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Yabe T, Tsuruyama Y, Nomura K, Fujii A, Matsuda Y, Okada K, Yamakoshi S, Hamabe Y, Omote S, Shioya A, Hayashi N, Fujimoto K, Todo Y, Tanaka T, Yamada S, Shimizu A, Miyazawa K, Yokoyama H, Furuichi K. Exploring the subtle and novel renal pathological changes in diabetic nephropathy using clustering analysis with deep learning. Sci Rep 2025; 15:2018. [PMID: 39814818 PMCID: PMC11735863 DOI: 10.1038/s41598-024-84588-6] [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: 07/26/2024] [Accepted: 12/24/2024] [Indexed: 01/18/2025] Open
Abstract
To decrease the number of chronic kidney disease (CKD), early diagnosis of diabetic kidney disease is required. We performed invariant information clustering (IIC)-based clustering on glomerular images obtained from nephrectomized kidneys of patients with and without diabetes. We also used visualizing techniques (gradient-weighted class activation mapping (Grad-CAM) and generative adversarial networks (GAN)) to identify the novel and early pathological changes on light microscopy in diabetic nephropathy. Overall, 13,251 glomerular images (7,799 images from diabetes cases and 5,542 images from non-diabetes cases) obtained from 45 patients in Kanazawa Medical University were clustered into 10 clusters by IIC. Diabetic clusters that mainly contained glomerular images from diabetes cases (Clusters 0, 1, and 2) and non-diabetic clusters that mainly contained glomerular images from non-diabetes cases (Clusters 8 and 9) were distinguished in the t-distributed stochastic neighbor embedding (t-SNE) analysis. Grad-CAM demonstrated that the outer portions of glomerular capillaries in diabetic clusters had characteristic lesions. Cycle-GAN showed that compared to Bowman's space, smaller glomerular tufts was a characteristic lesion of diabetic clusters. These findings might be the subtle and novel pathological changes on light microscopy in diabetic nephropathy.
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Affiliation(s)
- Tomohisa Yabe
- Department of Nephrology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, 920-0293, Ishikawa, Japan
| | - Yuko Tsuruyama
- Department of Internal medicine, Futatsuya Hospital, Kahoku, Japan
| | - Kazutoshi Nomura
- Department of Nephrology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, 920-0293, Ishikawa, Japan
| | - Ai Fujii
- Department of Nephrology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, 920-0293, Ishikawa, Japan
| | - Yuto Matsuda
- Department of Nephrology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, 920-0293, Ishikawa, Japan
| | - Keiichiro Okada
- Department of Nephrology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, 920-0293, Ishikawa, Japan
| | - Shogo Yamakoshi
- Division of Electrical, Information and Communication Engineering, Kanazawa University, Kanazawa, Japan
| | - Yuya Hamabe
- Division of Electrical, Information and Communication Engineering, Kanazawa University, Kanazawa, Japan
| | - Shogo Omote
- Division of Electrical, Information and Communication Engineering, Kanazawa University, Kanazawa, Japan
| | - Akihiro Shioya
- Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Uchinada, Japan
| | - Norifumi Hayashi
- Department of Nephrology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, 920-0293, Ishikawa, Japan
| | - Keiji Fujimoto
- Department of Nephrology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, 920-0293, Ishikawa, Japan
| | - Yuki Todo
- Faculty of Electrical, Information and Communication Engineering, Kanazawa University, Kanazawa, Japan
| | - Tatsuro Tanaka
- Department of Urology, Kanazawa Medical University, Uchinada, Japan
| | - Sohsuke Yamada
- Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Uchinada, Japan
| | - Akira Shimizu
- Department of Analytic human pathology, Nippon Medical School, Sendagi, Japan
| | | | - Hitoshi Yokoyama
- Department of Nephrology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, 920-0293, Ishikawa, Japan
| | - Kengo Furuichi
- Department of Nephrology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, 920-0293, Ishikawa, Japan.
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Makvandi K, Eliasson B, Carlsen HK, Baid-Agrawal S. Burden and Excess Risk of Adverse Outcomes in Patients With Type 1 Diabetes Using KDIGO Classification: A National Cohort Study. Diabetes Care 2025; 48:106-117. [PMID: 39565836 DOI: 10.2337/dc24-0908] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Accepted: 10/18/2024] [Indexed: 11/22/2024]
Abstract
OBJECTIVE The widely adopted Kidney Disease: Improving Global Outcomes (KDIGO) classification system has been underused in assessing the burden and risk of adverse outcomes in type 1 diabetes. This observational study aimed to clarify how each KDIGO category correlates with adverse outcomes in this patient group. RESEARCH DESIGN AND METHODS In a cohort of 40,199 individuals with type 1 diabetes from the Swedish National Diabetes Register, we aimed to investigate the 1) prevalence of different KDIGO categories at baseline; 2) incidence of adverse kidney and cardiovascular (CV) outcomes, including mortality, within each category; and 3) association of baseline category with excess risk of five outcomes: a 40% decline in estimated glomerular filtration rate (eGFR), kidney failure, major adverse kidney/CV events, and all-cause mortality. Cox regression analyses were conducted using three different reference categories: 1) the conventional low-risk "combined G1A1 + G2A1"; 2) "G1A1" alone to assess whether G2A1 had excess risk; and 3) "G1bA1" alone to evaluate whether eGFR ≥105 mL/min/1.73 m2 had increased risk. RESULTS Among 39,067 included patients, with a mean follow-up of 9.1 years, 18.5% presented with chronic kidney disease (CKD), defined as eGFR <60 mL/min/1.73 m2 and/or albuminuria. A progressive increase in the incidence and adjusted hazard ratio for all studied outcomes was found with advancing eGFR and albuminuria categories, including in G2A1 (non-CKD). An eGFR ≥105 mL/min/1.73 m2 without albuminuria was not associated with increased risk. CONCLUSIONS A progressively increasing burden of all studied adverse outcomes was observed with advancing KDIGO categories. Even individuals with preserved eGFR and normoalbuminuria (G2A1), conventionally perceived as non-CKD, had an excess risk for all outcomes.
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Affiliation(s)
- Kianoush Makvandi
- Department of Molecular and Clinical Medicine, The Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Nephrology, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Björn Eliasson
- Department of Molecular and Clinical Medicine, The Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- National Diabetes Register, Centre of Registries in Region Western Sweden, Gothenburg, Sweden
| | - Hanne Krage Carlsen
- National Diabetes Register, Centre of Registries in Region Western Sweden, Gothenburg, Sweden
| | - Seema Baid-Agrawal
- Department of Molecular and Clinical Medicine, The Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Transplant Center, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden
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Zeng W, Ying D, Chen B, Wang P. Endothelial Dysfunction in the Tubule Area Accelerates the Progression of Early Diabetic Kidney Disease. Physiol Res 2024; 73:1013-1024. [PMID: 39903891 PMCID: PMC11835216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2024] [Accepted: 09/03/2024] [Indexed: 02/06/2025] Open
Abstract
Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. Therefore, understanding the molecular regulatory mechanisms underlying the pathogenesis of DKD is imperative. In this study, we aimed to explore the molecular mechanisms of tubule region endothelial dysfunction in early DKD. Early-stage DKD model was established in 16-week-old female db/db mice for 16 weeks. Body weight, glucose level, and urine albumin-to-creatinine ratio (UACR) were measured. Hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining were performed to evaluate pathological lesions. RNA sequencing data of the kidneys and integrated publicly available single-cell and spatial transcriptome datasets were used to investigate the mechanism of endothelial dysfunction. There was a significant increase in body weight (p = 0.001), glucose levels (p=0.0008), and UACR (p=0.006) in db/db mice compared with db/m mice. H&E and PAS staining showed that vacuolar lesions and protein casts of tubules were the major histopathological changes observed in early-stage DKD mice. The apoptotic pathway in endothelial cells was notably activated in DKD, and Thbs1 was identified as the central gene involved in this apoptotic process. Deconvolution of the cell composition in the RNA sequencing data showed a decrease in the proportion of endothelial cells in the DKD mice. Further analysis of the activity and regulatory network of transcription factors showed that Creb1 was activated in both mouse and human early-stage DKD, suggesting that Creb1 activation may be involved in early kidney injury. The endothelial cell apoptotic pathway is activated in DKD, and the proportion of endothelial cells was reduced in the DKD mice, which is significantly associated with Thbs1. Keywords: Diabetic kidney disease, Endothelial dysfunction, RNA sequencing,Thbs1, Creb1.
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Affiliation(s)
- W Zeng
- Blood Purification Center & Department of Nephrology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
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Xing J, Huang L, Ren W, Mei X. Risk factors for rapid kidney function decline in diabetes patients. Ren Fail 2024; 46:2398188. [PMID: 39258389 PMCID: PMC11391878 DOI: 10.1080/0886022x.2024.2398188] [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: 06/10/2024] [Revised: 08/15/2024] [Accepted: 08/23/2024] [Indexed: 09/12/2024] Open
Abstract
Diabetic nephropathy, as a severe microvascular complication of diabetes, manifests in four clinical types: classic, albuminuria regression, a rapid decline in kidney function (RDKF), and non-proteinuric or non-albuminuric DKD. Rapidly progressive diabetic nephropathy advances to end-stage renal disease more swiftly than the typical form, posing significant risks. However, a comprehensive understanding of rapidly progressive diabetic nephropathy is currently lacking. This article reviewed latest developments in genetic and clinical risk factors associated with rapidly progressive diabetic nephropathy, aiming to broad perspectives concerning the diagnosis and interventions of this condition.
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Affiliation(s)
- Jixin Xing
- Department of Nephrology, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, China
| | - Linxi Huang
- Department of Nephrology, PLA Navy No. 905 Hospital, Naval Medical University (Second Military Medical University), Shanghai, China
| | - Weifu Ren
- Department of Nephrology, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, China
| | - Xiaobin Mei
- Department of Nephrology, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, China
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Poulsen CG, Jesse K, Carstensen B, Frimodt-Møller M, Hansen TW, Persson F, Vistisen D, Rossing P. Prognosis for Type 1 Diabetes with Diabetic Nephropathy between 2000 and 2020 - Changes in Kidney Function Decline Over Time and Development of Cardiovascular Disease, Kidney Failure, and Mortality. Kidney Int Rep 2024; 9:3403-3413. [PMID: 39698347 PMCID: PMC11652190 DOI: 10.1016/j.ekir.2024.09.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 09/13/2024] [Accepted: 09/16/2024] [Indexed: 12/20/2024] Open
Abstract
Introduction Individuals with type 1 diabetes (T1D) and diabetic nephropathy (DN) experience progressive kidney function decline and high risk of cardiovascular disease (CVD) and mortality. This study explored changes in kidney function decline in new-onset DN between 2000 and 2020 and provided an updated prognosis for risk of kidney failure, CVD, and mortality. Methods This is a register-based cohort study in T1D with new-onset DN (severely increased albuminuria) between 2000 and 2020 at Steno Diabetes Center Copenhagen, Denmark. Data were derived from electronic health records and national registers. Kidney function development was expressed as trajectories of estimated glomerular filtration rate (eGFR) and measured GFR (mGFR) using mixed-effects models. The prognosis was presented in probabilities of developing complications, stratified by sex, prior CVD, and risk factor control by using simulations based on Poisson regression analysis. Results The cohort comprised 591 individuals with median (interquartile range [IQR]) age at DN onset of 53 (39-66) years and 57% were male. In 283 participants, mGFR were available. Plots of eGFR trajectories illustrated tendencies toward higher eGFR in more recent years; however, this was not confirmed in mGFR trajectories. Poor risk factor control, prior CVD, and male sex impacted mortality and morbidity rates negatively. For men and women with fair risk factor control and no prior CVD, the 10-year mortality rate from onset of DN was 28% and 26%, respectively. For men and women with poor risk factor control and CVD prior to DN onset, the 10-year-mortality rate was 62% for each sex. Conclusion The results do not support an improved prognosis for T1D and DN, emphasizing the urgent need for new therapeutic approaches.
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Affiliation(s)
| | - Kristin Jesse
- Clinical Epidemiological Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
| | - Bendix Carstensen
- Clinical Epidemiological Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
| | | | - Tine W. Hansen
- Complications Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Frederik Persson
- Complications Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
| | - Dorte Vistisen
- Clinical Epidemiological Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
- Novo Nordisk Denmark A/S, Copenhagen, Denmark
| | - Peter Rossing
- Complications Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Song T, Wang R, Zhou X, Chen W, Chen Y, Liu Z, Men L. Metabolomics and molecular dynamics unveil the therapeutic potential of epalrestat in diabetic nephropathy. Int Immunopharmacol 2024; 140:112812. [PMID: 39094360 DOI: 10.1016/j.intimp.2024.112812] [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: 05/19/2024] [Revised: 07/12/2024] [Accepted: 07/24/2024] [Indexed: 08/04/2024]
Abstract
Diabetic nephropathy (DN) is one of the leading clinical causes of end-stage renal failure. The classical aldose reductase (AR) inhibitor epalrestat shows beneficial effect on renal dysfunction induced by DN, with metabolic profile and molecular mechanisms remains to be investigated further. In the current study, integrated untargeted metabolomics, network pharmacology and molecular dynamics approaches were applied to explore the therapeutic mechanisms of epalrestat against DN. Firstly, untargeted serum and urine metabolomics analysis based on UPLC-Q-TOF-MS was performed, revealed that epalrestat could regulate the metabolic disorders of amino acids metabolism, arachidonic acid metabolism, pyrimidine metabolism and citrate cycle metabolism pathways after DN. Subsequently, metabolomics-based network analysis was carried out to predict potential active targets of epalrestat, mainly involving AGE-RAGE signaling pathway, TNF signaling pathway and HIF-1 signaling pathway. Moreover, a 100 ns molecular dynamics approach was employed to validate the interactions between epalrestat and the core targets, showing that epalrestat could form remarkable tight binding with GLUT1 and NFκB than it with AR. Surface-plasmon resonance assay further verified epalrestat could bind GLUT1 and NFκB proteins specifically. Overall, integrated system network analysis not only demonstrated that epalrestat could attenuate DN induced metabolic disorders and renal injuries, but also revealed that it could interact with multi-targets to play a synergistic regulatory role in the treatment of DN.
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Affiliation(s)
- Tongtong Song
- College of Basic Medical Sciences, Jilin University, Changchun 130021, PR China
| | - Rongjin Wang
- School of Pharmaceutical Sciences, Jilin University, Changchun 130021, PR China
| | - Xiaoyue Zhou
- The First Hospital of Jilin University, Changchun 130052, PR China
| | - Weijia Chen
- College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, PR China
| | - Ying Chen
- The First Hospital of Jilin University, Changchun 130052, PR China
| | - Zhongying Liu
- School of Pharmaceutical Sciences, Jilin University, Changchun 130021, PR China
| | - Lihui Men
- College of Basic Medical Sciences, Jilin University, Changchun 130021, PR China.
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Deng Y, Zhang S, Luo Z, He P, Ma X, Ma Y, Wang J, Zheng L, Tian N, Dong S, Zhang X, Zhang M. VCAM1: an effective diagnostic marker related to immune cell infiltration in diabetic nephropathy. Front Endocrinol (Lausanne) 2024; 15:1426913. [PMID: 39319258 PMCID: PMC11420029 DOI: 10.3389/fendo.2024.1426913] [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: 05/02/2024] [Accepted: 08/13/2024] [Indexed: 09/26/2024] Open
Abstract
Introduction The role of immune cells in the pathogenesis and advancement of diabetic nephropathy (DN) is crucial. The objective of this study was to identify immune-cell-related biomarkers that could potentially aid in the diagnosis and management of DN. Methods The GSE96804 dataset was obtained from the Gene Expression Omnibus (GEO) database. Then, screen for intersections between differentially expressed genes (DEGs) and immune-related genes (IRGs). Identify core genes through protein-protein interaction (PPI) networks and the Cytoscape plugin. Subsequently, functional enrichment analysis was conducted. In addition, ROC analysis is performed to accurately identify diagnostic biomarkers. Apply the CIBERSORT algorithm to evaluate the proportion of immune cell infiltration. Finally, the mRNA, protein, and immunofluorescence expression of the biomarker was validated in the DN rat model. Results The study yielded 74 shared genes associated with DN. Enrichment analysis indicated significant enrichment of these genes in focal adhesion, the humoral immune response, activation of the immune response, Cytokine-cytokine receptor interaction, and IL-17 signaling pathway. The optimal candidate gene VCAM1 was identified. The presence of VCAM1 in DN was further validated using the ROC curve. Analysis of immune cell infiltration matrices revealed a high abundance of monocytes, naïve B cells, memory B cells, and Macrophages M1/M2 in DN tissues. Correlation analysis identified one hub biomarker associated with immune-infiltrated cells in DN. Furthermore, our findings were validated through in vivo RT qPCR, WB, and IF techniques. Conclusions Our research indicates that VCAM1 is a signature gene associated with DN and is linked to the progression, treatment, and prognosis of DN. A comprehensive examination of immune infiltration signature genes may offer new perspectives on the clinical diagnosis and management of DN.
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Affiliation(s)
- Yuanyuan Deng
- Department of Nephrology, Tianjin Academy of Traditional Chinese Medicine, Tianjin, China
| | - Sai Zhang
- Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Zheng Luo
- College of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Pengfei He
- Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Xinyu Ma
- Department of Clinical Medicine, Tianjin Medical University, Tianjin, China
| | - Yu Ma
- Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Jing Wang
- Department of Nephrology, Tianjin Academy of Traditional Chinese Medicine, Tianjin, China
| | - Liyang Zheng
- Department of Nephrology, Tianjin Academy of Traditional Chinese Medicine, Tianjin, China
| | - Ni Tian
- Department of Nephrology, Tianjin Academy of Traditional Chinese Medicine, Tianjin, China
| | - Shaoning Dong
- Department of Nephrology, Tianjin Academy of Traditional Chinese Medicine, Tianjin, China
| | - Xingkun Zhang
- Department of Nephrology, Tianjin Academy of Traditional Chinese Medicine, Tianjin, China
| | - Mianzhi Zhang
- Department of Nephrology, Tianjin Academy of Traditional Chinese Medicine, Tianjin, China
- Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
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Ayis S, Mangelis A, Fountoulakis N, Collins J, Alobaid TS, Gnudi L, Hopkins D, Vas P, Thomas S, Goubar A, Karalliedde J. Ten years trajectories of estimated glomerular filtration rate (eGFR) in a multiethnic cohort of people with type 1 diabetes and preserved renal function. BMJ Open 2024; 14:e083186. [PMID: 39260863 PMCID: PMC11409247 DOI: 10.1136/bmjopen-2023-083186] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Accepted: 07/31/2024] [Indexed: 09/13/2024] Open
Abstract
OBJECTIVES We aim to evaluate estimated glomerular filtration rate (eGFR) patterns of progression in a multiethnic cohort of people with type I diabetes mellitus and with baseline eGFR ≥45 mL/min/1.73 m2. DESIGN Observational cohort. SETTING People with a clinical diagnosis of type 1 diabetes, attending two university hospital-based outpatient diabetes clinics, in South London between 2004 and 2018. PARTICIPANTS We studied 1495 participants (52% females, 81% white, 12% African-Caribbean and 7% others). PRIMARY AND SECONDARY OUTCOME MEASURES Clinical measures including weight and height, systolic blood pressure, diastolic blood pressure and laboratory results (such as serum creatinine, urine albumin to creatinine ratio (ACR), HbA1c were collected from electronic health records (EHRs) and eGFR was estimated by the Chronic Kidney Disease-Epidemiology Collaboration. Ethnicity was self-reported. RESULTS Five predominantly linear patterns/groups of eGFR trajectories were identified. Group I (8.5%) had a fast eGFR decline (>3 mL/min/1.73 m2 year). Group II (23%) stable eGFR, group III (29.8%), groups IV (26.3%) and V (12.4%) have preserved eGFR with no significant fall. Group I had the highest proportion (27.6%) of African-Caribbeans. Significant differences between group I and the other groups were observed in age, gender, HbA1C, systolic and diastolic blood pressure, body mass index, cholesterol and urine ACR, p<0.05 for all. At 10 years of follow-up, 33% of group I had eGFR <30 and 16.5%<15 (mL/min/1.73 m2). CONCLUSIONS Distinct trajectories of eGFR were observed in people with type 1 diabetes. The group with the highest risk of eGFR decline had a greater proportion of African-Caribbeans compared with others and has higher prevalence of traditional modifiable risk factors for kidney disease.
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Affiliation(s)
- Salma Ayis
- Population Health Sciences, King's College London, London, UK
| | | | - Nikolaos Fountoulakis
- King’s Health Partners and School of Cardiovascular Medicine & Sciences, King’s College London, London, UK
| | - Julian Collins
- King's College Hospital NHS Trust, King's College London, London, UK
| | | | - Luigi Gnudi
- King’s Health Partners and King's College London British Heart Foundation Centre of Excellence, School of Cardiovascular & Metabolic Medicine and Sciences, King's College London, London, UK
| | - David Hopkins
- King's College Hospital NHS Foundation Trust / King's Health Partners, King's College London, London, UK
| | - Prashanth Vas
- Diabetes and Endocrinology, King's College Hospital NHS Foundation Trust, London, UK
| | - Stephen Thomas
- Guy's and St Thomas' NHS Trust, King’s Health Partners, London, UK
| | - Aicha Goubar
- Population Health Sciences, King's College London, London, UK
| | - Janaka Karalliedde
- King’s Health Partners and King's College London British Heart Foundation Centre of Excellence, School of Cardiovascular & Metabolic Medicine and Sciences, King's College London, London, UK
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Casey C, Buckley CM, Kearney PM, Griffin MD, Dinneen SF, Griffin TP. The impact of social deprivation on development and progression of diabetic kidney disease. HRB Open Res 2024; 7:53. [PMID: 39301450 PMCID: PMC11411243 DOI: 10.12688/hrbopenres.13941.1] [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: 07/29/2024] [Indexed: 09/22/2024] Open
Abstract
Introduction Diabetes is one of the leading causes of chronic kidney disease. Social deprivation is recognised as a risk factor for complications of diabetes, including diabetic kidney disease. The effect of deprivation on rate of decline in renal function has not been explored in the Irish Health System to date. The objective of this study is to explore the association between social deprivation and the development/progression of diabetic kidney disease in a cohort of adults living with diabetes in Ireland. Methods This is a retrospective cohort study using an existing dataset of people living with diabetes who attended the diabetes centre at University Hospital Galway from 2012 to 2016. The variables included in this dataset include demographic variables, type and duration of diabetes, clinical variables such as medication use, blood pressure and BMI and laboratory data including creatinine, urine albumin to creatinine to ratio, haemoglobin A1c and lipids. This dataset will be updated with laboratory data until January 2023. Individual's addresses will be used to calculate deprivation indices using the Pobal Haase Pratschke (HP) deprivation index. Rate of renal function decline will be calculated using linear mixed-effect models. The relationship between deprivation and renal function will be assessed using linear regression (absolute and relative rate of renal function decline based on eGFR) and logistic regression models (rapid vs. non-rapid decline).
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Affiliation(s)
- Caoimhe Casey
- School of Public Health, University College Cork, Cork, County Cork, Ireland
- Centre for Diabetes, Endocrinology and Metabolism, Galway University Hospitals, Galway, County Galway, Ireland
| | - Claire M Buckley
- School of Public Health, University College Cork, Cork, County Cork, Ireland
| | - Patricia M Kearney
- School of Public Health, University College Cork, Cork, County Cork, Ireland
| | - Matthew D Griffin
- Regenerative Medicine Institute (REMEDI) at CURAM SFI Research Centre for Medical Devices, School of Medicine, University of Galway, Galway, County Galway, Ireland
- Department of Nephrology, Galway University Hospital, Galway, County Galway, Ireland
| | - Sean F Dinneen
- Centre for Diabetes, Endocrinology and Metabolism, Galway University Hospitals, Galway, County Galway, Ireland
- School of Medicine, University of Galway, Galway, County Galway, Ireland
| | - Tomas P Griffin
- Centre for Diabetes, Endocrinology and Metabolism, Galway University Hospitals, Galway, County Galway, Ireland
- School of Medicine, University of Galway, Galway, County Galway, Ireland
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Rossing P, Groop PH, Singh R, Lawatscheck R, Tuttle KR. Prevalence of Chronic Kidney Disease in Type 1 Diabetes Among Adults in the U.S. Diabetes Care 2024; 47:1395-1399. [PMID: 38857124 PMCID: PMC11272963 DOI: 10.2337/dc24-0335] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Accepted: 05/02/2024] [Indexed: 06/12/2024]
Abstract
OBJECTIVE The prevalence of chronic kidney disease (CKD) in adults ≥18 years of age with type 1 diabetes in the U.S. was determined using National Health and Nutrition Examination Survey (NHANES) data. RESEARCH DESIGN AND METHODS A modified treatment-based algorithm applying a subset of NHANES diabetes questionnaires was used. The number of respondents with CKD and type 1 diabetes was weighted (extrapolated) to the U.S. population. RESULTS Based on data between 2015 and 2018, type 1 diabetes was identified in 47 out of 19,225 adults with evaluable kidney function data. CKD was present in 20 out of 47 people identified with type 1 diabetes. The weighted estimate of CKD in type 1 diabetes was 21.5%, corresponding to 258,196 (95% CI 71,189-445,203) people in the U.S. CONCLUSIONS Applying a conservative approach in our study indicates that CKD is common in adults with type 1 diabetes in the U.S.
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Affiliation(s)
- Peter Rossing
- Steno Diabetes Center Copenhagen, Herlev, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Per-Henrik Groop
- Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland
- Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
- Department of Diabetes, Central Clinical School, Monash University, Melbourne, Australia
| | | | | | - Katherine R. Tuttle
- Providence Inland Northwest Health, University of Washington School of Medicine, Spokane, WA
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Zahr NM, Pfefferbaum A. Serum albumin and white matter hyperintensities. Transl Psychiatry 2024; 14:233. [PMID: 38824150 PMCID: PMC11144249 DOI: 10.1038/s41398-024-02953-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Revised: 05/15/2024] [Accepted: 05/20/2024] [Indexed: 06/03/2024] Open
Abstract
People living with HIV and those diagnosed with alcohol use disorders (AUD) relative to healthy individuals commonly have low levels of serum albumin, substantiated as an independent predictor of cardiovascular events. White matter hyperintensities (WMH)-a neuroimaging feature of cerebral small vessel disease-are also related to cardiovascular disease. Despite consensus regarding associations between high levels of urine albumin and WMH prevalence, and low serum albumin levels and impaired cognitive functioning, relations between serum albumin and WMH burdens have rarely been evaluated. Here, a sample including 160 individuals with AUD, 142 living with HIV, and 102 healthy controls was used to test the hypothesis that serum albumin would be inversely related to WMH volumes and directly related to cognitive performance in the two diagnostic groups. Although serum albumin and periventricular WMH volumes showed an inverse relationship in both AUD and HIV groups, this relationship persisted only in the HIV group after consideration of traditional cardiovascular (i.e., age, sex, body mass index (BMI), nicotine use, hypertension, diabetes), study-relevant (i.e., race, socioeconomic status, hepatitis C virus status), and disease-specific (i.e., CD4 nadir, HIV viral load, HIV duration) factors. Further, serum albumin contributed more significantly than periventricular WMH volume to variance in performance on a verbal learning and memory composite score in the HIV group only. Relations in both HIV and AUD groups between albumin and hematological red blood cell markers (e.g., hemoglobin, hematocrit) suggest that in this sample, serum albumin reflects hematological abnormalities. Albumin, a simple serum biomarker available in most clinical settings, may therefore help identify periventricular WMH burden and performance levels in specific cognitive domains in people living with HIV. Whether serum albumin contributes mechanistically to periventricular WMH in HIV will require additional investigation.
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Affiliation(s)
- Natalie M Zahr
- Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
- Neuroscience Program, SRI International, Menlo Park, CA, USA.
| | - Adolf Pfefferbaum
- Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
- Neuroscience Program, SRI International, Menlo Park, CA, USA
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12
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Chen Z, Satake E, Pezzolesi MG, Dom ZIM, Stucki D, Kobayashi H, Syreeni A, Johnson AT, Wu X, Dahlström EH, King JB, Groop PH, Rich SS, Sandholm N, Krolewski AS, Natarajan R. Integrated analysis of blood DNA methylation, genetic variants, circulating proteins, microRNAs, and kidney failure in type 1 diabetes. Sci Transl Med 2024; 16:eadj3385. [PMID: 38776390 PMCID: PMC11806497 DOI: 10.1126/scitranslmed.adj3385] [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: 06/28/2023] [Accepted: 04/30/2024] [Indexed: 05/25/2024]
Abstract
Variation in DNA methylation (DNAmet) in white blood cells and other cells/tissues has been implicated in the etiology of progressive diabetic kidney disease (DKD). However, the specific mechanisms linking DNAmet variation in blood cells with risk of kidney failure (KF) and utility of measuring blood cell DNAmet in personalized medicine are not clear. We measured blood cell DNAmet in 277 individuals with type 1 diabetes and DKD using Illumina EPIC arrays; 51% of the cohort developed KF during 7 to 20 years of follow-up. Our epigenome-wide analysis identified DNAmet at 17 CpGs (5'-cytosine-phosphate-guanine-3' loci) associated with risk of KF independent of major clinical risk factors. DNAmet at these KF-associated CpGs remained stable over a median period of 4.7 years. Furthermore, DNAmet variations at seven KF-associated CpGs were strongly associated with multiple genetic variants at seven genomic regions, suggesting a strong genetic influence on DNAmet. The effects of DNAmet variations at the KF-associated CpGs on risk of KF were partially mediated by multiple KF-associated circulating proteins and KF-associated circulating miRNAs. A prediction model for risk of KF was developed by adding blood cell DNAmet at eight selected KF-associated CpGs to the clinical model. This updated model significantly improved prediction performance (c-statistic = 0.93) versus the clinical model (c-statistic = 0.85) at P = 6.62 × 10-14. In conclusion, our multiomics study provides insights into mechanisms through which variation of DNAmet may affect KF development and shows that blood cell DNAmet at certain CpGs can improve risk prediction for KF in T1D.
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Affiliation(s)
- Zhuo Chen
- Department of Diabetes Complications and Metabolism, Arthur Riggs Diabetes & Metabolism Research Institute and Beckman Research Institute of City of Hope; Duarte, CA, 91010, USA
| | - Eiichiro Satake
- Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center; Boston, MA, 02215, USA
- Department of Medicine, Harvard Medical School; Boston, MA, 02215, USA
| | - Marcus G Pezzolesi
- Department of Internal Medicine, Division of Nephrology and Hypertension, University of Utah School of Medicine; Salt Lake City, UT, 84132, USA
| | - Zaipul I Md Dom
- Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center; Boston, MA, 02215, USA
- Department of Medicine, Harvard Medical School; Boston, MA, 02215, USA
| | - Devorah Stucki
- Department of Internal Medicine, Division of Nephrology and Hypertension, University of Utah School of Medicine; Salt Lake City, UT, 84132, USA
| | - Hiroki Kobayashi
- Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center; Boston, MA, 02215, USA
- Department of Medicine, Harvard Medical School; Boston, MA, 02215, USA
- Division of Nephrology, Hypertension, and Endocrinology, Nihon University School of Medicine, Tokyo, Japan
| | - Anna Syreeni
- Folkhälsan Research Center, Helsinki, Finland
- Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Adam T. Johnson
- Department of Internal Medicine, Division of Nephrology and Hypertension, University of Utah School of Medicine; Salt Lake City, UT, 84132, USA
| | - Xiwei Wu
- Department of Computational and Quantitative Medicine, Beckman Research Institute of City of Hope; Duarte, CA, 91010, USA
- Integrative Genomics Core, Beckman Research Institute of City of Hope; Duarte, CA, 91010, USA
| | - Emma H Dahlström
- Folkhälsan Research Center, Helsinki, Finland
- Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Jaxon B. King
- Department of Internal Medicine, Division of Nephrology and Hypertension, University of Utah School of Medicine; Salt Lake City, UT, 84132, USA
| | - Per-Henrik Groop
- Folkhälsan Research Center, Helsinki, Finland
- Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
- Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia
| | - Stephen S Rich
- Center for Public Health Genomics and Department of Public Health Sciences, University of Virginia, Charlottesville, VA, 22908, USA
| | - Niina Sandholm
- Folkhälsan Research Center, Helsinki, Finland
- Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Andrzej S Krolewski
- Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center; Boston, MA, 02215, USA
- Department of Medicine, Harvard Medical School; Boston, MA, 02215, USA
| | - Rama Natarajan
- Department of Diabetes Complications and Metabolism, Arthur Riggs Diabetes & Metabolism Research Institute and Beckman Research Institute of City of Hope; Duarte, CA, 91010, USA
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Jin Q, Liu T, Ma F, Fu T, Yang L, Mao H, Wang Y, Peng L, Li P, Zhan Y. Roles of Sirt1 and its modulators in diabetic microangiopathy: A review. Int J Biol Macromol 2024; 264:130761. [PMID: 38467213 DOI: 10.1016/j.ijbiomac.2024.130761] [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: 12/27/2023] [Revised: 02/03/2024] [Accepted: 03/07/2024] [Indexed: 03/13/2024]
Abstract
Diabetic vascular complications include diabetic macroangiopathy and diabetic microangiopathy. Diabetic microangiopathy is characterised by impaired microvascular endothelial function, basement membrane thickening, and microthrombosis, which may promote renal, ocular, cardiac, and peripheral system damage in diabetic patients. Therefore, new preventive and therapeutic strategies are urgently required. Sirt1, a member of the nicotinamide adenine dinucleotide-dependent histone deacetylase class III family, regulates different organ growth and development, oxidative stress, mitochondrial function, metabolism, inflammation, and aging. Sirt1 is downregulated in vascular injury and microangiopathy. Moreover, its expression and distribution in different organs correlate with age and play critical regulatory roles in oxidative stress and inflammation. This review introduces the background of diabetic microangiopathy and the main functions of Sirt1. Then, the relationship between Sirt1 and different diabetic microangiopathies and the regulatory roles mediated by different cells are described. Finally, we summarize the modulators that target Sirt1 to ameliorate diabetic microangiopathy as an essential preventive and therapeutic measure for diabetic microangiopathy. In conclusion, targeting Sirt1 may be a new therapeutic strategy for diabetic microangiopathy.
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Affiliation(s)
- Qi Jin
- Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Tongtong Liu
- Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Fang Ma
- Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Tongfei Fu
- Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Liping Yang
- Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Huimin Mao
- Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yuyang Wang
- Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Liang Peng
- China-Japan Friendship Hospital, Institute of Clinical Medical Sciences, Beijing, China.
| | - Ping Li
- China-Japan Friendship Hospital, Institute of Clinical Medical Sciences, Beijing, China.
| | - Yongli Zhan
- Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
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14
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Tomita-Yagi A, Ozeki-Okuno N, Watanabe-Uehara N, Komaki K, Umehara M, Sawada-Yamauchi H, Minamida A, Sunahara Y, Matoba Y, Nakamura I, Nakata T, Nakai K, Ida T, Yamashita N, Kamezaki M, Kirita Y, Taniguchi T, Konishi E, Matoba S, Tamagaki K, Kusaba T. The importance of proinflammatory failed-repair tubular epithelia as a predictor of diabetic kidney disease progression. iScience 2024; 27:109020. [PMID: 38357667 PMCID: PMC10865398 DOI: 10.1016/j.isci.2024.109020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Revised: 11/17/2023] [Accepted: 01/22/2024] [Indexed: 02/16/2024] Open
Abstract
The immense public health burden of diabetic kidney disease (DKD) has led to an increase in research on the pathophysiology of advanced DKD. The present study focused on the significance of proinflammatory vascular cell adhesion molecule 1 (VCAM1)+ tubules in DKD progression. A retrospective cohort study of DKD patients showed that the percentage of VCAM1+ tubules in kidney samples was correlated with poor renal outcomes. We established an advanced DKD model by partial resection of the kidneys of db/db mice and demonstrated that it closely resembled the human advanced DKD phenotype, with tissue hypoxia, tubular DNA damage, tissue inflammation, and high tubular VCAM1 expression. Luseogliflozin ameliorated tissue hypoxia and proinflammatory responses, including VCAM1+ expression, in tubules. These findings suggest the potential of tubular VCAM1 as a histological marker for poor DKD outcomes. SGLT2 inhibitors may attenuate tissue hypoxia and subsequent tissue inflammation in advanced DKD, thereby ameliorating tubular injury.
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Affiliation(s)
- Aya Tomita-Yagi
- Department of Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Natsuko Ozeki-Okuno
- Department of Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Noriko Watanabe-Uehara
- Department of Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Kazumi Komaki
- Department of Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Minato Umehara
- Department of Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Hiroko Sawada-Yamauchi
- Department of Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Atsushi Minamida
- Department of Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yasuto Sunahara
- Department of Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yayoi Matoba
- Department of Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Itaru Nakamura
- Department of Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Tomohiro Nakata
- Department of Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Kunihiro Nakai
- Department of Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Tomoharu Ida
- Department of Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Noriyuki Yamashita
- Department of Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Michitsugu Kamezaki
- Department of Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yuhei Kirita
- Department of Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Takuya Taniguchi
- Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Eiichi Konishi
- Department of Surgical Pathology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Satoaki Matoba
- Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Keiichi Tamagaki
- Department of Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Tetsuro Kusaba
- Department of Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
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15
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Zahr N, Pfefferbaum A. Serum albumin and white matter hyperintensities. RESEARCH SQUARE 2024:rs.3.rs-3822513. [PMID: 38260299 PMCID: PMC10802700 DOI: 10.21203/rs.3.rs-3822513/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/24/2024]
Abstract
Urine albumin, high in kidney disease, predicts cardiovascular incidents and CNS white matter hyperintensity (WMH) burdens. Serum albumin - a more general biomarker which can be low in several disorders - including kidney and liver disease, malnutrition, and inflammation - also predicts cardiovascular events and is associated with cognitive impairment in several clinical populations; relations between serum albumin and WMH prevalence, however, have rarely been evaluated. In a sample of 160 individuals with alcohol use disorder (AUD), 142 infected with HIV, and 102 healthy controls, the hypothesis was tested that lower serum albumin levels would predict larger WMH volumes and worse cognitive performance irrespective of diagnosis. After considering traditional cardiovascular risk factors (e.g., age, sex, body mass index (BMI), nicotine use, hypertension, diabetes) and study-relevant variables (i.e., primary diagnoses, race, socioeconomic status, hepatitis C virus status), serum albumin survived false discovery rate (FDR)-correction in contributing variance to larger periventricular but not deep WMH volumes. This relationship was salient in the AUD and HIV groups, but not the control group. In secondary analyses, serum albumin and periventricular WMH along with age, sex, diagnoses, BMI, and hypertension were considered for hierarchical contribution to variance in performance in 4 cognitive domains. Albumin survived FDR-correction for significantly contributing to visual and verbal learning and memory performance after accounting for diagnosis. Relations between albumin and markers of liver integrity [e.g., aspartate transaminase (AST)] and blood status (e.g., hemoglobin, red blood cell count, red cell distribution width) suggest that in this sample, albumin reflects both liver dysfunction and hematological abnormalities. The current results suggest that albumin, a simple serum biomarker available in most clinical settings, can predict variance in periventricular WMH volumes and performance in visual and verbal learning and memory cognitive domains. Whether serum albumin contributes mechanistically to periventricular WMH prevalence will require additional investigation.
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16
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Scurt FG, Ganz MJ, Herzog C, Bose K, Mertens PR, Chatzikyrkou C. Association of metabolic syndrome and chronic kidney disease. Obes Rev 2024; 25:e13649. [PMID: 37783465 DOI: 10.1111/obr.13649] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Accepted: 09/15/2023] [Indexed: 10/04/2023]
Abstract
The prevalence of kidney disease is increasing rapidly worldwide, reflecting rising rates of obesity, diabetes, and associated metabolic syndrome (MetS). Chronic kidney disease and related comorbidities such as obesity, diabetes, and hypertension place a significant financial burden on healthcare systems. Despite the widespread use of RAAS inhibitors, intensive blood pressure and glycemic control, and newer therapeutic options consisting of sodium/glucose cotransporter-2 (SGLT-2) inhibitors or glucagon-like peptide-1 (GLP-1) receptor agonists, a significant risk of progression to end-stage renal disease remains in the high-risk obese and diabetic population. The MetS is a cluster of cardiovascular risk factors that adversely affect the development and progression of chronic kidney failure. According to the criteria of the World Health Organization, it is defined by visceral adiposity, impaired glucose tolerance or insulin resistance, atherogenic dyslipidemia, raised blood pressure, and microalbuminuria with a albumin-to-creatinine ratio ≥30 mg/g. At molecular level MetS is marked by a proinflammatory state and increased oxidative stress leading to various pathophysiological changes causing endothelial dysfunction and a hypercoagulable state. Because the kidney is a highly vascularized organ, it is especially susceptible for those microvascular changes. Therefore, the MetS and its individual components are associated with the premature development, acceleration, and progression of chronic kidney disease. Therefore, it is becoming increasingly important to elucidate the underlying mechanisms of MetS-associated chronic kidney disease in order to develop new strategies for preventing and slowing the progression of renal disease. In this review, we will elucidate (i) the renal structural, hemodynamic, and metabolic changes that occur in obesity and obesity-related kidney injury; (ii) the clinicopathological characteristics of obesity-related kidney injury, primarily focusing on obesity-associated glomerulopathy; (iii) the potential additional factors or predisposing factors that may turn patients more susceptible to renal structural or functional compensatory failure and subsequent injury.
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Affiliation(s)
- Florian G Scurt
- University Clinic for Nephrology and Hypertension, Diabetology and Endocrinology, Medical Faculty, Otto-von Guericke University Magdeburg, Magdeburg, Germany
| | - Maximilian J Ganz
- University Clinic for Nephrology and Hypertension, Diabetology and Endocrinology, Medical Faculty, Otto-von Guericke University Magdeburg, Magdeburg, Germany
| | - Carolin Herzog
- University Clinic for Nephrology and Hypertension, Diabetology and Endocrinology, Medical Faculty, Otto-von Guericke University Magdeburg, Magdeburg, Germany
| | - Katrin Bose
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Magdeburg, Magdeburg, Germany
| | - Peter R Mertens
- University Clinic for Nephrology and Hypertension, Diabetology and Endocrinology, Medical Faculty, Otto-von Guericke University Magdeburg, Magdeburg, Germany
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17
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Ye Q, Xu G, Yuan H, Mi J, Xie Y, Li H, Li Z, Huang G, Chen X, Li W, Yang R. Urinary PART1 and PLA2R1 Could Potentially Serve as Diagnostic Markers for Diabetic Kidney Disease Patients. Diabetes Metab Syndr Obes 2023; 16:4215-4231. [PMID: 38162802 PMCID: PMC10757812 DOI: 10.2147/dmso.s445341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Accepted: 12/08/2023] [Indexed: 01/03/2024] Open
Abstract
Background Diabetic kidney disease (DKD) is a chronic renal disease which could eventually develop into renal failure. Though albuminuria and estimated glomerular filtration rate (eGFR) are helpful for the diagnosis of DKD, the lack of specific biomarkers reduces the efficiency of therapeutic interventions. Methods Based on bulk-seq of 56 urine samples collected at different time points (including 11 acquired from DKD patients and 11 from healthy controls), in corporation of scRNA-seq data of urine samples and snRNA-seq data of renal punctures from DKD patients (retrieved from NCBI GEO Omnibus), urine-kidney specific genes were identified by Multiple Biological Information methods. Results Forty urine-kidney specific genes/differentially expressed genes (DEGs) were identified to be highly related to kidney injury and proteinuria for the DKD patients. Most of these genes participate in regulating glucagon and apoptosis, among which, urinary PART1 (mainly derived from distal tubular cells) and PLA2R1 (podocyte cell surface marker) could be used together for the early diagnosis of DKD. Moreover, urinary PART1 was significantly associated with multiple clinical indicators, and remained stable over time in urine. Conclusion Urinary PART1 and PLA2R1 could be shed lights on the discovery and development of non-invasive diagnostic method for DKD, especially in early stages.
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Affiliation(s)
- Qinglin Ye
- Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530005, People’s Republic of China
| | - Guiling Xu
- Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530005, People’s Republic of China
| | - Hao Yuan
- Centre for Genomic and Personalized Medicine, Guangxi key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, 530021, People’s Republic of China
- Department of Immunology, School of Basic Medical Sciences, Guangxi Medical University, Nanning, 530021, People’s Republic of China
| | - Junhao Mi
- Centre for Genomic and Personalized Medicine, Guangxi key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, 530021, People’s Republic of China
- Department of Immunology, School of Basic Medical Sciences, Guangxi Medical University, Nanning, 530021, People’s Republic of China
| | - Yuli Xie
- Centre for Genomic and Personalized Medicine, Guangxi key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, 530021, People’s Republic of China
- Department of Immunology, School of Basic Medical Sciences, Guangxi Medical University, Nanning, 530021, People’s Republic of China
| | - Haoyu Li
- Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530005, People’s Republic of China
| | - Zhejun Li
- Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530005, People’s Republic of China
| | - Guanwen Huang
- Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530005, People’s Republic of China
| | - Xuesong Chen
- Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530005, People’s Republic of China
| | - Wei Li
- Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530005, People’s Republic of China
| | - Rirong Yang
- Centre for Genomic and Personalized Medicine, Guangxi key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, 530021, People’s Republic of China
- Department of Immunology, School of Basic Medical Sciences, Guangxi Medical University, Nanning, 530021, People’s Republic of China
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18
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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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19
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Xu C, Ha X, Yang S, Tian X, Jiang H. Advances in understanding and treating diabetic kidney disease: focus on tubulointerstitial inflammation mechanisms. Front Endocrinol (Lausanne) 2023; 14:1232790. [PMID: 37859992 PMCID: PMC10583558 DOI: 10.3389/fendo.2023.1232790] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2023] [Accepted: 09/19/2023] [Indexed: 10/21/2023] Open
Abstract
Diabetic kidney disease (DKD) is a serious complication of diabetes that can lead to end-stage kidney disease. Despite its significant impact, most research has concentrated on the glomerulus, with little attention paid to the tubulointerstitial region, which accounts for the majority of the kidney volume. DKD's tubulointerstitial lesions are characterized by inflammation, fibrosis, and loss of kidney function, and recent studies indicate that these lesions may occur earlier than glomerular lesions. Evidence has shown that inflammatory mechanisms in the tubulointerstitium play a critical role in the development and progression of these lesions. Apart from the renin-angiotensin-aldosterone blockade, Sodium-Glucose Linked Transporter-2(SGLT-2) inhibitors and new types of mineralocorticoid receptor antagonists have emerged as effective ways to treat DKD. Moreover, researchers have proposed potential targeted therapies, such as inhibiting pro-inflammatory cytokines and modulating T cells and macrophages, among others. These therapies have demonstrated promising results in preclinical studies and clinical trials, suggesting their potential to treat DKD-induced tubulointerstitial lesions effectively. Understanding the immune-inflammatory mechanisms underlying DKD-induced tubulointerstitial lesions and developing targeted therapies could significantly improve the treatment and management of DKD. This review summarizes the latest advances in this field, highlighting the importance of focusing on tubulointerstitial inflammation mechanisms to improve DKD outcomes.
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Affiliation(s)
- Chengren Xu
- Division of Nephrology, Department of Internal Medicine, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China
| | - Xiaowen Ha
- Division of Nephrology, Department of Internal Medicine, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China
| | - Shufen Yang
- Division of Nephrology, Department of Internal Medicine, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China
| | - Xuefei Tian
- Section of Nephrology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, United States
| | - Hong Jiang
- Division of Nephrology, Department of Internal Medicine, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China
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20
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Martin WP, Docherty NG. A Systems Nephrology Approach to Diabetic Kidney Disease Research and Practice. Nephron Clin Pract 2023; 148:127-136. [PMID: 37696257 PMCID: PMC7617272 DOI: 10.1159/000531823] [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: 03/05/2023] [Accepted: 06/05/2023] [Indexed: 09/13/2023] Open
Abstract
BACKGROUND Diagnosis and staging of diabetic kidney disease (DKD) via the serial assessment of routine laboratory indices lacks the granularity required to resolve the heterogeneous disease mechanisms driving progression in the individual patient. A systems nephrology approach may help resolve mechanisms underlying this clinically apparent heterogeneity, paving a way for targeted treatment of DKD. SUMMARY Given the limited access to kidney tissue in routine clinical care of patients with DKD, data derived from renal tissue in preclinical model systems, including animal and in vitro models, can play a central role in the development of a targeted systems-based approach to DKD. Multi-centre prospective cohort studies, including the Kidney Precision Medicine Project (KPMP) and the European Nephrectomy Biobank (ENBiBA) project, will improve access to human diabetic kidney tissue for research purposes. Integration of diverse data domains from such initiatives including clinical phenotypic data, renal and retinal imaging biomarkers, histopathological and ultrastructural data, and an array of molecular omics (transcriptomics, proteomics, etc.) alongside multi-dimensional data from preclinical modelling offers exciting opportunities to unravel individual-level mechanisms underlying progressive DKD. The application of machine and deep learning approaches may particularly enhance insights derived from imaging and histopathological/ultrastructural data domains. KEY MESSAGES Integration of data from multiple model systems (in vitro, animal models, and patients) and from diverse domains (clinical phenotypic, imaging, histopathological/ultrastructural, and molecular omics) offers potential to create a precision medicine approach to DKD care wherein the right treatments are offered to the right patients at the right time.
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Affiliation(s)
- William P. Martin
- Diabetes Complications Research Centre, School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, DublinD04 V1W8, Ireland
| | - Neil G. Docherty
- Diabetes Complications Research Centre, School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, DublinD04 V1W8, Ireland
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Bae J, Lee BW. Significance of Diabetic Kidney Disease Biomarkers in Predicting Metabolic-Associated Fatty Liver Disease. Biomedicines 2023; 11:1928. [PMID: 37509567 PMCID: PMC10377561 DOI: 10.3390/biomedicines11071928] [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: 06/15/2023] [Revised: 07/04/2023] [Accepted: 07/06/2023] [Indexed: 07/30/2023] Open
Abstract
Metabolic-associated fatty liver disease (MAFLD) and diabetic kidney disease (DKD) share various pathophysiological factors, and epidemiological evidence suggests that these two diseases are associated. Albuminuria and the estimated glomerular filtration rate, which are conventional biomarkers of DKD, are reportedly associated with the risk or severity of MAFLD. Recently, novel DKD biomarkers reflecting renal tubular injury have been introduced to complement conventional DKD markers. In this article, we looked at previous studies that showed an association between MAFLD and DKD, and also reviewed the significance of DKD biomarkers as predictive risk factors for MAFLD.
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Affiliation(s)
- Jaehyun Bae
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Catholic Kwandong University College of Medicine, International St. Mary's Hospital, Incheon 22711, Republic of Korea
| | - Byung-Wan Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
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An L, Wang D, Shi X, He Y, Lee Y, Lu J. Differences in prevalence and management of chronic kidney disease among T2DM inpatients at the grassroots in Beijing and Taiyuan: a retrospective study. JOURNAL OF HEALTH, POPULATION, AND NUTRITION 2023; 42:61. [PMID: 37408009 DOI: 10.1186/s41043-023-00406-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Accepted: 06/28/2023] [Indexed: 07/07/2023]
Abstract
PURPOSE Chronic kidney disease (CKD) has been one of the most common complications in type 2 diabetes mellitus (T2DM) patients. This retrospective study aimed to investigate the regional differences in the prevalence and management of CKD in T2DM inpatients from two grassroots hospitals in Beijing and Taiyuan. METHODS The sociodemographic status, health history, lifestyle information, biochemical parameters and drug choices of the patients were collected from the Diabetes Care Information System using a retrospective cross-sectional analysis. The presence of CKD was defined as albuminuria (urine albumin-to-creatinine ratio of ≥ 30 mg/g) and/or as a reduced estimated glomerular filtration rate (< 60 ml/min/1.73 m2). RESULTS 858 patients with T2DM in Beijing and 1,085 patients with T2DM in Taiyuan were included, with a median age of 61.0 and 61.9 years, respectively. The duration of diabetes was 10.5 and 10.3 years, respectively. The prevalence of CKD in Beijing (39.2%) was significantly higher than in Taiyuan (22.4%). The overall ABC control (A = haemoglobin A1c; B = blood pressure; C = cholesterol) in both the Beijing and Taiyuan groups were not ideal. Patients with CKD tended to use insulin, renin-angiotensin-aldosterone system (RAAS) inhibitors, sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and dyslipidaemia therapy in Taiyuan than in Beijing. The actual proportion of carbohydrate, fat and protein in calories was 49.6%:35.4%:14.4% in Beijing and 61.5%:27.8%:10.8% in Taiyuan. CONCLUSIONS The higher prescription rates of RAAS inhibitors, SGLT-2i and dyslipidaemia therapy may underlie the fluctuations in the prevalence of CKD in Beijing or Taiyuan. Intensive insulin therapy and personal nutritional guidance, along with the extensive use of RAAS inhibitors, SGLT-2i and dyslipidaemia therapy during follow-up, can all play a positive role in the management of CKD in patients with T2DM in both Beijing and Taiyuan.
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Affiliation(s)
- Lingwang An
- Department of Endocrinology, Beijing Ruijing Diabetes Hospital, Beijing, 100079, China
| | - Dandan Wang
- Department of Endocrinology, Beijing Ruijing Diabetes Hospital, Beijing, 100079, China
| | - Xiaorong Shi
- Department of Endocrinology, Taiyuan Diabetes Hospital, Taiyuan, 030013, China
| | - Yali He
- Department of Endocrinology, Taiyuan Diabetes Hospital, Taiyuan, 030013, China
| | - Yaujiunn Lee
- Department of Metabolism and Endocrinology, Lee's Clinic, Pingtung, 90000, Taiwan, China
| | - Juming Lu
- Department of Endocrinology, Beijing Ruijing Diabetes Hospital, Beijing, 100079, China.
- Department of Endocrinology, The General Hospital of the People's Liberation Army, Ch No. 28 of Fuxing Road, Haidian District, Beijing, 100853, China.
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Bueno Junior CR, Bano A, Tang Y, Sun X, Abate A, Hall E, Mitri J, Morieri ML, Shah H, Doria A. Rapid kidney function decline and increased risk of heart failure in patients with type 2 diabetes: findings from the ACCORD cohort : Rapid kidney function decline and heart failure in T2D. Cardiovasc Diabetol 2023; 22:131. [PMID: 37365586 PMCID: PMC10291814 DOI: 10.1186/s12933-023-01869-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Accepted: 05/28/2023] [Indexed: 06/28/2023] Open
Abstract
BACKGROUND Impaired kidney function and albuminuria are associated with increased risk of heart failure (HF) in patients with type 2 diabetes (T2D). We investigated whether rapid kidney function decline over time is an additional determinant of increased HF risk in patients with T2D, independent of baseline kidney function, albuminuria, and other HF predictors. METHODS Included in the study were 7,539 participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study with baseline urinary albumin-to-creatinine ratio (UACR) data, who had completed 4 years of follow-up and had ≥ 3 eGFR measurements during that period (median eGFR/year = 1.9, IQR 1.7-3.2). The association between rapid kidney function decline (eGFR loss ≥ 5 ml/min/1.73 m2/year) and odds of HF hospitalization or HF death during the first 4 years of follow-up was estimated by logistic regression. The improvement in risk discrimination provided by adding rapid kidney function decline to other HF risk factors was evaluated as the increment in the area under the Receiving Operating Characteristics curve (ROC AUC) and integrated discrimination improvement (IDI). RESULTS Over 4 years of follow-up, 1,573 participants (20.9%) experienced rapid kidney function decline and 255 (3.4%) experienced a HF event. Rapid kidney function decline was associated with a ~ 3.2-fold increase in HF odds (3.23, 95% CI, 2.51-4.16, p < 0.0001), independent of baseline CVD history. This estimate was not attenuated by adjustment for potential confounders, including eGFR and UACR at baseline as well as at censoring (3.74; 95% CI 2.63-5.31). Adding rapid kidney function decline during follow-up to other clinical predictors (WATCH-DM score, eGFR, and UACR at study entry and end of follow-up) improved HF risk classification (ROC AUC = + 0.02, p = 0.027; relative IDI = + 38%, p < 0.0001). CONCLUSIONS In patients with T2D, rapid kidney function decline is associated with a marked increase in HF risk, independent of starting kidney function and/or albuminuria. These findings highlight the importance of serial eGFR measurements over time to improve HF risk estimation in T2D.
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Affiliation(s)
- Carlos Roberto Bueno Junior
- Research Division, Joslin Diabetes Center, Boston, MA, USA
- Department of Medicine, Harvard Medical School, Boston, MA, USA
- School of Physical Education and Sport, Medical School, College of Nursing of Ribeirao Preto, University of Sao Paulo (USP), Ribeirao Preto, Sao Paulo, Brazil
| | - Arjola Bano
- Research Division, Joslin Diabetes Center, Boston, MA, USA
- Department of Medicine, Harvard Medical School, Boston, MA, USA
- Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland
- Department of Cardiology, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Yaling Tang
- Research Division, Joslin Diabetes Center, Boston, MA, USA
- Department of Medicine, Harvard Medical School, Boston, MA, USA
| | - Xiuqin Sun
- Research Division, Joslin Diabetes Center, Boston, MA, USA
- Department of Medicine, Harvard Medical School, Boston, MA, USA
- Department of Endocrine and Metabolism, Peking University Shuang Hospital, Beijing, China
| | - Alex Abate
- Research Division, Joslin Diabetes Center, Boston, MA, USA
| | - Elizabeth Hall
- Research Division, Joslin Diabetes Center, Boston, MA, USA
- Department of Medicine, Harvard Medical School, Boston, MA, USA
| | - Joanna Mitri
- Research Division, Joslin Diabetes Center, Boston, MA, USA
- Department of Medicine, Harvard Medical School, Boston, MA, USA
| | - Mario Luca Morieri
- Department of Medicine, Metabolic Disease Unit, University of Padova, University Hospital of Padova, Padova, Italy
| | - Hetal Shah
- Research Division, Joslin Diabetes Center, Boston, MA, USA
- Department of Medicine, Harvard Medical School, Boston, MA, USA
| | - Alessandro Doria
- Research Division, Joslin Diabetes Center, Boston, MA, USA.
- Department of Medicine, Harvard Medical School, Boston, MA, USA.
- Research Division, Joslin Diabetes Center, One Joslin Place, Boston, MA, 02215, USA.
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Tan Y, Li R, Zhou P, Li N, Xu W, Zhou X, Yan Q, Yu J. Huobahuagen tablet improves renal function in diabetic kidney disease: a real-world retrospective cohort study. Front Endocrinol (Lausanne) 2023; 14:1166880. [PMID: 37404303 PMCID: PMC10315672 DOI: 10.3389/fendo.2023.1166880] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Accepted: 05/30/2023] [Indexed: 07/06/2023] Open
Abstract
Objective We aimed to explore the value of Huobahuagen tablet (HBT) in improving decreased renal function for patients with diabetic kidney disease (DKD) over time. Methods This was a single-center, retrospective, real-world study on eligible 122 DKD patients who continued to use HBT + Huangkui capsule (HKC) therapy or HKC therapy without interruption or alteration in Jiangsu Province Hospital of Chinese Medicine from July 2016 to March 2022. The primary observation outcomes included estimated glomerular filtration rate (eGFR) at baseline and 1-, 3-, 6-, 9-, and 12-month follow-up visits and changes in eGFR from baseline (ΔeGFR). Propensity score (PS) and inverse probability treatment weighting (IPTW) were used to control for confounders. Results eGFR was significantly higher in the HBT + HKC group than in the HKC alone group at the 6-, 9-, and 12-month follow-up visits (p = 0.0448, 0.0002, and 0.0037, respectively), indicating the superiority of HBT + HKC over HBT alone. Furthermore, the ΔeGFR of the HBT + HKC group was significantly higher than that of the HKC alone group at the 6- and 12-month follow-up visits (p = 0.0369 and 0.0267, respectively). In the DKD G4 patients, eGFR was higher in the HBT + HKC group at the 1-, 3-, 6-, 9-, and 12-month follow-up visits compared with baseline, with statistically significant differences at the 1-, 3-, and 6- month follow-up visits (p = 0.0256, 0.0069, and 0.0252, respectively). The fluctuations in ΔeGFR ranged from 2.54 ± 4.34 to 5.01 ± 5.55 ml/min/1.73 m2. Change in the urinary albumin/creatinine ratio from baseline did not exhibit a significant difference between the two groups at any of the follow-up visits (p > 0.05 for all). Adverse event incidence was low in both groups. Conclusion The findings of this study based on real-world clinical practice indicate that HBT + HKC therapy exhibited better efficacy in improving and protecting renal function with a favorable safety profile than HKC therapy alone. However, further large-scale prospective randomized controlled trials are warranted to confirm these results.
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Affiliation(s)
- Ying Tan
- Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
- The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, China
| | - Ruihan Li
- Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
- The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, China
| | - Peipei Zhou
- Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
- The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, China
| | - Nan Li
- Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Weilong Xu
- Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Xiqiao Zhou
- Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Qianhua Yan
- Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Jiangyi Yu
- Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
- The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, China
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Wang X, Ren L, Huang Y, Feng Z, Zhang G, Dai H. The Role of Tubulointerstitial Markers in Differential Diagnosis and Prognosis in Patients with Type 2 Diabetes and Biopsy Proven Diabetic Kidney Disease. Clin Chim Acta 2023:117448. [PMID: 37331550 DOI: 10.1016/j.cca.2023.117448] [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: 11/25/2022] [Revised: 05/15/2023] [Accepted: 06/13/2023] [Indexed: 06/20/2023]
Abstract
OBJECTIVE To evaluate the potential application of tubularinterstitial biomarkers in the differential diagnosis of diabetic kidney disease (DKD) from non-diabetic kidney disease (NDKD), as well as investigate key clinical and pathological parameters to help improve the stratification of patients according to end-stage renal disease risk. METHODS 132 type 2 diabetic patients with chronic kidney disease were enrolled. Patients were categorized into 2 groups according to the renal biopsy results: DKD (n=61) and NDKD (n=71).The independent factors of the occurrence of DKD and the diagnostic implications of tubular biomarkers were explored by logistic regression and receiver-operating characteristic curve analysis. Furthermore, predictors were analyzed by least absolute shrinkage and selection operator regression, and constructed a new model for predicting the unfavorable renal outcomes through Cox proportional hazard regression analysis. RESULTS Serum neutrophil gelatinase-associated lipocalin (sNGAL) (OR= 1.007; 95%CI = [1.003, 1.012], p = 0.001) was identified as an independent risk factor for the occurrence of DKD in diabetic patients with CKD. Tubular biomarkers including sNGAL, N-acetyl-β-D-glucosaminidase and β2 microglobulin (β2-MG) could complement albuminuria for DKD detection (AUC = 0.926, specificity = 90.14%, sensitivity = 80.33%).Moreover, among of the 47 variables, 4 predictors such as sNGAL, interstitial fibrosis and tubular atrophy (IFTA)score, β2-MG and estimated glomerular filtration rate were selected to construct a new model for predicting the unfavorable renal outcomes through regression analysis. sNGAL (HR = 1.004; 95%CI = [1.001, 1.007], p = 0.013), IFTA score of 2 (HR = 4.283; 95%CI = [1.086, 16.881], p = 0.038), and IFTA score of 3 (HR = 6.855; 95%CI = [1.766, 26.610], p = 0.005) were considered to be independent risk factors for unfavorable renal outcomes. CONCLUSIONS Tubulointerstitial injury in DKD is independently associated with renal function decline and routinely detected tubular biomarkers are able to enhance the level of non-invasive diagnosis of DKD beyond traditional factors.
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Affiliation(s)
- Xijian Wang
- Department of Nephrology, Affiliated Hospital of Nantong University, Nantong Jiangsu, 226001, PR China
| | - Liang Ren
- Department of Nephrology, Affiliated Hospital of Nantong University, Nantong Jiangsu, 226001, PR China
| | - Ying Huang
- Department of Nephrology, Affiliated Hospital of Nantong University, Nantong Jiangsu, 226001, PR China
| | - Zhengang Feng
- Department of Nephrology, Affiliated Hospital of Nantong University, Nantong Jiangsu, 226001, PR China
| | - Guangdi Zhang
- Department of Nephrology, Affiliated Hospital of Nantong University, Nantong Jiangsu, 226001, PR China
| | - Houyong Dai
- Department of Nephrology, Affiliated Hospital of Nantong University, Nantong Jiangsu, 226001, PR China.
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Lin Z, Zhang D, Zhang X, Guo W, Wang W, Zhang Y, Liu Z, Bi Y, Wu M, Lin Z, Lu X. Extracellular status of thrombospondin-2 in type 2 diabetes mellitus and utility as a biomarker in the determination of early diabetic kidney disease. BMC Nephrol 2023; 24:154. [PMID: 37259071 DOI: 10.1186/s12882-023-03216-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2023] [Accepted: 05/24/2023] [Indexed: 06/02/2023] Open
Abstract
OBJECTIVE Thrombospondin-2 (TSP-2) is a multifunctional matricellular glycoprotein correlated with glucose homeostasis, insulin sensitivity, and estimated glomerular filtration rate. Investigation of the association of TSP-2 with type 2 diabetes mellitus (T2DM) and the potential diagnostic value of serum TSP-2 for detecting early diabetic kidney disease (DKD) is needed. RESEARCH DESIGN AND METHODS An enzyme-linked immunosorbent assay was used for detection serum TSP-2 levels in 494 Chinese T2DM subjects. The protein expression of TSP-2 in the kidney and other tissues were tested by western blotting. RESULTS Serum TSP-2 levels in T2DM subjects were significantly higher than in healthy individuals. Serum TSP-2 correlated positively with triglycerides, serum uric acid, creatinine, platelets, and urinary albumin-to-creatinine ratio (UACR), but negatively with estimated glomerular filtration rate, after adjusting for age, sex, and T2DM duration. Logistic regression analysis demonstrated an independent association between serum TSP-2 and early DKD. Furthermore, the high UACR identified at risk of early DKD increased significantly from 0.78 (95%CI 0.73-0.83) to 0.82 (95%CI 0.77-0.86, p < 0.001) when added to a clinical model consisting of TSP-2 and age. In db/db mice, serum TSP-2 levels were elevated. TSP-2 expression was markedly increased in the kidney tissue compared with that in db/m and m/m mice. Furthermore, serum TSP-2 expression correlated well with UACR in mice. CONCLUSIONS TSP-2 is a novel glycoprotein associated with early DKD in patients with T2DM. The paradoxical increase of serum TSP-2 in T2DM individuals may be due to a compensatory response to chronic inflammatory and renal vascular endothelial growth, warranting further investigation.
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Affiliation(s)
- Zhenzhen Lin
- The 3rd Affiliated Hospital of Wenzhou Medical University (Ruian People's Hospital), Wenzhou, 325200, China
| | - Didong Zhang
- School of Pharmaceutical College, Wenzhou Medical University, Wenzhou, China
| | - Xinxin Zhang
- School of Pharmaceutical College, Wenzhou Medical University, Wenzhou, China
| | - Wanxie Guo
- School of Pharmaceutical College, Wenzhou Medical University, Wenzhou, China
| | - Wenjun Wang
- School of Pharmaceutical College, Wenzhou Medical University, Wenzhou, China
| | - Yingchao Zhang
- School of Pharmaceutical College, Wenzhou Medical University, Wenzhou, China
| | - Zhen Liu
- School of Pharmaceutical College, Wenzhou Medical University, Wenzhou, China
| | - Yanxue Bi
- School of Pharmaceutical College, Wenzhou Medical University, Wenzhou, China
| | - Maolan Wu
- School of Pharmaceutical College, Wenzhou Medical University, Wenzhou, China
| | - Zhuofeng Lin
- School of Pharmaceutical College, Wenzhou Medical University, Wenzhou, China.
- The 1st Affiliated Hospital of Wenzhou Medical Unversity, South Baixiang Town, Wenzhou, 325000, China.
- Laboratory Animal Center of Wenzhou Medical University, Wenzhou, China.
| | - Xuemian Lu
- The 3rd Affiliated Hospital of Wenzhou Medical University (Ruian People's Hospital), Wenzhou, 325200, China.
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Jin X, Yang X, Xu Y, Liang J, Liu C, Guo Q, Wang W, Feng Z, Yuan Y, Zhou H, Zhang Z, Jiang W, Liang Y, Lu B, Shao J, Zhong Y, Gu P. Differential correlation between time in range and eGFR or albuminuria in type 2 diabetes. Diabetol Metab Syndr 2023; 15:92. [PMID: 37386515 DOI: 10.1186/s13098-023-01071-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Accepted: 04/27/2023] [Indexed: 07/01/2023] Open
Abstract
INTRODUCTION As a CGM-derived indicator, 'time in range' (TIR) is emerging as a key indicator for accurate assessment of glycaemic control. However, there is few report focusing on the correlation of TIR with albumuria and renal fuction. The aim of this work was to investigate whether TIR, as well as nocturnal TIR and hypoglycaemic events is related to the presence and severity of albuminuria and decrease of eGFR in type 2 diabetes. RESEARCH DESIGN AND METHODS A total of 823 patients were enrolled in this study. All patients received continuous glucose monitoring, TIR indicating the percentage of time that blood glucose was in the range of 3.9-10.0 mmol/L. The Spearman analysis was applied to analyze the relationship between TIR (or nocturnal TIR) and ACR. Logistic regression was used to explore whether TIR (or nocturnal TIR) is an independent risk factor for albuminuria. RESULTS The prevalence of albuminuria decreased with increasing TIR quartiles. Binary logistic regression revealed that TIR as well as nocturnal TIR was obviously related to the presence of albuminuria. Multiple regression analysis found that only nocturnal TIR was obviously related to the severity of albuminuria. In our study, eGFR was significantly associated with the number of hypoglycemic events. CONCLUSIONS In T2DM patients, TIR and nocturnal TIR is associated with the presence of albuminuria independent of HbA1c and GV metrics. Nocturnal TIR shows better correlation than TIR. The role of TIR especially nocturnal TIR in the evaluation of diabetes kidney disease should be emphasized.
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Affiliation(s)
- Xuguang Jin
- Medical School, Affiliated Jinling Hospital, Department of Endocrinology, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China
| | - Xinyi Yang
- Medical School, Affiliated Jinling Hospital, Department of Endocrinology, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China
| | - Yixin Xu
- Medical School, Affiliated Jinling Hospital, Department of Endocrinology, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China
| | - Jingjing Liang
- Medical School, Affiliated Jinling Hospital, Department of Endocrinology, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China
| | - Chunyan Liu
- Medical School, Affiliated Jinling Hospital, Department of Endocrinology, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China
| | - Qingyu Guo
- Medical School, Affiliated Jinling Hospital, Department of Endocrinology, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China
| | - Wei Wang
- Medical School, Affiliated Jinling Hospital, Department of Endocrinology, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China
| | - Zhouqin Feng
- Medical School, Affiliated Jinling Hospital, Department of Endocrinology, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China
| | - Yanyu Yuan
- Department of Endocrinology, the affiliated Jinling Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Hui Zhou
- Department of Endocrinology, Jinling Hospital, First School of Clinical Medicine, Southern Medical University, Nanjing, China
| | - Zhen Zhang
- Department of Endocrinology, Jinling Hospital, First School of Clinical Medicine, Southern Medical University, Nanjing, China
| | - Wenwen Jiang
- Department of Endocrinology, the affiliated Jinling Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Yue Liang
- Medical School, Affiliated Jinling Hospital, Department of Endocrinology, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China
| | - Bin Lu
- Medical School, Affiliated Jinling Hospital, Department of Endocrinology, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China
| | - Jiaqing Shao
- Medical School, Affiliated Jinling Hospital, Department of Endocrinology, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China.
| | - Yong Zhong
- Medical School, Affiliated Jinling Hospital, Department of Endocrinology, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China.
| | - Ping Gu
- Medical School, Affiliated Jinling Hospital, Department of Endocrinology, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, China.
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Nakagawa Y, Kaseda R, Suzuki Y, Watanabe H, Otsuka T, Yamamoto S, Kaneko Y, Goto S, Terada Y, Haishi T, Sasaki S, Narita I. Sodium Magnetic Resonance Imaging Shows Impairment of the Counter-current Multiplication System in Diabetic Mice Kidney. KIDNEY360 2023; 4:582-590. [PMID: 36963113 PMCID: PMC10278814 DOI: 10.34067/kid.0000000000000072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Accepted: 01/17/2023] [Indexed: 03/26/2023]
Abstract
Key Points 23Na MRI allows us to noninvasively assess sodium distribution. We propose the utility of 23Na MRI for evaluating functional changes in diabetic kidney disease and not as a marker reflecting structural damage. 23Na MRI may be an early marker for structures beyond the glomeruli, enabling prompt intervention with novel efficacious tubule-targeting therapies. Background Sodium magnetic resonance imaging can noninvasively assess sodium distribution, specifically sodium concentration in the countercurrent multiplication system in the kidney, which forms a sodium concentration gradient from the cortex to the medulla, enabling efficient water reabsorption. This study aimed to investigate whether sodium magnetic resonance imaging can detect changes in sodium concentrations under normal conditions in mice and in disease models, such as a mouse model with diabetes mellitus. Methods We performed sodium and proton nuclear magnetic resonance imaging using a 9.4-T vertical standard-bore superconducting magnet. Results A condition of deep anesthesia, with widened breath intervals, or furosemide administration in 6-week-old C57BL/6JJcl mice showed a decrease in both tissue sodium concentrations in the medulla and sodium concentration gradients from the cortex to the medulla. Furthermore, sodium magnetic resonance imaging revealed reductions in the sodium concentration in the medulla and in the gradient from the cortex to the medulla in BKS.Cg-Leprdb+/+ Leprdb/Jcl mice at very early type 2 diabetes mellitus stages compared with corresponding control BKS.Cg-m+/m+/Jcl mice. Conclusions The kidneys of BKS.Cg-Leprdb+/+ Leprdb/Jcl mice aged 6 weeks showed impairments in the countercurrent multiplication system. We propose the utility of 23Na MRI for evaluating functional changes in diabetic kidney disease and not as a marker that reflects structural damage. Thus, 23Na MRI may be a potentially very early marker for structures beyond the glomerulus; this may prompt intervention with novel efficacious tubule-targeting therapies.
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Affiliation(s)
- Yusuke Nakagawa
- Division of Clinical Nephrology and Rheumatology, Kidney Research Center, Niigata University, Niigata, Niigata, Japan
| | - Ryohei Kaseda
- Division of Clinical Nephrology and Rheumatology, Kidney Research Center, Niigata University, Niigata, Niigata, Japan
| | - Yuya Suzuki
- Division of Clinical Nephrology and Rheumatology, Kidney Research Center, Niigata University, Niigata, Niigata, Japan
| | - Hirofumi Watanabe
- Division of Clinical Nephrology and Rheumatology, Kidney Research Center, Niigata University, Niigata, Niigata, Japan
| | - Tadashi Otsuka
- Division of Clinical Nephrology and Rheumatology, Kidney Research Center, Niigata University, Niigata, Niigata, Japan
| | - Suguru Yamamoto
- Division of Clinical Nephrology and Rheumatology, Kidney Research Center, Niigata University, Niigata, Niigata, Japan
| | - Yoshikatsu Kaneko
- Division of Clinical Nephrology and Rheumatology, Kidney Research Center, Niigata University, Niigata, Niigata, Japan
| | - Shin Goto
- Division of Clinical Nephrology and Rheumatology, Kidney Research Center, Niigata University, Niigata, Niigata, Japan
| | - Yasuhiko Terada
- Institute of Applied Physics, University of Tsukuba, Tsukuba, Ibaraki, Japan
| | - Tomoyuki Haishi
- MRTechnology Inc., Tsukuba, Ibaraki, Japan
- Department of Radiological Sciences, School of Health Sciences at Narita, International University of Health and Welfare, Narita, Chiba, Japan
| | - Susumu Sasaki
- Faculty of Engineering, Niigata University, Niigata, Niigata, Japan
| | - Ichiei Narita
- Division of Clinical Nephrology and Rheumatology, Kidney Research Center, Niigata University, Niigata, Niigata, Japan
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Luo M, Zhang Z, Lu Y, Feng W, Wu H, Fan L, Guan B, Dai Y, Tang D, Dong X, Yun C, Hocher B, Liu H, Li Q, Yin L. Urine metabolomics reveals biomarkers and the underlying pathogenesis of diabetic kidney disease. Int Urol Nephrol 2023; 55:1001-1013. [PMID: 36255506 DOI: 10.1007/s11255-022-03326-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 07/28/2022] [Indexed: 11/28/2022]
Abstract
PURPOSE Diabetic kidney disease (DKD) is the most common complication of type 2 diabetes mellitus (T2DM), and its pathogenesis is not yet fully understood and lacks noninvasive and effective diagnostic biomarkers. In this study, we performed urine metabolomics to identify biomarkers for DKD and to clarify the potential mechanisms associated with disease progression. METHODS We applied a liquid chromatography-mass spectrometry-based metabolomics method combined with bioinformatics analysis to investigate the urine metabolism characteristics of 79 participants, including healthy subjects (n = 20), T2DM patients (n = 20), 39 DKD patients that included 19 DKD with microalbuminuria (DKD + micro) and 20 DKD with macroalbuminuria (DKD + macro). RESULTS Seventeen metabolites were identified between T2DM and DKD that were involved in amino acid, purine, nucleotide and primarily bile acid metabolism. Ultimately, a combined model consisting of 2 metabolites (tyramine and phenylalanylproline) was established, which had optimal diagnostic performance (area under the curve (AUC) = 0.94). We also identified 19 metabolites that were co-expressed within the DKD groups and 41 metabolites specifically expressed in the DKD + macro group. Ingenuity pathway analysis revealed three interaction networks of these 60 metabolites, involving the sirtuin signaling pathway and ferroptosis signaling pathway, as well as the downregulation of organic anion transporter 1, which may be important mechanisms that mediate the progression of DKD. CONCLUSIONS This work reveals the metabolic alterations in T2DM and DKD, constructs a combined model to distinguish them and delivers a novel strategy for studying the underlying mechanism and treatment of DKD.
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Affiliation(s)
- Maolin Luo
- Department of Nephrology and Blood Purification, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, 510632, China
- Department of Endocrinology and Metabolism, People's Hospital of Liwan District, Guangzhou, 510380, People's Republic of China
| | - Zeyu Zhang
- Department of Nephrology and Blood Purification, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, 510632, China
- The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, CN, 518020, People's Republic of China
| | - Yongping Lu
- Department of Nephrology and Blood Purification, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, 510632, China
| | - Weifeng Feng
- Department of Traditional Chinese Medicine, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, 510632, People's Republic of China
| | - Hongwei Wu
- Department of Nephrology and Blood Purification, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, 510632, China
| | - Lijing Fan
- Department of Nephrology and Blood Purification, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, 510632, China
| | - Baozhang Guan
- Department of Nephrology and Blood Purification, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, 510632, China
| | - Yong Dai
- The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, CN, 518020, People's Republic of China
| | - Donge Tang
- The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, CN, 518020, People's Republic of China
| | - Xiangnan Dong
- Department of Nephrology and Blood Purification, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, 510632, China
| | - Chen Yun
- Department of Nephrology, Charité -Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany
| | - Berthold Hocher
- Department of Nephrology and Blood Purification, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, 510632, China
- Department of Nephrology, Charité -Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany
- Department of Medicine Nephrology, University Medicai Centre Mannheim, Heidelberg, Germany
| | - Haiping Liu
- The Second People's Hospital of Lianping County, Guangdong, 517139, People's Republic of China.
| | - Qiang Li
- Dongguan Hospital of Guangzhou University of Traditional Chinese Medicine, Guangdong, 523000, People's Republic of China.
| | - Lianghong Yin
- Department of Nephrology and Blood Purification, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, 510632, China.
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Mohammed MM, Alnajim EK, Hussein MAA, Hadi NR. RISK FACTORS FOR DIABETIC NEPHROPATHY IN DIABETES MELLITUS TYPE 1. WIADOMOSCI LEKARSKIE (WARSAW, POLAND : 1960) 2023; 76:145-154. [PMID: 36883503 DOI: 10.36740/wlek202301120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/09/2023]
Abstract
OBJECTIVE The aim: To find the risk factors of microalbuminuria and estimated Glomerular Filtration Rate (eGFR) in patients with type 1 diabetes mellitus. PATIENTS AND METHODS Materials and methods: One hundred ten patients of type 1 diabetes mellitus in this cross-sectional study at diabetic and endocrinology center in Al-Najaf during the period from September 2021 to March 2022. All patients were asked about sociodemographic characteristics (age, gender, smoking, duration of DM type1, family history of DM type1), measured (body mass index BMI, blood pressure) and laboratory investigations done to all patients (G.U.E, s. creatinine, lipid profile, HBA1C, calculated estimated Glomerular Filtration Rate (eGFR) and Spot Urine Albumin-Creatinine Ratio (ACR). RESULTS Results: Out of 110 patients, 62 male and 48 female, the mean age was (22±12). The patients with microalbuminuria (ACR ≥ 30 mg/g) show statistically significant with increase HBA1C, duration of DM type 1, total cholesterol (T.C), low density lipoprotein (LDL), triglycerides (TG) and family history of DM type 1, while there were not statistically significant with age, gender, smoking, BMI, eGFR, high density lipoprotein (HDL) and hypertension. Patients with eGFR<90mL/min/1.73m2 show statistically significant with increase HBA1C, duration of DM type1, LDL, TG, T.C, while significantly decrease in HDL and there were not statistically significant with age, gender, smoking, family history of DM type 1, BMI and hypertension. CONCLUSION Conclusions: The degree of glycemic control, duration of type1 (DM) and dyslipidemia were associated with increased microalbuminuria and reduced eGFR (nephropathy). Family history of DM type1 was risk factor for microalbuminuria.
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Affiliation(s)
| | | | | | - Najah R Hadi
- FACULTY OF MEDICINE, UNIVERSITY OF KUFA, NAJAF, IRAQ
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31
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Sourij H, Edlinger R, Prischl FC, Kaser S, Horn S, Antlanger M, Paulweber B, Aberer F, Brix J, Cejka D, Stingl H, Kautzky-Willer A, Schmaldienst S, Clodi M, Rosenkranz A, Mayer G, Oberbauer R, Säemann M. [Diabetic kidney disease (update 2023) : Position paper of the Austrian Diabetes Association and the Austrian Society for Nephrology]. Wien Klin Wochenschr 2023; 135:182-194. [PMID: 37101040 PMCID: PMC10133372 DOI: 10.1007/s00508-022-02147-3] [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: 12/21/2022] [Indexed: 04/28/2023]
Abstract
Epidemiological investigations have shown that approximately 2-3% of all Austrians have diabetes mellitus with renal involvement, leaving 250,000 people in Austria affected. The risk of occurrence and progression of this disease can be attenuated by lifestyle interventions as well as optimization of blood pressure, blood glucose control and special drug classes. The present article represents the joint recommendations of the Austrian Diabetes Association and the Austrian Society of Nephrology for the diagnostic and treatment strategies of diabetic kidney disease.
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Affiliation(s)
- Harald Sourij
- Klinische Abteilung für Endokrinologie und Diabetologie, Trials Unit für Interdisziplinäre Metabolische Medizin, Medizinische Universität Graz, Auenbruggerplatz 15, 8036, Graz, Österreich.
| | - Roland Edlinger
- 3. Medizinische Abteilung mit Stoffwechselerkrankungen und Nephrologie, Klinik Hietzing, Wien, Österreich
| | - Friedrich C Prischl
- Abteilung für Innere Medizin IV, Klinikum Wels-Grieskirchen, Wels, Österreich
| | - Susanne Kaser
- Universitätsklinik für Innere Medizin I, Medizinische Universität Innsbruck, Innsbruck, Österreich
| | - Sabine Horn
- Abteilung für Innere Medizin, LKH Villach, Villach, Österreich
| | - Marlies Antlanger
- Universitätsklinik für Innere Medizin 2, Kepler Universitätsklinikum Linz, Linz, Österreich
| | - Bernhard Paulweber
- Universitätsklinik für Innere Medizin I, Landeskrankenhaus Salzburg, Uniklinikum der PMU, Salzburg, Österreich
| | - Felix Aberer
- Klinische Abteilung für Endokrinologie und Diabetologie, Medizinische Universität Graz, Graz, Österreich
| | - Johanna Brix
- 1. Medizinischen Abteilung mit Diabetologie, Endokrinologie und Nephrologie, Klinik Landstraße, Wien, Österreich
| | - Daniel Cejka
- Abteilung für Innere Medizin 3, Ordensklinikum Linz, Elisabethinen, Linz, Österreich
| | - Harald Stingl
- Abteilung für Innere Medizin, LKH Melk, Melk, Österreich
| | - Alexandra Kautzky-Willer
- Klinische Abteilung für Endokrinologie und Stoffwechsel, Universitätsklinik für Innere Medizin III, Medizinische Universität Wien, Wien, Österreich
| | | | - Martin Clodi
- Abteilung für Innere Medizin, Krankenhaus Barmherzige Brüder Linz, Linz, Österreich
| | - Alexander Rosenkranz
- Klinische Abteilung für Nephrologie, Universitätsklinik für Innere Medizin, Medizinische Universität Graz, Graz, Österreich
| | - Gert Mayer
- Nephrologie und Hypertensiologie, Universitätsklinik für Innere Medizin IV, Medizinische Universität Innsbruck, Innsbruck, Österreich
| | - Rainer Oberbauer
- Klinische Abteilung für Nephrologie und Dialyse, Universitätsklinik für Innere Medizin III, Medizinische Universität Wien, Wien, Österreich
| | - Marcus Säemann
- 6. Medizinische Abteilung mit Nephrologie & Dialyse, Klinik Ottakring, Wien, Österreich
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Li H, Dai W, Liu Z, He L. Renal Proximal Tubular Cells: A New Site for Targeted Delivery Therapy of Diabetic Kidney Disease. Pharmaceuticals (Basel) 2022; 15:ph15121494. [PMID: 36558944 PMCID: PMC9786989 DOI: 10.3390/ph15121494] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2022] [Revised: 11/28/2022] [Accepted: 11/29/2022] [Indexed: 12/04/2022] Open
Abstract
Diabetic kidney disease (DKD) is a major complication of diabetes mellitus (DM) and the leading cause of end-stage kidney disease (ESKD) worldwide. A significant number of drugs have been clinically investigated for the treatment of DKD. However, a large proportion of patients still develop end-stage kidney disease unstoppably. As a result, new effective therapies are urgently needed to slow down the progression of DKD. Recently, there is increasing evidence that targeted drug delivery strategies such as large molecule carriers, small molecule prodrugs, and nanoparticles can improve drug efficacy and reduce adverse side effects. There is no doubt that targeted drug delivery strategies have epoch-making significance and great application prospects for the treatment of DKD. In addition, the proximal tubule plays a very critical role in the progression of DKD. Consequently, the purpose of this paper is to summarize the current understanding of proximal tubule cell-targeted therapy, screen for optimal targeting strategies, and find new therapeutic approaches for the treatment of DKD.
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Affiliation(s)
| | | | | | - Liyu He
- Correspondence: ; Tel.: +86-731-8529-2064
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33
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Trifonova OP, Maslov DL, Balashova EE, Lichtenberg S, Lokhov PG. Potential Plasma Metabolite Biomarkers of Diabetic Nephropathy: Untargeted Metabolomics Study. J Pers Med 2022; 12:1889. [PMID: 36422065 PMCID: PMC9692474 DOI: 10.3390/jpm12111889] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 11/04/2022] [Accepted: 11/09/2022] [Indexed: 09/21/2023] Open
Abstract
Diabetic nephropathy (DN) is one of the specific complications of diabetes mellitus and one of the leading kidney-related disorders, often requiring renal replacement therapy. Currently, the tests commonly used for the diagnosis of DN, albuminuria (AU) and glomerular filtration rate (GFR), have limited sensitivity and specificity and can usually be noted when typical morphological changes in the kidney have already been manifested. That is why the extreme urgency of the problem of early diagnosis of this disease exists. The untargeted metabolomics analysis of blood plasma samples from 80 patients with type 1 diabetes and early and late stages of DN according to GFR was performed using direct injection mass spectrometry and bioinformatics analysis for diagnosing signatures construction. Among the dysregulated metabolites, combinations of 15 compounds, including amino acids and derivatives, monosaccharides, organic acids, and uremic toxins were selected for signatures for DN diagnosis. The selected metabolite combinations have shown high performance for diagnosing of DN, especially for the late stage (up to 99%). Despite the metabolite signature determined for the early stage of DN being characterized by a diagnostic performance of 81%, these metabolites as potential biomarkers might be useful in the evaluation of treatment of the disease, especially at early stages that may reduce the risk of kidney failure development.
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Affiliation(s)
- Oxana P. Trifonova
- Institute of Biomedical Chemistry, 10 Building 8, Pogodinskaya Street, 119121 Moscow, Russia
| | - Dmitry L. Maslov
- Institute of Biomedical Chemistry, 10 Building 8, Pogodinskaya Street, 119121 Moscow, Russia
| | - Elena E. Balashova
- Institute of Biomedical Chemistry, 10 Building 8, Pogodinskaya Street, 119121 Moscow, Russia
| | - Steven Lichtenberg
- Institute of Biomedical Chemistry, 10 Building 8, Pogodinskaya Street, 119121 Moscow, Russia
- Metabometrics, Inc., 651 N Broad Street, Suite 205 #1370, Middletown, DE 19709, USA
| | - Petr G. Lokhov
- Institute of Biomedical Chemistry, 10 Building 8, Pogodinskaya Street, 119121 Moscow, Russia
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Liu H, Feng J, Tang L. Early renal structural changes and potential biomarkers in diabetic nephropathy. Front Physiol 2022; 13:1020443. [PMID: 36425298 PMCID: PMC9679365 DOI: 10.3389/fphys.2022.1020443] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Accepted: 10/26/2022] [Indexed: 08/10/2023] Open
Abstract
Diabetic nephropathy is one of the most serious microvascular complications of diabetes mellitus, with increasing prevalence and mortality. Currently, renal function is assessed clinically using albumin excretion rate and glomerular filtration rate. But before the appearance of micro-albumin, the glomerular structure has been severely damaged. Glomerular filtration rate based on serum creatinine is a certain underestimate of renal status. Early diagnosis of diabetic nephropathy has an important role in improving kidney function and delaying disease progression with drugs. There is an urgent need for biomarkers that can characterize the structural changes associated with the kidney. In this review, we focus on the early glomerular and tubular structural alterations, with a detailed description of the glomerular injury markers SMAD1 and Podocalyxin, and the tubular injury markers NGAL, Netrin-1, and L-FABP in the context of diabetic nephropathy. We have summarized the currently studied protein markers and performed bioprocess analysis. Also, a brief review of proteomic and scRNA-seq method in the search of diabetic nephropathy.
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Affiliation(s)
- Hao Liu
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China
| | - Jianguo Feng
- Department of Anesthesiology, The Affiliated Hospital of Southwest Medical University; Laboratory of Anesthesiology, Southwest Medical University, Luzhou, China
| | - Liling Tang
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China
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35
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Xie Y, Jin D, Qiu H, Lin L, Sun S, Li D, Sha F, Zhou W, Jia M. Assessment of urinary podocalyxin as an alternative marker for urinary albumin creatinine ratio in early stage of diabetic kidney disease in older patients. Nefrologia 2022; 42:664-670. [PMID: 36402681 DOI: 10.1016/j.nefroe.2022.11.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Accepted: 08/01/2021] [Indexed: 06/16/2023] Open
Abstract
This study's objective is to evaluate the correlation relationship between Podocalyxin (PCX), an urinary marker of podocytes, urinary albumin-creatinine ratio (ACR) and the predictive value of PCX in the routine screen of early diabetic kidney disease (DKD) among older people. We also aimed to explore its prediction value despite of other metabolic factor and how PCX alters in the predictive power for early stage of diabetic nephropathy. In retrospective, 320 cases of older patients diagnosed with type 2 diabetes mellitus who met both inclusion and exclusion criteria were collected and divided with levels of urinary albumin, that is, normal albuminuria group, microalbuminuria group and healthy group. The correlation coefficient between PCX and ACR, and the odds ratio of PCX were gauged in the study. Area under the receiver operating characteristic (ROC) curve was also calculated. There were 188 patients in the normal group with urine ACR<30mg/g, and 132 patients in the microproteinuria group with urine ACR 30-300mg/g. 132 cases of DKD diagnosed with ACR, among them, 104 cases of DKD were predicted by PCX. The percentage correction value was 78.8%. The following parameters such as gender, age, course of disease, glycated hemoglobin, triglyceride, total cholesterol, BMI, blood pressure, uric acid, and eGFR were used as variables for adjustment to establish the prediction model of urine PCX and ACR. Multiple logistic regression test was carried out to evaluate against the predictive ability of the model. The area under the ROC curve corresponding to the regression model after adjustment is 0.952. Although factors such as the course of disease, HbA1C, UA, and eGFR could influence on the predictive ability of PCX, PCX still has a good ability to predict early DKD in older patients. Therefore, it could be used as a diagnostic indicator for early-stage DKD in older patients.
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Affiliation(s)
- Yuxian Xie
- Department of Nephrology, People's Hospital of Suzhou New District, Suzhou, China
| | - Donghua Jin
- Department of Nephrology, People's Hospital of Suzhou New District, Suzhou, China
| | - Hong Qiu
- Department of Nephrology, People's Hospital of Suzhou New District, Suzhou, China
| | - Lihua Lin
- Department of Nephrology, People's Hospital of Suzhou New District, Suzhou, China
| | - Shaobo Sun
- Department of Nephrology, People's Hospital of Suzhou New District, Suzhou, China
| | - Damei Li
- Department of Nephrology, People's Hospital of Suzhou New District, Suzhou, China
| | - Feifei Sha
- Department of Nephrology, People's Hospital of Suzhou New District, Suzhou, China
| | - Wenming Zhou
- Department of Nephrology, People's Hospital of Suzhou New District, Suzhou, China
| | - Miao Jia
- Department of Nephrology, People's Hospital of Suzhou New District, Suzhou, China.
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Hirakawa Y, Yoshioka K, Kojima K, Yamashita Y, Shibahara T, Wada T, Nangaku M, Inagi R. Potential progression biomarkers of diabetic kidney disease determined using comprehensive machine learning analysis of non-targeted metabolomics. Sci Rep 2022; 12:16287. [PMID: 36175470 PMCID: PMC9523033 DOI: 10.1038/s41598-022-20638-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2022] [Accepted: 09/15/2022] [Indexed: 12/03/2022] Open
Abstract
Diabetic kidney disease is the main cause of end-stage renal disease worldwide. The prediction of the clinical course of patients with diabetic kidney disease remains difficult, despite the identification of potential biomarkers; therefore, novel biomarkers are needed to predict the progression of the disease. We conducted non-targeted metabolomics using plasma and urine of patients with diabetic kidney disease whose estimated glomerular filtration rate was between 30 and 60 mL/min/1.73 m2. We analyzed how the estimated glomerular filtration rate changed over time (up to 30 months) to detect rapid decliners of kidney function. Conventional logistic analysis suggested that only one metabolite, urinary 1-methylpyridin-1-ium (NMP), was a promising biomarker. We then applied a deep learning method to identify potential biomarkers and physiological parameters to predict the progression of diabetic kidney disease in an explainable manner. We narrowed down 3388 variables to 50 using the deep learning method and conducted two regression models, piecewise linear and handcrafted linear regression, both of which examined the utility of biomarker combinations. Our analysis, based on the deep learning method, identified systolic blood pressure and urinary albumin-to-creatinine ratio, six identified metabolites, and three unidentified metabolites including urinary NMP, as potential biomarkers. This research suggests that the machine learning method can detect potential biomarkers that could otherwise escape identification using the conventional statistical method.
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Affiliation(s)
- Yosuke Hirakawa
- Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan
| | - Kentaro Yoshioka
- Kyowa Kirin Co., Ltd., Tokyo, Japan.,Division of Chronic Kidney Disease Pathophysiology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan
| | | | | | | | - Takehiko Wada
- Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara, Japan
| | - Masaomi Nangaku
- Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
| | - Reiko Inagi
- Division of Chronic Kidney Disease Pathophysiology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
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Bandiera C, Lam L, Locatelli I, Dotta-Celio J, Duarte D, Wuerzner G, Pruijm M, Zanchi A, Schneider MP. Understanding reasons and factors for participation and non-participation to a medication adherence program for patients with diabetic kidney disease in Switzerland: a mixed methods study. Diabetol Metab Syndr 2022; 14:140. [PMID: 36167584 PMCID: PMC9516833 DOI: 10.1186/s13098-022-00898-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Accepted: 08/24/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND An interprofessional medication adherence intervention led by pharmacists, combining motivational interviews and feedback with electronic monitor (EM) drug assessment, was offered to all consecutive patients with diabetic kidney disease (DKD) (estimated glomerular filtration rate < 60 mL/min/1.73 m2) visiting their nephrologist or endocrinologist. Approximately 73% (202/275) of eligible patients declined to participate, and the factors and reasons for refusal were investigated. METHODS Sociodemographic and clinical data of included patients and those who refused were collected retrospectively for those who had previously signed the general consent form. Multivariate logistic regression analysis was performed to identify independent variables associated with non-participation. Patients who refused or accepted the adherence study were invited to participate in semi-structured interviews. Verbatim transcription, thematic analysis, and inductive coding were performed. RESULTS Patients who refused to participate were older (n = 123, mean age 67.7 years, SD:10.4) than those who accepted (n = 57, mean age 64.0 years, SD:10.0, p = 0.027) and the proportion of women was higher among them than among patients who accepted it (30.9% vs 12.3%, p = 0.007). The time from diabetes diagnosis was longer in patients who refused than in those who accepted (median 14.2 years IQR 6.9-22.7 vs. 8.6 years, IQR 4.5-15.9, p = 0.003). Factors associated with an increased risk of non-participation were female sex (OR 3.8, 95% CI 1.4-10.0, p = 0.007) and the time from diabetes diagnosis (OR 1.05, 95% CI 1.01-1.09, p = 0.019). The included patients who were interviewed (n = 14) found the interprofessional intervention useful to improve their medication management, support medication literacy, and motivation. Patients who refused to participate and who were interviewed (n = 16) explained no perceived need, did not agree to use EM, and perceived the study as a burden and shared that the study would have been beneficial if introduced earlier in their therapeutic journey. Other barriers emerged as difficult relationships with healthcare providers, lack of awareness of the pharmacist's role, and negative perception of clinical research. CONCLUSIONS Investigating the factors and reasons for participation and non-participation in a study helps tailor intervention designs to the needs of polypharmacy patients. Patients who refused the adherence intervention may not be aware of the benefits of medication management and medication literacy. There is an urgent need to advocate for interprofessional outpatient collaborations to support medication adherence in patients with DKD. Trial registration Clinicaltrials.gov NCT04190251_PANDIA IRIS.
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Affiliation(s)
- Carole Bandiera
- School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland
- Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Geneva, Switzerland
- Center for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland
| | - Liliane Lam
- School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland
| | - Isabella Locatelli
- Center for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland
| | - Jennifer Dotta-Celio
- Center for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland
| | - Dina Duarte
- Service of Nephrology and Hypertension, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Gregoire Wuerzner
- Service of Nephrology and Hypertension, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Menno Pruijm
- Service of Nephrology and Hypertension, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Anne Zanchi
- Service of Nephrology and Hypertension, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
- Service of Endocrinology, Diabetes and Metabolism, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Marie P. Schneider
- School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland
- Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Geneva, Switzerland
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Prandi FR, Barone L, Lecis D, Belli M, Sergi D, Milite M, Lerakis S, Romeo F, Barillà F. Biomolecular Mechanisms of Cardiorenal Protection with Sodium-Glucose Co-Transporter 2 Inhibitors. Biomolecules 2022; 12:1349. [PMID: 36291558 PMCID: PMC9599693 DOI: 10.3390/biom12101349] [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] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Revised: 09/22/2022] [Accepted: 09/22/2022] [Indexed: 11/16/2022] Open
Abstract
Diabetes mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia and associated with an increased risk of morbidity and mortality, primarily from cardiovascular and renal diseases. Sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) are novel drugs for the treatment of type 2 DM and heart failure (HF). SGLT2-Is mediate protective effects on both the renal and cardiovascular systems. This review addresses the current knowledge on the biomolecular mechanisms of the cardiorenal protective effects of SGLT2-Is, which appear to act mainly through non-glucose-mediated pathways. Cardiorenal protection mechanisms lead to reduced chronic renal disease progression and improved myocardial and coronary endothelial function. Concomitantly, it is possible to observe reflected changes in biomarkers linked with diabetic kidney disease and HF.
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Affiliation(s)
- Francesca Romana Prandi
- Division of Cardiology, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy
- Department of Cardiology, Mount Sinai Hospital, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Lucy Barone
- Division of Cardiology, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy
| | - Dalgisio Lecis
- Division of Cardiology, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy
| | - Martina Belli
- Division of Cardiology, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy
- Cardiovascular Imaging Unit, San Raffaele Scientific Institute, 20132 Milan, Italy
| | - Domenico Sergi
- Division of Cardiology, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy
| | - Marialucia Milite
- Division of Cardiology, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy
| | - Stamatios Lerakis
- Department of Cardiology, Mount Sinai Hospital, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Francesco Romeo
- Faculty of Medicine, Unicamillus-Saint Camillus International University of Health and Medical Sciences, 00131 Rome, Italy
| | - Francesco Barillà
- Division of Cardiology, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy
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Khanijou V, Zafari N, Coughlan MT, MacIsaac RJ, Ekinci EI. Review of potential biomarkers of inflammation and kidney injury in diabetic kidney disease. Diabetes Metab Res Rev 2022; 38:e3556. [PMID: 35708187 PMCID: PMC9541229 DOI: 10.1002/dmrr.3556] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Revised: 02/18/2022] [Accepted: 04/02/2022] [Indexed: 11/17/2022]
Abstract
Diabetic kidney disease is expected to increase rapidly over the coming decades with rising prevalence of diabetes worldwide. Current measures of kidney function based on albuminuria and estimated glomerular filtration rate do not accurately stratify and predict individuals at risk of declining kidney function in diabetes. As a result, recent attention has turned towards identifying and assessing the utility of biomarkers in diabetic kidney disease. This review explores the current literature on biomarkers of inflammation and kidney injury focussing on studies of single or multiple biomarkers between January 2014 and February 2020. Multiple serum and urine biomarkers of inflammation and kidney injury have demonstrated significant association with the development and progression of diabetic kidney disease. Of the inflammatory biomarkers, tumour necrosis factor receptor-1 and -2 were frequently studied and appear to hold most promise as markers of diabetic kidney disease. With regards to kidney injury biomarkers, studies have largely targeted markers of tubular injury of which kidney injury molecule-1, beta-2-microglobulin and neutrophil gelatinase-associated lipocalin emerged as potential candidates. Finally, the use of a small panel of selective biomarkers appears to perform just as well as a panel of multiple biomarkers for predicting kidney function decline.
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Affiliation(s)
- Vuthi Khanijou
- Melbourne Medical SchoolUniversity of MelbourneAustin HealthMelbourneVictoriaAustralia
| | - Neda Zafari
- Department of MedicineUniversity of MelbourneAustin HealthMelbourneVictoriaAustralia
| | - Melinda T. Coughlan
- Department of DiabetesCentral Clinical SchoolMonash UniversityAlfred Medical Research AllianceMelbourneVictoriaAustralia
- Baker Heart & Diabetes InstituteMelbourneVictoriaAustralia
| | - Richard J. MacIsaac
- Department of Endocrinology & DiabetesSt. Vincent's Hospital Melbourne and University of MelbourneMelbourneVictoriaAustralia
| | - Elif I. Ekinci
- Melbourne Medical SchoolUniversity of MelbourneAustin HealthMelbourneVictoriaAustralia
- Department of EndocrinologyAustin HealthMelbourneVictoriaAustralia
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Mangelis A, Fountoulakis N, Corcillo A, Collins J, Vas P, Hussain S, Hopkins D, Gnudi L, Thomas S, Ayis S, Karalliedde J. African Caribbean Ethnicity Is an Independent Predictor of Significant Decline in Kidney Function in People With Type 1 Diabetes. Diabetes Care 2022; 45:2095-2102. [PMID: 36044663 DOI: 10.2337/dc22-0815] [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: 04/26/2022] [Accepted: 05/22/2022] [Indexed: 02/03/2023]
Abstract
OBJECTIVE The aim of the study was to identify the demographic and clinical features in an urban cohort of people with type 1 diabetes who developed a ≥50% decline in estimated glomerular filtration rate (eGFR). RESEARCH DESIGN AND METHODS We evaluated 5,261 people with type 1 diabetes (51% female, 13.4% African Caribbean) with baseline eGFR >45 mL/min/1.73 m2 between 2004 and 2018. The primary end point was an eGFR decline of ≥50% from baseline with a final eGFR <30 mL/min/1.73 m2. eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. RESULTS Of the cohort, 263 (5%) reached the primary end point. These individuals were more likely to be of African Caribbean ethnicity, be older, have a longer duration of diabetes, have higher systolic blood pressure and HbA1c, have more prevalent retinopathy, and have higher albuminuria (all P < 0.05). In multivariable Cox regression models, African Caribbean ethnicity emerged as a significant risk factor for the primary end point (hazard ratio 1.57, 95% CI 1.19, 2.08) compared with other ethnicities and independent of established risk factors (P < 0.01). The incidence rate for the primary end point in African Caribbean people was double that in non-African Caribbean people (16 vs. 7.7 per 1000 patient-years, P < 0.001). A similar significant independent impact of African Caribbean ethnicity for secondary end points (≥40% and ≥30% fall in eGFR) was observed. CONCLUSIONS We report a novel observation that African Caribbean ethnicity increased the risk of kidney function loss in people with type 1 diabetes, an effect that was independent of traditional risk factors. Further studies are needed to examine the associated pathophysiology that may explain this observation.
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Affiliation(s)
- Anastasios Mangelis
- School of Population Health and Environmental Sciences, King's College London, London, U.K
| | - Nikolaos Fountoulakis
- King's Health Partners and School of Cardiovascular Medicine and Sciences, King's College London, London, U.K
| | - Antonella Corcillo
- King's Health Partners and School of Cardiovascular Medicine and Sciences, King's College London, London, U.K
| | - Julian Collins
- King's Health Partners and School of Cardiovascular Medicine and Sciences, King's College London, London, U.K
| | - Prashant Vas
- King's Health Partners and School of Cardiovascular Medicine and Sciences, King's College London, London, U.K
| | - Sufyan Hussain
- King's Health Partners and School of Cardiovascular Medicine and Sciences, King's College London, London, U.K
| | - David Hopkins
- King's Health Partners and School of Cardiovascular Medicine and Sciences, King's College London, London, U.K
| | - Luigi Gnudi
- King's Health Partners and School of Cardiovascular Medicine and Sciences, King's College London, London, U.K
| | - Stephen Thomas
- King's Health Partners and School of Cardiovascular Medicine and Sciences, King's College London, London, U.K
| | - Salma Ayis
- School of Population Health and Environmental Sciences, King's College London, London, U.K
| | - Janaka Karalliedde
- King's Health Partners and School of Cardiovascular Medicine and Sciences, King's College London, London, U.K
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Ganz MJ, Bender ST, Gross C, Bose K, Mertens PR, Scurt FG. Metabolisches Syndrom und Nierenkrankheiten. DIE NEPHROLOGIE 2022; 17:291-303. [DOI: 10.1007/s11560-022-00595-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 07/07/2022] [Indexed: 01/04/2025]
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Eto E, Maeda Y, Sonoda N, Nakashima N, Kobayashi K, Takayanagi R, Ogawa Y, Inoguchi T. Association of serum total bilirubin levels with progressive renal decline and end-stage kidney disease: 10-year observational cohort study in Japanese patients with diabetes. PLoS One 2022; 17:e0271179. [PMID: 35819962 PMCID: PMC9275719 DOI: 10.1371/journal.pone.0271179] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Accepted: 06/24/2022] [Indexed: 11/18/2022] Open
Abstract
Objective Previous reports have demonstrated the association of serum bilirubin levels with the progression of diabetic nephropathy. The objective of this study is to assess the association of basal bilirubin levels with progressive renal decline (PRD) and end-stage kidney disease (ESKD). Methods A total of 298 patients with diabetes who visited Kyushu University Hospital (Japan) were recruited and followed up for 10 years. PRD was defined as a negative change in estimated glomerular filtration ratio (eGFR) >3.7%/year, 2.5th percentile. Logistic regression analysis was performed to evaluate the association of total bilirubin levels with PRD and its cut-off point was determined by receiver operating characteristic (ROC) analysis. Kaplan-Meier method and Cox hazard regression analysis were used to evaluate the predictive ability of its cut-off point for ESKD. Results Logistic regression model showed that total bilirubin levels were significantly associated with PRD, and ROC analysis showed that its cut-off point was 0.5 mg/dL. Kaplan-Meier method showed that the percent of patients who reached two endpoints, composite endpoint (ESKD or doubling of creatinine level) or 30% eGFR decline, was significantly higher in the low bilirubin group than in the high bilirubin group (18.5% vs 11.0%, P = 0.045; 49.1% vs 42.1%, P = 0.045, respectively, log-rank test). Cox hazard regression models confirmed the independence of the predictive ability of its cut-off point. Conclusions Serum total bilirubin levels were negatively associated with PRD in diabetic nephropathy and its cut-off point was 0.5 mg/dL. It may be clinically useful for identifying patients at high risk of ESKD.
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Affiliation(s)
- Erina Eto
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yasutaka Maeda
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Noriyuki Sonoda
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Naoki Nakashima
- Medical Information Center, Kyushu University Hospital, Fukuoka, Japan
| | - Kunihisa Kobayashi
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Ryoichi Takayanagi
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yoshihiro Ogawa
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Toyoshi Inoguchi
- Fukuoka City Health Promotion Support Center, Fukuoka City Medical Association, Fukuoka, Japan
- * E-mail:
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An L, Yu Q, Tang H, Li X, Wang D, Tang Q, Xing H, He Y, Zhao X, Zhao S, Lee Y, Lu J. The Prevalence, Progress and Risk Factor Control of Chronic Kidney Disease in Chinese Adults With Type 2 Diabetes Mellitus in Primary Care. Front Endocrinol (Lausanne) 2022; 13:859266. [PMID: 35757423 PMCID: PMC9226338 DOI: 10.3389/fendo.2022.859266] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Accepted: 04/27/2022] [Indexed: 11/28/2022] Open
Abstract
Objective This study aimed to evaluate the prevalence of chronic kidney disease (CKD) in Chinese adults with T2DM in primary care, and the association of HbA1c, blood pressure (BP) and triglycerides (TG), i.e. ABC control at follow up (FU) with the progress and regression of CKD. Methods A total of 5123 patients with ≥3 measurements of estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), HbA1c, BP, LDL-C and TG, and FU ≥ 12 months were included into final analysis. The presence of CKD was defined as the presence of albuminuria (UACR ≥ 30 mg/g), impaired eGFR (eGFR < 60 ml/min/1.73 m2) or both, and was categorised as low, moderate and high/very high risk. The change of CKD risk for outcome was categorised as stable (no change), progress (risk increase) and regress (risk decrease) from baseline to the last visits (LV). Results The prevalence of CKD, impaired eGFR and albuminuria was 29.6%, 5.8% and 27.1% at baseline, with 70.4%, 20.3%, 7.0% and 2.3% of patients distributed in low, moderate, high and very high risk group. There were 3457 (67.5%), 1120 (21.8%) and 546 (10.7%) patients had CKD outcome risk stable, progressed and regressed respectively. The proportion of patients reaching targets of BP ≤ 130/80 mmHg, HbA1c<7.5%, LDL-C<2.60 mmol/L increased from baseline to FU and LV, together with increased usage of insulin, RAS inhibitors and lipid lowering medications. After multivariable adjustment, the HbA1c<7.5% (OR: 0.66, 95%CI 0.56-0.78), TG< 1.7 mmol/L (OR: 0.81, 95%CI 0.68-0.96) at FU and BP ≤ 130/80 mmHg at LV (OR: 0.82, 95%CI 0.70-0.95) was negatively associated with CKD outcome risk progress. Conclusion The prevalence of CKD was high with 21.8% of patients progressing to higher CKD outcome risk at FU, attention should be paid on long term and better ABC control.
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Affiliation(s)
- Lingwang An
- Department of Endocrinology, Beijing Ruijing Diabetes Hospital, Beijing, China
| | - Qiuzhi Yu
- Department of Endocrinology, Heilongjiang Ruijing Diabetes Hospital, Haerbin, China
| | - Hong Tang
- Department of Share-care center, Chengdu Ruien Diabetes Hospital, Chengdu, China
| | - Xianglan Li
- Department of Endocrinology, Beijing Ruijing Diabetes Hospital, Beijing, China
| | - Dandan Wang
- Department of Endocrinology, Beijing Ruijing Diabetes Hospital, Beijing, China
| | - Qi Tang
- Department of Endocrinology, Beijing Ruijing Diabetes Hospital, Beijing, China
| | - Haiyang Xing
- Department of Endocrinology, Beijing Ruijing Diabetes Hospital, Beijing, China
| | - Yali He
- Department of Endocrinology, Taiyuan Diabetes Hospital, Taiyuan, China
| | - Xiaona Zhao
- Department of Endocrinology, Heilongjiang Ruijing Diabetes Hospital, Haerbin, China
| | - Shuhui Zhao
- Department of Endocrinology, Lanzhou Ruijing Diabetes Hospital, Lanzhou, China
| | - Yaujiunn Lee
- Department of Metabolism and Endocrinology, Lee’s Clinic, Pingtung, Taiwan
| | - Juming Lu
- Department of Endocrinology, Beijing Ruijing Diabetes Hospital, Beijing, China
- Department of Endocrinology, The General Hospital of the People’s Liberation Army, Beijing, China
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Wang Y, Ding L, Wang R, Guo Y, Yang Z, Yu L, Wang L, Liang Y, Tang L. Circ_0004951 Promotes Pyroptosis of Renal Tubular Cells via the NLRP3 Inflammasome in Diabetic Kidney Disease. Front Med (Lausanne) 2022; 9:828240. [PMID: 35733856 PMCID: PMC9207212 DOI: 10.3389/fmed.2022.828240] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Accepted: 05/06/2022] [Indexed: 12/25/2022] Open
Abstract
Background Diabetic kidney disease (DKD) has become the leading cause of chronic kidney disease (CKD) in many countries. Recent studies have shown that circular RNA and pyroptosis play an important role in pathogenesis of DKD. Methods We analyzed expression patterns of circRNAs in human kidney biopsy tissues obtained from type 2 DKD (n = 9) and nephrectomy (n = 9) patients. Next, we cultured human renal tubular epithelial cells (HK2) in high glucose condition and detected circ_0004951, miR-93-5p, NLR Pyrin Domain Containing 3 (NLRP3) inflammasome-related indicators and pyroptosis. Furthermore, we performed Bioinformatics analysis and dual-luciferase reporter assay to analyze the relationship among circ_0004951, miR-93-5p and NLRP3. Results Circ_0004951 was significantly upregulated in kidney tissues from DKD patients and HK2 in high glucose condition vs. control. Knockdown of circ_0004951 mediated a significant suppression of HK2 pyroptosis, while results from bioinformatics analysis revealed that circ_0004951 has binding sites with miR-93-5p and miR-93-5p could bind to NLRP3. Results from dual-luciferase reporter assay further corroborated this finding. Finally, observations from rescue experiments showed that down-regulation of miR-93-5p and upregulation of NLRP3 markedly attenuated the anti-pyroptosis and anti-inflammatory effects of circ_0004951 knockdown on HK2. Conclusion Circ_0004951 promotes pyroptosis of renal tubular epithelial cells in DKD via the miR-93-5p/NLRP3 inflammasome pathway, suggesting its potential for clinical diagnosis and treatment of DKD.
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Affiliation(s)
- Yulin Wang
- Department of Nephrology, Zhengzhou University First Affiliated Hospital, Henan, China
| | - Li Ding
- Henan Sheng Zhiyebing Fangzhi Yanjiu Yuan, Henan Institute for Occupational Medicine, The Third People's Hospital of Henan Province, Henan, China
| | - Ruiqiang Wang
- Department of Nephrology, Zhengzhou University First Affiliated Hospital, Henan, China
| | - Yanhong Guo
- Department of Nephrology, Zhengzhou University First Affiliated Hospital, Henan, China
| | - ZiJun Yang
- Department of Nephrology, Zhengzhou University First Affiliated Hospital, Henan, China
| | - Lu Yu
- Department of Nephrology, Zhengzhou University First Affiliated Hospital, Henan, China
| | - LiuWei Wang
- Department of Nephrology, Zhengzhou University First Affiliated Hospital, Henan, China
| | - Yan Liang
- Department of Nephrology, Zhengzhou University First Affiliated Hospital, Henan, China
| | - Lin Tang
- Department of Nephrology, Zhengzhou University First Affiliated Hospital, Henan, China
- *Correspondence: Lin Tang
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Liu X, Du H, Sun Y, Shao L. Role of abnormal energy metabolism in the progression of chronic kidney disease and drug intervention. Ren Fail 2022; 44:790-805. [PMID: 35535500 PMCID: PMC9103584 DOI: 10.1080/0886022x.2022.2072743] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Chronic kidney disease (CKD) is a severe clinical syndrome with significant socioeconomic impact worldwide. Orderly energy metabolism is essential for normal kidney function and energy metabolism disorders are increasingly recognized as an important player in CKD. Energy metabolism disorders are characterized by ATP deficits and reactive oxygen species increase. Oxygen and mitochondria are essential for ATP production, hypoxia and mitochondrial dysfunction both affect the energy production process. Renin-angiotensin and adenine signaling pathway also play important regulatory roles in energy metabolism. In addition, disturbance of energy metabolism is a key factor in the development of hereditary nephropathy such as autosomal dominant polycystic kidney disease. Currently, drugs with clinically clear renal function protection, such as Angiotensin II Type 1 receptor blockers and fenofibrate, have been proven to improve energy metabolism disorders. The sodium-glucose co-transporter inhibitors 2 that can mediate glucose metabolism disorders not only delay the progress of diabetic nephropathy, but also have significant protective effects in non-diabetic nephropathy. Hypoxia-inducible factor enhances ATP production to the kidney by improving renal oxygen supply and increasing glycolysis, and the mitochondria targeted peptides (SS-31) plays a protective role by stabilizing the mitochondrial inner membrane. Moreover, several drugs are being studied and are predicted to have potential renal protective properties. We propose that the regulation of energy metabolism represents a promising strategy to delay the progression of CKD.
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Affiliation(s)
- Xuyan Liu
- Department of Nephrology, The Affiliated Qingdao Municipal Hospital of Qingdao University, Qingdao, China
| | - Huasheng Du
- Department of Nephrology, The Affiliated Qingdao Municipal Hospital of Qingdao University, Qingdao, China
| | - Yan Sun
- Department of Nephrology, The Affiliated Qingdao Municipal Hospital of Qingdao University, Qingdao, China
| | - Leping Shao
- Department of Nephrology, The Affiliated Qingdao Municipal Hospital of Qingdao University, Qingdao, China
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GÜLTAŞ B, ÖZGÜL Ö, CANDER S. Retrospective evaluation of microalbuminuria and GFR levels of diabetic patients taking DPP-4 Inhibitor, GLP-1 Analog, or SGLT-2 Inhibitor. TURKISH JOURNAL OF INTERNAL MEDICINE 2022. [DOI: 10.46310/tjim.1072857] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
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Yu L, Wang Y, Guo YH, Wang L, Yang Z, Zhai ZH, Tang L. HIF-1α Alleviates High-Glucose-Induced Renal Tubular Cell Injury by Promoting Parkin/PINK1-Mediated Mitophagy. Front Med (Lausanne) 2022; 8:803874. [PMID: 35186974 PMCID: PMC8850720 DOI: 10.3389/fmed.2021.803874] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Accepted: 12/14/2021] [Indexed: 11/13/2022] Open
Abstract
It is well-established that mitophagy leads to Diabetic Nephropathy (DN) and renal failure. Mitophagy mediated by a Hypoxia-inducible factor-1α (HIF-1α) plays a beneficial role in many diseases. Nevertheless, the mechanisms underlying HIF-1α-mediated mitophagy in DN remain unclear. This study defines the role of HIF-1α mediated mitophagy in DN. The expression of HIF-1α was upregulated in HK-2 cells in an High-Glucose (HG) environment, and the YC-1 (a specific inhibitor of HIF-1α) further exacerbated the hypoxia-induced mitochondrial dysfunction. Conversely, the HIF-1α-mediated protective effect was strengthened by scavenger N-acetylcysteine (NAC), a type of reactive oxygen species. Moreover, HIF-1α-Parkin/PINK1-mediated mitophagy prevented apoptosis and ROS production in HK-2 cells subjected to HG exposure. In summary, HIF-1α mediated mitophagy on HK-2 cells under HG conditions could alleviate DN, suggesting that it has huge prospects for DN treatment.
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Affiliation(s)
- Lu Yu
- First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yulin Wang
- College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Yan Hong Guo
- First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Liuwei Wang
- First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zijun Yang
- First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zi Han Zhai
- First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Lin Tang
- First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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48
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Tagaya M, Kume S, Yasuda-Yamahara M, Kuwagata S, Yamahara K, Takeda N, Tanaka Y, Chin-Kanasaki M, Nakae Y, Yokoi H, Mukoyama M, Ishihara N, Nomura M, Araki SI, Maegawa H. Inhibition of mitochondrial fission protects podocytes from albumin-induced cell damage in diabetic kidney disease. Biochim Biophys Acta Mol Basis Dis 2022; 1868:166368. [DOI: 10.1016/j.bbadis.2022.166368] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Revised: 02/03/2022] [Accepted: 02/08/2022] [Indexed: 12/13/2022]
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49
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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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50
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Miller RG, Orchard TJ, Costacou T. 30-Year Cardiovascular Disease in Type 1 Diabetes: Risk and Risk Factors Differ by Long-term Patterns of Glycemic Control. Diabetes Care 2022; 45:142-150. [PMID: 34782353 PMCID: PMC8753768 DOI: 10.2337/dc21-1381] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Accepted: 10/07/2021] [Indexed: 02/03/2023]
Abstract
OBJECTIVE We hypothesized that there is heterogeneity in long-term patterns of glycemic control with respect to cardiovascular disease (CVD) development in type 1 diabetes and that risk factors for CVD differ by glycemic control pattern. Thus, we estimated associations between data-derived latent HbA1c trajectories and 30-year CVD risk in the Pittsburgh Epidemiology of Diabetes Complications (EDC) study of childhood-onset (<17 years old) type 1 diabetes. RESEARCH DESIGN AND METHODS Participants (n = 536 with two or more HbA1c measurements [median 6] and CVD-free at baseline; mean age 27 and diabetes duration 18 years) were followed from 1986 to 1988 to 2016 to 2018 to ascertain CVD incidence (CVD death, myocardial infarction, stroke, coronary revascularization or blockage ≥50%, ischemic electrocardiogram, or angina). Latent HbA1c trajectories and their association with time-to-CVD incidence were simultaneously assessed using joint latent class mixed models. RESULTS Two HbA1c trajectories with respect to differential CVD risk were identified: low (HbA1c ∼8% [64 mmol/mol] and improving over follow-up, 76% of cohort) and high (HbA1c ∼10% [86 mmol/mol] and stable, 24%). Overall, 30-year CVD incidence was 47.4% (n = 253); major adverse cardiovascular event incidence was 31.0% (n = 176). High HbA1c was associated with threefold increased CVD risk versus low HbA1c. Both groups had similar age and diabetes duration. Non-HDL cholesterol and estimated glomerular filtration rate were associated with CVD risk only in low HbA1c; albumin excretion rate was associated with CVD risk only in high HbA1c. CONCLUSIONS These risk factor differences suggest that pathways to CVD may differ by glycemic control, potentially resulting in important implications for prognosis in type 1 diabetes.
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Affiliation(s)
- Rachel G. Miller
- Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA
| | - Trevor J. Orchard
- Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA
| | - Tina Costacou
- Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA
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