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Wang M, Yao F, Chen N, Wu T, Yan J, Du L, Zeng S, Du C. The advance of single cell transcriptome to study kidney immune cells in diabetic kidney disease. BMC Nephrol 2024; 25:412. [PMID: 39550562 PMCID: PMC11568691 DOI: 10.1186/s12882-024-03853-y] [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: 08/16/2024] [Accepted: 11/05/2024] [Indexed: 11/18/2024] Open
Abstract
Diabetic kidney disease (DKD) is a prevalent microvascular complication of diabetes mellitus and a primary cause of end-stage renal disease (ESRD). Increasing studies suggest that immune cells are involved in regulating renal inflammation, which contributes to the progression of DKD. Compared with conventional methods, single-cell sequencing technology is more developed technique that has advantages in resolving cellular heterogeneity, parallel multi-omics studies, and discovering new cell types. ScRNA-seq helps researchers to analyze specifically gene expressions, signaling pathways, intercellular communication as well as their regulations in various immune cells of kidney biopsy and urine samples. It is still challenging to investigate the function of each cell type in the pathophysiology of kidney due to its complex and heterogeneous structure and function. Here, we discuss the application of single-cell transcriptomics in the field of DKD and highlight several recent studies that explore the important role of immune cells including macrophage, T cells, B cells etc. in DKD through scRNA-seq analyses. Through combing the researches of scRNA-seq on immune cells in DKD, this review provides novel perspectives on the pathogenesis and immune therapeutic strategy for DKD.
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Affiliation(s)
- Mengjia Wang
- Department of Pathology, Key Laboratory of Kidney Diseases of Hebei Province, Hebei Medical University, Shijiazhuang, 050017, China
| | - Fang Yao
- Department of Pathology, Key Laboratory of Kidney Diseases of Hebei Province, Hebei Medical University, Shijiazhuang, 050017, China
- Center of Metabolic Diseases and Cancer Research, Institute of Medical and Health Science, Hebei Medical University, Shijiazhuang, China
| | - Ning Chen
- Department of Pathology, The First Hospital of Hebei Medical University, Shijiazhuang, China
| | - Ting Wu
- Department of Pathology, Key Laboratory of Kidney Diseases of Hebei Province, Hebei Medical University, Shijiazhuang, 050017, China
- Center of Metabolic Diseases and Cancer Research, Institute of Medical and Health Science, Hebei Medical University, Shijiazhuang, China
| | - Jiaxin Yan
- Department of Pathology, Key Laboratory of Kidney Diseases of Hebei Province, Hebei Medical University, Shijiazhuang, 050017, China
- Center of Metabolic Diseases and Cancer Research, Institute of Medical and Health Science, Hebei Medical University, Shijiazhuang, China
| | - Linshan Du
- Department of Pathology, Key Laboratory of Kidney Diseases of Hebei Province, Hebei Medical University, Shijiazhuang, 050017, China
| | - Shijie Zeng
- Department of Pathology, Key Laboratory of Kidney Diseases of Hebei Province, Hebei Medical University, Shijiazhuang, 050017, China
| | - Chunyang Du
- Department of Pathology, Key Laboratory of Kidney Diseases of Hebei Province, Hebei Medical University, Shijiazhuang, 050017, China.
- Center of Metabolic Diseases and Cancer Research, Institute of Medical and Health Science, Hebei Medical University, Shijiazhuang, China.
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Farhadi F, Sharififar F, Jafari M, Rahimi VB, Askari N, Askari VR. Hallmarks of Quercetin Benefits as a Functional Supplementary in the Management of Diabetes Mellitus-Related Maladies: From Basic to Clinical Applications. Curr Drug Metab 2024; 25:653-669. [PMID: 39878112 DOI: 10.2174/0113892002339410250108031621] [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: 06/28/2024] [Revised: 11/27/2024] [Accepted: 12/05/2024] [Indexed: 01/31/2025]
Abstract
Quercetin (QE), a particular flavonoid, is well known for its medicinal effects, including anti-oxidant, hypoglycemic, and anti-inflammatory effects. In this review, the findings of QE effects on diabetes STZinduced, alloxan-induced, and its complications have been summarized with a particular focus on in vitro, in vivo, and clinical trials. Consequently, QE mediates several mechanisms, including ameliorating tumor necrosis factor (TNF)-α, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interleukin (IL)-1β, IL-8, and IL-10 expression, increasing insulin glucose uptake to inhibit insulin resistance. Moreover, QE stimulates insulin secretion and attenuates insulin resistance through various pathways, namely transient KATP channel, motivating peroxisome proliferator-activated receptor expression, increasing glucose transporter-4, and decreasing inducible nitric oxide synthase in skeletal muscle. QE has protective effects on the complications caused by diabetes, such as polycystic ovary syndrome, high-fat diet-induced obesity, diabetic-induced hepatic damage, vascular inflammation, nephropathy, and neuropathy.
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Affiliation(s)
- Faegheh Farhadi
- Herbal and Traditional Medicines Research Center, Department of Pharmacognosy, School of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran
| | - Fariba Sharififar
- Herbal and Traditional Medicines Research Center, Department of Pharmacognosy, School of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran
| | - Mandana Jafari
- Herbal and Traditional Medicines Research Center, Department of Pharmacognosy, School of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran
| | - Vafa Baradaran Rahimi
- Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Cardiovascular Diseases, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Nafiseh Askari
- Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Vahid Reza Askari
- Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran
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Galectin-1 in Obesity and Type 2 Diabetes. Metabolites 2022; 12:metabo12100930. [PMID: 36295832 PMCID: PMC9606923 DOI: 10.3390/metabo12100930] [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] [Received: 08/31/2022] [Revised: 09/26/2022] [Accepted: 09/26/2022] [Indexed: 11/06/2022] Open
Abstract
Galectin-1 is a carbohydrate-binding protein expressed in many tissues. In recent years, increasing evidence has emerged for the role of galectin-1 in obesity, insulin resistance and type 2 diabetes. Galectin-1 has been highly conserved through evolution and is involved in key cellular functions such as tissue maturation and homeostasis. It has been shown that galectin-1 increases in obesity, both in the circulation and in the adipose tissue of human and animal models. Several proteomic studies have independently identified an increased galectin-1 expression in the adipose tissue in obesity and in insulin resistance. Large population-based cohorts have demonstrated associations for circulating galectin-1 and markers of insulin resistance and incident type 2 diabetes. Furthermore, galectin-1 is associated with key metabolic pathways including glucose and lipid metabolism, as well as insulin signalling and inflammation. Intervention studies in animal models alter animal weight and metabolic profile. Several studies have also linked galectin-1 to the progression of complications in diabetes, including kidney disease and retinopathy. Here, we review the current knowledge on the clinical potential of galectin-1 in obesity and type 2 diabetes.
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You Y, Hua Z. An intelligent intervention strategy for patients to prevent chronic complications based on reinforcement learning. Inf Sci (N Y) 2022. [DOI: 10.1016/j.ins.2022.07.080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Huang YM, Chen WM, Chen M, Shia BC, Wu SY. Sarcopenia Is an Independent Risk Factor for Severe Diabetic Nephropathy in Type 2 Diabetes: A Long-Term Follow-Up Propensity Score-Matched Diabetes Cohort Study. J Clin Med 2022; 11:2992. [PMID: 35683381 PMCID: PMC9181390 DOI: 10.3390/jcm11112992] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Revised: 05/21/2022] [Accepted: 05/24/2022] [Indexed: 02/08/2023] Open
Abstract
Background: Diabetic nephropathy is a common cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD) worldwide and results in tremendous wastage of medical resources. Determining the indicators of diabetic nephropathy, such as sarcopenia, and implementing early interventions to prevent disease progression is crucial. Purpose: The effect of sarcopenia on the risk of severe diabetic nephropathy in patients with type 2 diabetes (T2DM) remains unclear. Patients and Methods: We recruited patients with T2DM and categorized them into two groups, propensity score−matched at a ratio of 1:1, according to whether they had sarcopenia. We subsequently compared the groups’ risk of severe diabetic nephropathy. Results: The matching process yielded a final cohort of 105,166 patients with T2DM (52,583 and 52,583 in the sarcopenia and nonsarcopenia groups, respectively) who were eligible for inclusion in subsequent analyses. According to both the univariate and multivariate Cox regression analyses, the adjusted hazard ratio (aHR) (95% confidence interval) of severe diabetic nephropathy for the sarcopenia diabetes group compared with the control group was 1.10 (1.08−1.13; p < 0.001). Conclusion: The patients with T2DM and sarcopenia were at a higher risk of severe diabetic nephropathy than were those without sarcopenia. Our results may serve as a valuable reference for relevant government authorities in establishing health policies to promote early detection of sarcopenia and exercise to help patients with T2DM overcome sarcopenia.
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Affiliation(s)
- Yen-Min Huang
- Division of Hematology and Oncology, Department of Internal Medicine, Hemophilia and Thrombosis Treatment Center, Chang Gung Memorial Hospital, Keelung 204, Taiwan;
- Division of Hematology and Oncology, Department of Internal Medicine, Lotung Poh-Ai Hospital, Yilan 265, Taiwan
| | - Wan-Ming Chen
- Graduate Institute of Business Administration, College of Management, Fu Jen Catholic University, Taipei 242, Taiwan; (W.-M.C.); (M.C.); (B.-C.S.)
- Artificial Intelligence Development Center, Fu Jen Catholic University, Taipei 242, Taiwan
| | - Mingchih Chen
- Graduate Institute of Business Administration, College of Management, Fu Jen Catholic University, Taipei 242, Taiwan; (W.-M.C.); (M.C.); (B.-C.S.)
| | - Ben-Chang Shia
- Graduate Institute of Business Administration, College of Management, Fu Jen Catholic University, Taipei 242, Taiwan; (W.-M.C.); (M.C.); (B.-C.S.)
- Artificial Intelligence Development Center, Fu Jen Catholic University, Taipei 242, Taiwan
| | - Szu-Yuan Wu
- Graduate Institute of Business Administration, College of Management, Fu Jen Catholic University, Taipei 242, Taiwan; (W.-M.C.); (M.C.); (B.-C.S.)
- Artificial Intelligence Development Center, Fu Jen Catholic University, Taipei 242, Taiwan
- Department of Food Nutrition and Health Biotechnology, College of Medical and Health Science, Asia University, Taichung 413, Taiwan
- Big Data Center, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan 265, Taiwan
- Division of Radiation Oncology, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Yilan 265, Taiwan
- Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung 413, Taiwan
- Centers for Regional Anesthesia and Pain Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 110, Taiwan
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Wallace AS, Chang AR, Shin JI, Reider J, Echouffo-Tcheugui JB, Grams ME, Selvin E. Obesity and Chronic Kidney Disease in US Adults With Type 1 and Type 2 Diabetes Mellitus. J Clin Endocrinol Metab 2022; 107:1247-1256. [PMID: 35080610 PMCID: PMC9016431 DOI: 10.1210/clinem/dgab927] [Citation(s) in RCA: 50] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Indexed: 01/28/2023]
Abstract
OBJECTIVE Obesity is a global public health challenge and strongly associated with type 2 diabetes (T2D), but its burden and effects are not well understood in people with type 1 diabetes (T1D). Particularly, the link between obesity and chronic kidney disease (CKD) in T1D is poorly characterized. RESEARCH DESIGN AND METHODS We included all T1D and, for comparison, T2D in the Geisinger Health System from 2004 to 2018. We evaluated trends in obesity (body mass index ≥ 30 kg/m2), low estimated glomerular filtration rate (eGFR) (≤60 mL/min/1.73m2), and albuminuria (urine albumin-to-creatinine ratio ≥ 30 mg/g). We used multivariable logistic regression to evaluate the independent association of obesity with CKD in 2018. RESULTS People with T1D were younger than T2D (median age 39 vs 62 years). Obesity increased in T1D over time (32.6% in 2004 to 36.8% in 2018), while obesity in T2D was stable at ~60%. The crude prevalence of low eGFR was higher in T2D than in T1D in all years (eg, 30.6% vs 16.1% in 2018), but after adjusting for age differences, prevalence was higher in T1D than T2D in all years (eg, 16.2% vs 9.3% in 2018). Obesity was associated with increased odds of low eGFR in T1D [adjusted odds ratio (AOR) = 1.52, 95% CI 1.12-2.08] and T2D (AOR = 1.29, 95% CI 1.23-1.35). CONCLUSIONS Obesity is increasing in people with T1D and is associated with increased risk of CKD. After accounting for age, the burden of CKD in T1D exceeded the burden in T2D, suggesting the need for increased vigilance and assessment of kidney-protective medications in T1D.
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Affiliation(s)
- Amelia S Wallace
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
- Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD, USA
| | - Alex R Chang
- Department of Population and Health Sciences, Geisinger, Danville, PA, USA
- Kidney Health Research Institute, Geisinger, Danville, PA, USA
- Department of Nephrology, Geisinger, Danville, PA, USA
| | - Jung-Im Shin
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
- Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD, USA
| | - Jodie Reider
- Endocrinology, Diabetes & Metabolism, Internal Medicine, Geisinger, Danville, PA, USA
| | - Justin B Echouffo-Tcheugui
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA
| | - Morgan E Grams
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
- Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD, USA
- Department of Internal Medicine, Division of Nephrology, Johns Hopkins University, Baltimore, MD, USA
| | - Elizabeth Selvin
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
- Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD, USA
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Herring W, Ciarametaro M, Mauskopf J, Wamble D, Sils B, Dubois R. What might have happened: the impact of interrupting entry of innovative drugs on disease outcomes in the United States. Expert Rev Pharmacoecon Outcomes Res 2022; 22:529-541. [PMID: 35098840 DOI: 10.1080/14737167.2022.2035219] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
INTRODUCTION This study estimated the extent to which drug innovations over the past 30 years may have improved outcomes for six diseases. AREAS COVERED We analyzed six diseases (ischemic heart disease, lung cancer, breast cancer, human immunodeficiency virus [HIV] infection, type 2 diabetes mellitus, and rheumatoid arthritis [RA]) with significant mortality or morbidity for which there have been major drug innovations over the past 30 years. We used US data from the Global Burden of Disease (GBD) database and a patient registry to perform counterfactual time series analyses predicting the improved health outcomes that may have been associated with major drug innovations. For 5 conditions using data from the GBD study, years of life lost per individual with the condition could have been higher by 17.1% (breast cancer) to 660.6% (HIV infection) in 2017 had the major drug innovations not been introduced. For RA, using patient registry data, patients' functional status could have been 11.5% worse had biological therapies not been introduced. EXPERT OPINION Over the next 5 years, policies targeting drug prices should be broadened to include all health care services. In addition, the value of the pharmaceutical industry for generating rapid responses to new diseases should be recognized.
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Affiliation(s)
- William Herring
- RTI Health Solutions, Research Triangle Park, North Carolina, USA
| | | | | | - David Wamble
- RTI Health Solutions, Research Triangle Park, North Carolina, USA (D Wamble is no longer with RTI Health Solutions.)
| | - Brian Sils
- National Pharmaceutical Council, Washington, District of Columbia, USA
| | - Robert Dubois
- National Pharmaceutical Council, Washington, District of Columbia, USA
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Wang J, Yen F, Lin K, Shin S, Hsu Y, Hsu C. Epidemiological characteristics of diabetic kidney disease in Taiwan. J Diabetes Investig 2021; 12:2112-2123. [PMID: 34529360 PMCID: PMC8668071 DOI: 10.1111/jdi.13668] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 09/02/2021] [Accepted: 09/12/2021] [Indexed: 12/17/2022] Open
Abstract
Diabetic kidney disease (DKD) is a critical microvascular complication of diabetes. With the continuous increase in the prevalence of diabetes since 2000, the prevalence of DKD has also been increasing in past years. The prevalence of DKD among individuals with type 2 diabetes in Taiwan increased from 13.32% in 2000 to 17.92% in 2014. The cumulative incidence of DKD among individuals with type 1 diabetes in Taiwan was higher than 30% during 1999-2012. DKD is the leading cause of end-stage renal disease (ESRD), with a prevalence of approximately 45% in a population on chronic dialysis in Taiwan. Among individuals with type 2 diabetes, the prevalence of ESRD in the receipt of dialysis also increased from 1.32% in 2005 to 1.47% in 2014. Risk factors for DKD development are age, race, family history, hyperglycemia, hypertension, dyslipidemia, dietary patterns, and lifestyles. Prognostic factors that aggravate DKD progression include age, family history, sex, glycemic control, blood pressure (BP), microvascular complications, and atherosclerosis. This review summarizes updated information on the onset and progression of DKD, particularly in the Taiwanese population. Translating these epidemiological features is essential to optimizing the kidney care and improving the prognosis of DKD in Asian populations.
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Affiliation(s)
- Jun‐Sing Wang
- Division of Endocrinology and MetabolismDepartment of Internal MedicineTaichung Veterans General HospitalTaichungTaiwan
- Faculty of MedicineSchool of MedicineNational Yang‐Ming UniversityTaipeiTaiwan
- Rong Hsing Research Center for Translational MedicineInstitute of Biomedical ScienceNational Chung Hsing UniversityTaichungTaiwan
- PhD Program in Translational MedicineNational Chung Hsing UniversityTaichungTaiwan
| | | | - Kun‐Der Lin
- Department of Internal MedicineKaohsiung Municipal Ta‐Tung HospitalKaohsiung Medical University HospitalKaohsiung Medical UniversityKaohsiungTaiwan
- Division of Endocrinology and MetabolismDepartment of Internal MedicineKaohsiung Medical University Hospital and College of MedicineKaohsiung Medical UniversityKaohsiungTaiwan
| | - Shyi‐Jang Shin
- Division of Endocrinology and MetabolismDepartment of Internal MedicineKaohsiung Medical University Hospital and College of MedicineKaohsiung Medical UniversityKaohsiungTaiwan
- Grander ClinicKaohsiungTaiwan
| | - Yueh‐Han Hsu
- Department of Internal MedicineDitmanson Medical Foundation Chia‐Yi Christian HospitalChia‐Yi CityTaiwan
- Department of NursingMin‐Hwei College of Health Care ManagementTainan CityTaiwan
| | - Chih‐Cheng Hsu
- Institute of Population Health SciencesNational Health Research InstituteZhunan, MiaoliTaiwan
- Department of Health Services AdministrationChina Medical UniversityTaichung CityTaiwan
- Department of Family MedicineMin‐Sheng General HospitalTaoyuanTaiwan
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Du C, Ren Y, Li G, Yang Y, Yan Z, Yao F. Single Cell Transcriptome Helps Better Understanding Crosstalk in Diabetic Kidney Disease. Front Med (Lausanne) 2021; 8:657614. [PMID: 34485320 PMCID: PMC8415842 DOI: 10.3389/fmed.2021.657614] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2021] [Accepted: 07/26/2021] [Indexed: 12/20/2022] Open
Abstract
Years of research revealed that crosstalk extensively existed among kidney cells, cell factors and metabolites and played an important role in the development of diabetic kidney disease (DKD). In the last few years, single-cell RNA sequencing (scRNA-seq) technology provided new insight into cellular heterogeneity and genetic susceptibility regarding DKD at cell-specific level. The studies based on scRNA-seq enable a much deeper understanding of cell-specific processes such as interaction between cells. In this paper, we aim to review recent progress in single cell transcriptomic analyses of DKD, particularly highlighting on intra- or extra-glomerular cell crosstalk, cellular targets and potential therapeutic strategies for DKD.
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Affiliation(s)
- Chunyang Du
- Key Laboratory of Kidney Diseases of Hebei Province, Department of Pathology, Hebei Medical University, Shijiazhuang, China
| | - Yunzhuo Ren
- Key Laboratory of Kidney Diseases of Hebei Province, Department of Pathology, Hebei Medical University, Shijiazhuang, China
| | - Guixin Li
- Department of Burn, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yan Yang
- Key Laboratory of Kidney Diseases of Hebei Province, Department of Pathology, Hebei Medical University, Shijiazhuang, China
| | - Zhe Yan
- Department of Nephrology, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Fang Yao
- Key Laboratory of Kidney Diseases of Hebei Province, Department of Pathology, Hebei Medical University, Shijiazhuang, China
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Zhu S, Li J, Zhao X. Comparative risk of new-onset hyperkalemia for antihypertensive drugs in patients with diabetic nephropathy: A Bayesian network meta-analysis. Int J Clin Pract 2021; 75:e13940. [PMID: 33332696 DOI: 10.1111/ijcp.13940] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Revised: 12/02/2020] [Accepted: 12/10/2020] [Indexed: 12/01/2022] Open
Abstract
Several randomised controlled trials (RCTs) have evaluated the risk of hyperkalemia of antihypertensive drugs on diabetic nephropathy, yet the results are conflicting. We searched MEDLINE, Embase, The Cochrane Library, and Web of Science for RCTs investigating the risk of antihypertensive drugs on hyperkalemia in diabetic nephropathy from inception to May 31, 2020. Direct comparative meta-analysis showed that the proportion of patients with hyperkalemia was significantly higher in the ARB, aldosterone antagonist, renin inhibitor group than in the placebo group. Moreover, the risk of hyperkalemia in the ARB group was higher than that in the CCB group. Network meta-analysis showed the risk of hyperkalemia in the ARB, aldosterone antagonist, and renin inhibitor group was higher than in the placebo group, but there was no statistical difference between the CCB, ACEI, β blocker, endothelin inhibitor, and diuretic groups than in the placebo group. The possibility of antihypertensive drugs in risk of hyperkalemia being the worst treatment was aldosterone antagonist (98.8%), followed by ARB (73.8%), renin inhibitor (63.8%), diuretic (53.1%), ACEI (46.9%), β blocker (36.8%), endothelin inhibitor (35.2%), placebo (27.1%), and finally CCB (14.3.1%). Therefore, aldosterone antagonist seems worse than other antihypertensive drugs in the risk of hyperkalemia in patients with diabetic nephropathy.
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Affiliation(s)
- Simin Zhu
- Department of Rheumatology and Immunology, Endocrinology Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning City, China
| | - Juan Li
- Department of Internal Medicine, Hubei University of Science and Technology, Xianning City, China
| | - Xinyuan Zhao
- Department of Internal Medicine, Hubei University of Science and Technology, Xianning City, China
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11
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Wu H, Lau ESH, Yang A, Szeto CC, Ma RCW, Kong APS, Chow E, So WY, Chan JCN, Luk AOY. Trends in kidney failure and kidney replacement therapy in people with diabetes in Hong Kong, 2002-2015: A retrospective cohort study. LANCET REGIONAL HEALTH-WESTERN PACIFIC 2021; 11:100165. [PMID: 34327367 PMCID: PMC8315404 DOI: 10.1016/j.lanwpc.2021.100165] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Revised: 04/12/2021] [Accepted: 04/19/2021] [Indexed: 12/14/2022]
Abstract
Background There are limited population-wide trend data on kidney failure and kidney replacement therapy (KRT) in people with diabetes. We conducted a retrospective cohort study to report incidence trends of kidney failure and KRT and related mortality in people with diabetes in Hong Kong between 2002 and 2015. Methods We used territory-wide electronic medical records including laboratory, diagnostic and procedural data to identify people with kidney failure and KRT. We used Joinpoint regression models to estimate the average annual percent change (AAPC) of kidney failure and KRT incidence for entire study period, and annual percent change (APC) for each linear trend segment, along with 1-year and 5-year mortality rates. Findings During 4.9 million person-years of follow-up of 712,222 people with diabetes, 31,425 developed kidney failure, among whom 23.0% (n=7,233) received KRT. The incidence of kidney failure declined by 46.8% from 2002 to 2007 (APC: -11.6, 95% CI: -16.3, -6.7), then flattened from 2007 to 2015 (APC: -0.9, 95% CI: -3.1, 1.3). The incidence of KRT remained constant (AAPC: -1.6, 95% CI: -4.4, 1.2). The 1-year mortality rates declined statistically significantly after both kidney failure and KRT. The 5-year mortality rates declined after kidney failure but the decline was not statistically significant after KRT. Interpretation The findings of our study highlight the importance of developing new strategies to prevent a looming epidemic of kidney failure in people with diabetes in Hong Kong. Funding Asia Diabetes Foundation
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Key Words
- AAPC, Average annual percent change
- APC, Annual percent change
- EMR, Electronic medical record
- HA, Hospital Authority
- HD, Hemodialysis
- HKDSD, Hong Kong Diabetes Surveillance Database
- KRT, Kidney replacement therapy
- PD, Peritoneal dialysis
- RAAS, Renin-angiotensin-aldosterone system
- RAMP-DM, Risk Assessment and Management Programme-Diabetes Mellitus
- diabetes
- incidence
- kidney failure
- kidney replacement therapy
- mortality
- trend
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Affiliation(s)
- Hongjiang Wu
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
| | - Eric S H Lau
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
| | - Aimin Yang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.,Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
| | - Cheuk-Chun Szeto
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
| | - Ronald C W Ma
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.,Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.,Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
| | - Alice P S Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.,Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.,Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
| | - Elaine Chow
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
| | - Wing-Yee So
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.,Hong Kong Hospital Authority, Hong Kong Special Administrative Region, People's Republic of China
| | - Juliana C N Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.,Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.,Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
| | - Andrea O Y Luk
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.,Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.,Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China
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12
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Korakas E, Ikonomidis I, Markakis K, Raptis A, Dimitriadis G, Lambadiari V. The Endothelial Glycocalyx as a Key Mediator of Albumin Handling and the Development of Diabetic Nephropathy. Curr Vasc Pharmacol 2020; 18:619-631. [PMID: 31889495 DOI: 10.2174/1570161118666191224120242] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Revised: 11/20/2019] [Accepted: 11/20/2019] [Indexed: 02/06/2023]
Abstract
The endothelial glycocalyx is a complex mesh of proteoglycans, glycoproteins and other soluble components, which cover the vascular endothelium. It plays an important role in many physiological processes including vascular permeability, transduction of shear stress and interaction of blood cells and other molecules with the vascular wall. Its complex structure makes its precise assessment challenging, and many different visualization techniques have been used with varying results. Diabetes, one of the main disease models where disorders of the glycocalyx are present, causes degradation of the glycocalyx through a variety of molecular pathways and especially through oxidative stress due to the action of reactive oxygen species. As the glycocalyx has been primarily studied in the glomerular endothelium, more evidence points towards a vital role in albumin handling and, consequently, in diabetic nephropathy. Therefore, the maintenance or restoration of the integrity of the glycocalyx seems a promising therapeutic target. In this review, we consider the structural and functional capacities of the endothelial glycocalyx, the available methods for its evaluation, the mechanisms through which diabetes leads to glycocalyx degradation and albuminuria, and possible treatment options targeting the glycocalyx.
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Affiliation(s)
- Emmanouil Korakas
- Second Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Ignatios Ikonomidis
- Second Cardiology Department, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Konstantinos Markakis
- Second Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Athanasios Raptis
- Second Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - George Dimitriadis
- Second Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Vaia Lambadiari
- Second Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
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13
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Endoglin Promotes Myofibroblast Differentiation and Extracellular Matrix Production in Diabetic Nephropathy. Int J Mol Sci 2020; 21:ijms21207713. [PMID: 33081058 PMCID: PMC7589772 DOI: 10.3390/ijms21207713] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Revised: 10/07/2020] [Accepted: 10/13/2020] [Indexed: 02/07/2023] Open
Abstract
Diabetic nephropathy (DN) is a complication of diabetes mellitus that can lead to proteinuria and a progressive decline in renal function. Endoglin, a co-receptor of TGF-β, is known primarily for regulating endothelial cell function; however, endoglin is also associated with hepatic, cardiac, and intestinal fibrosis. This study investigates whether endoglin contributes to the development of interstitial fibrosis in DN. Kidney autopsy material from 80 diabetic patients was stained for endoglin and Sirius Red and scored semi-quantitatively. Interstitial endoglin expression was increased in samples with DN and was correlated with Sirius Red staining (p < 0.001). Endoglin expression was also correlated with reduced eGFR (p = 0.001), increased creatinine (p < 0.01), increased systolic blood pressure (p < 0.05), hypertension (p < 0.05), and higher IFTA scores (p < 0.001). Biopsy samples from DN patients were also co-immunostained for endoglin together with CD31, CD68, vimentin, or α-SMA Endoglin co-localized with both the endothelial marker CD31 and the myofibroblast marker α-SMA. Finally, we used shRNA to knockdown endoglin expression in a human kidney fibroblast cell line. We found that TGF-β1 stimulation upregulated SERPINE1, CTGF, and ACTA2 mRNA and α-SMA protein, and that these effects were significantly reduced in fibroblasts after endoglin knockdown. Taken together, these data suggest that endoglin plays a role in the pathogenesis of interstitial fibrosis in DN.
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14
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Yang C, Wang H, Zhao X, Matsushita K, Coresh J, Zhang L, Zhao MH. CKD in China: Evolving Spectrum and Public Health Implications. Am J Kidney Dis 2019; 76:258-264. [PMID: 31492486 DOI: 10.1053/j.ajkd.2019.05.032] [Citation(s) in RCA: 138] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2018] [Accepted: 05/29/2019] [Indexed: 01/17/2023]
Abstract
Diabetes is the leading cause of kidney failure worldwide, whereas glomerulonephritis has been predominant in developing countries such as China. The prevalence of obesity and diabetes has increased dramatically in developing countries, substantially affecting the patterns of chronic kidney disease (CKD) observed in these regions. Using data from the Hospital Quality Monitoring System to evaluate changes in the spectrum of non-dialysis-dependent CKD in China, we have observed an increase in the percentage of patients with CKD due to diabetes, which has exceeded that of CKD due to glomerulonephritis since 2011, as well as an increase in hypertensive nephropathy and, in some regions, obstructive kidney disease (mostly associated with kidney stones). The growth of noncommunicable diseases under profound societal and environmental changes has shifted the spectrum of CKD in China toward patterns similar to those of developed countries, which will have enormous impacts on the Chinese health care system. There is much to be done regarding public health interventions, including the establishment of a national CKD surveillance system, improvement in the management of diabetes and hypertension, and enhancement of the affordability and accessibility of kidney replacement therapy. Reducing the burden of CKD will require joint efforts from government, the medical community (including practitioners other than nephrologists), and the public.
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Affiliation(s)
- Chao Yang
- Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China
| | - Haibo Wang
- Center for Data Science in Health and Medicine, Peking University, Beijing, China; China Standard Medical Information Research Center, Shenzhen, China
| | - Xinju Zhao
- Renal Division, Department of Medicine, Peking University People's Hospital, Beijing, China
| | - Kunihiro Matsushita
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
| | - Josef Coresh
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
| | - Luxia Zhang
- Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China; Center for Data Science in Health and Medicine, Peking University, Beijing, China.
| | - Ming-Hui Zhao
- Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China; Peking-Tsinghua Center for Life Sciences, Beijing, China
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15
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Isometric Resistance Training and Branched-Chain Amino Acids Supplementation Can Improve Dialysis Adequacy: A Clinical Trial. Nephrourol Mon 2019. [DOI: 10.5812/numonthly.91175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
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16
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Penno G, Solini A, Orsi E, Bonora E, Fondelli C, Trevisan R, Vedovato M, Cavalot F, Lamacchia O, Scardapane M, Nicolucci A, Pugliese G. Non-albuminuric renal impairment is a strong predictor of mortality in individuals with type 2 diabetes: the Renal Insufficiency And Cardiovascular Events (RIACE) Italian multicentre study. Diabetologia 2018; 61:2277-2289. [PMID: 30032426 DOI: 10.1007/s00125-018-4691-2] [Citation(s) in RCA: 74] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2018] [Accepted: 06/12/2018] [Indexed: 02/07/2023]
Abstract
AIMS/HYPOTHESIS Non-albuminuric renal impairment has become the prevailing diabetic kidney disease (DKD) phenotype in individuals with type 2 diabetes and an estimated GFR (eGFR) <60 ml min-1 1.73 m-2. In the present study, we compared the rate and determinants of all-cause death in individuals with this phenotype with those in individuals with albuminuric phenotypes. METHODS This observational prospective cohort study enrolled 15,773 individuals with type 2 diabetes in 2006-2008. Based on baseline albuminuria and eGFR, individuals were classified as having: no DKD (Alb-/eGFR-), albuminuria alone (Alb+/eGFR-), reduced eGFR alone (Alb-/eGFR+), or both albuminuria and reduced eGFR (Alb+/eGFR+). Vital status on 31 October 2015 was retrieved for 15,656 individuals (99.26%). RESULTS Mortality risk adjusted for confounders was lowest for Alb-/eGFR- (reference category) and highest for Alb+/eGFR+ (HR 2.08 [95% CI 1.88, 2.30]), with similar values for Alb+/eGFR- (1.45 [1.33, 1.58]) and Alb-/eGFR+ (1.58 [1.43, 1.75]). Similar results were obtained when individuals were stratified by sex, age (except in the lowest age category) and prior cardiovascular disease. In normoalbuminuric individuals with eGFR <45 ml min-1 1.73 m-2, especially with low albuminuria (10-29 mg/day), risk was higher than in microalbuminuric and similar to macroalbuminuric individuals with preserved eGFR. Using recursive partitioning and amalgamation analysis, prevalent cardiovascular disease and lower HDL-cholesterol were the most relevant correlates of mortality in all phenotypes. Higher albuminuria within the normoalbuminuric range was associated with death in non-albuminuric DKD, whereas the classic 'microvascular signatures', such as glycaemic exposure and retinopathy, were correlates of mortality only in individuals with albuminuric phenotypes. CONCLUSIONS/INTERPRETATION Non-albuminuric renal impairment is a strong predictor of mortality, thus supporting a major prognostic impact of renal dysfunction irrespective of albuminuria. Correlates of death partly differ from the albuminuric forms, indicating that non-albuminuric DKD is a distinct phenotype. TRIAL REGISTRATION ClinicalTrials.gov NCT00715481.
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Affiliation(s)
- Giuseppe Penno
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Anna Solini
- Department of Surgical, Medical, Molecular and Critical Area Pathology, University of Pisa, Pisa, Italy
| | - Emanuela Orsi
- Diabetes Unit, IRCCS 'Cà Granda - Ospedale Maggiore Policlinico' Foundation, Milan, Italy
| | - Enzo Bonora
- Division of Endocrinology, Diabetes and Metabolism, University and Hospital Trust of Verona, Verona, Italy
| | | | - Roberto Trevisan
- Endocrinology and Diabetes Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy
| | - Monica Vedovato
- Department of Clinical and Experimental Medicine, University of Padua, Padua, Italy
| | - Franco Cavalot
- Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy
| | - Olga Lamacchia
- Department of Medical Sciences, University of Foggia, Foggia, Italy
| | - Marco Scardapane
- Centre for Outcomes Research and Clinical Epidemiology (CORESEARCH), Pescara, Italy
| | - Antonio Nicolucci
- Centre for Outcomes Research and Clinical Epidemiology (CORESEARCH), Pescara, Italy
| | - Giuseppe Pugliese
- Department of Clinical and Molecular Medicine, 'La Sapienza' University, Via di Grottarossa, 1035-1039, 00189, Rome, Italy.
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17
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Chaabouni Y, Yaich S, Khedhiri A, Zayen MA, Kharrat M, Kammoun K, Jarraya F, Hmida MB, Damak J, Hachicha J. [Epidemiological profile of terminal chronic renal failure in the region of Sfax]. Pan Afr Med J 2018; 29:64. [PMID: 29875945 PMCID: PMC5987075 DOI: 10.11604/pamj.2018.29.64.12159] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2017] [Accepted: 06/25/2017] [Indexed: 11/11/2022] Open
Abstract
Introduction Terminal chronic renal failure is a truly global public health problem. In 2011, the cost of management of patients on dialysis has surpassed 90 million dinars (37.000 euro) in Tunisia, nearly 5% of the overall health spending. A better knowledge of the epidemiological profile of terminal chronic renal failure contributes to the implementation and evaluation of health strategies aimed to improve prevention and disease management. This study aimed to describe the epidemiological profile of incident cases in the Sfax Governorate over the period of 10 years. Methods We conducted a descriptive retrospective study over the period from January 2003 to December 2012. The incident cases of terminal chronic renal failure in the Sfax Governorate were included in the study. Results The diagnosis of terminal chronic renal failure was made in 1708 cases: 957 men and 751 women (sex-ratio = 1.27). The average age was 58.4 years [10-100 years]. The study of the evolution of the average age during the study period showed a tendency to increase with positive correlation coefficient (0.749) and p = 0.006. The main causal nephropathy was diabetic nephropathy (21.5%), with a significant increase in its frequency from one year to the other (positive correlation coefficient (0.770) with p = 0.009). Hemodialysis was the dialysis technique of choice, performed in 96% of patients. Conclusion A national registry is indispensable in order to better understand the epidemiological profile of terminal chronic renal failure in Tunisia and to improve its management.
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Affiliation(s)
- Yosr Chaabouni
- Service de Néphrologie, CHU Hedi Chaker, Sfax, Tunisie, Unité de Recherche de Pathologie Rénale, Faculté de Médecine, Sfax, Tunisie
| | - Sourour Yaich
- Service de Médecine Communautaire, CHU Hedi Chaker, Sfax, Tunisie
| | - Azza Khedhiri
- Service de Néphrologie, CHU HediChaker, Sfax, Tunisie
| | | | - Mahmoud Kharrat
- Service de Néphrologie, CHU Hedi Chaker, Sfax, Tunisie, Unité de Recherche de Pathologie Rénale, Faculté de Médecine, Sfax, Tunisie
| | - Khawla Kammoun
- Service de Néphrologie, CHU Hedi Chaker, Sfax, Tunisie, Unité de Recherche de Pathologie Rénale, Faculté de Médecine, Sfax, Tunisie
| | - Faical Jarraya
- Service de Néphrologie, CHU Hedi Chaker, Sfax, Tunisie, Unité de Recherche de Pathologie Rénale, Faculté de Médecine, Sfax, Tunisie
| | - Mohamed Ben Hmida
- Service de Néphrologie, CHU Hedi Chaker, Sfax, Tunisie, Unité de Recherche de Pathologie Rénale, Faculté de Médecine, Sfax, Tunisie
| | - Jamal Damak
- Service de Médecine Communautaire, CHU Hedi Chaker, Sfax, Tunisie
| | - Jamil Hachicha
- Service de Néphrologie, CHU Hedi Chaker, Sfax, Tunisie, Unité de Recherche de Pathologie Rénale, Faculté de Médecine, Sfax, Tunisie
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18
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Impact of Diabetes Mellitus on the Risk of End-Stage Renal Disease in Patients with Systemic Lupus Erythematosus. Sci Rep 2018; 8:6008. [PMID: 29662119 PMCID: PMC5902607 DOI: 10.1038/s41598-018-24529-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2018] [Accepted: 04/05/2018] [Indexed: 02/07/2023] Open
Abstract
Systemic lupus erythematosus (SLE) patients are associated with insulin resistance and are at higher risk to develop diabetes mellitus (DM). SLE and DM could lead to renal failure respectively. However, it is unknown whether DM increases the risk of end-stage renal disease (ESRD) in SLE patients. This study aimed to evaluate potential synergistic effect of DM on SLE patients for development of ESRD. We conducted this study by using National Health Insurance Research Database of Taiwan. We recruited SLE patients with newly-diagnosed DM as the study cohort. A comparison cohort at a 1:1 ratio of SLE patients without DM matched by age, sex, age at the diagnosis of SLE, duration between diagnosis of SLE and DM, and various comorbidities through propensity score matching were recruited. After 5.01 ± 3.13 years follow-up, the incidence of ESRD was significantly higher in the DM group than in the non-DM group (Incidence rate ratio: 2.71; 95% CI: 1.70-4.32). After control of confounding factors, DM was not an independent risk factor of ESRD. After starting dialysis, DM patients had a similar mortality rate to those without DM. In summary, SLE patients superimposed with subsequent DM are associated with potentially higher risk to develop ESRD.
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19
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Menne J, Eulberg D, Beyer D, Baumann M, Saudek F, Valkusz Z, Więcek A, Haller H. C-C motif-ligand 2 inhibition with emapticap pegol (NOX-E36) in type 2 diabetic patients with albuminuria. Nephrol Dial Transplant 2018; 32:307-315. [PMID: 28186566 PMCID: PMC5410979 DOI: 10.1093/ndt/gfv459] [Citation(s) in RCA: 94] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2015] [Accepted: 12/22/2015] [Indexed: 01/23/2023] Open
Abstract
Background Emapticap pegol (NOX-E36) is a Spiegelmer® that specifically binds and inhibits the pro-inflammatory chemokine C-C motif-ligand 2 (CCL2) (also called monocyte-chemotactic protein 1). The objective of this exploratory study was to evaluate the safety and tolerability as well as the renoprotective and anti-diabetic potential of emapticap in type 2 diabetic patients with albuminuria. Methods A randomized, double-blind, placebo-controlled Phase IIa study was initiated in 75 albuminuric type 2 diabetics. Emapticap at 0.5 mg/kg and placebo were administered subcutaneously twice weekly for 12 weeks to 50 and 25 patients, respectively, followed by a treatment-free phase of 12 weeks. Results Twice weekly subcutaneous treatment with emapticap over 3 months was generally safe and well tolerated and reduced the urinary albumin/creatinine ratio (ACR) from baseline to Week 12 by 29% (P < 0.05); versus placebo a non-significant ACR reduction of 15% was observed (P = 0.221). The maximum difference, 26% (P = 0.064) between emapticap and placebo, was seen 8 weeks after discontinuation of treatment. At Week 12, the HbA1c changed by −0.31% in the emapticap versus +0.05% in the placebo group (P = 0.146). The maximum difference for HbA1c was observed 4 weeks after the last dose with −0.35% for emapticap versus +0.12% for placebo (P = 0.026). No relevant change in blood pressure or estimated glomerular filtration rate was seen between the treatment groups throughout the study. A post hoc analysis with exclusion of patients with major protocol violations, dual RAS blockade or haematuria increased the ACR difference between the two treatment arms to 32% at Week 12 (P = 0.014) and 39% at Week 20 (P = 0.010). Conclusions Inhibition of the CCL2/CCL2 receptor axis with emapticap pegol was generally safe and well tolerated. Beneficial effects on ACR and HbA1c were observed in this exploratory study, which were maintained after cessation of treatment. Taken together, emapticap may have disease-modifying effects that warrant further investigation in adequately powered confirmatory studies.
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Affiliation(s)
- Jan Menne
- Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany
| | | | | | | | - Frantisek Saudek
- Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Zsuzsanna Valkusz
- Albert Szent-Györgyi Health Center, University of Szeged, Szeged, Hungary
| | - Andrzej Więcek
- Department of Nephrology, Endocrinology and Metabolic Diseases, Medical University of Silesia, Katowice, Poland
| | - Hermann Haller
- Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany
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20
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Kramer H, Boucher RE, Leehey D, Fried L, Wei G, Greene T, Rosas SE, Cooper R, Cao G, Beddhu S. Increasing Mortality in Adults With Diabetes and Low Estimated Glomerular Filtration Rate in the Absence of Albuminuria. Diabetes Care 2018; 41:775-781. [PMID: 29436384 PMCID: PMC5860846 DOI: 10.2337/dc17-1954] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2017] [Accepted: 01/06/2018] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Improved blood pressure control and use of renin-angiotensin-aldosterone system blockers have altered the clinical presentation or phenotype of chronic kidney disease (CKD) in U.S. adults with diabetes. These changes may influence mortality. RESEARCH DESIGN AND METHODS Data from the National Health and Nutrition Examination Surveys (NHANES) 1988-2006 were used to examine mortality trends in adults with diabetes, defined as physician diagnosis, fasting glucose ≥126 mg/dL, HbA1c >6.5% (48 mmol/mol), or use of glucose-lowering medications. Mortality trends by CKD phenotype (estimated glomerular filtration rate [eGFR] and urine albumin-to-creatinine ratio [ACR] level) were obtained via linkage with the National Death Index through 31 December 2011 while accounting for the complex survey design. RESULTS From 1988 to 2006, adults with an eGFR <60 mL/min/1.73 m2 and an ACR <30 mg/g increased from ∼0.9 million (95% CI 0.7, 1.1) or 6.6% of the total population with diabetes during years 1988-1994 to 2.4 million (95% CI 1.9, 2.9) or 10.1% of the total population with diabetes during years 2007-2010. Mortality rates generally trended downward for adults with diabetes and an ACR ≥30 mg/g but increased in those with eGFR <60 mL/min/1.73 m2 and an ACR <30 mg/g from 35 deaths per 1,000 person-years (95% CI 22, 55) during years 1988-1994 to 51 deaths per 1,000 person-years (95% CI 33, 83) during years 2003-2006. CONCLUSIONS ACR values are decreasing in U.S. adults with diabetes, but optimal management strategies are needed to reduce mortality in those with a low eGFR and an ACR <30 mg/g.
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Affiliation(s)
- Holly Kramer
- Department of Public Health Sciences, Loyola University Chicago, Maywood, IL .,Division of Nephrology and Hypertension, Department of Medicine, Loyola University Chicago, Maywood, IL.,Hines Veterans Affairs Medical Center, Hines, IL
| | - Robert E Boucher
- Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT
| | - David Leehey
- Division of Nephrology and Hypertension, Department of Medicine, Loyola University Chicago, Maywood, IL.,Hines Veterans Affairs Medical Center, Hines, IL
| | - Linda Fried
- Veterans Affairs Pittsburgh Healthcare System and Division of Nephrology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA
| | - Guo Wei
- Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT
| | - Tom Greene
- Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT
| | - Sylvia E Rosas
- Joslin Diabetes Center and Division of Nephrology, Department of Medicine, Beth Israel Deaconess Hospital, Boston, MA
| | - Richard Cooper
- Department of Public Health Sciences, Loyola University Chicago, Maywood, IL
| | - Guichan Cao
- Department of Public Health Sciences, Loyola University Chicago, Maywood, IL
| | - Srinivasan Beddhu
- Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT.,Veterans Affairs Salt Lake City Health Care System, Salt Lake City, UT
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21
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Cheisson G, Jacqueminet S, Cosson E, Ichai C, Leguerrier AM, Nicolescu-Catargi B, Ouattara A, Tauveron I, Valensi P, Benhamou D. Perioperative management of adult diabetic patients. Preoperative period. Anaesth Crit Care Pain Med 2018; 37 Suppl 1:S9-S19. [PMID: 29559406 DOI: 10.1016/j.accpm.2018.02.020] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2017] [Revised: 02/17/2018] [Accepted: 02/26/2018] [Indexed: 12/27/2022]
Abstract
In diabetic patients undergoing surgery, we recommend assessing glycaemic control preoperatively by assessing glycated haemoglobin (HbA1c) levels and recent capillary blood sugar (glucose) levels, and to adjust any treatments accordingly before surgery, paying particular attention to specific complications of diabetes. Gastroparesis creates a risk of stasis and aspiration of gastric content at induction of anaesthesia requiring the use of a rapid sequence induction technique. Cardiac involvement can be divided into several types. Coronary disease is characterised by silent myocardial ischaemia, present in 30-50% of T2D patients. Diabetic cardiomyopathy is a real cause of heart failure. Finally, cardiac autonomic neuropathy (CAN), although rarely symptomatic, should be investigated because it causes an increased risk of cardiovascular events and a risk of sudden death. Several signs are suggestive of CAN, and confirmation calls for close perioperative surveillance. Chronic diabetic kidney disease (diabetic nephropathy) aggravates the risk of perioperative acute renal failure, and we recommend measurement of the glomerular filtration rate preoperatively. The final step of the consultation concerns the management of antidiabetic therapy. Preoperative glucose infusion is not necessary if the patient is not receiving insulin. Non-insulin drugs are not administered on the morning of the intervention except for metformin, which is not administered from the evening before. The insulins are injected at the usual dose the evening before. The insulin pump is maintained until the patient arrives in the surgical unit. It should be remembered that insulin deficiency in a T1D patient leads to ketoacidosis within a few hours.
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Affiliation(s)
- Gaëlle Cheisson
- Service d'anesthésie - réanimation chirurgicale, hôpitaux universitaires Paris-Sud, AP-HP, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre, France
| | - Sophie Jacqueminet
- Institut de cardio-métabolisme et nutrition, hôpital de la Pitié-Salpêtrière, AP-HP, 75013 Paris, France; Département du diabète et des maladies métaboliques, hôpital de la Pitié-Salpêtrière, 75013 Paris, France
| | - Emmanuel Cosson
- Département d'endocrinologie-diabétologie-nutrition, hôpital Jean-Verdier, université Paris 13, Sorbonne Paris Cité, CRNH-IdF, CINFO, AP-HP, 93140 Bondy, France; Sorbonne Paris Cité, UMR U1153 INSERM / U1125 INRA / CNAM / université Paris 13, 93000 Bobigny, France
| | - Carole Ichai
- Service de réanimation Polyvalente, hôpital Pasteur 2, CHU de Nice, 30, voie Romaine, 06001 Nice cedex 1, France; IRCAN (INSERM U1081, CNRS UMR 7284), University Hospital of Nice, 06001 Nice, France
| | - Anne-Marie Leguerrier
- Service de diabétologie-endocrinologie, CHU de Rennes, CHU Hôpital Sud, 16, boulevard de Bulgarie, 35056 Rennes, France
| | - Bogdan Nicolescu-Catargi
- Service d'endocrinologie - maladies métaboliques, hôpital Saint-André, CHU de Bordeaux, 1, rue Jean-Burguet, 33000 Bordeaux, France
| | - Alexandre Ouattara
- Department of Anaesthesia and Critical Care II, Magellan Medico-Surgical Center, CHU de Bordeaux, 33000 Bordeaux, France; INSERM, UMR 1034, Biology of Cardiovascular Diseases, université Bordeaux, 33600 Pessac, France
| | - Igor Tauveron
- Service endocrinologie diabétologie, CHU de Clermont-Ferrand, 58, rue Montalembert, 63000 Clermont-Ferrand, France; UFR médecine, université Clermont-Auvergne, 28, place Henri-Dunant, 63000 Clermont-Ferrand, France; UMR CNRS 6293, INSERM U1103, génétique reproduction et développement, université Clermont-Auvergne, 63170 Aubière, France; Endocrinologie-diabétologie, CHU G. Montpied, BP 69, 63003 Clermont-Ferrand, France
| | - Paul Valensi
- Département d'endocrinologie-diabétologie-nutrition, hôpital Jean-Verdier, université Paris 13, Sorbonne Paris Cité, CRNH-IdF, CINFO, AP-HP, 93140 Bondy, France
| | - Dan Benhamou
- Service d'anesthésie - réanimation chirurgicale, hôpitaux universitaires Paris-Sud, AP-HP, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre, France.
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Patney V, Chaudhary K, Whaley-Connell A. Treatment of Diabetic Kidney Disease With Hypertension Control and Renin Angiotensin System Inhibition. Adv Chronic Kidney Dis 2018; 25:158-165. [PMID: 29580580 DOI: 10.1053/j.ackd.2017.11.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2017] [Revised: 11/16/2017] [Accepted: 11/28/2017] [Indexed: 02/07/2023]
Abstract
The global incidence and prevalence of diabetes continues to expand due primarily to the influences of obesity and the contribution of obesity to the progression of type 2 diabetes mellitus. The rising prevalence of type 2 diabetes has driven an increase in rates of CKD in the past 3 decades in the United States. In turn, so have the rates for complications related to type 2 diabetes including CKD, eg, diabetic kidney disease (DKD). Although incident rates for DKD have stabilized in the recent years, diabetes continues to be the leading cause of ESRD in the United States. The United Kingdom Prospective Diabetes Study data and other population-level studies support that lowering blood pressure reduces kidney disease and cardiovascular disease in patients with type 2 diabetes. Furthermore, strategies targeting renin-angiotensin-aldosterone system interruption have shown to improve DKD outcomes to a greater extent than other classes of antihypertensive regimens.
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Koye DN, Magliano DJ, Nelson RG, Pavkov ME. The Global Epidemiology of Diabetes and Kidney Disease. Adv Chronic Kidney Dis 2018; 25:121-132. [PMID: 29580576 PMCID: PMC11000253 DOI: 10.1053/j.ackd.2017.10.011] [Citation(s) in RCA: 380] [Impact Index Per Article: 54.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2017] [Revised: 10/17/2017] [Accepted: 10/23/2017] [Indexed: 12/21/2022]
Abstract
The prevalence of diabetes is increasing worldwide, with the greatest increases occurring in low- and middle-income countries. In most developed countries, type 2 diabetes is presently the leading cause of end-stage renal disease and also contributes substantially to cardiovascular disease. In countries with weaker economies type 2 diabetes is rapidly replacing communicable diseases as a leading cause of kidney disease and is increasingly competing for scarce health care resources. Here, we present a narrative review of the prevalence and incidence of diabetes-related kidney disease worldwide. Mortality among those with diabetes and kidney disease will also be explored. Given the high morbidity and mortality associated with chronic kidney disease, we will also examine the level of awareness of this disease among people who have it.
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Affiliation(s)
- Digsu N Koye
- Department of Clinical Diabetes and Epidemiology, Baker Heart and Diabetes Institute, Melbourne, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia; Department of Epidemiology and Biostatistics, Institute of Public Health, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia; Chronic Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ; and Division of Diabetes Translation, Centers for Disease Control and Prevention, Atlanta, GA
| | - Dianna J Magliano
- Department of Clinical Diabetes and Epidemiology, Baker Heart and Diabetes Institute, Melbourne, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia; Department of Epidemiology and Biostatistics, Institute of Public Health, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia; Chronic Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ; and Division of Diabetes Translation, Centers for Disease Control and Prevention, Atlanta, GA
| | - Robert G Nelson
- Department of Clinical Diabetes and Epidemiology, Baker Heart and Diabetes Institute, Melbourne, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia; Department of Epidemiology and Biostatistics, Institute of Public Health, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia; Chronic Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ; and Division of Diabetes Translation, Centers for Disease Control and Prevention, Atlanta, GA
| | - Meda E Pavkov
- Department of Clinical Diabetes and Epidemiology, Baker Heart and Diabetes Institute, Melbourne, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia; Department of Epidemiology and Biostatistics, Institute of Public Health, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia; Chronic Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ; and Division of Diabetes Translation, Centers for Disease Control and Prevention, Atlanta, GA.
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24
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Burrows NR, Li Y, Gregg EW, Geiss LS. Declining Rates of Hospitalization for Selected Cardiovascular Disease Conditions Among Adults Aged ≥35 Years With Diagnosed Diabetes, U.S., 1998-2014. Diabetes Care 2018; 41:293-302. [PMID: 29150530 PMCID: PMC6051534 DOI: 10.2337/dc17-1259] [Citation(s) in RCA: 50] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2017] [Accepted: 10/25/2017] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Reductions in heart attack and stroke hospitalizations are well documented in the U.S. population with diabetes. We extended trend analyses to other cardiovascular disease (CVD) conditions, including stroke by type, and used four additional years of data. RESEARCH DESIGN AND METHODS Using 1998-2014 National (Nationwide) Inpatient Sample (NIS) data, we estimated the number of discharges having acute coronary syndrome (ACS) (ICD-9 codes 410-411), cardiac dysrhythmia (427), heart failure (428), hemorrhagic stroke (430-432), or ischemic stroke (433.x1, 434, and 436) as first-listed diagnosis and diabetes (250) as secondary diagnosis. Hospitalization rates for adults aged ≥35 years were calculated using estimates from the population with and the population without diabetes from the National Health Interview Survey (NHIS) and age-adjusted to the 2000 U.S. standard population. Joinpoint regression was used to analyze trends and calculate an average annual percentage change (AAPC) with 95% confidence limits (CLs). RESULTS From 1998 to 2014, in the population with diabetes, age-adjusted hospitalization rates declined significantly for ACS (AAPC -4.6% per year [95% CL -5.3, -3.8]), cardiac dysrhythmia (-0.7% [-1.1, -0.2]), heart failure (-3.6% [-4.6, -2.7]), hemorrhagic stroke (-1.1% [-1.4, -0.7]), and ischemic stroke (-2.9% [-3.9, -1.8]). In the population without diabetes, rates also declined significantly for these conditions, with the exception of dysrhythmia. By 2014, rates in the population with diabetes population remained two to four times as high as those for the population without diabetes, with the largest difference in heart failure rates. CONCLUSIONS CVD hospitalization rates declined significantly in both the population with diabetes and the population without diabetes. This may be due to several factors, including new or more aggressive treatments and reductions in CVD risk factors and CVD incidence.
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Affiliation(s)
- Nilka Ríos Burrows
- Division of Diabetes Translation, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA
| | - YanFeng Li
- Division of Diabetes Translation, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA
| | - Edward W Gregg
- Division of Diabetes Translation, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA
| | - Linda S Geiss
- Division of Diabetes Translation, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA
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Calderon-Margalit R, Cohen-Dadi M, Opas D, Jaffe DH, Levine J, Ben-Yehuda A, Paltiel O, Manor O. Trends in the performance of quality indicators for diabetes care in the community and in diabetes-related health status: an Israeli ecological study. Isr J Health Policy Res 2018; 7:10. [PMID: 29343291 PMCID: PMC5773014 DOI: 10.1186/s13584-018-0206-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2017] [Accepted: 01/10/2018] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Israel is one of the few countries that have a national program for quality assessment of community healthcare. We aimed to evaluate whether improved performance in diabetes care was associated with improved health of diabetic patients on a national level. METHODS We conducted a nationwide ecological study estimating improvements in diabetes-related quality indicators and health outcomes. We estimated both correlations between composite measures of diabetes-related quality indicators and selected outcomes, and assessed through a joinpoint analysis whether trends in selected outcomes changed 4 years after the inception of the national program. RESULTS Between 2002 and 2010, the prevalence of diabetes in Israeli adults increased from 4.8% to 7.4%. During these years, an improvement was noticed in most quality indicators (from 53% to 75% for the composite score). Declines were noted in rates of blindness, diabetes-related end-stage kidney disease, lower limbs amputations and diabetes-related mortality. Significant accelerations in decline were noted for amputations in men and diabetes-related mortality in both Arab men and women 4 years after the inception of the national program. CONCLUSION This study suggests that Israel's national program for quality indicators in diabetes care in the community has probably had a significant impact on the health status of the whole population and may have contributed to narrowing gaps in life expectancy between Israeli Jews and Arabs. Future studies based on individual-level data are needed to confirm these results.
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Affiliation(s)
- Ronit Calderon-Margalit
- Hadassah-Hebrew University Braun School of Public Health, POB 12272, 9112102, Jerusalem, Israel.
| | - Michal Cohen-Dadi
- Hadassah-Hebrew University Braun School of Public Health, POB 12272, 9112102, Jerusalem, Israel
| | - Dana Opas
- Hadassah-Hebrew University Braun School of Public Health, POB 12272, 9112102, Jerusalem, Israel
| | - Dena H Jaffe
- Hadassah-Hebrew University Braun School of Public Health, POB 12272, 9112102, Jerusalem, Israel
| | - Jacob Levine
- Hadassah-Hebrew University Braun School of Public Health, POB 12272, 9112102, Jerusalem, Israel
| | | | - Ora Paltiel
- Hadassah-Hebrew University Braun School of Public Health, POB 12272, 9112102, Jerusalem, Israel
| | - Orly Manor
- Hadassah-Hebrew University Braun School of Public Health, POB 12272, 9112102, Jerusalem, Israel
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Eleftheriadis T, Pissas G, Antoniadi G, Liakopoulos V, Stefanidis I. Allopurinol protects human glomerular endothelial cells from high glucose-induced reactive oxygen species generation, p53 overexpression and endothelial dysfunction. Int Urol Nephrol 2018; 50:179-186. [PMID: 29094329 DOI: 10.1007/s11255-017-1733-5] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2017] [Accepted: 10/25/2017] [Indexed: 12/19/2022]
Abstract
PURPOSE Mitochondrial reactive oxygen species (ROS) overproduction in capillary endothelial cells is a prerequisite for the development of diabetic nephropathy. Inhibition of xanthine oxidase, another ROS generator, ameliorates experimental diabetic nephropathy. To test the hypothesis that the initial high glucose-induced ROS production by the mitochondria activates xanthine oxidase, which afterward remains as the major source of ROS, we cultured primary human glomerular endothelial cells (GEnC) under normal or high-glucose conditions, with or without the xanthine oxidase inhibitor allopurinol. METHODS ROS generation and nitric oxide synthase (NOS) activity were assessed by chemiluminescence or colorimetrically. Levels of intercellular adhesion molecule 1 (ICAM-1), p53 and phosphorylated p53 (p-p53) were assessed by western blotting. RESULTS Allopurinol prevented high glucose-induced ROS generation indicating that xanthine oxidase is the major source of ROS. Allopurinol protected GEnC from endothelial dysfunction since it prevented the high glucose-induced decrease in NOS activity and increase in ICAM-1 expression. Allopurinol reduced p53 and p-p53 levels induced by high glucose suggesting an axis of xanthine oxidase-derived ROS, DNA damage, p53 stabilization and endothelial dysfunction that may contribute to the pathogenesis of diabetic nephropathy. CONCLUSIONS Allopurinol protects GEnC from high glucose-induced ROS generation, p53 overexpression and endothelial dysfunction. These data provide a pathogenetic mechanism that supports the results of experimental and clinical studies about the beneficial effect of xanthine oxidase inhibitors on the development of diabetic nephropathy.
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Affiliation(s)
- Theodoros Eleftheriadis
- Department of Nephrology, Faculty of Medicine, University of Thessaly, Neo Ktirio, Mezourlo Hill, 41110, Larissa, Greece.
| | - Georgios Pissas
- Department of Nephrology, Faculty of Medicine, University of Thessaly, Neo Ktirio, Mezourlo Hill, 41110, Larissa, Greece
| | - Georgia Antoniadi
- Department of Nephrology, Faculty of Medicine, University of Thessaly, Neo Ktirio, Mezourlo Hill, 41110, Larissa, Greece
| | - Vassilios Liakopoulos
- Department of Nephrology, Faculty of Medicine, University of Thessaly, Neo Ktirio, Mezourlo Hill, 41110, Larissa, Greece
| | - Ioannis Stefanidis
- Department of Nephrology, Faculty of Medicine, University of Thessaly, Neo Ktirio, Mezourlo Hill, 41110, Larissa, Greece
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High glucose stimulates cell proliferation and Collagen IV production in rat mesangial cells through inhibiting AMPK-K ATP signaling. Int Urol Nephrol 2017; 49:2079-2086. [PMID: 28748494 DOI: 10.1007/s11255-017-1654-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2017] [Accepted: 07/06/2017] [Indexed: 01/22/2023]
Abstract
PURPOSE The present study investigated the putative mechanisms underlying effects of KATP channel on high glucose (HG)-induced mesangial cell proliferation and tissue inhibitors of metalloproteinases (TIMP)-2 and Collagen IV production. METHODS Rat mesangial cells were subjected to whole cell patch clamp to record the KATP channel currents under high glucose (HG, 30 mM) condition. Cell proliferation was measured using a CCK-8 assay. The production of TIMP-2 and Collagen IV and AMP-activated protein kinase (AMPK)-signaling pathway activity was assessed by ELISA and Western blotting, respectively. AMPK agonist (AICAR) was used to analyze the role of this kinase. The expression of KATP subunit (Kir6.1, Kir6.2, SUR1, SUR2A and SUR2B) was examined using quantitative real-time PCR (RT-PCR). RESULTS We found that HG was significant decreases in the expression of Kir6.1, SUB2A and SUB2B, three subunits of KATP, TIMP-2 production, KATP channel activity and AMPK activity, while it promoted the cell proliferation and Collagen IV production in rat mesangial cells. Pretreatment with KATP selective opener (diazoxide, DZX) significantly inhibited HG-induced mesangial cell proliferation, Collagen IV production and decrease in KATP channel activity in rat mesangial cells, which were reversed by pretreatment of 5-hydroxydecanoate, a selective inhibitor of KATP. Moreover, AICAR pretreatment inhibited HG-induced decrease in KATP channel activity. CONCLUSIONS Taken together, activating AMPK-KATP signaling may protect against HG-induced mesangial cell proliferation and Collagen IV production, and, thereby, provides new insights into the molecular mechanisms underlying early diabetic nephropathy (DN).
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Martínez-Castelao A, Górriz JL, Ortiz A, Navarro-González JF. ERBP guideline on management of patients with diabetes and chronic kidney disease stage 3B or higher. Metformin for all? Nefrologia 2017; 37:567-571. [PMID: 28669489 DOI: 10.1016/j.nefro.2017.06.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2017] [Accepted: 04/12/2017] [Indexed: 01/02/2023] Open
Affiliation(s)
- Alberto Martínez-Castelao
- Hospital Universitario Bellvitge, IDIBELL, Hospitalet, Barcelona, España; REDINREN, Instituto de Salud Carlos III, RD16/0009; GEENDIAB, España.
| | - José Luis Górriz
- REDINREN, Instituto de Salud Carlos III, RD16/0009; GEENDIAB, España; Hospital Clínico Universitario, Valencia, España
| | - Alberto Ortiz
- REDINREN, Instituto de Salud Carlos III, RD16/0009; GEENDIAB, España; IIS-Fundacion Jiménez Díaz, Universidad Autónoma de Madrid, Fundación Renal Iñigo Alvarez de Toledo-IRSIN, Madrid, España
| | - Juan F Navarro-González
- REDINREN, Instituto de Salud Carlos III, RD16/0009; GEENDIAB, España; Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, España.
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Viazzi F, Piscitelli P, Giorda C, Ceriello A, Genovese S, Russo GT, Fioretto P, Guida P, De Cosmo S, Pontremoli R. Association of kidney disease measures with risk of renal function worsening in patients with hypertension and type 2 diabetes. J Diabetes Complications 2017; 31:419-426. [PMID: 27884661 DOI: 10.1016/j.jdiacomp.2016.10.030] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2016] [Revised: 10/11/2016] [Accepted: 10/26/2016] [Indexed: 01/19/2023]
Abstract
AIMS To assess the role of kidney disease measures on the development of chronic kidney disease (CKD) in patients with type 2 diabetes (T2D) and hypertension (HT). METHODS Clinical records from a total of 17,160 patients with T2D and HT, a baseline estimated glomerular filtration rate (eGFR) values ≥60mL/min/1.73m2, evaluation for albuminuria and regular visits during a four-year follow-up were retrieved and analyzed. The incidence of eGFR <60mL/min/1.73m2 and/or a reduction >30% from baseline was evaluated. RESULTS At baseline 23% of patients (n=3873) had albuminuria. Over the 4-year follow-up 20% (n=3480) developed a renal endpoint 28% (n=1074) of those with albuminuria and 17% (n=2406) of those without albuminuria. The presence of baseline albuminuria entailed a 1.8 independent, greater risk of reaching stage 3 CKD. Patients with normal albuminuria showed a 1.54 (p<0.001) greater risk for each 5mL reduction (below 90mL/min) in baseline GFR. CONCLUSIONS In T2D patients with HT, eGFR reduction and albuminuria are independently associated with a greater risk of developing stage 3 CKD. While baseline albuminuria entails a greater renal risk, due to a larger occurrence of the non-albuminuric phenotype, renal function worsening is more likely to be observed in patients without albuminuria.
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Affiliation(s)
- Francesca Viazzi
- Università degli Studi and IRCCS Azienda Ospedaliera Universitaria San Martino-IST, Genova, Italy.
| | - Pamela Piscitelli
- Department of Medical Sciences, Scientific Institute "Casa Sollievo della Sofferenza", San Giovanni Rotondo (FG), Italy
| | - Carlo Giorda
- Diabetes and Metabolism Unit ASL Turin 5 Chieri (TO), Italy
| | - Antonio Ceriello
- Institut d'Investigacions Biomèdiques August Pii Sunyer (IDIBAPS) and Centro de Investigación Biomédicaen Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain; Department of Cardiovascular and Metabolic Diseases, IRCCS Gruppo Multimedica, Sesto San Giovanni, Milano, Italy
| | - Stefano Genovese
- Department of Cardiovascular and Metabolic Diseases, IRCCS Gruppo Multimedica, Sesto San Giovanni, Milano, Italy
| | - Giuseppina T Russo
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Paola Fioretto
- Department of Medicine, University of Padua, Padua, Italy
| | | | - Salvatore De Cosmo
- Department of Medical Sciences, Scientific Institute "Casa Sollievo della Sofferenza", San Giovanni Rotondo (FG), Italy
| | - Roberto Pontremoli
- Università degli Studi and IRCCS Azienda Ospedaliera Universitaria San Martino-IST, Genova, Italy
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Abiko A. What is the truth about renin angiotensin blockers for diabetic patients? Diabetol Int 2016; 7:334-337. [DOI: 10.1007/s13340-016-0285-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2016] [Indexed: 11/28/2022]
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Earle KA, Zitouni K, Pepe J, Karaflou M, Godbold J. Modulation of endogenous antioxidant defense and the progression of kidney disease in multi-heritage groups of patients with type 2 diabetes: PRospective EValuation of Early Nephropathy and its Treatment (PREVENT). J Transl Med 2016; 14:234. [PMID: 27492324 PMCID: PMC4973532 DOI: 10.1186/s12967-016-0975-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2016] [Accepted: 07/11/2016] [Indexed: 03/20/2023] Open
Abstract
Background Diabetes is the western world’s leading cause of end-stage renal disease. Glucose-dependent, oxidative stress is linked to the development of renal inflammation and sclerosis, which, in animal models of diabetes, can be prevented by anti-oxidative treatment. Patients of non-Caucasian heritage have low activity of the selenoprotein, antioxidant enzyme, glutathione peroxidase (GPx) and its co-factor vitamin E, which may be linked to their increased propensity to developing end-stage renal disease. Research design and methods We have designed a double-blind, randomized, placebo controlled study with selenium and/or vitamin E versus placebo as the interventions for patients with type 2 diabetes and chronic kidney disease (CKD) stages 1–3. A 2 × 2 factorial design will allow a balanced representation of the heritage groups exposed to each intervention. The primary biochemical outcome is change in GPx activity, and clinical outcome measure is the actual, rate of—and/or percentage change in estimated glomerular filtration rate (eGFR) from baseline. Analysis will be with a marginal model for longitudinal data using Generalized Estimating Equations corrected for measures of baseline serum antioxidant enzyme activities (GPx, superoxide dismutase and catalase), micronutrient levels (vitamins E and C), measures of inflammation (interleukin 6, c-reactive protein and monocyte chemoattractant protein-1) and markers of oxidative damage (plasma 8-isoprostaglandin F2α and urinary 8-hydroxydeoxyguanosine). Expected results The study will assess the relationship between GPx activity, oxidative stress, inflammation and eGFR. It will test the null hypothesis that antioxidant therapy does not influence the activity of GPx or other antioxidant enzymes and/or alter the rate of change in eGFR in these patient groups. Conclusions Outcome data on the effect of antioxidants in human diabetic renal disease is limited. Previous post hoc analyses have not shown a beneficial effect of vitamin E on renal function. A recent trial of a pharmaceutical antioxidant agent, improved eGFR, but in patients with advanced diabetes-related chronic kidney disease its use was associated with an increased incidence of cardiovascular events. We will explore whether the nutritional antioxidants, vitamin E and selenium alone, or in combination in patients at high risk of renal disease progression, forestalls a reduction in eGFR. The study will describe whether endogenous antioxidant enzyme defenses can be safely modified by this intervention and how this is associated with changes in markers of oxidative stress. Trial registration ISRCTN 97358113. Registered 21st September 2009
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Affiliation(s)
- Kenneth A Earle
- St Georges University Hospitals NHS Foundation Trust, Blackshaw Road, London, SW 17 0RE, UK. .,Clinical Sciences Division, St. Georges University of London, London, UK.
| | - Karima Zitouni
- Clinical Sciences Division, St. Georges University of London, London, UK
| | - John Pepe
- Richmond University, Staten Island, New York, USA
| | - Maria Karaflou
- St Georges University Hospitals NHS Foundation Trust, Blackshaw Road, London, SW 17 0RE, UK.,Clinical Sciences Division, St. Georges University of London, London, UK
| | - James Godbold
- Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, USA
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Gentile G, Remuzzi G. Novel Biomarkers for Renal Diseases? None for the Moment (but One). SLAS DISCOVERY 2016; 21:655-670. [DOI: 10.1177/1087057116629916] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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Eleftheriadis T, Tsogka K, Pissas G, Antoniadi G, Liakopoulos V, Stefanidis I. Activation of general control nonderepressible 2 kinase protects human glomerular endothelial cells from harmful high-glucose-induced molecular pathways. Int Urol Nephrol 2016; 48:1731-9. [DOI: 10.1007/s11255-016-1377-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2016] [Accepted: 07/18/2016] [Indexed: 11/25/2022]
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Prognostic Value of Proinflammatory Markers in Patients After Kidney Transplantation in Relation to the Presence of Diabetes. Transplant Proc 2016; 48:1604-7. [DOI: 10.1016/j.transproceed.2016.03.008] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2015] [Revised: 02/16/2016] [Accepted: 03/01/2016] [Indexed: 12/29/2022]
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Gregg EW, Sattar N, Ali MK. The changing face of diabetes complications. Lancet Diabetes Endocrinol 2016; 4:537-47. [PMID: 27156051 DOI: 10.1016/s2213-8587(16)30010-9] [Citation(s) in RCA: 371] [Impact Index Per Article: 41.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2016] [Revised: 03/22/2016] [Accepted: 03/23/2016] [Indexed: 12/16/2022]
Abstract
The global increase in type 2 diabetes prevalence is well documented, but international trends in complications of type 2 diabetes are less clear. The available data suggest large reductions in classic complications of type 2 diabetes in high-income countries over the past 20 years, predominantly reductions in myocardial infarction, stroke, amputations, and mortality. These trends might be accompanied by less obvious, but still important, changes in the character of morbidity in people with diabetes. In the USA, for example, substantial reductions in macrovascular complications in adults aged 65 years or older mean that a large proportion of total complications now occur among adults aged 45-64 years instead, rates of renal disease could persist more than other complications, and obesity-related type 2 diabetes could have increasing effect in youth and adults under 45 years of age. Additionally, the combination of decreasing mortality and increasing diabetes prevalence has increased the overall mean years lived with diabetes and could lead to a diversification of diabetes morbidity, including continued high rates of renal disease, ageing-related disability, and cancers. Unfortunately, data on trends in diabetes-related complications are limited to only about a dozen countries, most of which are high income, leaving the changing character for countries of low and middle income ambiguous.
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Affiliation(s)
- Edward W Gregg
- Division of Diabetes Translation, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA, USA.
| | - Naveed Sattar
- Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK
| | - Mohammed K Ali
- Division of Diabetes Translation, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA, USA; Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA
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Lattenist L, Ochodnický P, Ahdi M, Claessen N, Leemans JC, Satchell SC, Florquin S, Gerdes VE, Roelofs JJTH. Renal endothelial protein C receptor expression and shedding during diabetic nephropathy. J Thromb Haemost 2016; 14:1171-82. [PMID: 26990852 DOI: 10.1111/jth.13315] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2014] [Accepted: 01/14/2016] [Indexed: 11/30/2022]
Abstract
UNLABELLED Essentials Endothelial protein C receptor (EPCR) promotes diabetic nephropathy (DN) outcome improvement. Renal expression and shedding of EPCR were measured in diabetic patients with or without DN. Inhibition of metalloproteinase-driven EPCR shedding restored glomerular endothelium phenotype. EPCR shedding through metalloproteinase ADAM17 contributes to the worsening of DN. SUMMARY Background Diabetic nephropathy (DN) represents the leading cause of end-stage renal disease. The endothelial protein C receptor (EPCR) and its ligand (activated protein C) have been shown to ameliorate the phenotype of DN in mice. EPCR activity can be regulated by proteolytic cleavage involving ADAMs, yielding a soluble form of EPCR (sEPCR). Objective To characterize the renal expression and shedding of EPCR during DN. Methods EPCR levels were measured in plasma, urine and biopsy samples of diabetic patients with (n = 73) or without (n = 63) DN. ADAM-induced cleavage of EPCR was investigated in vitro with a human glomerular endothelium cell line. Results DN patients showed higher plasma and urinary levels of sEPCR than diabetic controls (112.2 versus 135.2 ng mL(-1) and 94.35 versus 140.6 ng mL(-1) , respectively). Accordingly, glomerular endothelial EPCR expression was markedly reduced in patients with DN, and this was associated with increased glomerular expression of ADAM-17 and ADAM-10. In vitro, EPCR shedding was induced by incubation of glomerular endothelium in high-glucose medium, and this shedding was suppressed by ADAM-17 inhibition or silencing, which led to improved vascular endothelial cadherin (VE-cadherin) expression and reduced mRNA expression of transforming growth factor (TGF)-β. In addition, EPCR silencing led to minor effects on VE-cadherin but to a significant increase in TGF-β mRNA expression. Conclusion Inhibition of ADAM-driven glomerular EPCR shedding restored the endothelial phenotype of glomerular endothelium, whereas EPCR silencing led to enhanced expression of TGF-β, a marker of endothelial-mesenchymal transition. These findings demonstrate that EPCR shedding driven by ADAMs contributes to the worsening of DN.
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Affiliation(s)
- L Lattenist
- Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
| | - P Ochodnický
- Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
| | - M Ahdi
- Department of Internal Medicine, Slotervaart Hospital, Amsterdam, the Netherlands
| | - N Claessen
- Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
| | - J C Leemans
- Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
| | - S C Satchell
- Academic Renal Unit, University of Bristol, Bristol, UK
| | - S Florquin
- Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
- Department of Pathology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands
| | - V E Gerdes
- Department of Internal Medicine, Slotervaart Hospital, Amsterdam, the Netherlands
- Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
| | - J J T H Roelofs
- Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
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White S, Chadban S. Diabetic kidney disease in Australia: current burden and future projections. Nephrology (Carlton) 2016; 19:450-8. [PMID: 24888506 DOI: 10.1111/nep.12281] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/22/2014] [Indexed: 11/28/2022]
Abstract
Diabetes mellitus is now the most common cause of new cases of end-stage kidney disease treated with kidney replacement therapy in Australia. In addition to the approximately 5000 Australians receiving maintenance dialysis or living with a kidney transplant as a consequence of diabetes, many die from untreated end-stage kidney disease due to diabetes (DM-ESKD) each year. For every Australian receiving renal replacement therapy due to diabetes, at least 50 others have earlier stages of diabetic kidney disease (DKD). Based on projected increases in type 2 diabetes prevalence, the size of this underlying population with DKD will potentially exceed half a million by 2025. In addition to the risk of developing DM-ESKD, this population is at increased risk of premature cardiovascular morbidity and all-cause mortality. Higher rates of hospitalization, use of specialist services and prescription drugs mean that those with DKD also incur significantly greater health care costs compared with those with diabetes or chronic kidney disease alone. However, in contrast to the increasing prevalence of diabetes and early stages of DKD, recent trends in the incidence of DM-ESKD suggest that better management in the earlier stages of DKD has been successful in slowing rates of disease progression. Simultaneous improvements in use of renin-angiotensin inhibitors and improved glycaemic and blood pressure control are likely to be largely responsible for this trend. Primary prevention, maximizing early detection of DKD and optimal management of diabetes and kidney disease hold great potential to attenuate the future health burden attributable to DKD in Australia.
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Affiliation(s)
- Sarah White
- Charles Perkins Centre and Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia
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Narres M, Claessen H, Droste S, Kvitkina T, Koch M, Kuss O, Icks A. The Incidence of End-Stage Renal Disease in the Diabetic (Compared to the Non-Diabetic) Population: A Systematic Review. PLoS One 2016; 11:e0147329. [PMID: 26812415 PMCID: PMC4727808 DOI: 10.1371/journal.pone.0147329] [Citation(s) in RCA: 127] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2015] [Accepted: 01/01/2016] [Indexed: 12/15/2022] Open
Abstract
End-stage renal disease (ESRD) in diabetes is a life threatening complication resulting in a poor prognosis for patients as well as high medical costs. The aims of this systematic review were (1) to evaluate the incidence of ESRD due to all causes and due to diabetic nephropathy in the diabetic population and differences between incidences of ESRD with respect to sex, ethnicity, age and regions, (2) to compare incidence rates in the diabetic and non-diabetic population, and (3) to investigate time trends. The systematic review was conducted according to the PRISMA group guidelines by performing systematic literature searches in the biomedical databases until January 3rd 2015; thirty-two studies were included. Among patients with incident type 1 diabetes the 30-year cumulative incidence ranged from 3.3% to 7.8%. Among patients with prevalent diabetes, incidence rates of ESRD due to all causes ranged from 132.0 to 167.0 per 100,000 person-years, whereas incidence rates of ESRD due to diabetic nephropathy varied from 38.4 to 804.0 per 100,000 person-years. The incidence of ESRD in the diabetic population was higher compared to the non-diabetic population, and relative risks varied from 6.2 in the white population to 62.0 among Native Americans. The results regarding time trends were inconsistent. The review conducted demonstrates the considerable variation of incidences of ESRD among the diabetic population. Consistent findings included an excess risk when comparing the diabetic to the non-diabetic population and ethnic differences. We recommend that newly designed studies should use standardized methods for the determination of ESRD and population at risk.
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MESH Headings
- Databases, Factual
- Diabetes Mellitus, Type 1/complications
- Diabetes Mellitus, Type 1/epidemiology
- Diabetes Mellitus, Type 1/ethnology
- Diabetes Mellitus, Type 2/complications
- Diabetes Mellitus, Type 2/epidemiology
- Diabetes Mellitus, Type 2/ethnology
- Diabetic Nephropathies/complications
- Diabetic Nephropathies/ethnology
- Humans
- Incidence
- Kidney Failure, Chronic/epidemiology
- Kidney Failure, Chronic/ethnology
- Kidney Failure, Chronic/etiology
- Risk Factors
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Affiliation(s)
- Maria Narres
- Institute for Biometrics and Epidemiology, German Diabetes Center, Düsseldorf, Germany
| | - Heiner Claessen
- Institute for Biometrics and Epidemiology, German Diabetes Center, Düsseldorf, Germany
| | - Sigrid Droste
- Department of Public Health, Heinrich-Heine-University, Düsseldorf, Germany
| | - Tatjana Kvitkina
- Institute for Biometrics and Epidemiology, German Diabetes Center, Düsseldorf, Germany
- Department of Public Health, Heinrich-Heine-University, Düsseldorf, Germany
| | - Michael Koch
- Center of Nephrology, Mettmann, Germany
- Clinic of Nephrology, Heinrich-Heine-University, Düsseldorf, Germany
| | - Oliver Kuss
- Institute for Biometrics and Epidemiology, German Diabetes Center, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
| | - Andrea Icks
- Institute for Biometrics and Epidemiology, German Diabetes Center, Düsseldorf, Germany
- Department of Public Health, Heinrich-Heine-University, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
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Hwang JC, Jiang MY, Lu YH, Weng SF. Impact of HCV Infection on Diabetes Patients for the Risk of End-Stage Renal Failure. Medicine (Baltimore) 2016; 95:e2431. [PMID: 26817874 PMCID: PMC4998248 DOI: 10.1097/md.0000000000002431] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Both diabetes mellitus (DM) and hepatitis C virus infection (HCVI) are associated with chronic kidney disease (CKD). The aim of this study was to evaluate whether HCVI increases the risk of end-stage renal disease (ESRD) in patients with DM.The National Health Insurance Research database of Taiwan was used to conduct this study. After excluding patients with a prior history of CKD, all patients with a first diagnosis of DM from January 1, 2000 to December 31, 2002 were enrolled. The patients who also had HCVI were defined as index cases (HCV group, n = 9787). A comparison cohort at a 1:1 ratio of random incident patients with DM without HCVI matched by age, sex, age at the diagnosis of DM, duration between the diagnosis of DM and the index date, and various comorbidities through propensity score matching were recruited (non-HCV group, n = 9787). The patients were followed until December 31, 2011.The cumulative incidence rate of developing ESRD was significantly higher in the HCV(+) group than in the non-HCV group (P = 0.008). The incidence rate ratio (IRR) for the risk of ESRD was also significantly higher in the HCV(+) group (IRR: 1.44; 95% CI: 1.09-1.89) than in the non-HCV group, especially for those with a younger age (<50 years; IRR: 2.05; 95% CI: 1.22-3.45) and HCVI within 4 years after the diagnosis of DM (IRR: 1.85; 95% CI: 1.16-2.97). After adjusting for comorbidities in multivariate Cox proportional hazard regression analysis, HCVI (HR: 1.47; 95% CI: 1.11-1.93) was an independent factor for developing ESRD in the patients with DM. After starting dialysis for ESRD, the HCV(+) patients had a similar mortality rate to those without HCVI (P = 0.84).HCVI increases the risk of developing ESRD in patients with DM, especially in younger patients and in those who develop HCVI sooner after a diagnosis of DM.
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Affiliation(s)
- Jyh-Chang Hwang
- From the Division of Nephrology, Chi Mei Medical Center, Tainan, Taiwan (JCH, MYJ, YHL); Department of Hospital and Health Care Administration, Chia Nan University of Pharmacy and Science, Tainan, Taiwan (JCH, SFW); and Division of Medical Research, Chi Mei Medical Center, Tainan, Taiwan (SFW)
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Montero RM, Covic A, Gnudi L, Goldsmith D. Diabetic nephropathy: What does the future hold? Int Urol Nephrol 2015; 48:99-113. [PMID: 26438328 PMCID: PMC4705119 DOI: 10.1007/s11255-015-1121-y] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2015] [Accepted: 09/19/2015] [Indexed: 12/24/2022]
Abstract
The consensus management of diabetic nephropathy (DN) in 2015 involves good control of glycaemia, dyslipidaemia and blood pressure (BP). Blockade of the renin-angiotensin-aldosterone system using angiotensin-converting enzyme inhibitors, angiotensin-2 receptor blockers or mineralocorticoid inhibitors are key therapeutic approaches, shown to be beneficial once overt nephropathy is manifest, as either, or both, of albuminuria and loss of glomerular filtration rate. Some significant additional clinical benefits in slowing the progression of DN was reported from the Remission clinic experience, where simultaneous intensive control of BP, tight glycaemic control, weight loss, exercise and smoking cessation were prioritised in the management of DN. This has not proved possible to translate to more conventional clinical settings. This review briefly looks over the history and limitations of current therapy from landmark papers and expert reviews, and following an extensive PubMed search identifies the most promising clinical biomarkers (both established and proposed). Many challenges need to be addressed urgently as in order to obtain novel therapies in the clinic; we also need to examine what we mean by remission, stability and progression of DN in the modern era.
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Affiliation(s)
- R M Montero
- Renal, Dialysis and Transplantation Unit, Guy's and St Thomas' Hospital, London, UK.
| | - A Covic
- Hospital "C.I.Parhon" and University of Medicine "Grigore T Popa", Iasi, Romania
| | - L Gnudi
- Cardiovascular Division, Department of Diabetes and Endocrinology, Guy's and St Thomas' Hospital, School of Medicine and Life Science, King's College London, London, UK
| | - D Goldsmith
- Renal, Dialysis and Transplantation Unit, Guy's and St Thomas' Hospital, London, UK
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Brück K, Stel VS, Fraser S, De Goeij MCM, Caskey F, Abu-Hanna A, Jager KJ. Translational research in nephrology: chronic kidney disease prevention and public health. Clin Kidney J 2015; 8:647-55. [PMID: 26613019 PMCID: PMC4655791 DOI: 10.1093/ckj/sfv082] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2015] [Accepted: 08/03/2015] [Indexed: 12/17/2022] Open
Abstract
This narrative review evaluates translational research with respect to five important risk factors for chronic kidney disease (CKD): physical inactivity, high salt intake, smoking, diabetes and hypertension. We discuss the translational research around prevention of CKD and its complications both at the level of the general population, and at the level of those at high risk, i.e. people at increased risk for CKD or CKD complications. At the population level, all three lifestyle risk factors (physical inactivity, high salt intake and smoking) have been translated into implemented measures and clear population health improvements have been observed. At the ‘high-risk’ level, the lifestyle studies reviewed have tended to focus on the individual impact of specific interventions, and their wider implementation and impact on CKD practice are more difficult to establish. The treatment of both diabetes and hypertension appears to have improved, however the impact on CKD and CKD complications was not always clear. Future studies need to investigate the most effective translational interventions in low and middle income countries.
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Affiliation(s)
- Katharina Brück
- ERA-EDTA Registry , Department of Medical Informatics, Academic Medical Center - University of Amsterdam , Amsterdam , The Netherlands
| | - Vianda S Stel
- ERA-EDTA Registry , Department of Medical Informatics, Academic Medical Center - University of Amsterdam , Amsterdam , The Netherlands
| | - Simon Fraser
- Academic Unit of Primary Care and Population Sciences , University of Southampton , Southampton , UK
| | - Moniek C M De Goeij
- Department of Public Health , Academic Medical Center (AMC) - University of Amsterdam , Amsterdam , The Netherlands
| | | | - Ameen Abu-Hanna
- Department of Medical Informatics , Academic Medical Center - University of Amsterdam , Amsterdam , The Netherlands
| | - Kitty J Jager
- ERA-EDTA Registry , Department of Medical Informatics, Academic Medical Center - University of Amsterdam , Amsterdam , The Netherlands
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Affiliation(s)
- Mark E Molitch
- Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL
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43
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Abstract
IN BRIEF Hypertension is prevalent in most individuals with diabetic kidney disease (DKD). Failure to treat hypertension appropriately in this subgroup of patients results in an increased risk of cardiovascular morbidity and mortality, as well as a faster progression of kidney disease. The current guidance for appropriate treatment of hypertension in this high-risk population provides an opportunity to improve both kidney and cardiovascular outcomes. This review discusses the current state of evidence-based hypertension management in patients with DKD.
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Affiliation(s)
- Vikram Patney
- University of Missouri Columbia School of Medicine, Department of Medicine, Division of Nephrology and Hypertension, Columbia, MO
| | - Adam Whaley-Connell
- University of Missouri Columbia School of Medicine, Department of Medicine, Division of Nephrology and Hypertension, Columbia, MO
- Research Service, Harry S. Truman Memorial Veterans’ Hospital, Columbia, MO
| | - George Bakris
- The University of Chicago Medicine, ASH Comprehensive Hypertension Center, Chicago, IL
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Abstract
The kidney is arguably the most important target of microvascular damage in diabetes. A substantial proportion of individuals with diabetes will develop kidney disease owing to their disease and/or other co-morbidity, including hypertension and ageing-related nephron loss. The presence and severity of chronic kidney disease (CKD) identify individuals who are at increased risk of adverse health outcomes and premature mortality. Consequently, preventing and managing CKD in patients with diabetes is now a key aim of their overall management. Intensive management of patients with diabetes includes controlling blood glucose levels and blood pressure as well as blockade of the renin-angiotensin-aldosterone system; these approaches will reduce the incidence of diabetic kidney disease and slow its progression. Indeed, the major decline in the incidence of diabetic kidney disease (DKD) over the past 30 years and improved patient prognosis are largely attributable to improved diabetes care. However, there remains an unmet need for innovative treatment strategies to prevent, arrest, treat and reverse DKD. In this Primer, we summarize what is now known about the molecular pathogenesis of CKD in patients with diabetes and the key pathways and targets implicated in its progression. In addition, we discuss the current evidence for the prevention and management of DKD as well as the many controversies. Finally, we explore the opportunities to develop new interventions through urgently needed investment in dedicated and focused research. For an illustrated summary of this Primer, visit: http://go.nature.com/NKHDzg.
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Aroda VR, Getaneh A. Guiding diabetes screening and prevention: rationale, recommendations and remaining challenges. Expert Rev Endocrinol Metab 2015; 10:381-398. [PMID: 30293496 DOI: 10.1586/17446651.2015.1054280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Advances made in diabetes management are not sufficient to reduce morbidity, mortality and cost without making prevention efforts at various levels imperative for substantial impact. Research has demonstrated the efficacy of lifestyle intervention and medications in preventing type 2 diabetes among diverse high-risk groups commonly identified with oral glucose tolerance testing. Efficacy, sustainability and safety data are most comprehensive for lifestyle and metformin, with other medications also demonstrating efficacy and potential in the pharmacoprevention of diabetes. Subsequent implementation studies have demonstrated feasibility of lifestyle intervention programs at health centers, communities, and at local and national government levels. Challenges remain in widespread translation and reaching and engaging at-risk individuals and populations.
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Affiliation(s)
- Vanita R Aroda
- a 1 MedStar Health Research Institute, Hyattsville, MD, USA
- b 2 Georgetown University School of Medicine, WA, USA
| | - Asqual Getaneh
- a 1 MedStar Health Research Institute, Hyattsville, MD, USA
- c 3 MedStar Washington Hospital Center, WA, USA
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The Concept and the Epidemiology of Diabetic Nephropathy Have Changed in Recent Years. J Clin Med 2015; 4:1207-16. [PMID: 26239554 PMCID: PMC4484995 DOI: 10.3390/jcm4061207] [Citation(s) in RCA: 97] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2015] [Revised: 04/27/2015] [Accepted: 05/11/2015] [Indexed: 11/22/2022] Open
Abstract
Diabetes Mellitus (DM) is a growing worldwide epidemic. It was estimated that more than 366 million people would be affected. DM has spread its presence over the world due to lifestyle changes, increasing obesity and ethnicities, among others. Diabetic nephropathy (DN) is one of the most important DM complications. A changing concept has been introduced from the classical DN to diabetic chronic kidney disease (DCKD), taking into account that histological kidney lesions may vary from the nodular or diffuse glomerulosclerosis to tubulointerstitial and/or vascular lesions. Recent data showed how primary and secondary prevention were the key to reduce cardiovascular episodes and improve life expectancy in diabetic patients. A stabilization in the rate of end stage kidney disease has been observed in some countries, probably due to the increased awareness by primary care physicians about the prognostic importance of chronic kidney disease (CKD), better control of blood pressure and glycaemia and the implementation of protocols and clinical practice recommendations about the detection, prevention and treatment of CKD in a coordinated and multidisciplinary management of the DM patient. Early detection of DM and DCKD is crucial to reduce morbidity, mortality and the social and economic impact of DM burden in this population.
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Palmer SC, Mavridis D, Navarese E, Craig JC, Tonelli M, Salanti G, Wiebe N, Ruospo M, Wheeler DC, Strippoli GFM. Comparative efficacy and safety of blood pressure-lowering agents in adults with diabetes and kidney disease: a network meta-analysis. Lancet 2015; 385:2047-56. [PMID: 26009228 DOI: 10.1016/s0140-6736(14)62459-4] [Citation(s) in RCA: 254] [Impact Index Per Article: 25.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND The comparative efficacy and safety of pharmacological agents to lower blood pressure in adults with diabetes and kidney disease remains controversial. We aimed to investigate the benefits and harms of blood pressure-lowering drugs in this population of patients. METHODS We did a network meta-analysis of randomised trials from around the world comparing blood pressure-lowering agents in adults with diabetic kidney disease. Electronic databases (the Cochrane Collaboration, Medline, and Embase) were searched systematically up to January, 2014, for trials in adults with diabetes and kidney disease comparing orally administered blood pressure-lowering drugs. Primary outcomes were all-cause mortality and end-stage kidney disease. We also assessed secondary safety and cardiovascular outcomes. We did random-effects network meta-analysis to obtain estimates for primary and secondary outcomes and we presented these estimates as odds ratios or standardised mean differences with 95% CIs. We ranked the comparative effects of all drugs against placebo with surface under the cumulative ranking (SUCRA) probabilities. FINDINGS 157 studies comprising 43,256 participants, mostly with type 2 diabetes and chronic kidney disease, were included in the network meta-analysis. No drug regimen was more effective than placebo for reducing all-cause mortality. However, compared with placebo, end-stage renal disease was significantly less likely after dual treatment with an angiotensin-receptor blocker (ARB) and an angiotensin-converting-enzyme (ACE) inhibitor (odds ratio 0·62, 95% CI 0·43-0·90) and after ARB monotherapy (0·77, 0·65-0·92). No regimen significantly increased hyperkalaemia or acute kidney injury, although combined ACE inhibitor and ARB treatment had the lowest rank among all interventions because of borderline increases in estimated risks of these harms (odds ratio 2·69, 95% CI 0·97-7·47 for hyperkalaemia; 2·69, 0·98-7·38 for acute kidney injury). INTERPRETATION No blood pressure-lowering strategy prolonged survival in adults with diabetes and kidney disease. ACE inhibitors and ARBs, alone or in combination, were the most effective strategies against end-stage kidney disease. Any benefits of combined ACE inhibitor and ARB treatment need to be balanced against potential harms of hyperkalaemia and acute kidney injury. FUNDING Canterbury Medical Research Foundation, Italian Medicines Agency.
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Affiliation(s)
- Suetonia C Palmer
- Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand
| | - Dimitris Mavridis
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece; Department of Primary Education, University of Ioannina, Ioannina, Greece
| | - Eliano Navarese
- Department of Cardiology and Internal Medicine, Nicolaus Copernicus University, Collegium Medicum, Bydgoszcz, Poland
| | - Jonathan C Craig
- Sydney School of Public Health, University of Sydney, Sydney, Australia
| | - Marcello Tonelli
- Cumming School of Medicine, Health Sciences Centre, University of Calgary, Calgary, AB, Canada
| | - Georgia Salanti
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
| | - Natasha Wiebe
- Department of Medicine, Division of Nephrology and Immunology, University of Alberta, AB, Canada
| | - Marinella Ruospo
- Department of Translational Medicine, Division of Nephrology and Transplantation, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy; Diaverum Medical Scientific Office, Diaverum Sweden AB, Lund, Sweden
| | - David C Wheeler
- Royal Free and University College Medical School, London, UK
| | - Giovanni F M Strippoli
- Sydney School of Public Health, University of Sydney, Sydney, Australia; Diaverum Medical Scientific Office, Diaverum Sweden AB, Lund, Sweden; Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy.
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Prischl FC, Auinger M, Säemann M, Mayer G, Rosenkranz AR, Wallner M, Kramar R. Diabetes-related end-stage renal disease in Austria 1965-2013. Nephrol Dial Transplant 2015; 30:1920-7. [PMID: 25977308 DOI: 10.1093/ndt/gfv113] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2014] [Accepted: 03/23/2015] [Indexed: 11/12/2022] Open
Abstract
BACKGROUND Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD) in Austria, accounting for a high burden of morbidity and mortality. In this nationwide study, we aimed to evaluate the incidence and fate of patients with DKD-ESRD over time. METHODS Data (collected annually) from the Austrian Dialysis- and Transplant Registry were analysed for the development of ESRD due to DKD from 1965 to 2013. RESULTS Over 48 years, 8322 and 22 975 patients with ESRD due to diabetes and non-diabetes, respectively, entered dialysis. While DKD-ESRD-patients were not dialysed until 1974, in 1975 seven type 1- and one type 2-diabetics started dialysis (1.06 per million population-PMP). In the mid-eighties, DKD-ESRD-patients increasingly were accepted for dialysis (1986: 14.53 PMP, 1996: 31.16 PMP). After a peak incidence of 415 diabetic ESRD-patients in 2006 (50.19 PMP), numbers decreased continuously thereafter (2013: 299 patients, 35.73 PMP). Mean age at start of dialysis increased over time and was lower in type 1- and higher in type 2- compared with non-diabetic patients. Five-year-survival-probability in two diabetic ESRD-cohorts, starting in 2007/08 and 10 years earlier was calculated. Five-year-survival was 28% in 1997/98 and 37.5% in 2007/08. Adjusted relative risk reduction was 33% (HR 0.67, CI 95% 0.57-0.78; P < 0.001). CONCLUSION Despite a growing prevalence of diabetes, the incidence of diabetic ESRD has decreased after 2006. Five-year-survival-probability has improved over 10 years. Multifactorial therapeutic interventions may have resulted in this improvement.
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Affiliation(s)
- Friedrich C Prischl
- Division of Nephrology, 4th Department of Medicine, Klinikum Wels-Grieskirchen, Wels, Austria
| | - Martin Auinger
- 3rd Department of Internal Medicine, Hospital Hietzing, Vienna, Austria
| | - Marcus Säemann
- Department for Nephrology and Dialysis, University Clinic for Internal Medicine 3, Medical University of Vienna, Vienna, Austria
| | - Gert Mayer
- Department of Internal Medicine 4 (Nephrology and Hypertension), Medical University of Innsbruck, Innsbruck, Austria
| | - Alexander R Rosenkranz
- Clinical Division of Nephrology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
| | - Manfred Wallner
- Division of Nephrology, 4th Department of Medicine, Klinikum Wels-Grieskirchen, Wels, Austria
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Pinho NAD, Oliveira RDCBD, Pierin AMG. Hypertensive patients with and without kidney disease: assessment of risk factors. Rev Esc Enferm USP 2015; 49 Spec No:101-8. [PMID: 26761699 DOI: 10.1590/s0080-623420150000700015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2015] [Accepted: 08/20/2015] [Indexed: 11/22/2022] Open
Abstract
Objective To compare hypertensive patients with and without chronic kidney disease and identify factors associated with their clinical condition and antihypertensive treatment. Method This was a cross-sectional study conducted with patients hospitalized in a general medical ward at a university hospital in the city of São Paulo, Brazil. Data were collected from medical records. Significance was set at p<0.05. Results Of the 386 patients studied, 59.3% presented hypertension and, of these, 37.5% presented chronic kidney disease. The data showed an independent association between chronic kidney disease and prior history of diabetes (OR 1.86; CI 1.02-3.41), congestive heart failure (OR 3.42; CI 1.36-9.03) and living with a partner (OR 1.99; CI 1.09-3.69). Regarding antihypertensive treatment, there was a difference (p<0.05) between hypertensive patients with and without chronic kidney disease in terms of administering healthcare treatment (93.2% versus 77.7%); ongoing use of antihypertensive drugs, (79.1% versus 66.4%); higher number of antihypertensive drugs; the use of beta-adrenergic blockers (34.9%versus 19.6%), calcium channel blockers (29.1%versus 11.2%), loop diuretics (30.2%versus 10.5%) and vasodilators (9.3%versus 2.1%). Conclusion The hypertensive patients with chronic kidney disease presented a more compromised clinical profile; however, the attitudes of these patients toward antihypertensive treatment were more positive than those without chronic kidney disease.
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Affiliation(s)
| | | | - Angela Maria Geraldo Pierin
- Departamento de Enfermagem Médico-Cirúrgica, Escola de Enfermagem, Universidade de São Paulo, São Paulo, SP, Brasil
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van Dijk PR, Kramer A, Logtenberg SJJ, Hoitsma AJ, Kleefstra N, Jager KJ, Bilo HJG. Incidence of renal replacement therapy for diabetic nephropathy in the Netherlands: Dutch diabetes estimates (DUDE)-3. BMJ Open 2015; 5:e005624. [PMID: 25636789 PMCID: PMC4316478 DOI: 10.1136/bmjopen-2014-005624] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
OBJECTIVES Describe the incidence, prevalence and survival of patients needing renal replacement therapy (RRT) for end-stage renal disease (ESRD) due to diabetes mellitus (DM)-related glomerulosclerosis or nephropathy (diabetic nephropathy, DN) in the Netherlands. DESIGN Using the national registry for RRT (RENINE-registry), data of all Dutch individuals initiating RRT for ESRD and having DN as primary diagnosis in the period 2000-2012 were obtained. SETTING Observational study in the Netherlands. PATIENTS Patients with ESRD needing RRT for DN. OUTCOME MEASUREMENTS Age and gender adjusted incidence and prevalence of RRT for DN in the period 2000-2012. In addition, trends in time and patient's survival were examined. RESULTS The prevalence of DM in the general population increased from approximately 466 000 in 2000 to 815 000 in 2011. The number of individuals who started RRT with DN as primary diagnosis was 17.4 per million population (pmp) in 2000 and 19.1 pmp in 2012, with an annual percentage change (APC) of 0.8% (95% CI -0.4 to 2.0). For RRT due to type 1 DN, the incidence decreased from 7.3 to 3.5 pmp (APC -4.8%, 95% CI -6.5 to -3.1) while it increased for type 2 DN from 10.1 to 15.6 pmp (APC 3.1%, 95% CI 1.3 to 4.8). After 2009, the prevalence of RRT for DN remained stable (APC 1.0%, 95% CI -0.4 to 2.5). Compared to the period 2000-2004, patients initiating RRT and dialysis in 2005-2009 had better survival, HRs 0.8 (95% CI 0.7 to 0.8) and 0.8 (95% CI 0.7 to 0.9), respectively, while survival after kidney transplantation remained stable, HR 0.8, 95% CI 0.5 to 1.1). CONCLUSIONS Over the last decade, the incidence of RRT for DN was stable, with a decrease in RRT due to type 1 DN and an increase due to type 2 DN, while survival increased.
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Affiliation(s)
| | - Anneke Kramer
- Department of Medical Informatics, Academic Medical Center, University of Amsterdam, ERA-EDTA Registry, Amsterdam, The Netherlands
| | - Susan J J Logtenberg
- Diabetes Centre, Isala, Zwolle, The Netherlands
- Department of Internal Medicine, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
| | - Andries J Hoitsma
- Department of Nephrology, Radboud University Medical Centre, Nijmegen, The Netherlands
- RENINE Registry, Leiden, The Netherlands
| | - Nanne Kleefstra
- Diabetes Centre, Isala, Zwolle, The Netherlands
- Department of Internal Medicine, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
| | - Kitty J Jager
- Department of Medical Informatics, Academic Medical Center, University of Amsterdam, ERA-EDTA Registry, Amsterdam, The Netherlands
| | - Henk J G Bilo
- Diabetes Centre, Isala, Zwolle, The Netherlands
- Department of Internal Medicine, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
- Department of Internal Medicine, Isala, Zwolle, The Netherlands
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