 2308 3329Department of Nephrology and Laboratory Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641 Japan
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Lee CH, Tsai CI, Su YC, Lin SY, Lee IT, Li TC. Traditional Chinese medicine body constitution predicts new-onset diabetic albuminuria in patients with type 2 diabetes: Taichung diabetic body constitution prospective cohort study. Medicine (Baltimore) 2022; 101:e32342. [PMID: 36550881 PMCID: PMC9771319 DOI: 10.1097/md.0000000000032342] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
This prospective cohort study explored whether body constitution (BC) independently predicts new-onset albuminuria in persons with type 2 diabetes mellitus (T2DM) enrolled in the diabetes care management program (DCMP) of a medical center, providing evidence of integrating traditional Chinese medicine into DCMP for improving care quality. Persons with T2DM (n = 426) originally without albuminuria enrolled in DCMP were recruited in 2010 and were then followed up to 2015 for detecting new-onset albuminuria. The participants received urinalysis and blood test annually. Albuminuria was determined by an elevated urinary albumin/creatinine ratio (≥ 30 µg/mg), and poor glucose control was defined as Glycosylated hemoglobin above or equal to 7%. BC type (Yin deficiency, Yang deficiency, and phlegm stasis) was assessed using a well-validated body constitution questionnaire at baseline. Risk factors for albuminuria (sociodemographic factors, diabetes history, lifestyle behaviors, lipid profile, blood pressure, and kidney function) were also recorded. Hazard ratios (HR) of albuminuria for BC were estimated using multivariate Cox proportional hazards model. During the 4-year follow-up period, albuminuria occurred in 30.5% of participants (n = 130). The HR indicated that Yin deficiency was significantly associated with an increased risk of new-onset albuminuria in persons with T2DM and good glucose control after adjustment for other risk factors (HR = 2.09; 95% confidence interval = 1.05-4.17, P = .04), but not in those with poor glucose control. In persons with T2DM and poor glucose control, phlegm stasis was also significantly associated with a higher risk of albuminuria (2.26; 1.03-4.94, P = .04) after multivariate adjustment, but not in those with good glucose control. In addition to already-known risk factors, BC is an independent and significant factor associated with new-onset albuminuria in persons with T2DM. Our results imply Yin deficiency and phlegm stasis interacting with glucose control status may affect new-onset albuminuria in persons with T2DM.
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Affiliation(s)
- Cheng-Hung Lee
- Department of Traditional Chinese Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- Department of Post‐Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
- Center for General Education of Tunghai University, Tunghai University, Taichung, Taiwan
| | - Chia-I Tsai
- Department of Traditional Chinese Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- Department of Post‐Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
- Center for General Education of Tunghai University, Tunghai University, Taichung, Taiwan
| | - Yi-Chang Su
- National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan
| | - Shih-Yi Lin
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- Center for Geriatrics and Gerontology, Taichung Veterans General Hospital, Taichung, Taiwan
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - I-Te Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Tsai-Chung Li
- Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan
- Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung, Taiwan
- * Correspondence: Tsai-Chung Li, China Medical University, No. 100, Sec. 1, Jingmao Rd., Beitun Dist., Taichung City 406040, Taiwan R.O.C. (e-mail: )
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Liaw J, Harhay M, Setoguchi S, Gerhard T, Dave CV. Trends in Prescribing Preferences for Antidiabetic Medications Among Patients With Type 2 Diabetes in the U.K. With and Without Chronic Kidney Disease, 2006-2020. Diabetes Care 2022; 45:2316-2325. [PMID: 35984049 DOI: 10.2337/dc22-0224] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Accepted: 07/05/2022] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To evaluate trends in antidiabetic medication initiation patterns among patients with type 2 diabetes mellitus (T2DM) with and without chronic kidney disease (CKD). RESEARCH DESIGN AND METHODS A retrospective cohort study using the UK Clinical Practice Research Datalink (2006-2020) was conducted to evaluate the overall, first-, and second line (after metformin) medication initiation patterns among patients with CKD (n = 38,622) and those without CKD (n = 230,963) who had T2DM. RESULTS Relative to other glucose-lowering therapies, metformin initiations declined overall but remained the first-line treatment of choice for both patients with and those without CKD. Sodium-glucose cotransporter-2 (SGLT2i) use increased modestly among patients with CKD, but this increase was more pronounced among patients without CKD; by 2020, patients without CKD, compared with patients with CKD, were three (28.5% vs. 9.4%) and six (46.3% vs. 7.9%) times more likely to initiate SGLT2i overall and as second-line therapy, respectively. Glucagon-like peptide 1 receptor agonist (GLP-1RA) use was minimal regardless of CKD status (<5%), whereas both dipeptidyl peptidase-4 inhibitor (DPP4i) and sulfonylurea use remained high among patients with CKD. For instance, by 2020, and among patients with CKD, DPP4i and sulfonylureas constituted 28.3% and 20.6% of all initiations, and 57.4% and 30.3% of second-line initiations, respectively. CONCLUSIONS SGLT2i use increased among patients with T2DM, but this increase was largely driven by patients without CKD. Work is needed to identify barriers associated with the uptake of therapies with proven cardiorenal benefits (e.g., SGLT2i, GLP-1RA) among patients with CKD.
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Affiliation(s)
- Julia Liaw
- Center for Pharmacoepidemiology and Treatment Science, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, NJ
- Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ
| | - Meera Harhay
- Department of Medicine, Drexel University College of Medicine, Philadelphia, PA
- Department of Epidemiology and Biostatistics, Drexel University Dornsife School of Public Health, Philadelphia, PA
- Department of Medicine, Renal Electrolyte and Hypertension Division, University of Pennsylvania Health System, Philadelphia, PA
| | - Soko Setoguchi
- Center for Pharmacoepidemiology and Treatment Science, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, NJ
- Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ
| | - Tobias Gerhard
- Center for Pharmacoepidemiology and Treatment Science, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, NJ
- Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ
| | - Chintan V Dave
- Center for Pharmacoepidemiology and Treatment Science, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, NJ
- Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ
- Department of Veterans Affairs-New Jersey Health Care System, East Orange, NJ
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26
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Grochowalska K, Pikul P, Piwkowska A. Insights into the regulation of podocyte and glomerular function by lactate and its metabolic sensor G-protein-coupled receptor 81. J Cell Physiol 2022; 237:4097-4111. [PMID: 36084306 DOI: 10.1002/jcp.30874] [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: 05/04/2022] [Revised: 08/04/2022] [Accepted: 08/25/2022] [Indexed: 11/10/2022]
Abstract
Podocytes and their foot processes are an important cellular layer of the renal filtration barrier that is involved in regulating glomerular permeability. Disturbances of podocyte function play a central role in the development of proteinuria in diabetic nephropathy. The retraction and effacement of podocyte foot processes that form slit diaphragms are a common feature of proteinuria. Correlations between the retraction of foot processes and the development of proteinuria are not well understood. Unraveling peculiarities of podocyte energy metabolism notably under diabetic conditions will provide insights into the pathogenesis of diabetic nephropathy. Intracellular metabolism in the cortical area of podocytes is regulated by glycolysis, whereas energy balance in the central area is controlled by oxidative phosphorylation and glycolysis. High glucose concentrations were recently reported to force podocytes to switch from mitochondrial oxidative phosphorylation to glycolysis, resulting in lactic acidosis. In this review, we hypothesize that the lactate receptor G-protein-coupled receptor 81 (also known as hydroxycarboxylic acid receptor 81) may contribute to the control of podocyte function in both health and disease.
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Affiliation(s)
- Klaudia Grochowalska
- Laboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Gdansk, Poland
| | - Piotr Pikul
- Laboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Gdansk, Poland
| | - Agnieszka Piwkowska
- Laboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Gdansk, Poland.,Department of Molecular Biotechnology, Faculty of Chemistry, University of Gdansk, Gdansk, Poland
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27
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Rachubik P, Szrejder M, Rogacka D, Typiak M, Audzeyenka I, Kasztan M, Pollock DM, Angielski S, Piwkowska A. Insulin controls cytoskeleton reorganization and filtration barrier permeability via the PKGIα-Rac1-RhoA crosstalk in cultured rat podocytes. BIOCHIMICA ET BIOPHYSICA ACTA. MOLECULAR CELL RESEARCH 2022; 1869:119301. [PMID: 35642843 DOI: 10.1016/j.bbamcr.2022.119301] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 05/16/2022] [Accepted: 05/19/2022] [Indexed: 06/15/2023]
Abstract
Podocyte foot processes are an important cellular layer of the glomerular barrier that regulates glomerular permeability. Insulin via the protein kinase G type Iα (PKGIα) signaling pathway regulates the balance between contractility and relaxation (permeability) of the podocyte barrier by regulation of the actin cytoskeleton. This mechanism was shown to be disrupted in diabetes. Rho family guanosine-5'-triphosphates (GTPases) are dynamic modulators of the actin cytoskeleton and expressed in cells that form the glomerular filtration barrier. Thus, changes in Rho GTPase activity may affect glomerular permeability to albumin. The present study showed that Rho family GTPases control podocyte migration and permeability. Moreover these processes are regulated by insulin in PKGIα-dependent manner. Modulation of the PKGI-dependent activity of Rac1 and RhoA GTPases with inhibitors or small-interfering RNA impair glomerular permeability to albumin. We also demonstrated this mechanism in obese, insulin-resistant Zucker rats. We propose that PKGIα-Rac1-RhoA crosstalk is necessary in proper organization of the podocyte cytoskeleton and consequently the stabilization of glomerular architecture and regulation of filtration barrier permeability.
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Affiliation(s)
- Patrycja Rachubik
- Mossakowski Medical Research Institute, Polish Academy of Sciences, Laboratory of Molecular and Cellular Nephrology, Gdańsk, Poland
| | - Maria Szrejder
- Mossakowski Medical Research Institute, Polish Academy of Sciences, Laboratory of Molecular and Cellular Nephrology, Gdańsk, Poland
| | - Dorota Rogacka
- Mossakowski Medical Research Institute, Polish Academy of Sciences, Laboratory of Molecular and Cellular Nephrology, Gdańsk, Poland; University of Gdańsk, Faculty of Chemistry, Department of Molecular Biotechnology, Gdańsk, Poland
| | - Marlena Typiak
- Mossakowski Medical Research Institute, Polish Academy of Sciences, Laboratory of Molecular and Cellular Nephrology, Gdańsk, Poland; University of Gdańsk, Faculty of Biology, Department of General and Medical Biochemistry, Gdańsk, Poland
| | - Irena Audzeyenka
- Mossakowski Medical Research Institute, Polish Academy of Sciences, Laboratory of Molecular and Cellular Nephrology, Gdańsk, Poland; University of Gdańsk, Faculty of Chemistry, Department of Molecular Biotechnology, Gdańsk, Poland
| | - Małgorzata Kasztan
- Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - David M Pollock
- Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Stefan Angielski
- Mossakowski Medical Research Institute, Polish Academy of Sciences, Laboratory of Molecular and Cellular Nephrology, Gdańsk, Poland
| | - Agnieszka Piwkowska
- Mossakowski Medical Research Institute, Polish Academy of Sciences, Laboratory of Molecular and Cellular Nephrology, Gdańsk, Poland; University of Gdańsk, Faculty of Chemistry, Department of Molecular Biotechnology, Gdańsk, Poland.
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28
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Moreno-Gómez-Toledano R, Vélez-Vélez E, Arenas MI, Saura M, Bosch RJ. Association between urinary concentrations of bisphenol A substitutes and diabetes in adults. World J Diabetes 2022; 13:521-531. [PMID: 36051427 PMCID: PMC9329846 DOI: 10.4239/wjd.v13.i7.521] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 04/26/2022] [Accepted: 06/22/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Due to new restrictions on the use of bisphenol A (BPA), industries are beginning to replace it with derived molecules such as bisphenol S and F (BPS and BPF). There is extensive evidence in the academic literature on the potential health effects of BPA, which is known to be a diabetogenic molecule. However, there are few publications related to new compounds derived from BPA. AIM To perform an epidemiological study of urinary BPS and BPF in the American National Health and Nutrition Examination Survey (NHANES) cohort, and analyze their possible relationship with diabetes mellitus. METHODS NHANES datasets from 2013 to 2016 were used due to the urinary BPF and BPS availability. Data from 3658 adults were analyzed to perform regression analysis exploring the possible relationship between BPA-derived compounds and diabetes. RESULTS Descriptive statistics, linear regression modeling, and logistic regression analysis revealed a significant relationship between urinary BPS, but not BPF, and diabetes risk. Additionally, a relationship was observed between both compounds and hypertension and a slight relationship between BPF and dyslipidemia. CONCLUSION In the present study, a strong relationship between urinary BPS, not BPF, and diabetes risk has been determined. BPA substitute molecules do not exempt the population from potential health risks.
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Affiliation(s)
| | - Esperanza Vélez-Vélez
- Fundación Jiménez Díaz School of Nursing, Jiménez Díaz Foundation, Autonomous University of Madrid, Madrid 28040, Spain
| | - María I Arenas
- Universidad de Alcalá, Department of Biomedicine and Biotechnology,Alcalá de Henares 28871, Spain
| | - Marta Saura
- Universidad de Alcalá, Department of Biological Systems/Physiology Unit, Alcalá de Henares 28871, Spain
- Centro de Investigación en Red de Enfermedades Cardiovasculares, Instituto Ramón y Cajal de Investigación Sanitaria, Madrid 28034, Spain
| | - Ricardo J Bosch
- Universidad de Alcalá, Department of Biological Systems/Physiology Unit, Alcalá de Henares 28871, Spain
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29
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Sateesh J, Guha K, Dutta A, Sengupta P, Yalamanchili D, Donepudi NS, Surya Manoj M, Sohail SS. A comprehensive review on advancements in tissue engineering and microfluidics toward kidney-on-chip. BIOMICROFLUIDICS 2022; 16:041501. [PMID: 35992641 PMCID: PMC9385224 DOI: 10.1063/5.0087852] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 07/19/2022] [Indexed: 06/15/2023]
Abstract
This review provides a detailed literature survey on microfluidics and its road map toward kidney-on-chip technology. The whole review has been tailored with a clear description of crucial milestones in regenerative medicine, such as bioengineering, tissue engineering, microfluidics, microfluidic applications in biomedical engineering, capabilities of microfluidics in biomimetics, organ-on-chip, kidney-on-chip for disease modeling, drug toxicity, and implantable devices. This paper also presents future scope for research in the bio-microfluidics domain and biomimetics domain.
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Affiliation(s)
| | - Koushik Guha
- Department of Electronics and Communication Engineering, National MEMS Design Centre, National Institute of Technology Silchar, Assam 788010, India
| | - Arindam Dutta
- Urologist, RG Stone Urology and Laparoscopic Hospital, Kolkata, West Bengal, India
| | | | | | - Nanda Sai Donepudi
- Medical Interns, Government Siddhartha Medical College, Vijayawada, India
| | - M. Surya Manoj
- Department of Electronics and Communication Engineering, National MEMS Design Centre, National Institute of Technology Silchar, Assam 788010, India
| | - Sk. Shahrukh Sohail
- Department of Electronics and Communication Engineering, National MEMS Design Centre, National Institute of Technology Silchar, Assam 788010, India
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Kotake Y, Karashima S, Kawakami M, Hara S, Aono D, Konishi S, Kometani M, Mori H, Takeda Y, Yoneda T, Nambo H, Furukawa K. Impact of salt intake on urinary albumin excretion in patients with type 2 diabetic nephropathy: a retrospective cohort study based on a generalized additive model. Endocr J 2022; 69:577-583. [PMID: 34937811 DOI: 10.1507/endocrj.ej21-0447] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Diabetic kidney disease is an important and common cause of end-stage renal disease. Measurement of urinary albumin excretion (UAE) requires the diagnosis of the stage of diabetic nephropathy and the prognosis of renal function. We aimed to analyze the impact of lifestyle modification on UAE in patients with stage 2 and 3 type 2 diabetic nephropathy who received comprehensive medical care, using a generalized additive model (GAM), an explanatory machine learning model. In this retrospective observational study, we used changes in HbA1c, systolic blood pressure (SBP), and diastolic blood pressure (DBP) levels; body mass index (BMI); and daily salt intake as factors contributing to changes in UAE. In total, 269 patients with type 2 diabetic nephropathy were enrolled (stage 2, 217 patients; stage 3, 52 patients). The rankings that contributed to changes in UAE over 6 months by permutation importance were the changes in daily salt intake, HbA1c, SBP, DBP, and BMI. GAM, which predicts the change in UAE, showed that with increase in the changes in salt intake, SBP, and HbA1c, the delta UAE tended to increase. Salt intake was the most contributory factor for the changes in UAE, and daily salt intake was the best lifestyle factor to explain the changes in UAE. Strict control of salt intake may have beneficial effects on improving UAE in patients with stage 2 and 3 diabetic nephropathy.
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Affiliation(s)
- Yuka Kotake
- Division of Economics, Graduate School of Human and Socio-Environmental Studies, Kanazawa University, Kanazawa, Japan
| | | | - Masaki Kawakami
- School of Electrical, Information, and Communication Engineering, College of Science and Engineering, Kanazawa University, Kanazawa, Japan
| | - Satoshi Hara
- Medical Education Research Center, Kanazawa University, Medical Education Research Center, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan
| | - Daisuke Aono
- Department of Endocrinology and Metabolism, Kanazawa University Hospital, Kanazawa, Japan
| | - Seigo Konishi
- Department of Endocrinology and Metabolism, Kanazawa University Hospital, Kanazawa, Japan
| | - Mitsuhiro Kometani
- Department of Endocrinology and Metabolism, Kanazawa University Hospital, Kanazawa, Japan
| | - Hiroyuki Mori
- University of Michigan Medical School, Department of Molecular & Integrative Physiology, Ann Arbor, MI, USA
| | - Yoshiyu Takeda
- Department of Internal Medicine, Asanogawa General Hospital, Kanazawa, Japan
| | - Takashi Yoneda
- Department of Endocrinology and Metabolism, Kanazawa University Hospital, Kanazawa, Japan
- Institute of Transdisciplinary Sciences, Kanazawa University, Kanazawa, Japan
- Department of Health Promotion and Medicine of the Future, Kanazawa University, Kanazawa, Japan
| | - Hidetaka Nambo
- School of Electrical, Information, and Communication Engineering, College of Science and Engineering, Kanazawa University, Kanazawa, Japan
| | - Kenji Furukawa
- Center of Diabetes and Metabolism, Japan Community Healthcare Organization Kanazawa Hospital, Kanazawa, Japan
- Health Care Center, Japan Advanced Institute of Science and Technology, Nomi, Japan
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Vincent BP, Randhawa G, Cook E. Barriers towards deceased organ donation among Indians living globally: an integrative systematic review using narrative synthesis. BMJ Open 2022; 12:e056094. [PMID: 35623762 PMCID: PMC9150163 DOI: 10.1136/bmjopen-2021-056094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
OBJECTIVES To understand the barriers towards deceased organ donation among Indians living globally. DESIGN Integrative systematic review using narrative synthesis. DATA SOURCES CINAHL, Medline full-text, PsycInfo, Scopus, Global Health, Web of Science, and PubMed Central, Indian Journal of Transplantation and Google Scholar. TIME PERIOD 1 January 1994 to 31 December 2021. PARTICIPANTS Individuals of Indian origin living globally. RESULTS Eighty-nine studies were included with more than 29 000 participants and quality of the studies were assessed using Joanna Briggs Institute's critical appraisal tool. Though majority of the participants had knowledge toward organ donation with a positive influence on willingness, the gap between knowledge and willingness was huge, with minimal registration influenced by the complex sociocultural constructs. Various sociocultural constructs such as family, fear and mistrust, religion, and bodily issues play a vital role. Differences were identified in willingness to donate and register between southern and other regions of India. Indian's organ donation behaviour in other geographical locations differed based on the socioreligious background of the country they lived in such as in Malaysia, Canada and the UK. However, they were collective in decision-making and had complex sociocultural interference irrespective of the country the individual lived which differed only in their next generations. CONCLUSION Though this study showed the complex relationship, and its influences on organ donation behaviour, lacunae were identified to further understand how such complex interactions determine or inform the behaviour. Also, methodological issues were identified, where this particular population outside India were collectively studied with their neighbouring population which are not homogenous. Studies in India majorly addressed a similar aim using similar methods which produced repetition of studies leading to lack of diversified, wider and in-depth research. Therefore, while this systematic review addressed the barriers toward organ donation among Indians living globally, it also informs various gaps in research and also methodological issues. PROSPERO REGISTRATION NUMBER CRD42019155274.
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Affiliation(s)
- Britzer Paul Vincent
- Institute for Health Research, University of Bedfordshire Faculty of Health and Social Sciences, Luton, UK
| | - Gurch Randhawa
- Institute for Health Research, University of Bedfordshire Faculty of Health and Social Sciences, Luton, UK
| | - Erica Cook
- Department of Psychology, University of Bedfordshire - Luton Campus, Luton, UK
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Donate-Correa J, Sanchez-Niño MD, González-Luis A, Ferri C, Martín-Olivera A, Martín-Núñez E, Fernandez-Fernandez B, Tagua VG, Mora-Fernández C, Ortiz A, Navarro-González JF. Repurposing drugs for highly prevalent diseases: pentoxifylline, an old drug and a new opportunity for diabetic kidney disease. Clin Kidney J 2022; 15:2200-2213. [PMID: 36381364 PMCID: PMC9664582 DOI: 10.1093/ckj/sfac143] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Indexed: 11/30/2022] Open
Abstract
Diabetic kidney disease is one of the most frequent complications in patients with diabetes and constitutes a major cause of end-stage kidney disease. The prevalence of diabetic kidney disease continues to increase as a result of the growing epidemic of diabetes and obesity. Therefore, there is mounting urgency to design and optimize novel strategies and drugs that delay the progression of this pathology and contain this trend. The new approaches should go beyond the current therapy focussed on the control of traditional risk factors such as hyperglycaemia and hypertension. In this scenario, drug repurposing constitutes an economic and feasible approach based on the discovery of useful activities for old drugs. Pentoxifylline is a nonselective phosphodiesterase inhibitor currently indicated for peripheral artery disease. Clinical trials and meta-analyses have shown renoprotection secondary to anti-inflammatory and antifibrotic effects in diabetic patients treated with this old known drug, which makes pentoxifylline a candidate for repurposing in diabetic kidney disease.
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Affiliation(s)
- Javier Donate-Correa
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
- GEENDIAB (Grupo Español para el estudio de la Nefropatía Diabética), Sociedad Española de Nefrología, Santander, Spain
- RICORS2040 (RD21/0005/0013), Instituto de Salud Carlos III, Madrid, Spain
| | - María Dolores Sanchez-Niño
- Departamento de Nefrología e Hipertensión, IIS-Fundación Jiménez Díaz y Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain
| | - Ainhoa González-Luis
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
- Escuela de doctorado, Universidad de La Laguna
| | - Carla Ferri
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
- Escuela de doctorado, Universidad de La Laguna
| | - Alberto Martín-Olivera
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
- Escuela de doctorado, Universidad de La Laguna
| | - Ernesto Martín-Núñez
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
- RICORS2040 (RD21/0005/0013), Instituto de Salud Carlos III, Madrid, Spain
| | - Beatriz Fernandez-Fernandez
- Departamento de Nefrología e Hipertensión, IIS-Fundación Jiménez Díaz y Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain
- RICORS2040 (RD21/0005/0001), Instituto de Salud Carlos III, Madrid, Spain
| | - Víctor G Tagua
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
| | - Carmen Mora-Fernández
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
- GEENDIAB (Grupo Español para el estudio de la Nefropatía Diabética), Sociedad Española de Nefrología, Santander, Spain
- RICORS2040 (RD21/0005/0013), Instituto de Salud Carlos III, Madrid, Spain
| | - Alberto Ortiz
- Departamento de Nefrología e Hipertensión, IIS-Fundación Jiménez Díaz y Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain
- RICORS2040 (RD21/0005/0001), Instituto de Salud Carlos III, Madrid, Spain
| | - Juan F Navarro-González
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
- GEENDIAB (Grupo Español para el estudio de la Nefropatía Diabética), Sociedad Española de Nefrología, Santander, Spain
- RICORS2040 (RD21/0005/0013), Instituto de Salud Carlos III, Madrid, Spain
- Servicio de Nefrología, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
- Instituto de Tecnologías Biomédicas, Universidad de La Laguna, Santa Cruz de Tenerife, Spain
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Matsushita K, Gao Y, Sang Y, Ballew SH, Salameh M, Allison M, Selvin E, Coresh J. Comparative mortality according to peripheral artery disease and coronary heart disease/stroke in the United States. Atherosclerosis 2022; 354:57-62. [PMID: 35584971 DOI: 10.1016/j.atherosclerosis.2022.04.029] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 03/25/2022] [Accepted: 04/26/2022] [Indexed: 01/29/2023]
Abstract
BACKGROUND AND AIMS A recent trial reported that patients with peripheral artery disease (PAD) without coronary heart disease or stroke (CHD/stroke) had worse prognosis than those with CHD/stroke without PAD. However, community-based data are lacking. The purpose of this study was to compare mortality according to the status of PAD and CHD/stroke in the general population. METHODS In 6780 participants (aged ≥40 years) from the National Health and Nutrition Examination Surveys 1999-2004, we compared mortality risk according to PAD (ankle-brachial index ≤0.9) and CHD/stroke (self-report) at baseline using the Kaplan-Meier method and multivariable Cox models accounting for sampling weights. RESULTS The prevalence of having both PAD and CHD/stroke was 1.6%. The prevalence of PAD without CHD/stroke and CHD/stroke without PAD was 4.1% and 8.5%, respectively (85.8% without PAD or CHD/stroke). Over a median follow-up of 12.8 years, 21.2% died. Individuals with both PAD and CHD/stroke had the worst survival (25.5% at 12 years). Those with PAD without CHD/stroke had the second worst prognosis (47.7%), followed by those with CHD/stroke without PAD (53.2%) and those without CHD/stroke or PAD (87.2%). Adjusted hazard ratio of mortality was 2.70 (95% CI, 2.07-3.53) for PAD with CHD/stroke, 1.81 (1.54-2.12) in CHD/stroke without PAD, and 1.68 (1.35-2.08) in PAD without CHD/stroke vs. no CHD/stroke or PAD. CONCLUSIONS In the US adults, PAD contributed to increased mortality in persons with and without CHD/stroke. The prognosis of PAD without CHD/stroke was no better than that of CHD/stroke without PAD. These results suggest the importance of recognizing the presence of PAD in the community.
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Eswarappa M, Suryadevara S, R R, K B MK, K C G, Tyagi P, V A. Non-diabetic Kidney Disease in Diabetic Population: A Single-Center Study From South India. Cureus 2022; 14:e23899. [PMID: 35530914 PMCID: PMC9077023 DOI: 10.7759/cureus.23899] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/04/2022] [Indexed: 11/28/2022] Open
Abstract
Introduction: Diabetic kidney disease (DKD) is the commonest cause of chronic kidney disease and end-stage kidney disease worldwide, consequently it has become an important productive implication to the healthcare system. This study was conducted to assess the prevalence of non-DKD (NDKD) in diabetic patients from south India. Objective: To assess the prevalence of NDKD in type 2 diabetes mellitus patients presenting to a tertiary care hospital from south India and also to analyze clinical clues to establish a diagnosis of NDKD. Patient and methods: It is a retrospective observational study of analyzing patient characteristics and renal biopsies. All Diabetic patients with a clinical suspicion of non-diabetic kidney disease who underwent renal biopsy during the study period between January 2012 and June 2017 were included. Based on the biopsy findings, the patients were classified into three groups (isolated diabetic nephropathy, isolated NDKD, and NDKD with underlying diabetic nephropathy) and patients’ characteristics were compared between the groups for analysis. Results: A total of 236 renal biopsies were analyzed for the study. Of that, 114 had features of DKD, 78 NDKD with diabetic nephropathy (DN) and 44 had isolated NDKD. Acute interstitial nephritis was the most common cause of NDKD. Conclusion: From the current study, the long duration of diabetes mellitus beyond five years and hypertension beyond two years reasonably predict DKD.
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Geng Z, Dong B, Lv W, Wang Z, Wang X, Huang Y, Wang Y, Xu L. LncRNA ZFAS1 regulates the proliferation, oxidative stress, fibrosis, and inflammation of high glucose-induced human mesangial cells via the miR-588/ROCK1 axis. Diabetol Metab Syndr 2022; 14:21. [PMID: 35090549 PMCID: PMC8796624 DOI: 10.1186/s13098-022-00791-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Accepted: 01/08/2022] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Diabetic nephropathy (DN) is a critical and the most common microvascular complication and its pathogenesis is still faintly understood. Thus, this study was performed to examine the long non-coding RNA ZNFX1 Antisense Gene Protein 1 (lncRNA ZFAS1) biological function and mechanism of regulation in DN. METHOD Human glomerular mesangial cells (HGMC) were induced with high glucose (HG, 25 mM) to establish HG-induced cell viability, pro-inflammation observed in DN. After, target miRNA and mRNA were predicted through Lncbase and Targetscan. Subsequently, the expression of ZFAS1, miR-588, and ROCK1 in DN clinical samples and cell-model was examined through qRT-PCR and western blot analysis. We upheld the targeted interaction between miR-588 and ZFAS1 or ROCK1 through a dual-luciferase reporter assay. The proliferation of the cell was also examined through CCK-8 assay, while the level of HG-induced oxidative stress was established by measuring reactive oxygen species (ROS) level, and also the activities of antioxidant enzymes in the cell. Lastly, the level of accumulated extracellular matrix (ECM) protein-fibronectin and collagen type IV, and inflammatory cytokines produced by the cell was analyzed through western blot analysis and ELISA. RESULTS ZFAS1 was significantly upregulated in the DN blood samples and HG-induced HGMC. Prediction result revealed that the ZFAS1 endogenously targets the miR-588 seed sequence while miR-588 plays a role in post-transcriptional regulation of ROCK1 mRNA. Moreover, we found that miR-588 expression was significantly downregulated in DN blood samples and negatively correlates with ZFAS1 expression. Further results show that silencing ZFAS1 had a protective effect on HG-induced proliferation, oxidative stress, fibrosis, and inflammation in HGMC while miR-588 inhibition and ROCK1 overexpression reversed this effect. CONCLUSIONS Altogether, our data suggest that ZFAS1 regulates the proliferation, oxidative stress, fibrosis, and inflammation of high glucose-induced diabetic nephropathy through the miR-588/ROCK1 axis.
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Affiliation(s)
- Zhuang Geng
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, People's Republic of China
| | - Bingzi Dong
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, People's Republic of China
| | - Wenshan Lv
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, People's Republic of China
| | - Zhongchao Wang
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, People's Republic of China
| | - Xiang Wang
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, People's Republic of China
| | - YaJing Huang
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, People's Republic of China
| | - Yangang Wang
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, People's Republic of China.
| | - Lili Xu
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, People's Republic of China.
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Banerjee D, Winocour P, Chowdhury TA, De P, Wahba M, Montero R, Fogarty D, Frankel AH, Karalliedde J, Mark PB, Patel DC, Pokrajac A, Sharif A, Zac-Varghese S, Bain S, Dasgupta I. Management of hypertension and renin-angiotensin-aldosterone system blockade in adults with diabetic kidney disease: Association of British Clinical Diabetologists and the Renal Association UK guideline update 2021. BMC Nephrol 2022; 23:9. [PMID: 34979961 PMCID: PMC8722287 DOI: 10.1186/s12882-021-02587-5] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Accepted: 10/28/2021] [Indexed: 12/31/2022] Open
Abstract
People with type 1 and type 2 diabetes are at risk of developing progressive chronic kidney disease (CKD) and end-stage kidney failure. Hypertension is a major, reversible risk factor in people with diabetes for development of albuminuria, impaired kidney function, end-stage kidney disease and cardiovascular disease. Blood pressure control has been shown to be beneficial in people with diabetes in slowing progression of kidney disease and reducing cardiovascular events. However, randomised controlled trial evidence differs in type 1 and type 2 diabetes and different stages of CKD in terms of target blood pressure. Activation of the renin-angiotensin-aldosterone system (RAAS) is an important mechanism for the development and progression of CKD and cardiovascular disease. Randomised trials demonstrate that RAAS blockade is effective in preventing/ slowing progression of CKD and reducing cardiovascular events in people with type 1 and type 2 diabetes, albeit differently according to the stage of CKD. Emerging therapy with sodium glucose cotransporter-2 (SGLT-2) inhibitors, non-steroidal selective mineralocorticoid antagonists and endothelin-A receptor antagonists have been shown in randomised trials to lower blood pressure and further reduce the risk of progression of CKD and cardiovascular disease in people with type 2 diabetes. This guideline reviews the current evidence and makes recommendations about blood pressure control and the use of RAAS-blocking agents in different stages of CKD in people with both type 1 and type 2 diabetes.
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Affiliation(s)
- D Banerjee
- St George's Hospitals NHS Foundation Trust, London, UK
| | - P Winocour
- ENHIDE, East and North Herts NHS Trust, Stevenage, UK
| | | | - P De
- City Hospital, Birmingham, UK
| | - M Wahba
- St Helier Hospital, Carshalton, UK
| | | | - D Fogarty
- Belfast Health and Social Care Trust, Belfast, UK
| | - A H Frankel
- Imperial College Healthcare NHS Trust, London, UK
| | | | - P B Mark
- University of Glasgow, Glasgow, UK
| | - D C Patel
- Royal Free London NHS Foundation Trust, London, UK
| | - A Pokrajac
- West Hertfordshire Hospitals, London, UK
| | - A Sharif
- University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | | | - S Bain
- Swansea University, Swansea, UK
| | - I Dasgupta
- University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
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Moreno-Gómez-Toledano R, Arenas MI, Muñoz-Moreno C, Olea-Herrero N, Reventun P, Izquierdo-Lahuerta A, Antón-Cornejo A, González-Santander M, Zaragoza C, Saura M, Bosch RJ. Comparison of the renal effects of bisphenol A in mice with and without experimental diabetes. Role of sexual dimorphism. Biochim Biophys Acta Mol Basis Dis 2022; 1868:166296. [DOI: https:/doi.org/10.1016/j.bbadis.2021.166296] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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YANG X, ZHANG Y, YANG N, YU X, GAO X, ZHAO M. Parthenolide regulates DNMT1-mediated methylation of VDR promoter to relieve podocyte damage in mice with diabetic nephropathy. FOOD SCIENCE AND TECHNOLOGY 2022. [DOI: 10.1590/fst.51221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Affiliation(s)
| | | | - Ni YANG
- University of Chinese Medicine, China
| | - Xiao YU
- University of Chinese Medicine, China
| | - Xin GAO
- University of Chinese Medicine, China
| | - Meiyun ZHAO
- Xi’an Hospital of Traditional Chinese Medicine, China
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Moreno-Gómez-Toledano R, Arenas MI, Muñoz-Moreno C, Olea-Herrero N, Reventun P, Izquierdo-Lahuerta A, Antón-Cornejo A, González-Santander M, Zaragoza C, Saura M, Bosch RJ. Comparison of the renal effects of bisphenol A in mice with and without experimental diabetes. Role of sexual dimorphism. Biochim Biophys Acta Mol Basis Dis 2022; 1868:166296. [PMID: 34718120 DOI: 10.1016/j.bbadis.2021.166296] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Revised: 10/19/2021] [Accepted: 10/21/2021] [Indexed: 02/06/2023]
Abstract
Bisphenol-A (BPA), a chemical -xenoestrogen- used in the production of the plastic lining of food and beverage containers, is present in the urine of almost the entire population. Recent studies have shown that BPA exposure is associated with podocytopathy, increased urinary albumin excretion (UAE), and hypertension. Since these changes are characteristic of early diabetic nephropathy (DN), we explored the renal effects of BPA and diabetes including the potential role of sexual dimorphism. Male and female mice were included in the following animals' groups: control mice (C), mice treated with 21.2 mg/kg of BPA in the drinking water (BPA), diabetic mice induced by streptozotocin (D), and D mice treated with BPA (D + BPA). Male mice form the D + BPA group died by the tenth week of the study due probably to hydro-electrolytic disturbances. Although BPA treated mice did not show an increase in serum creatinine, as observed in D and D + BPA groups, they displayed similar alteration to those of the D group, including increased in kidney damage biomarkers NGAL and KIM-1, UAE, hypertension, podocytopenia, apoptosis, collapsed glomeruli, as well as TGF-β, CHOP and PCNA upregulation. UAE, collapsed glomeruli, PCNA staining, TGF-β, NGAL and animal survival, significantly impaired in D + BPA animals. Moreover, UAE, collapsed glomeruli and animal survival also displayed a sexual dimorphism pattern. In conclusion, oral administration of BPA is capable of promoting in the kidney alterations that resemble early DN. Further translational studies are needed to clarify the potential role of BPA in renal diseases, particularly in diabetic patients.
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Affiliation(s)
- Rafael Moreno-Gómez-Toledano
- Universidad de Alcalá, Laboratory of Renal Physiology and Experimental Nephrology, Group of Pathophysiology of the Cardiovascular, Renal and Nervous Systems, Department of Biological Systems/Physiology Unit, Alcalá de Henares, Spain
| | - María I Arenas
- Universidad de Alcalá, Department of Biomedicine and Biotechnology, Alcalá de Henares, Spain
| | - Carmen Muñoz-Moreno
- Universidad de Alcalá, Laboratory of Renal Physiology and Experimental Nephrology, Group of Pathophysiology of the Cardiovascular, Renal and Nervous Systems, Department of Biological Systems/Physiology Unit, Alcalá de Henares, Spain
| | - Nuria Olea-Herrero
- Universidad de Alcalá, Laboratory of Renal Physiology and Experimental Nephrology, Group of Pathophysiology of the Cardiovascular, Renal and Nervous Systems, Department of Biological Systems/Physiology Unit, Alcalá de Henares, Spain
| | - Paula Reventun
- Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Adriana Izquierdo-Lahuerta
- University Rey Juan Carlos, Biochemistry and Molecular Biology Area, Department of Basic Sciences of Health, Alcorcon, Spain
| | - Alba Antón-Cornejo
- Clinical Analysis Service, Principe de Asturias Hospital, Alcalá de Henares, Spain
| | - Marta González-Santander
- Universidad de Alcalá, Laboratory of Renal Physiology and Experimental Nephrology, Group of Pathophysiology of the Cardiovascular, Renal and Nervous Systems, Department of Biological Systems/Physiology Unit, Alcalá de Henares, Spain
| | - Carlos Zaragoza
- Unidad de Investigación Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS)/Facultad de Medicina Universidad Francisco de Vitoria, Pozuelo de Alarcón, Madrid, Spain; Centro de Investigación en Red de Enfermedades Cardiovasculares (CIBERCV), Spain
| | - Marta Saura
- Universidad de Alcalá, Laboratory of Pathophysiology of the Vascular Wall, Group of Pathophysiology of the Cardiovascular, Renal and Nervous Systems, IRICYS, Department of System Biology/Physiology Unit, Alcalá de Henares, Spain
| | - Ricardo J Bosch
- Universidad de Alcalá, Laboratory of Renal Physiology and Experimental Nephrology, Group of Pathophysiology of the Cardiovascular, Renal and Nervous Systems, Department of Biological Systems/Physiology Unit, Alcalá de Henares, Spain.
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Netere AK, Muhammad EA, Asres MS, Teklie MT. Renal outcomes of diabetic patients treated with combination therapy of ACE inhibitors plus either thiazide diuretics or calcium channel blockers: comparative retrospective cohort study in Northwestern Ethiopia. BMJ Open 2021; 11:e048442. [PMID: 34824108 PMCID: PMC8627402 DOI: 10.1136/bmjopen-2020-048442] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2020] [Accepted: 10/25/2021] [Indexed: 11/04/2022] Open
Abstract
OBJECTIVE The study determined the comparative renal functions on patients with diabetes treated with ACE inhibitors (ACEIs) plus either thiazide diuretics or calcium channel blockers (CCBs) in Northwestern Ethiopia. DESIGN Retrospective cohort study design was employed to collect the data from medical records of patients with diabetes followed for 1-5 years (N=404). SETTING The medical records of patients in chronic diabetic follow-up clinics of the hospital. PARTICIPANTS All the patients with diabetes medical records in Northwestern Ethiopian specialised hospital. MAIN OUTCOME MEASURES Exposures were ACEIs plus thiazide diuretics or CCBs collected from March to June 2020. Outcomes were defined as declining in estimated glomerular filtration rate (eGFR) values by ≥30% from the baseline recorded from 2015 to 2019. Descriptive and analytical statistics were illustrated to compare the study groups. Kaplan-Meier with log- rank test was used to plot the survival analyses curve. Potential factors substantially associated to renal events were examined using cox proportional hazards model. RESULT About 20% of patients developed renal events and significant numbers were from hydrochlorothiazide (HCT) users. The mean eGFR levels were significantly higher in patients on CCBs users over the follow-up years compared with HCT-based users. The CCBs users had an 18.8 mL/min/1.73 m2 higher in eGFR levels at the end of the follow-up period than HCT users (p<0.001). HCT users had shorter survival probability overtime to develop the outcomes compared with CCBs users (p=0.003). The CCBs-based regimen prevented risks of declining in renal function by 56.4% than HCT (p=0.001). Hazards of declining in eGFR levels were 93% higher for the patients with initial systolic blood pressure (SBP) levels were more than 150 mm Hg (p=0.006). CONCLUSION Compared with HCT, patients on CCBs had significantly prevented risks of renal events. However, both groups appeared with the same cardiovascular events. HCT-based regimen and higher initial SBP levels were significantly associated with eGFR reductions.
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Affiliation(s)
| | - Esmael Ali Muhammad
- Department of Human Nutrition Institute of Public Health, University of Gondar, Gondar, Ethiopia
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Ojakäär T, Koychev I. Secondary Prevention of Dementia: Combining Risk Factors and Scalable Screening Technology. Front Neurol 2021; 12:772836. [PMID: 34867762 PMCID: PMC8634660 DOI: 10.3389/fneur.2021.772836] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Accepted: 10/11/2021] [Indexed: 11/13/2022] Open
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is the most common cause of dementia. Over a third of dementia cases are estimated to be due to potentially modifiable risk factors, thus offering opportunities for both identification of those most likely to be in early disease as well as secondary prevention. Diabetes, hypertension and chronic kidney failure have all been linked to increased risk for AD and dementia and through their high prevalence are particularly apt targets for initiatives to reduce burden of AD. This can take place through targeted interventions of cardiovascular risk factors (shown to improve cognitive outcomes) or novel disease modifying treatments in people with confirmed AD pathology. The success of this approach to secondary prevention depends on the availability of inexpensive and scalable methods for detecting preclinical and prodromal dementia states. Developments in blood-based biomarkers for Alzheimer's disease are rapidly becoming a viable such method for monitoring large at-risk groups. In addition, digital technologies for remote monitoring of cognitive and behavioral changes can add clinically relevant data to further improve personalisation of prevention strategies. This review sets the scene for this approach to secondary care of dementia through a review of the evidence for cardiovascular risk factors (diabetes, hypertension and chronic kidney disease) as major risk factors for AD. We then summarize the developments in blood-based and cognitive biomarkers that allow the detection of pathological states at the earliest possible stage. We propose that at-risk cohorts should be created based on the interaction between cardiovascular and constitutional risk factors. These cohorts can then be monitored effectively using a combination of blood-based biomarkers and digital technologies. We argue that this strategy allows for both risk factor reduction-based prevention programmes as well as for optimisation of any benefits offered by current and future disease modifying treatment through rapid identification of individuals most likely to benefit from them.
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Affiliation(s)
| | - Ivan Koychev
- Department of Psychiatry, University of Oxford, Oxford, United Kingdom
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Lai YJ, Chen YY, Ku PW, Chen LJ, Yen YF. Association between uric acid level and incidence of albuminuria in patients with type 2 diabetes mellitus: A 4.5-year cohort study. Medicine (Baltimore) 2021; 100:e27496. [PMID: 34731131 PMCID: PMC8519260 DOI: 10.1097/md.0000000000027496] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 09/23/2021] [Indexed: 01/05/2023] Open
Abstract
Using animal models and molecular biology researches, hyperuricemia has been shown to instruct renal arteriolopathy, arterial hypertension, and microvascular injury involving the renin-angiotensin system and resulting in renal function impairment. Nevertheless, the association between uric acid levels and the development of albuminuria has been under-investigated in patients with type 2 diabetes mellitus. Patients with type 2 diabetes and regular outpatient visits were recruited from the Puli Branch of the Taichung Veterans General Hospital in Taiwan since January 2014. Demographics, lifestyle features, and medical history were gathered by well-trained interviewers. All participants underwent comprehensive physical examinations, including a biochemical assay of venous blood specimens and urine samples after an 8-hour overnight fast. Participants were followed until June 2018. The primary outcome was the albuminuria incidence. Univariable and multivariable Cox regression analysis were employed to explore the relation between uric acid and incident albuminuria. Uric acid cutoffs for incident albuminuria were determined with the receiver operator characteristic curve. We included 247 qualified subjects (mean age: 64.78 years old [standard deviation = 11.29 years]; 138 [55.87%] men). During a 4.5-year follow-up duration, 20 subjects with incident albuminuria were recognized. Serum uric acid was significantly associated with an increased risk of incident albuminuria (adjusted hazard ratio = 2.39; 95% confidence interval: 1.53-3.75; P < .001) with potential confounders adjustment. The uric acid cutoff point was 6.9 mg/dL (area under the curve 0.708, sensitivity 60.0%, specificity 84.58%) for incident albuminuria. Serum uric acid was associated with incident albuminuria among patients with type 2 diabetes.
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Affiliation(s)
- Yun-Ju Lai
- School of Medicine, National Yang Ming University, Taipei, Taiwan
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Puli Branch of Taichung Veterans General Hospital, Nantou, Taiwan
- Department of Exercise Health Science, National Taiwan University of Sport, Taichung, Taiwan
- Department of Health Care Management, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan
| | - Yu-Yen Chen
- School of Medicine, National Yang Ming University, Taipei, Taiwan
- Department of Ophthalmology, Taichung Veterans General Hospital, Taichung, Taiwan
- School of Medicine, Chung-Shan Medical University, Taichung, Taiwan
- Community Medicine Research Center and Institute of Public Health, National Yang-Ming University, Taipei, Taiwan
- National Chung Hsing University, Taichung, Taiwan
| | - Po-Wen Ku
- Graduate Institute of Sports and Health, National Changhua University of Education, Changhua, Taiwan
| | - Li-Jung Chen
- Department of Exercise Health Science, National Taiwan University of Sport, Taichung, Taiwan
| | - Yung-Feng Yen
- Department of Health Care Management, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Section of Infectious Diseases, Taipei City Hospital, Taipei City Government, Taipei, Taiwan
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Li Y, Su X, Ye Q, Guo X, Xu B, Guan T, Chen A. The predictive value of diabetic retinopathy on subsequent diabetic nephropathy in patients with type 2 diabetes: a systematic review and meta-analysis of prospective studies. Ren Fail 2021; 43:231-240. [PMID: 33478336 PMCID: PMC7833016 DOI: 10.1080/0886022x.2020.1866010] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
This systematic review and meta-analysis aimed to assess the predictive value of diabetic retinopathy (DR) on further diabetic nephropathy (DN) risk in patients with type 2 diabetes (T2D) based on the prospective cohort studies. PubMed, Embase, and the Cochrane Library were systematically searched for eligible prospective cohort studies through March 2020. The predictive value of DR was assessed using sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the receiver operating characteristic curve (AUC) through the bivariate generalized linear mixed model and the random-effects model. Ten prospective cohort studies recruited 635 patients with T2D. The pooled sensitivity and specificity of DR for predicted DN were noted to be 0.64 (95% CI, 0.54–0.73) and 0.77 (95% CI, 0.60–0.88), respectively. The pooled PLR and NLR of DR for predicted DN were 2.72 (95% CI, 1.42–5.19) and 0.47 (95% CI, 0.33–0.67), respectively. The summary DOR for the relationship between DR and subsequent DN for T2D patients was 5.53 (95% CI, 2.00–15.30), and the AUC of DR for predicted DN was 0.73 (95% CI, 0.69–0.77). This study found significant associations between DR and subsequent DN risk for patients with T2D. Moreover, the predictive value of DR on subsequent DN risk was relatively lower.
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Affiliation(s)
- Yu Li
- Division of Nephrology, Zhongshan Hospital, Xiamen University, Xiamen, PR China
| | - Xiaoxuan Su
- Division of Nephrology, Zhongshan Hospital, Xiamen University, Xiamen, PR China
| | - Qing Ye
- Division of Nephrology, Zhongshan Hospital, Xiamen University, Xiamen, PR China
| | - Xiaodan Guo
- Division of Nephrology, Zhongshan Hospital, Xiamen University, Xiamen, PR China
| | - Bo Xu
- Division of Nephrology, Zhongshan Hospital, Xiamen University, Xiamen, PR China
| | - Tianjun Guan
- Division of Nephrology, Zhongshan Hospital, Xiamen University, Xiamen, PR China.,Teaching Hospital of Fujian Medical University, Xiamen, PR China
| | - Anqun Chen
- Division of Nephrology, Zhongshan Hospital, Xiamen University, Xiamen, PR China
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Hong X, Huang L, Zhang Y, Shen X, Weng S, Zeng F, Zhao F, Yan S. Stronger Association of Albuminuria with the Risk of Vascular Complications than Estimated Glomerular Filtration Rate in Type 2 Diabetes. Kidney Blood Press Res 2021; 46:550-562. [PMID: 34428770 DOI: 10.1159/000515163] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Accepted: 02/10/2021] [Indexed: 11/19/2022] Open
Abstract
INTRODUCTION Albuminuria is a risk factor for macro- and microvascular complications of type 2 diabetes (T2D).With an increasing trend of normoalbuminuria, however, of the 2 predictors - estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) - which one is a better predictor of vascular complications of T2D is not clear. OBJECTIVE This study aimed to compare the impacts of albuminuria and eGFR on patients with T2D associated with micro- and macrovascular complications. METHODS This retrospective study recruited 4,715 patients with T2D and grouped them based on the values of UACR (high UACR: ≥30 mg/g, low UACR: <30 mg/g) and eGFR (mL/[min × 1.73 m2]) (G1: eGFR ≥ 90; G2: eGFR = 60-89; G3-5: eGFR < 60) from April 2008 to November 2018. Logistic regression analysis was carried out for risk factors in patients with diabetic retinopathy (DR), diabetic peripheral neuropathy (DPN), peripheral arterial disease (PAD), left ventricular remodeling, diastolic disorders, and carotid atherosclerotic plaque in 6 different groups: low UACR + G1 (control group), low UACR + G2, low UACR + G3-5, high UACR + G1, high UACR + G2, and high UACR + G3-5. Patients were grouped according to the change in the UACR value (UACR-decreased group: ≤-30%, UACR-stable group: -30 to 30%, and UACR-increased group ≥30%), eGFR value (eGFR-decreased group: >3%, and eGFR-stable group: ≤3%) and followed up. RESULTS Compared with the control group, patients with higher albuminuria and lower eGFR had higher adjusted odds ratio (OR) trends of complications, especially in the high UACR + G3-5 group. The OR of 2.010, 3.444, 1.633, 2.742, and 3.014 were obtained for DR, DPN, PAD, left ventricular remodeling, and diastolic disorders, respectively. No statistically significant difference was found in the risk of complications within each one of 2 phenotypes, regardless of the change in the eGFR. After grouping by eGFR, the regression analysis of the urinary protein level in each stage revealed that a majority of complications had a statistically significant difference, except for DR and PAD in the high UACR + G3-5 group. DR in the follow-up study had a higher risk in the UACR-stable/increased group than the UACR-decreased group (UACR stable: OR = 2.568; 95% confidence interval (CI): 1.128-5.849; p = 0.025; UACR increased: OR = 2.489; 95% CI: 1.140-5.433; p = 0.022). CONCLUSION UACR is a more predictive risk factor for diabetic complications compared with a reduced eGFR.
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Affiliation(s)
- Xinyu Hong
- Department of Endocrinology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.,Fujian Province Clinical Research Center for Metabolic Diseases, Fuzhou, China.,Diabetes Research Institute of Fujian Province, Fuzhou, China.,Metabolic Diseases Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Lingning Huang
- Department of Endocrinology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.,Fujian Province Clinical Research Center for Metabolic Diseases, Fuzhou, China.,Diabetes Research Institute of Fujian Province, Fuzhou, China.,Metabolic Diseases Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Yongze Zhang
- Department of Endocrinology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.,Fujian Province Clinical Research Center for Metabolic Diseases, Fuzhou, China.,Diabetes Research Institute of Fujian Province, Fuzhou, China.,Metabolic Diseases Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Ximei Shen
- Department of Endocrinology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.,Fujian Province Clinical Research Center for Metabolic Diseases, Fuzhou, China.,Diabetes Research Institute of Fujian Province, Fuzhou, China.,Metabolic Diseases Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Suiyan Weng
- Department of Endocrinology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.,Fujian Province Clinical Research Center for Metabolic Diseases, Fuzhou, China.,Diabetes Research Institute of Fujian Province, Fuzhou, China.,Metabolic Diseases Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Feihui Zeng
- Department of Endocrinology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.,Fujian Province Clinical Research Center for Metabolic Diseases, Fuzhou, China.,Diabetes Research Institute of Fujian Province, Fuzhou, China.,Metabolic Diseases Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Fengying Zhao
- Department of Endocrinology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.,Fujian Province Clinical Research Center for Metabolic Diseases, Fuzhou, China.,Diabetes Research Institute of Fujian Province, Fuzhou, China.,Metabolic Diseases Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Sunjie Yan
- Department of Endocrinology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.,Fujian Province Clinical Research Center for Metabolic Diseases, Fuzhou, China.,Diabetes Research Institute of Fujian Province, Fuzhou, China.,Metabolic Diseases Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
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Sun L, Sun C, Zhou S, Zhang L, Hu W. Tamsulosin attenuates high glucose- induced injury in glomerular endothelial cells. Bioengineered 2021; 12:5184-5194. [PMID: 34402375 PMCID: PMC8806910 DOI: 10.1080/21655979.2021.1955527] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Diabetic nephropathy (DN) is a common complication of diabetes. Tamsulosin is a selective α1-AR antagonist. α1-AR is expressed widely in kidney tissues and has displayed its various physiological functions. However, whether Tamsulosin has affects DN is unknown. To our knowledge, this is the first time it has been examined whether Tamsulosin possesses a beneficial effect in high glucose-challenged glomerular endothelial cells (GECs). Firstly, we found that Tamsulosin reduced high glucose-induced expressions of TNF-α, IL-6, and IL-8. Secondly, Tamsulosin alleviated high glucose-induced expressions of MMP-2 and MMP-9. Thirdly, Tamsulosin inhibited the expressions of VCAM-1 and ICAM-1. Importantly, our results indicate that Tamsulosin inhibited high glucose-induced expressions of fibrosis factors such as Col-1 and TGF-β1. Additionally, we found that Tamsulosin ameliorated oxidative stress via reducing the generation of ROS and preventing the activation of p38. Mechanistically, we found that Tamsulosin attenuated high glucose-induced activation of NF-κB. Based on these findings, we conclude that Tamsulosin could attenuate high glucose-induced injury in GECs through alleviating oxidative stress and inflammatory response.
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Affiliation(s)
- Lin Sun
- Department of Pharmacy Intravenous Admixture Service, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Chengmin Sun
- Department of Traditional Chinese Medicine, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Shibo Zhou
- Inpatient Department Central Pharmacy, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Lan Zhang
- Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Wenping Hu
- Department of Nephrology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
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Vlacho B, Mata-Cases M, Mundet-Tudurí X, Vallès-Callol JA, Real J, Farre M, Cos X, Khunti K, Mauricio D, Franch-Nadal J. Analysis of the Adherence and Safety of Second Oral Glucose-Lowering Therapy in Routine Practice From the Mediterranean Area: A Retrospective Cohort Study. Front Endocrinol (Lausanne) 2021; 12:708372. [PMID: 34335477 PMCID: PMC8318034 DOI: 10.3389/fendo.2021.708372] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Accepted: 06/29/2021] [Indexed: 01/23/2023] Open
Abstract
The aims of our study was compare adherence measured by the medical possession ratio (MPR), time until discontinuation and describe adverse events after adding a DPP-4i, SGLT-2i, or sulfonylureas (SU) to metformin in a primary care population with insufficient glycemic control. We used routinely-collected health data from the SIDIAP database. The included subjects were matched by propensity score. The follow-up period was up to 24 months or premature discontinuation. The primary outcomes were the percentage of subjects with good adherence, treatment discontinuation and adverse events among treatment groups. The proportion of patients with good adherence (MPR> 0.8) after the addition of DPP-4i, SGLT-2i or SU was 53.6%, 68.7%, and 43.0%, respectively. SGLT-2i users were 1.7 times more likely to achieve good adherence compared with DPP-4i users (odds ratio [OR]:1.72, 98% confidence interval [CI]:1.51, 1.96), and 2.8 times more likely compared with SU users (OR: 0.35, 98% CI: 0.07, 0.29). The discontinuation hazard ratios were 1.43 (98%CI: 1.26; 1.62) and 1.60 (98%CI: 1.42; 1.81) times higher among SGLT-2i and SU users than DPP-4i users during the follow-up period. No differences were observed for adverse events among the treatment groups. In conclusion, in our real-world setting, the combination of SGLT-2i with metformin was associated with better adherence. The mean time until discontinuation was longer in the SGLT-2i group in comparison with the DPP-4i or SU groups.
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Affiliation(s)
- Bogdan Vlacho
- Grup de Recerca Epidemiològica en Diabetis des de l'Atenció Primària (DAP-CAT) Group, Unitat de Suport a la Recerca Barcelona, Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain
- Clinical Trials Unit, Germans Trias i Pujol Health Science Research Institute (IGTP), Barcelona, Spain
- Pharmacology Department, Universitat Autònoma de Barcelona (UAB), Cerdanyola del Vallès, Spain
| | - Manel Mata-Cases
- Grup de Recerca Epidemiològica en Diabetis des de l'Atenció Primària (DAP-CAT) Group, Unitat de Suport a la Recerca Barcelona, Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain
- CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Xavier Mundet-Tudurí
- Grup de Recerca Epidemiològica en Diabetis des de l'Atenció Primària (DAP-CAT) Group, Unitat de Suport a la Recerca Barcelona, Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain
- Departament of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Spain
| | - Joan-Antoni Vallès-Callol
- Grup de Recerca Epidemiològica en Diabetis des de l'Atenció Primària (DAP-CAT) Group, Unitat de Suport a la Recerca Barcelona, Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain
| | - Jordi Real
- Grup de Recerca Epidemiològica en Diabetis des de l'Atenció Primària (DAP-CAT) Group, Unitat de Suport a la Recerca Barcelona, Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain
- CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Magi Farre
- Pharmacology Department, Universitat Autònoma de Barcelona (UAB), Cerdanyola del Vallès, Spain
- Clinical Pharmacology Unit, Hospital Universitari Germans Trias i Pujol, Badalona, Spain
| | - Xavier Cos
- Grup de Recerca Epidemiològica en Diabetis des de l'Atenció Primària (DAP-CAT) Group, Unitat de Suport a la Recerca Barcelona, Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain
- Primary and Hospital Innovation Department, Innovation Office at Institut Català de la Salut, Barcelona, Spain
| | - Kamlesh Khunti
- Diabetes Research Centre, College of Life Sciences, University of Leicester, Leicester, United Kingdom
| | - Dídac Mauricio
- Grup de Recerca Epidemiològica en Diabetis des de l'Atenció Primària (DAP-CAT) Group, Unitat de Suport a la Recerca Barcelona, Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain
- CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Endocrinology and Nutrition, Hospital Universitari de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Bellaterra, Spain
- Departament of Medicine, University of Vic - Central University of Catalonia, Vic, Spain
| | - Josep Franch-Nadal
- Grup de Recerca Epidemiològica en Diabetis des de l'Atenció Primària (DAP-CAT) Group, Unitat de Suport a la Recerca Barcelona, Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain
- CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
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da Silva TA, Abreu LG, Esteves Lima RP. A meta-analysis on the effect of periodontal treatment on the glomerular filtration rate of chronic kidney disease individuals: A systematic review and meta-analysis was conducted to assess the impact of the periodontal treatment on the glomerular filtration rate of individuals with chronic kidney disease. SPECIAL CARE IN DENTISTRY 2021; 41:670-678. [PMID: 34231240 DOI: 10.1111/scd.12625] [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] [Received: 05/26/2021] [Accepted: 06/06/2021] [Indexed: 12/11/2022]
Abstract
AIMS The purpose of the present systematic review and meta-analysis was to assess the impact of periodontal treatment on the glomerular filtration rate (GFR) of individuals with chronic kidney disease (CKD). METHODS Searches were conducted in five databases. Restrictions on publication date or language were not imposed. Studies reporting the GFR of CKD individuals before and after periodontal treatment were included. Studies' selection, extraction of data and assessment of risk of bias were performed by two reviewers independently. The Methodological Index for non-randomized studies was employed for risk of bias assessment. Meta-analysis was carried out. RESULTS One hundred ninety-two references were retrieved and three studies were included. In all studies included, the periodontal intervention performed was non-surgical therapy. The three studies together assessed 77 individuals. The follow-up of participants after periodontal treatment varied between 3 and 6 months. Meta-analysis demonstrated that the GFR of individuals with CKD increased (improvement) after periodontal treatment (mean difference = 7.01, confidence interval = 0.66 - 13.36, I2 = 0%). Overall, included studies presented low risk of bias. CONCLUSION Despite the limited evidence of this systematic review and meta-analysis, periodontal treatment seems to improve the GFR of CKD individuals, with positive repercussions on their renal function.
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Affiliation(s)
- Thales Araújo da Silva
- Division of Periodontology, Dentistry School, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | - Lucas Guimarães Abreu
- Division of Pediatric Dentistry, Dentistry School, Federal University of Minas Gerais, Belo Horizonte, Brazil
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Farah RI, Al-Sabbagh MQ, Momani MS, Albtoosh A, Arabiat M, Abdulraheem AM, Aljabiri H, Abufaraj M. Diabetic kidney disease in patients with type 2 diabetes mellitus: a cross-sectional study. BMC Nephrol 2021; 22:223. [PMID: 34134654 PMCID: PMC8207700 DOI: 10.1186/s12882-021-02429-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Accepted: 05/31/2021] [Indexed: 12/16/2022] Open
Abstract
Aim Diabetic kidney disease (DKD) is a major long-term complication of diabetes mellitus (DM). Given the paucity of data on DKD in Jordan, we aimed to evaluate the prevalence, characteristics and correlates of DKD in Jordanian patients with type 2 DM. Methods This cross-sectional study included 1398 adult patients with type 2 DM who sought medical advice in the endocrinology clinic between March and September 2019. Demographic, clinical and laboratory data were reviewed. DKD was defined as reduced eGFR, and/or albuminuria. Three regression models were constructed to identify factors associated with CKD stages, albuminuria and DKD. Results Overall, 701 (50.14%) patients had DKD, with a median age of 59.71 ± 11.36 years. Older age, high triglycerides, and low high-density lipoprotein were associated with DKD (multivariable odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.01–1.03, p < 0.01; OR: 1.1, 95% CI: 1.01–1.2; and OR: 0.98, 95% CI: 0.97–0.99, p < 0.01 respectively). Metformin and renin-angiotensin system blockers were negatively associated with albuminuria and chronic kidney disease stages (p < 0.01). Conclusion Our study demonstrated that approximately one half of patients with type 2 DM had DKD. Further studies are necessary to understand this high prevalence and the underlying factors. Future research are needed to assess implementing targeted community-based intervention.
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Affiliation(s)
- Randa I Farah
- Department of Internal Medicine, School of Medicine, University of Jordan, Amman, Jordan.
| | | | - Munther S Momani
- Department of Internal Medicine, School of Medicine, University of Jordan, Amman, Jordan
| | - Asma Albtoosh
- Department of Internal Medicine, School of Medicine, University of Jordan, Amman, Jordan
| | - Majd Arabiat
- Department of Internal Medicine, School of Medicine, University of Jordan, Amman, Jordan
| | | | | | - Mohammad Abufaraj
- Division of Urology, Department of Special Surgery, Jordan University Hospital, The University of Jordan, Amman, Jordan.,Department of Urology, Medical University of Vienna, Vienna, Austria
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Kene K, Wondimnew T, Welde M, Mateos T, Adugna T, Gerema U, Abdisa D, Abera D. Prevalence and determinants of Impaired Serum Creatinine and Urea among type 2 diabetic patients of jimma medical center, Jimma, Southwestern Ethiopia, 2019. ENDOCRINE AND METABOLIC SCIENCE 2021. [DOI: 10.1016/j.endmts.2021.100096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
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Santoro D, Torreggiani M, Pellicanò V, Cernaro V, Messina RM, Longhitano E, Siligato R, Gembillo G, Esposito C, Piccoli GB. Kidney Biopsy in Type 2 Diabetic Patients: Critical Reflections on Present Indications and Diagnostic Alternatives. Int J Mol Sci 2021; 22:5425. [PMID: 34063872 PMCID: PMC8196671 DOI: 10.3390/ijms22115425] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 05/11/2021] [Accepted: 05/18/2021] [Indexed: 12/15/2022] Open
Abstract
Roughly 3% of patients worldwide with a new diagnosis of type 2 diabetes mellitus (T2DM) already have an overt nephropathy at diagnosis and about 20-30% of the remaining ones develop a complication of this kind later in life. The early identification of kidney disease in diabetic patients is important as it slows its progression, which is important not only because this reduces the need for renal replacement therapy, but also because it decreases the high rate of mortality and morbidity associated with a reduction in kidney function. The increasing prevalence of type 2 diabetes and the consequent greater probability of finding different types of kidney diseases in diabetic patients frequently gives rise to overlapping diagnoses, a definition encompassing the differential diagnosis between diabetic and non-diabetic kidney disease. The issue is made more complex by the acknowledgement of the increasing frequency of presentations of what is termed "diabetic kidney disease" without relevant proteinuria, in particular in T2DM patients. Distinguishing between diabetes related and non-diabetes related forms of kidney disease in diabetic patients is not only a semantic question, as different diseases require different clinical management. However, while the urologic and macrovascular complications of diabetes, as well as overlapping parenchymal damage, can be diagnosed by means of imaging studies, often only a kidney biopsy will make a differential diagnosis possible. In fact, the coexistence of typical diabetic lesions, such as nodular glomerulopathy or glomerulosclerosis, with different glomerular, vascular and tubulo-interstitial alterations has been extensively described, and an analysis of the dominant histological pattern can contribute to determining what therapeutic approach should be adopted. However, due to the high frequency of kidney diseases, and to the fact that T2DM patients are often affected by multiple comorbidities, a kidney biopsy is not generally performed in T2DM patients. What follows is a review aiming to discuss the diagnostic work-up, on the base of clinical, laboratory and imaging criteria, and evaluate the present indications and alternatives to renal biopsy.
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Affiliation(s)
- Domenico Santoro
- Unit of Nephrology, Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy; (D.S.); (V.P.); (V.C.); (R.M.M.); (E.L.); (R.S.); (G.G.)
| | - Massimo Torreggiani
- Néphrologie et Dialyse, Centre Hospitalier Le Mans, 194 Avenue Rubillard, 72037 Le Mans, France;
| | - Vincenzo Pellicanò
- Unit of Nephrology, Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy; (D.S.); (V.P.); (V.C.); (R.M.M.); (E.L.); (R.S.); (G.G.)
| | - Valeria Cernaro
- Unit of Nephrology, Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy; (D.S.); (V.P.); (V.C.); (R.M.M.); (E.L.); (R.S.); (G.G.)
| | - Roberta Maria Messina
- Unit of Nephrology, Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy; (D.S.); (V.P.); (V.C.); (R.M.M.); (E.L.); (R.S.); (G.G.)
| | - Elisa Longhitano
- Unit of Nephrology, Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy; (D.S.); (V.P.); (V.C.); (R.M.M.); (E.L.); (R.S.); (G.G.)
| | - Rossella Siligato
- Unit of Nephrology, Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy; (D.S.); (V.P.); (V.C.); (R.M.M.); (E.L.); (R.S.); (G.G.)
| | - Guido Gembillo
- Unit of Nephrology, Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy; (D.S.); (V.P.); (V.C.); (R.M.M.); (E.L.); (R.S.); (G.G.)
| | - Ciro Esposito
- Unit of Nephrology and Dialysis, Department of Internal Medicine, ICS Maugeri S.p.A. SB, University of Pavia, 27100 Pavia, Italy;
| | - Giorgina Barbara Piccoli
- Néphrologie et Dialyse, Centre Hospitalier Le Mans, 194 Avenue Rubillard, 72037 Le Mans, France;
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